Sample records for saclay cea

  1. International Fusion Materials Irradiation Facility injector acceptance tests at CEA/Saclay: 140 mA/100 keV deuteron beam characterization

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

    Gobin, R., E-mail: rjgobin@cea.fr; Bogard, D.; Chauvin, N.

    In the framework of the ITER broader approach, the International Fusion Materials Irradiation Facility (IFMIF) deuteron accelerator (2 × 125 mA at 40 MeV) is an irradiation tool dedicated to high neutron flux production for future nuclear plant material studies. During the validation phase, the Linear IFMIF Prototype Accelerator (LIPAc) machine will be tested on the Rokkasho site in Japan. This demonstrator aims to produce 125 mA/9 MeV deuteron beam. Involved in the LIPAc project for several years, specialists from CEA/Saclay designed the injector based on a SILHI type ECR source operating at 2.45 GHz and a 2 solenoid lowmore » energy beam line to produce such high intensity beam. The whole injector, equipped with its dedicated diagnostics, has been then installed and tested on the Saclay site. Before shipment from Europe to Japan, acceptance tests have been performed in November 2012 with 100 keV deuteron beam and intensity as high as 140 mA in continuous and pulsed mode. In this paper, the emittance measurements done for different duty cycles and different beam intensities will be presented as well as beam species fraction analysis. Then the reinstallation in Japan and commissioning plan on site will be reported.« less

  2. Saclay Compact Accelerator-driven Neutron Sources (SCANS)

    NASA Astrophysics Data System (ADS)

    Marchix, A.; Letourneau, A.; Tran, HN; Chauvin, N.; Menelle, A.; Ott, F.; Schwindling, J.

    2018-06-01

    For next decade, the European neutron scattering community will face of important changes, as many facilities will close, strictly fission-based sources. This statement mainly concerns France with the planned closure of Orphee and ILL. At CEA-Saclay, the project SONATE has been launched in order to provide a high intensity neutron source in Saclay site, this project is based on Compact Accelerator-driven Neutron Sources technology coupled to high-intensity beams. The goal of SONATE is to develop a 50 kW target, aiming to produce at least a neutron yield of 1013 s-1 in pulse mode with a peak current of 100 mA. We have investigated in this document the best combinations of beam/target which would lead to this substantial neutron yields. Further investigations and tests have to be carry out, especially due to sparse data on thick target and such low-energy beams considered in this document. An intermediate step to the SONATE project is under test and development, called IPHI-NEUTRON, which would lead to provide a small-size neutron facility mainly devoted to neutron imagery for industry. This step is based on the existing 3 MeV proton beam, named IPHI. Best target candidates are Lithium and Beryllium, leading respectively to a neutron yield of about 2.1013 s-1 and 4.1012 s-1.

  3. Welcome to the Saclay Propeller Testing Center

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The history, organization, purpose, and activities of the Saclay Propeller Testing Center is described. A list is provided of all facilities, current and planned, and the types of tests done in each facility are summarized.

  4. Development activities on NIR large format MCT detectors for astrophysics and space science at CEA and SOFRADIR

    NASA Astrophysics Data System (ADS)

    Boulade, Olivier; Moreau, Vincent; Mulet, Patrick; Gravrand, Olivier; Cervera, Cyril; Zanatta, Jean-Paul; Castelein, Pierre; Guellec, Fabrice; Fièque, Bruno; Chorier, Philippe; Roumegoux, Julien

    2016-07-01

    CEA and SOFRADIR have been manufacturing and characterizing near infrared detectors in the frame of ESA's near infrared large format sensor array roadmap to develop a 2Kx2K large format low flux low noise device for space applications such as astrophysics. These detectors use HgCdTe as the absorbing material and p/n diode technology. The technological developments (photovoltaic technology, readout circuit, ...) are shared between CEA/LETI and SOFRADIR, both in Grenoble, while most of the performances are evaluated at CEA/IRFU in Saclay where a dedicated test facility has been developed, in particular to measure very low dark currents. The paper will present the current status of these developments at the end of ESA's NIRLFSA phase 2. The performances of the latest batch of devices meet or are very close to all the requirements (quantum efficiency, dark current, cross talk, readout noise, ...) even though a glow induced by the ROIC prevents the accurate measurement of the dark current. The current devices are fairly small, 640x512 15μm pixels, and the next phase of activity will target the development of a full size 2Kx2K detector. From the design and development, to the manufacturing and finally the testing, that type of detector requests a high level of mastering. An appropriate manufacturing and process chain compatible with such a size is needed at industrial level and results obtained with CEA technology coupled with Sofradir industrial experience and work on large dimension detector allow French actors to be confident to address this type of future missions.

  5. Present status of the low energy linac-based slow positron beam and positronium spectrometer in Saclay

    NASA Astrophysics Data System (ADS)

    Liszkay, L.; Comini, P.; Corbel, C.; Debu, P.; Grandemange, P.; Pérez, P.; Rey, J.-M.; Reymond, J.-M.; Ruiz, N.; Sacquin, Y.; Vallage, B.

    2014-04-01

    A new slow positron beamline featuring a large acceptance positronium lifetime spectrometer has been constructed and tested at the linac-based slow positron source at IRFU CEA Saclay, France. The new instrument will be used in the development of a dense positronium target cloud for the GBAR experiment. The GBAR project aims at precise measurement of the gravitational acceleration of antihydrogen in the gravitational field of the Earth. Beyond application in fundamental science, the positron spectrometer will be used in materials research, for testing thin porous films and layers by means of positronium annihilation. The slow positron beamline is being used as a test bench to develop further instrumentation for positron annihilation spectroscopy (Ps time-of-flight, pulsed positron beam). The positron source is built on a low energy linear electron accelerator (linac). The 4.3 MeV electron energy used is well below the photoneutron threshold, making the source a genuine on-off device, without remaining radioactivity. The spectrometer features large BGO (Bismuth Germanate) scintillator detectors, with sufficiently large acceptance to detect all ortho-positronium annihilation lifetime components (annihilation in vacuum and in nanopores).

  6. Neutron Activation and Thermoluminescent Detector Responses to a Bare Pulse of the CEA Valduc SILENE Critical Assembly

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

    Miller, Thomas Martin; Celik, Cihangir; McMahan, Kimberly L.

    This benchmark experiment was conducted as a joint venture between the US Department of Energy (DOE) and the French Commissariat à l'Energie Atomique (CEA). Staff at the Oak Ridge National Laboratory (ORNL) in the US and the Centre de Valduc in France planned this experiment. The experiment was conducted on October 11, 2010 in the SILENE critical assembly facility at Valduc. Several other organizations contributed to this experiment and the subsequent evaluation, including CEA Saclay, Lawrence Livermore National Laboratory (LLNL), the Y-12 National Security Complex (NSC), Babcock International Group in the United Kingdom, and Los Alamos National Laboratory (LANL). Themore » goal of this experiment was to measure neutron activation and thermoluminescent dosimeter (TLD) doses from a source similar to a fissile solution critical excursion. The resulting benchmark can be used for validation of computer codes and nuclear data libraries as required when performing analysis of criticality accident alarm systems (CAASs). A secondary goal of this experiment was to qualitatively test performance of two CAAS detectors similar to those currently and formerly in use in some US DOE facilities. The detectors tested were the CIDAS MkX and the Rocky Flats NCD-91. These detectors were being evaluated to determine whether they would alarm, so they were not expected to generate benchmark quality data.« less

  7. Development and characterisation of MCT detectors for space astrophysics at CEA

    NASA Astrophysics Data System (ADS)

    Boulade, O.; Baier, N.; Castelein, P.; Cervera, C.; Chorier, P.; Destefanis, G.; Fièque, B.; Gravrand, O.; Guellec, F.; Moreau, V.; Mulet, P.; Pinsard, F.; Zanatta, J.-P.

    2017-11-01

    The Laboratoire Electronique et Traitement de l'Information (LETI) of the Commissariat à l'Energie Atomique (CEA, Grenoble, France) has been involved in the development of infrared detectors based on HgCdTe (MCT) material for over 30 years, mainly for defence and security programs [1]. Once the building blocks are developed at LETI (MCT material process, diode technology, hybridization, …), the industrialization is performed at SOFRADIR (also in Grenoble, France) which also has its own R&D program [2]. In past years, LETI also developed infrared detectors for space astrophysics in the mid infrared range - the long wave detector of the ISOCAM camera onboard ISO - as well as in the far infrared range - the bolometer arrays of the Herschel/PACS photometer unit -, both instruments which were under the responsibility of the Astrophysics department of CEA (IRFU/SAp, Saclay, France). Nowadays, the infrared detectors used in space and ground based astronomical instruments all come from vendors in the US. For programmatic reasons - increase the number of available vendors, decrease the cost, mitigate possible export regulations, …- as well as political ones - spend european money in Europe -, the European Space Agency (ESA) defined two roadmaps (one in the NIR-SWIR range, one in the MWIR-LWIR range) that will eventually allow for the procurement of infrared detectors for space astrophysics within Europe. The French Space Agency (CNES) also started the same sort of roadmaps, as part of its contribution to the different space missions which involve delivery of instruments by French laboratories. It is important to note that some of the developments foreseen in these roadmaps also apply to Earth Observations. One of the main goal of the ESA and CNES roadmaps is to reduce the level of dark current in MCT devices at all wavelengths. The objective is to use the detectors at the highest temperature where the noise induced by the dark current stays compatible with the photon

  8. Relationship of serum CEA levels to tumour size and CEA content in nude mice bearing colonic-tumour xenografts.

    PubMed Central

    Lewis, J. C.; Keep, P. A.

    1981-01-01

    The relationship of serum carcinoembryonic antigen (CEA) levels to tumour size and antigen content was studied in nude mice bearing well differentiated, mucinous human colonic-tumour xenografts. Blood samples were taken from normal nude mice and others bearing xenografts, whose size had been calculated from in vivo measurements; saline and KCl extracts were made of a proportion of these tumours. Sera and tissue extracts were assayed for CEA activity by double-antibody radioimmunoassay. Extracts were also made from the livers and spleens of tumour-bearing and normal nude mice. All normal sera and 78% of sera from tumour-bearing animals had CEA values less than 11.4 ng/ml. No clear correlation was found between serum CEA levels greater than 11.4 ng/ml and tumour size or weight, or between serum CEA and tumour CEA concentrations or total CEA burden. The concentration of CEA in those tumours tested varied from 1 to 22 microgram/g. Our results confirm and extend the conclusions reached by others (Stragand et al., 1980) studying the significance of serum CEA levels with xenograft model systems. The complexity of factors contributing to circulating CEA is discussed in the light of our findings. Images Fig. 1 PMID:7284235

  9. [Significance of CEA in gastric and colorectal cancer].

    PubMed

    Uehara, K; Miyamoto, Y; Izuo, M; Shiozaki, H; Aiba, S; Matsumoto, H

    1985-04-01

    The determination of serum CEA (Sandwich method) and CEA staining (PAP method) of excised specimens were performed in patients with gastric or colorectal cancer, and the biological characteristics of each cancer and the factors to increase serum CEA were studied with the following results: As colonic cancer has strong CEA productivity, serum CEA can be useful for the detection of cancer, and especially effective for the postoperative observation. Gastric cancer has weak CEA productivity, and serum CEA is not so useful in the detection of cancer and the judgement of resectability. The CEA positive rate of tissue with CEA staining was 80% in gastric cancer, 100% in colonic cancer, and were nearly equal to the CEA positive rate of serum in the group of terminal stage. In the mode of CEA staining of cancerous cells, IV type was observed most frequently in gastric cancer, and I type in colonic cancer. Among the resected cases showing more than 7ng/ml serum CEA, differentiated type, lymph node metastasis (+), the degree of tissue staining with CEA staining, the mode of cell staining O or I type in gastric cancer and I type in colonic cancer were observed in common.

  10. A monoclonal antibody against neem leaf glycoprotein recognizes carcinoembryonic antigen (CEA) and restricts CEA expressing tumor growth.

    PubMed

    Das, Arnab; Barik, Subhasis; Banerjee, Saptak; Bose, Anamika; Sarkar, Koustav; Biswas, Jaydip; Baral, Rathindranath; Pal, Smarajit

    2014-10-01

    Carcinoembryonic antigen (CEA) is one of the promising tumor antigens mainly associated with carcinoma of the colon, lung, breast, etc. and received wide attention for cancer immunotherapy. Neem leaf glycoprotein (NLGP), an effective immunomodulator, is able to generate humoral and cellular immune responses in murine tumor models. We have generated a monoclonal antibody (mAb) against NLGP by fusing NLGP-immunized mice splenocytes with nonsecretory myeloma cells. A highly anti-NLGP mAb secreting clone (1C8; IgG2a in nature) has been identified and propagated in culture. 1C8 recognizes human CEA as good as NLGP by enzyme linked immunosorbent assay, Western blotting, and immunoprecipitation. 1C8 detects CEA on colon cancer tissues by immunochistochemistry. By flow cytometry, 1C8 specifically reacts with CEA(+) human (Colo-205, HCT-116, and HT-29) and mouse (CT-26) colon cancer cells, but it showed minimum reactivity with CEA(-) human (MCF7, SiHa, and SCC084) and mouse (B16MelF10) cancer cells. This anti-NLGP 1C8 mAb revealed significant antitumor activity and better survivability in vivo in animals bearing mouse (CT-26 in BALB/c) and human (Colo-205 in athymic nude) CEA(+) cancer cells. 1C8 has no direct influence on proliferation and migration of CEA(+) cells, however, NK cell-dependent strong antibody-dependent cellular cytotoxicity reaction toward CEA(+) cells and normalization of angiogenesis are chiefly associated with tumor growth restriction. Obtained results provided a new immunotherapeutic approach for the effective management of CEA(+) tumors.

  11. Evaluation of the concrete shield compositions from the 2010 criticality accident alarm system benchmark experiments at the CEA Valduc SILENE facility

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

    Miller, Thomas Martin; Celik, Cihangir; Dunn, Michael E

    In October 2010, a series of benchmark experiments were conducted at the French Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA) Valduc SILENE facility. These experiments were a joint effort between the United States Department of Energy Nuclear Criticality Safety Program and the CEA. The purpose of these experiments was to create three benchmarks for the verification and validation of radiation transport codes and evaluated nuclear data used in the analysis of criticality accident alarm systems. This series of experiments consisted of three single-pulsed experiments with the SILENE reactor. For the first experiment, the reactor was bare (unshielded), whereasmore » in the second and third experiments, it was shielded by lead and polyethylene, respectively. The polyethylene shield of the third experiment had a cadmium liner on its internal and external surfaces, which vertically was located near the fuel region of SILENE. During each experiment, several neutron activation foils and thermoluminescent dosimeters (TLDs) were placed around the reactor. Nearly half of the foils and TLDs had additional high-density magnetite concrete, high-density barite concrete, standard concrete, and/or BoroBond shields. CEA Saclay provided all the concrete, and the US Y-12 National Security Complex provided the BoroBond. Measurement data from the experiments were published at the 2011 International Conference on Nuclear Criticality (ICNC 2011) and the 2013 Nuclear Criticality Safety Division (NCSD 2013) topical meeting. Preliminary computational results for the first experiment were presented in the ICNC 2011 paper, which showed poor agreement between the computational results and the measured values of the foils shielded by concrete. Recently the hydrogen content, boron content, and density of these concrete shields were further investigated within the constraints of the previously available data. New computational results for the first experiment are now

  12. Neutron Activation Foil and Thermoluminescent Dosimeter Responses to a Polyethylene Reflected Pulse of the CEA Valduc SILENE Critical Assembly

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

    Miller, Thomas Martin; Celik, Cihangir; McMahan, Kimberly L.

    This benchmark experiment was conducted as a joint venture between the US Department of Energy (DOE) and the French Commissariat à l'Energie Atomique (CEA). Staff at the Oak Ridge National Laboratory (ORNL) in the US and the Centre de Valduc in France planned this experiment. The experiment was conducted on October 19, 2010 in the SILENE critical assembly facility at Valduc. Several other organizations contributed to this experiment and the subsequent evaluation, including CEA Saclay, Lawrence Livermore National Laboratory (LLNL), the Y-12 National Security Complex (NSC), Babcock International Group in the United Kingdom, and Los Alamos National Laboratory (LANL). Themore » goal of this experiment was to measure neutron activation and thermoluminescent dosimeter (TLD) doses from a source similar to a fissile solution critical excursion. The resulting benchmark can be used for validation of computer codes and nuclear data libraries as required when performing analysis of criticality accident alarm systems (CAASs). A secondary goal of this experiment was to qualitatively test performance of two CAAS detectors similar to those currently and formerly in use in some US DOE facilities. The detectors tested were the CIDAS MkX and the Rocky Flats NCD-91. The CIDAS detects gammas with a Geiger-Muller tube and the Rocky Flats detects neutrons via charged particles produced in a thin 6LiF disc depositing energy in a Si solid state detector. These detectors were being evaluated to determine whether they would alarm, so they were not expected to generate benchmark quality data.« less

  13. Neutron Activation Foil and Thermoluminescent Dosimeter Responses to a Lead Reflected Pulse of the CEA Valduc SILENE Critical Assembly

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

    Miller, Thomas Martin; Celik, Cihangir; Isbell, Kimberly McMahan

    This benchmark experiment was conducted as a joint venture between the US Department of Energy (DOE) and the French Commissariat à l'Energie Atomique (CEA). Staff at the Oak Ridge National Laboratory (ORNL) in the US and the Centre de Valduc in France planned this experiment. The experiment was conducted on October 13, 2010 in the SILENE critical assembly facility at Valduc. Several other organizations contributed to this experiment and the subsequent evaluation, including CEA Saclay, Lawrence Livermore National Laboratory (LLNL), the Y-12 National Security Complex (NSC), Babcock International Group in the United Kingdom, and Los Alamos National Laboratory (LANL). Themore » goal of this experiment was to measure neutron activation and thermoluminescent dosimeter (TLD) doses from a source similar to a fissile solution critical excursion. The resulting benchmark can be used for validation of computer codes and nuclear data libraries as required when performing analysis of criticality accident alarm systems (CAASs). A secondary goal of this experiment was to qualitatively test performance of two CAAS detectors similar to those currently and formerly in use in some US DOE facilities. The detectors tested were the CIDAS MkX and the Rocky Flats NCD-91. The CIDAS detects gammas with a Geiger-Muller tube, and the Rocky Flats detects neutrons via charged particles produced in a thin 6LiF disc, depositing energy in a Si solid-state detector. These detectors were being evaluated to determine whether they would alarm, so they were not expected to generate benchmark quality data.« less

  14. Mouse models expressing human carcinoembryonic antigen (CEA) as a transgene: Evaluation of CEA-based cancer vaccines

    PubMed Central

    Hance, Kenneth W.; Zeytin, Hasan E.; Greiner, John W.

    2010-01-01

    In recent years, investigators have carried out several studies designed to evaluate whether human tumor-associated antigens might be exploited as targets for active specific immunotherapy, specifically human cancer vaccines. Not too long ago such an approach would have been met with considerable skepticism because the immune system was believed to be a rigid discriminator between self and non-self which, in turn, protected the host from a variety of pathogens. That viewpoint has been challenged in recent years by a series of studies indicating that antigenic determinants of self have not induced absolute host immune tolerance. Moreover, under specific conditions that evoke danger signals, peptides from self-antigen can be processed by the antigen-presenting cellular machinery, loaded onto the major histocompatibility antigen groove to serve as targets for immune intervention. Those findings provide the rationale to investigate a wide range of tumor-associated antigens, including differentiation antigens, oncogenes, and tumor suppressor genes as possible immune-based targets. One of those tumor-associated antigens is the carcinoembryonic antigen (CEA). Described almost 40 years ago, CEA is a Mr 180–200,000 oncofetal antigen that is one of the more widely studied human tumor-associated antigens. This review will provide: (i) a brief overview of the CEA gene family, (ii) a summary of early preclinical findings on overcoming immune tolerance to CEA, and (iii) the rationale to develop mouse models which spontaneously develop gastrointestinal tumors and express the CEA transgene. Those models have been used extensively in the study of overcoming host immune tolerance to CEA, a self, tumor-associated antigen, and the experimental findings have served as the rationale for the design of early clinical trials to evaluate CEA-based cancer vaccines. PMID:15888344

  15. CEA monitoring of palliative treatment for colorectal carcinoma.

    PubMed Central

    Herrera, M A; Chu, T M; Holyoke, E D; Mittelman, A

    1977-01-01

    Palliative treatment was applied to 131 cases of unresectable or palliatively resected colorectal carcinoma being monitored with serial CEA determinations. There were 84 instances of disease progression with 67 (80%) of them showing an increase in CEA above pretreatment levels or maintaining high levels, and 17 (20%) showing a fall when compared to pretreatment values or maintaining low initial values. There was a clear-cut regression of the disease in only 9 instances. In all 9, the CEA clearly dropped or maintained low valles throughout the period of regression. No patient in regression had a rise or maintained an elevated CEA level. These changes in CEA followed closely the clinical response of our patient to the use of a particular agent, although for the Nitrosourea compounds there may be a tendency to lower the CEA regardless of the patient's tumor response to the drug. This could be due to the fact that the Nitrosoureas produce a diffuse block of cellular activity, both at the nucleous and cytoplasm; while other compounds act as alkylating agents or by inhibition of enzymes involved in the metabolism of nucleic acids (i.e., 5-FU inhibiting thymidylate synthetase). In general, longer survival was found in those patients who had initially lower levels of CEA as compared to those with high initial levels. The patients with a favorable CEA response to the treatment (falling CEA or maintained low value), even in many who did not show a clinical response had a longer survival than the group with rising or stable high levels. The main value in CEA monitoring of patients resides in its correlation with the amount of disease present and then its ability to detect progression of tumor mass which is not clinically measurable. PMID:64132

  16. cea-kil operon of the ColE1 plasmid.

    PubMed Central

    Sabik, J F; Suit, J L; Luria, S E

    1983-01-01

    We isolated a series of Tn5 transposon insertion mutants and chemically induced mutants with mutations in the region of the ColE1 plasmid that includes the cea (colicin) and imm (immunity) genes. Bacterial cells harboring each of the mutant plasmids were tested for their response to the colicin-inducing agent mitomycin C. All insertion mutations within the cea gene failed to bring about cell killing after mitomycin C treatment. A cea- amber mutation exerted a polar effect on killing by mitomycin C. Two insertions beyond the cea gene but within or near the imm gene also prevented the lethal response to mitomycin C. These findings suggest the presence in the ColE1 plasmid of an operon containing the cea and kil genes whose product is needed for mitomycin C-induced lethality. Bacteria carrying ColE1 plasmids with Tn5 inserted within the cea gene produced serologically cross-reacting fragments of the colicin E1 molecule, the lengths of which were proportional to the distance between the insertion and the promoter end of the cea gene. Images PMID:6298187

  17. The CEA-/lo colorectal cancer cell population harbors cancer stem cells and metastatic cells.

    PubMed

    Yan, Chang; Hu, Yibing; Zhang, Bo; Mu, Lei; Huang, Kaiyu; Zhao, Hui; Ma, Chensen; Li, Xiaolan; Tao, Deding; Gong, Jianping; Qin, Jichao

    2016-12-06

    Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA-/lo) levels of CEA. Our findings show that the abundance of CEA-/lo cells correlate with poor differentiation and poor prognosis, and moreover, CEA-/lo cells form more spheres in vitro, generate more tumors and exhibit a higher potential in developing liver and lung metastases than corresponding CEA+ cells. Applying RNAi-mediated approach, we found that IGF1R mediated tumorigenic and capacity of CEA-/lo cells but did not mediate those of CEA+ cells. Notably, our data demonstrated that CEA molecule was capable of protecting CEA-/lo cells from anoikis, implying that CEA+ cells, although themselves possessing less tumorigenic and metastatic capacity, may promote metastasis of CEA-/lo cells via secreting CEA molecule. Our observations suggest that, besides targeting CEA molecule, CEA-/lo cells may represent a critical source of tumor progression and metastasis, and should therefore be the target of future therapies.

  18. In vitro and in vivo comparison of binding of 99m-Tc-labeled anti-CEA MAb F33-104 with 99m-Tc-labeled anti-CEA MAb BW431/26.

    PubMed

    Watanabe, N; Oriuchi, N; Sugiyama, S; Kuroki, M; Matsuoka, Y; Tanada, S; Murata, H; Inoue, T; Sasaki, Y

    1999-01-01

    The purpose of this study was to assess the potential for radio-immunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tc-labeled anti-CEA MAb BW431/261 (31.4 +/- 0.95% vs. 11.9 +/- 0.55% at 100 ng/mL of soluble CEA, 83.5 +/- 2.84% vs. 54.0 +/- 2.54% at 10(7) of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 +/- 3.50% ID/g vs. 14.4 +/- 3.30% ID/g). 99m-Tc-activity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 +/- 2.10% ID/g vs. 8.01 +/- 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 +/- 1.70% ID/g vs. 8.10 +/- 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer.

  19. Introduction to the CEA family: structure, function and secretion.

    PubMed

    Von Kleist, S

    1992-01-01

    Due to the phenomenal progress in the field of tumor immunology that took place during the last twenty years, we dispose today of highly specific and sensitive techniques and reagents like monoclonal antibodies (MAbs). In this context the discovery in human carcinomas of tumor-associated antigens, such as CEA, was of primary importance, especially since the latter was found to have clinical relevance as a tumor marker. Based on animal models, a new in vivo technology for the detection of tumors and metastases was developed in recent years, that uses anti-CEA MAbs, or fragments of them, coupled to radio-isotopes. This technique, called radio-immunodetection (RAID), also paved the way for immunotherapeutic procedures, where again CEA served as the target-antigen. This new technique holds great promise, provided the epitope-specificity of the MAbs is well-controlled: it has been shown that CEA belongs to a large gene-family of at least 22 members, which can be subdivided into two subgroups (i.e., the CEA- and the PSG-subgroup) and which in turn belongs to the immunoglobulin-supergene family. Great structural similarities render the distinction of the various cross-reactive molecules by immunological means rather difficult.

  20. Carcinoembryonic antigen (CEA) levels in hookah smokers, cigarette smokers and non-smokers.

    PubMed

    Sajid, Khan Mohammad; Parveen, Riffat; Durr-e-Sabih; Chaouachi, Kamal; Naeem, Ayisha; Mahmood, Rubaida; Shamim, Rahat

    2007-12-01

    To find CEA levels in smokers of different categories (hookah smokers, cigarette smokers smoking different brands of cigarettes and different number of cigarettes per day) and to correlate CEA levels with type and rate of smoking. A total of 122 cigarette smokers (115 men and 7 women) and 14 hookah smokers (all men) with age ranging from 16-80 years were studied. CEA levels were also measured in 36 non-smokers who served as controls. Enhanced chemilumiscent immunometeric technique was applied to measure CEA levels in our subjects. The mean CEA levels of cigarette smokers were compared with the mean CEA levels observed in hookah smokers (7.16 +/- 10.4 ng/ml) and non-smokers (2.15 +/- 0.68 ng/ml). The mean value of CEA level observed in cigarette smokers, 9.19 +/- 14.9 ng/ml (n=122) was significantly higher than the levels in non-smokers and hookah smokers (p < 0.0067). It was also observed that CEA levels increased with the number of cigarettes smoked per day. The highest levels were observed in smokers who smoke more than 31 cigarettes per day. The smokers that use relatively cheaper brands of cigarettes had higher levels of CEA compared to those who use high quality brands. It was concluded that the brands of cigarettes (which were ranked on the basis of price) and the rate of smoking both play an important role in raising the CEA levels. Further the common belief that hookah also called narghile or shisha is a relatively safe mode of smoking is not completely correct; a significant proportion of hookah smokers have high levels of CEA although mean levels of hookah smokers were low compared to cigarette smokers.

  1. Levels of CEA among vinyl chloride and polyvinyl chloride exposed workers

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

    Anderson, H.A.; Snyder, J.; Lewinson, T.

    1978-09-01

    In 1974, vinyl chloride exposed workers were found to have an increased risk of malignant disease (hemangiosarcoma of the liver). We have examined 1,147 workers exposed to vinyl chloride monomer in three VC/PVC polymerization plants, and 269 workers from a PVC extrusion plant manufacturing PVC textile leather, exposed to much lower concentrations of vinyl chloride. Included among the comprehensive clinical and laboratory studies conducted was the CEA titer. We obtained, respectively, 1,115 and 248 CEA titers. Multiple factors were demonstrated which affected the distribution of CEA titers. Cigarette use had the greatest effect, followed by history of specific past illnessesmore » and alcohol intake history. After removing these possible confounding effects, the distribution of CEA titers among the polymerization workers was significantly different from the extrusion plant group and from an unexposed comparison group. Of the six job categories analyzed, only production and maintenance workers had CEA titer distributions significantly different from the comparison group and the extrusion workers. The investigation demonstrates that occupational exposures in VC/PVC polymerization plants can cause elevations in the CEA titers of otherwise healthy individuals. Prospective follow-up is necessary before conclusions can be drawn concerning the usefulness of the CEA titer as a predictive indicator of possible increased risk.« less

  2. [Antigens (CEA and CA 19-9) in diagnosis and prognosis colorectal cancer].

    PubMed

    Grotowski, Maciej

    2002-01-01

    carcinoembryonic antigen (CEA) was first described more than three decades ago, when its presence was demonstrated in fetal gut tissue and in tumors from gastrointestinal tract. Subsequently, CEA was detected in the circulation of patients and recognized as a serum marker for colorectal cancer. This tumor marker has not been advocated as a screening test for colorectal cancer, however a preoperative CEA serum level is useful for diagnosis and prognosis of recurrence and survival in colorectal cancer patients. The levels of CEA increased with increasing tumor stage. Expression of carbohydrate antigen (CA 19-9) has been described in various malignancies and also in colorectal cancer. This antigen also has not been advocated as a screening test for colorectal cancer. The levels of CA 19-9 increased in advanced stages of colorectal cancer. Despite its lower sensitivity than CEA in early stages of colorectal cancer, the combination of both antigens can provided more information than CEA alone for prognosis of recurrence and survival in those patients.

  3. [Usefulness of preoperative assay CEA and CA 19-9 in colorectal cancer patients].

    PubMed

    Grotowski, M; Maruszyński, M; Piechota, W

    2001-12-01

    Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) are well known tumor markers expressed by colorectal cancer (CRC), particularly in advanced cases. In this study serological expression of CEA and CA19-9 concerning different clinicopathological factors and sensitivity of diagnosis of CRC by combination of both markers were evaluated. Eighty one patients with diagnosed CRC were in this study included. According to Dukes' classification there were 11 in stage A, 34 in stage B, 17 in stage C and 19 in stage D. Blood samples were collected before operation. CEA and CA19-9 were determined by MEIA (normal range 0-3 ng/ml for CEA and 0-37 U/ml for CA19-9). The statistical analysis revealed that the CEA well correlated with histological type, liver metastasis and term of symptoms. The CA19-9 well correlated with liver metastasis, peritoneal dissemination, nodal involvement and cancer localization. The levels of CEA and CA19-9 increased with stage of the tumor, but only in stage D the difference was statistically significant (for CEA p = 0.005, for CA19-9 p = 0.039). At time of diagnosis 50.6% of the patients had elevated serum levels of CEA and 29.6% of CA19-9. In combination of both antigens this elevation was in 54.3% of CRC patients. The common use of CEA and CA19-9 was more efficacious in identification of patients at high risk. The combination assay of CEA and CA19-9 did not cause a significant increase of sensitivity in diagnosis CRC.

  4. Cancer imaging with CEA antibodies: historical and current perspectives.

    PubMed

    Goldenberg, D M

    1992-01-01

    This article reviews the history and status of cancer imaging with radiolabeled antibodies against carcinoembryonic antigen (CEA). Although CEA and many other cancer-associated antigens are not distinct for neoplasia, the quantitative increase of these markers in malignant tissues provides a sufficient differential for selective antibody targeting. Animal studies with xenografted human tumors provided the first evidence of the prospects of this technology, followed by initial clinical success with purified goat whole IgG antibodies to CEA, labeled with 131I and with the use of dual-isotope subtraction methods. Subsequently, improved and earlier imaging could be accomplished with monoclonal antibody fragments, which then would permit the use of shorter-lived radionuclides, such as 111In, 123I, and 99mTc. The preferred use of a monoclonal anti-CEA IgG Fab' fragment, labeled with 99mTc by a recently developed, simple and rapid kit, has enabled the detection of small lesions, including those in the liver, within 4 h of injection. By means of SPECT imaging, a high sensitivity and specificity for RAID could be achieved.

  5. Surface expression and CEA binding of hnRNP M4 protein in HT29 colon cancer cells.

    PubMed

    Laguinge, Luciana; Bajenova, Olga; Bowden, Emma; Sayyah, Jacqueline; Thomas, Peter; Juhl, Hartmut

    2005-01-01

    Carcinoembryonic antigen (CEA) has been shown to participate in the progression and metastatic growth of colorectal cancer. However, its biological function remains elusive. Recently, we found that CEA protects colon cancer cells from undergoing apoptosis, suggesting a complex role that includes signal transduction activity. Additionally, it was reported that CEA binds to Kupffer cells and macrophages to a membrane-anchored homolog of heterogeneous nuclear protein M4 (hnRNP M4), which subsequently was named CEA-receptor (CEAR). Cytoplasmatic and membranous expression of CEAR in CEA-positive colon cancer tissues prompted us to analyze the CEA-CEAR interaction in HT29 colon cancer cells. Both, CEA and CEAR were found on the cell surface of HT29 cells, as demonstrated by confocal microscopy. Imaging analysis suggested co-localization and, thus, interaction of both molecules. To confirm this observation, immunoprecipitation experiments and Western blot analysis were performed and indicated binding of CEA and CEAR. Immunoprecipitation of CEA resulted in a pull down of CEAR. The pull down of CEAR correlated with the amount of CEA as demonstrated by ribozyme targeting of CEA. Finally, external treatment of HT29 cells with soluble CEA induced tyrosine phosphorylation of CEAR, suggesting a CEA-dependent role of CEAR in signal transduction. Future experiments will elucidate whether the CEA-CEAR interaction is involved in CEA's antiapoptotic role and mediates the prometastatic properties of CEA in colon cancer cells.

  6. Demonstration of monoclonal anti-carcinoembryonic antigen (CEA) antibody internalization by electron microscopy, western blotting and radioimmunoassay.

    PubMed

    Tsaltas, G; Ford, C H; Gallant, M

    1992-01-01

    One of the important factors affecting the action of monoclonal antibodies (Mabs) or immunoconjugates on tumour sites depends on whether the Mab is internalized by the cancer cells in question. The underexplored subject of internalization is discussed in this paper, and a number of in vitro techniques for investigating internalization are evaluated, using a model which consists of a well characterized anti-carcinoembryonic antigen (anti-CEA) Mab and a number of CEA expressing human cancer cell lines. Employing two alternative radiolabeling assays, evidence for internalization of the anti-CEA Mab by a CEA-positive colorectal cancer cell line (LS174T) was obtained throughout the time intervals examined (5 min to 150 min). Electronmicroscopy employing horseradish-peroxidase labeled anti-CEA Mab and control antibody permitted direct visualization of anti-CEA Mab-related staining in intracellular compartments of a high CEA-expressor human colorectal cell line (SKCO1). Finally Western blots of samples derived from cytosolic and membrane components of solubilized cells from lung and colonic cancer cell lines provided evidence for internalized anti-CEA Mab throughout seven half hour intervals, starting at 5 minutes. Internalized anti-CEA was detected in all CEA expressing cell lines (LS174T, SKCO1, BENN) but not in the case of a very low CEA expressor line (COLO 320).

  7. Two Cases of Transiently Elevated Serum CEA Levels in Severe Hypothyroidism without Goiter.

    PubMed

    Sekizaki, Tomonori; Yamamoto, Chiho; Nomoto, Hiroshi

    2018-04-27

    Carcinoembryonic antigen (CEA), the level of which is known to increase in both patients with gastrointestinal cancers and those with non-neoplastic conditions, is one of the most widely-used tumor markers. Hypothyroidism is a common endocrinological disorder in which CEA levels can rise, and is sometimes overlooked as a diagnosis in the absence of typical symptoms or thyroid enlargement. We report the cases of two patients with non-goiterous severe hypothyroidism with markedly elevated CEA levels that effectively decreased with levothyroxine replacement therapy alone. Hypothyroidism should be considered as an important cause of unexplained high serum CEA levels in order to avoid unnecessary medical examination.

  8. Complete solid state lighting (SSL) line at CEA LETI

    NASA Astrophysics Data System (ADS)

    Robin, I. C.; Ferret, P.; Dussaigne, A.; Bougerol, C.; Salomon, D.; Chen, X. J.; Charles, M.; Tchoulfian, P.; Gasse, A.; Lagrange, A.; Consonni, M.; Bono, H.; Levy, F.; Desieres, Y.; Aitmani, A.; Makram-Matta, S.; Bialic, E.; Gorrochategui, P.; Mendizabal, L.

    2014-09-01

    With a long experience in optoelectronics, CEA-LETI has focused on Light Emitting Diode (LED) lighting since 2006. Today, all the technical challenges in the implementation of GaN LED based solid state lighting (SSL) are addressed at CEA-LETI who is now an RandD player throughout the entire value chain of LED lighting. The SSL Line at CEA-LETI first deals with the simulation of the active structures and LED devices. Then the growth is addressed in particular 2D growth on 200 mm silicon substrates. Then, technological steps are developed for the fabrication of LED dies with innovative architectures. For instance, Versatile LED Array Devices are currently being developed with a dedicated μLED technology. The objective in this case is to achieve monolithical LED arrays reported and interconnected through a silicon submount. In addition to the required bonding and 3D integration technologies, new solutions for LED chip packaging, thermal management of LED lamps and luminaires are also addressed. LETI is also active in Smart Lighting concepts which offer the possibility of new application fields for SSL technologies. An example is the recent development at CEA LETI of Visible Light Communication Technology also called LiFi. With this technology, we demonstrated a transmission rate up to 10 Mb/s and real time HD-Video transmission.

  9. Aeroacoustics research in Europe: The CEAS-ASC report on 2016 highlights

    NASA Astrophysics Data System (ADS)

    Wilson, Alexander G.

    2018-08-01

    The Council of European Aerospace Societies (CEAS) Aeroacoustics Specialists Committee (ASC) supports and promotes the interests of the scientific and industrial aeroacoustics community on the European scale, and European aeronautics activities internationally. Each year, the committee highlights several of the research and development projects in Europe. This paper is the 2016 issue of this collection of Aeroacoustic Highlights, compiled from contributions submitted to the CEAS-ASC. The contributions are classified under three main headings; Aircraft and Turbomachinery Noise, Experimental and Numerical Methods and Further Applications of Aeroacoustics. A concise summary of the CEAS-ASC workshop held in Southampton, England, in September 2016 is also included in this report.

  10. Diagnostic test pepsinogen I and combination with tumor marker CEA in gastric cancer

    NASA Astrophysics Data System (ADS)

    Sembiring, J.; Sarumpaet, K.; Ganie, R. A.

    2018-03-01

    Gastric cancer (GC) is the fifth leading cause of cancer and the third leading cause of cancer-related mortality globally. Human pepsinogens (HP) are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and GC. HP are biochemically and immunochemically classified into two groups: pepsinogen I (PG I) and PG II. Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in normal mucosal cells but increased amounts are associated with adenocarcinoma, especially colorectal cancer. CEA in combination with other tumour markers can be used in pre-operative staging and thereby assist in the planning of the type of surgery required and future management options. The purpose of this study was to diagnose test PG I and combination with tumor marker CEA in 32 patients suspected with GC. There was a significant difference in levels of CEA between GC group with non-GC with a value p <0.001. PGI sensitivity was 70.58% and specificity 93.3%. The sensitivity of PGI and CEA combination of 94.1% and specificity 80%. The area of AUC obtained was 92.7% at 95% confidence interval (82.7-100%). This AUC value indicated that the value of diagnostic accuracy of the PGI and CEA combinations of 92.7%.

  11. Anti-CEA-functionalized superparamagnetic iron oxide nanoparticles for examining colorectal tumors in vivo

    NASA Astrophysics Data System (ADS)

    Huang, Kai-Wen; Chieh, Jen-Jie; Lin, In-Tsang; Horng, Herng-Er; Yang, Hong-Chang; Hong, Chin-Yih

    2013-10-01

    Although the biomarker carcinoembryonic antigen (CEA) is expressed in colorectal tumors, the utility of an anti-CEA-functionalized image medium is powerful for in vivo positioning of colorectal tumors. With a risk of superparamagnetic iron oxide nanoparticles (SPIONPs) that is lower for animals than other material carriers, anti-CEA-functionalized SPIONPs were synthesized in this study for labeling colorectal tumors by conducting different preoperatively and intraoperatively in vivo examinations. In magnetic resonance imaging (MRI), the image variation of colorectal tumors reached the maximum at approximately 24 h. However, because MRI requires a nonmetal environment, it was limited to preoperative imaging. With the potentiality of in vivo screening and intraoperative positioning during surgery, the scanning superconducting-quantum-interference-device biosusceptometry (SSB) was adopted, showing the favorable agreement of time-varied intensity with MRI. Furthermore, biological methodologies of different tissue staining methods and inductively coupled plasma (ICP) yielded consistent results, proving that the obtained in vivo results occurred because of targeted anti-CEA SPIONPs. This indicates that developed anti-CEA SPIONPs owe the utilities as an image medium of these in vivo methodologies.

  12. Significance of CEA and VEGF as Diagnostic Markers of Colorectal Cancer in Lebanese Patients.

    PubMed

    Dbouk, Hashem A; Tawil, Ayman; Nasr, Fahd; Kandakarjian, Loucine; Abou-Merhi, Raghida

    2007-11-08

    Carcinoembryonic antigen and vascular endothelial growth factors are among the most important prognostic markers of colorectal cancer. Testing for these markers independently has been of limited value in screening for this tumor. The aim of this study is to determine the importance of simultaneous blood CEA and VEGF level determinations in diagnosis of colorectal cancer. Thirty-six patients diagnosed with colorectal cancer along with eight healthy controls were tested by ELISA for CEA and VEGF levels in serum and plasma, respectively. The positive predictive value of these markers was 95.4% for CEA and 89.5% for VEGF, and for combined CEA and VEGF was also high at 88%. Combined CEA and VEGF blood level assay constitutes a useful panel in detecting patients with colorectal cancer. Positive results allow selection of a subgroup of patients with a high tumor risk; therefore, such tests comprise valuable tumor diagnostic tests to add to current detection methods.

  13. Hookah smoking and cancer: carcinoembryonic antigen (CEA) levels in exclusive/ever hookah smokers.

    PubMed

    Sajid, Khan Mohammad; Chaouachi, Kamal; Mahmood, Rubaida

    2008-05-24

    We have recently published some work on CEA levels in hookah (also called narghile, shisha elsewhere) and cigarette smokers. Hookah smokers had higher levels of CEA than non-smokers although mean levels were low compared to cigarette smokers. However some of them were also users of other tobacco products (cigarettes, bidis, etc.). To find serum CEA levels in ever/exclusive hookah smokers, i.e. those who smoked only hookah (no cigarettes, bidis, etc.), prepared between 1 and 4 times a day with a quantity of up to 120 g of a tobacco-molasses mixture each (i.e. the tobacco weight equivalent of up to 60 cigarettes of 1 g each) and consumed in 1 to 8 sessions. Enhanced chemiluminescent immunometric technique was applied to measure CEA levels in serum samples from 59 exclusive male smokers with age ranging from 20-80 years (mean = 58.8 +/- 14.7 years) and 8-65 years of smoking (mean = 37.7 +/- 16.8). 36 non-smokers served as controls. Subjects were divided into 3 groups according to the number of preparations; the number of sessions and the total daily smoking time: Light (1; 1; < or = 20 minutes); Medium (1-3; 1-3; >20 min to < or = 2 hrs) and Heavy smokers (2-4; 3-8; >2 hrs to < or = 6 hrs). Because of the nature of distribution of CEA levels among our individuals, Wilcoxon's rank sum two-sample test was applied to compare the variables. The overall CEA levels in exclusive hookah smokers (mean: 3.58 +/- 2.61 ng/ml; n = 59) were not significantly different (p < or = 0.0937) from the levels in non-smokers (2.35 +/- 0.71 ng/ml). Mean levels in light, medium and heavy smokers were: 1.06 +/- 0.492 ng/ml (n = 5); 2.52 +/- 1.15 ng/ml (n = 28) and 5.11 +/- 3.08 ng/ml (n = 26) respectively. The levels in medium smokers and non-smokers were also not significantly different (p < or = 0.9138). In heavy smokers, the CEA levels were significantly higher than in non-smokers (p < or = 0.0001567). Overall CEA levels in exclusive hookah smokers were low compared to cigarette smokers

  14. Serum CEA levels in patients with gastric carcinoma correlate with the tumorigenicity of their xenografts in nude mice.

    PubMed

    Kiyama, T; Onda, M; Tokunaga, A; Okuda, T; Mizutani, T; Yoshiyuki, T; Shimizu, Y; Nishi, K; Matsukura, N; Tanaka, N

    1991-01-01

    We examined the correlation among preoperative serum carcinoembryonic antigen (CEA) levels, staining properties of the tumors by CEA immunohistochemistry and the tumorigenicity of their xenografts in nude mice, in 28 patients with gastric cancer. Eleven (40 per cent) of them were positive for serum CEA (greater than or equal to 2.5 ng/ml) and seven (25 per cent) of the xenografts were tumorigenic in nude mice. All the tumorigenic cases were positive for serum CEA (p less than 0.001) and the mean value of the serum CEA level in the patients with tumorigenic neoplasms was 20.8 ng/ml, being significantly higher than that (1.4 ng/ml) in the patients with non-tumorigenic neoplasms (p less than 0.001). Twenty-five of the 28 carcinomas (89 per cent) were positive for CEA staining in their cancer cells by the ABC method and CEA localization correlated with tumorigenicity (p less than 0.05). These results suggest that the serum CEA level in patients is correlated with the tumorigenicity of their gastric carcinoma xenografts in nude mice and may account for the poor prognosis of patients with high serum CEA.

  15. Hookah smoking and cancer: carcinoembryonic antigen (CEA) levels in exclusive/ever hookah smokers

    PubMed Central

    Sajid, Khan Mohammad; Chaouachi, Kamal; Mahmood, Rubaida

    2008-01-01

    Background We have recently published some work on CEA levels in hookah (also called narghile, shisha elsewhere) and cigarette smokers. Hookah smokers had higher levels of CEA than non-smokers although mean levels were low compared to cigarette smokers. However some of them were also users of other tobacco products (cigarettes, bidis, etc.). Objectives To find serum CEA levels in ever/exclusive hookah smokers, i.e. those who smoked only hookah (no cigarettes, bidis, etc.), prepared between 1 and 4 times a day with a quantity of up to 120 g of a tobacco-molasses mixture each (i.e. the tobacco weight equivalent of up to 60 cigarettes of 1 g each) and consumed in 1 to 8 sessions. Methods Enhanced chemiluminescent immunometric technique was applied to measure CEA levels in serum samples from 59 exclusive male smokers with age ranging from 20–80 years (mean = 58.8 ± 14.7 years) and 8–65 years of smoking (mean = 37.7 ± 16.8). 36 non-smokers served as controls. Subjects were divided into 3 groups according to the number of preparations; the number of sessions and the total daily smoking time: Light (1; 1; ≤ 20 minutes); Medium (1–3; 1–3; >20 min to ≤ 2 hrs) and Heavy smokers (2–4; 3–8; >2 hrs to ≤ 6 hrs). Because of the nature of distribution of CEA levels among our individuals, Wilcoxon's rank sum two-sample test was applied to compare the variables. Results The overall CEA levels in exclusive hookah smokers (mean: 3.58 ± 2.61 ng/ml; n = 59) were not significantly different (p ≤ 0.0937) from the levels in non-smokers (2.35 ± 0.71 ng/ml). Mean levels in light, medium and heavy smokers were: 1.06 ± 0.492 ng/ml (n = 5); 2.52 ± 1.15 ng/ml (n = 28) and 5.11 ± 3.08 ng/ml (n = 26) respectively. The levels in medium smokers and non-smokers were also not significantly different (p ≤ 0.9138). In heavy smokers, the CEA levels were significantly higher than in non-smokers (p ≤ 0.0001567). Conclusion Overall CEA levels in exclusive hookah smokers were

  16. Prospective randomised trial of early cytotoxic therapy for recurrent colorectal carcinoma detected by serum CEA.

    PubMed Central

    Hine, K R; Dykes, P W

    1984-01-01

    Of 663 patients treated with radical surgery for colorectal cancer, 52 showed a progressive rise in serum carcinoembryonic antigen (CEA) with no other evidence of recurrent disease and were randomised in a prospective study of chemotherapy. Twenty six patients in the treatment group received 5FU and methyl CCNU from the time of randomisation and the remaining 26 controls were given further therapy only if there were clinical indications. All patients were followed for five years or until their death and all but one (control) developed clinical evidence of recurrence. Overall there was no significant difference between the two groups with respect to disease free interval and survival. Whereas the rise in CEA in controls was generally progressive, marked inflections on the CEA curves were seen in the majority of patients receiving early treatment. Eight of 26 treated patients showed a fall in CEA of greater than 20% two months after starting therapy. These patients had a median disease free interval of 90 weeks and a median survival of 107 weeks, these figures being longer than those of treated patients who did not show a fall in CEA and control patients. The serum CEA therefore appeared to give important prognostic information in patients receiving cytotoxic treatment. Early therapy was generally well tolerated. PMID:6376291

  17. Uropathogenic E. coli Exploit CEA to Promote Colonization of the Urogenital Tract Mucosa

    PubMed Central

    Muenzner, Petra; Kengmo Tchoupa, Arnaud; Klauser, Benedikt; Brunner, Thomas; Putze, Johannes; Dobrindt, Ulrich; Hauck, Christof R.

    2016-01-01

    Attachment to the host mucosa is a key step in bacterial pathogenesis. On the apical surface of epithelial cells, members of the human carcinoembryonic antigen (CEA) family are abundant glycoproteins involved in cell-cell adhesion and modulation of cell signaling. Interestingly, several gram-negative bacterial pathogens target these receptors by specialized adhesins. The prototype of a CEACAM-binding pathogen, Neisseria gonorrhoeae, utilizes colony opacity associated (Opa) proteins to engage CEA, as well as the CEA-related cell adhesion molecules CEACAM1 and CEACAM6 on human epithelial cells. By heterologous expression of neisserial Opa proteins in non-pathogenic E. coli we find that the Opa protein-CEA interaction is sufficient to alter gene expression, to increase integrin activity and to promote matrix adhesion of infected cervical carcinoma cells and immortalized vaginal epithelial cells in vitro. These CEA-triggered events translate in suppression of exfoliation and improved colonization of the urogenital tract by Opa protein-expressing E. coli in CEA-transgenic compared to wildtype mice. Interestingly, uropathogenic E. coli expressing an unrelated CEACAM-binding protein of the Afa/Dr adhesin family recapitulate the in vitro and in vivo phenotype. In contrast, an isogenic strain lacking the CEACAM-binding adhesin shows reduced colonization and does not suppress epithelial exfoliation. These results demonstrate that engagement of human CEACAMs by distinct bacterial adhesins is sufficient to blunt exfoliation and to promote host infection. Our findings provide novel insight into mucosal colonization by a common UPEC pathotype and help to explain why human CEACAMs are a preferred epithelial target structure for diverse gram-negative bacteria to establish a foothold on the human mucosa. PMID:27171273

  18. Comparison of Ablation Predictions for Carbonaceous Materials Using CEA and JANAF-Based Species Thermodynamics

    NASA Technical Reports Server (NTRS)

    Milos, Frank S.

    2011-01-01

    In most previous work at NASA Ames Research Center, ablation predictions for carbonaceous materials were obtained using a species thermodynamics database developed by Aerotherm Corporation. This database is derived mostly from the JANAF thermochemical tables. However, the CEA thermodynamics database, also used by NASA, is considered more up to date. In this work, the FIAT code was modified to use CEA-based curve fits for species thermodynamics, then analyses using both the JANAF and CEA thermodynamics were performed for carbon and carbon phenolic materials over a range of test conditions. The ablation predictions are comparable at lower heat fluxes where the dominant mechanism is carbon oxidation. However, the predictions begin to diverge in the sublimation regime, with the CEA model predicting lower recession. The disagreement is more significant for carbon phenolic than for carbon, and this difference is attributed to hydrocarbon species that may contribute to the ablation rate.

  19. Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer.

    PubMed

    Geng, Biao; Liang, Man-Man; Ye, Xiao-Bing; Zhao, Wen-Ying

    2015-01-01

    The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.

  20. Multiple myeloma presenting as CEA-producing rectal cancer.

    PubMed

    Talamo, Giampaolo; Barochia, Amitkumar; Zangari, Maurizio; Loughran, Thomas P

    2010-03-31

    We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas.

  1. The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts

    PubMed Central

    Kadayifci, Abdurrahman; Al-Haddad, Mohammad; Atar, Mustafa; Dewitt, John M.; Forcione, David G.; Sherman, Stuart; Casey, Brenna W.; Fernandez-del Castillo, Carlos; Schmidt, C. Max; Pitman, Martha B.; Brugge, William R.

    2016-01-01

    Background and aims: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. Patients and methods: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. Results: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100 % and 93.2 %), but low sensitivity (48.3 % and 56.3 %) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8 %) and AUC (0.84) significantly compared to KRAS (65.3 % and 0.74) or CEA (65.8 % and 0.74) alone, but only in the clinical cohort (P < 0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73 % vs. 37 %, P = 0.001). The negative predictive value of KRAS mutation was 77.6 % in differentiating non-malignant cysts. Conclusions: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use. PMID:27092317

  2. Multiple myeloma presenting as CEA-producing rectal cancer

    PubMed Central

    Talamo, Giampaolo; Barochia, Amitkumar; Zangari, Maurizio; Loughran, Thomas P

    2010-01-01

    We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas. PMID:21139949

  3. Evaluation of serum CA27.29, CA15-3 and CEA in patients with breast cancer.

    PubMed

    Hou, M F; Chen, Y L; Tseng, T F; Lin, C M; Chen, M S; Huang, C J; Huang, Y S; Hsieh, J S; Huang, T J; Jong, S B; Huang, Y F

    1999-09-01

    The Truquant BR radioimmunoassay (RIA) using monoclonal antibody BR 27.29 to recognize a peptide sequence on the MUC-1 gene product for quantification of the CA 27.29 antigen in serum was used in this report to evaluate in 145 patients with breast cancer and compared the other conventional serum markers such as CA15-3 and CEA. The upper limit of normal (25 u/ml) was determined from CA27.29 values 12.4 +/- 4.1 u/ml (mean +/- 3 S.D.) for 112 female subjects apparently free of disease. The CA15-3 levels above 25 u/ml and CEA levels above 5 ng/ml were considered positive values. Thirty-seven cases of 145 patients studied had elevated CA 27.29 levels (sensitivity: 25.5%), 35 of 145 had positive CA15-3 levels (sensitivity 24.1%) and 27 of 145 patients had positive CEA levels (sensitivity: 18.6%) (p < 0.05). One hundred and ten cases of the breast cancer patients (75.8%) did not have metastatic disease. In this group CA 27.29 sensitivity was 6.4%, while CA15-3 sensitivity was 5.5% and CEA sensitivity was 4.5% (p > 0.05). Mean values were 10.2 +/- 9.2 u/ml for CA 27.29, 14.1 +/- 5.6 u/ml for CA 15-3 and 1.7 +/- 1.5 ng/ml for CEA. Thirty-five patients (24.2%) had metastatic disease. In this group CA 27.29 sensitivity was 85.7%, CA15-3 sensitivity was 82.8% and CEA sensitivity was 62.8% (p < 0.05). Mean values for CA27.29 was 152.6 +/- 131.6 u/ml, CA15-3 was 123.1 +/- 107.6 u/ml and 21.8 +/- 36.9 ng/ml of CEA. With regard to the correlation of three tumor markers with clinical stages, patients had significantly higher levels of CA27.29 than CEA, but they were similar to CA 15-3 in metastatic breast cancer. These results suggest CA27.29 to be more sensitive and specific than CEA, but that it is similar to CA15-3 for metastatic breast cancer detection and monitoring.

  4. Evaluation of predictive value of pleural CEA in patients with pleural effusions and histological findings: A prospective study and literature review.

    PubMed

    Tozzoli, Renato; Basso, Stefano M M; D'Aurizio, Federica; Metus, Paolo; Lumachi, Franco

    2016-11-01

    Pleural effusion recognizes heterogeneous etiology and pathogenesis and requires invasive diagnostic procedures. Usually, after pleural fluid analysis, 30-50% of patients with malignant pleural effusion exhibit negative pleural cytology, and the sensitivity of image-guided pleural needle-aspiration biopsy ranges between 60% and 70%. With the aim of differentiating between benign (BPE) and malignant (MPE) pleural effusions, several tumor markers have been assayed in the pleural fluid and the majority of studies focus on pleural carcinoembryonic antigen (p-CEA). The aims of this study were to evaluate (i) the diagnostic accuracy of p-CEA of patients with pleural effusions undergoing video-assisted thoracoscopic surgery (VATS) for diagnostic purpose, (ii) the relationship between p-CEA and serum CEA (s-CEA), and (iii) the usefulness of the p-CEA/s-CEA ratio in the diagnosis of malignant pleural effusions (MPE). We prospectively enrolled in the study 134 consecutive patients with pleural effusions, scheduled for having VATS and biopsy. The final diagnosis, based on histopathology of the VATS-guided specimens, was available for all patients. p-CEA and s-CEA was assayed with a chemiluminescence immunoassay method (CLIA), applied on the Maglumi 2000 Plus automated platform (SNIBE, Shenzen, China). The sensitivity and accuracy of p-CEA was significantly higher than that of pleural cytology at the same specificity comparing BPE with MPE and BPE with non-small lung cancer. The sensitivity of p-CEA and PC together reached 100% (BPE vs. NSCLC) and 91.5% (BPE vs. MPE excluding mesothelioma), respectively. The p-CEA measurement in patients with pleural effusion of uncertain etiology is a safe and cost-effective procedure, everywhere easily available, which may help clinicians in selecting patients for further evaluations. An elevated p-CEA level in a patient with pleural effusion and negative pleural cytology suggests the need of more invasive procedure (e.g. VATS

  5. Label-free fluorimetric detection of CEA using carbon dots derived from tomato juice.

    PubMed

    Miao, Hong; Wang, Lan; Zhuo, Yan; Zhou, Zinan; Yang, Xiaoming

    2016-12-15

    A facile-green strategy to synthesize carbon dots (CDs) with a quantum yield (QY) of nearly 13.9% has been built up, while tomato juice served as the carbon source. Interestingly, not only the precursor of CDs and the whole synthesis procedure were environmental-friendly, but this type of CDs also exhibited multiple advantages including high fluorescent QY, excellent photostability, non-toxicity and satisfactory stability. Significantly, a label-free sensitive assay for detecting carcinoembryonic antigen (CEA) in a continuous and recyclable way has been proposed on the basis of adsorption and desorption of aptamers by the surface of CDs through a competitive mechanism. To be specific, the richness of carboxyl groups of the CDs enabled strong adsorption of ssDNA to the surface of CDs through π-π stacking interactions, resulting in the effective fluorescence quenching by forming CDs-aptamer complexes. The stronger binding affinity between CEA and CEA-aptamer than the π-π stacking interactions has been taken advantage to achieve immediate recovery of the fluorescence of CDs once CEA was introduced. Thereby, quantitative evaluation of CEA concentration in a broad range from 1ngmL(-1) to 0.5ngmL(-1) with the detection limit of 0.3ngmL(-1) was realized in this way. This strategy can be applied in a recyclable way, broadening the sensing application of CDs with biocompatibility. Besides, the CDs were used for cell imaging, potentiating them towards diverse purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. General review of multispectral cooled IR development at CEA-Leti, France

    NASA Astrophysics Data System (ADS)

    Boulard, F.; Marmonier, F.; Grangier, C.; Adelmini, L.; Gravrand, O.; Ballet, P.; Baudry, X.; Baylet, J.; Badano, G.; Espiau de Lamaestre, R.; Bisotto, S.

    2017-02-01

    Multicolor detection capabilities, which bring information on the thermal and chemical composition of the scene, are desirable for advanced infrared (IR) imaging systems. This communication reviews intra and multiband solutions developed at CEA-Leti, from dual-band molecular beam epitaxy grown Mercury Cadmium Telluride (MCT) photodiodes to plasmon-enhanced multicolor IR detectors and backside pixelated filters. Spectral responses, quantum efficiency and detector noise performances, pros and cons regarding global system are discussed in regards to technology maturity, pixel pitch reduction, and affordability. From MWIR-LWIR large band to intra MWIR or LWIR bands peaked detection, results underline the full possibility developed at CEA-Leti.

  7. [Sensitivity, specificity and prognostic value of CEA in colorectal cancer: results of a Tunisian series and literature review].

    PubMed

    Bel Hadj Hmida, Y; Tahri, N; Sellami, A; Yangui, N; Jlidi, R; Beyrouti, M I; Krichen, M S; Masmoudi, H

    2001-01-01

    In order to determine the sensitivity of CEA in the diagnosis of colo-rectal carcinoma, we studied a series of 48 patients with colo-rectal carcinoma (1992-1996). The sensitivity was at 52% with a reference value of 5 ng/ml and 68.7% for a reference value of 2.5 ng/ml. With a reference value of 5 ng/ml, the sensitivity of CEA was at 37% only for patients with colo-rectal carcinoma at Dukes B stage, 66.6% for patients at stage C and 75% for patients at stage D. The dosage of CEA was carried out with a sandwich immunoenzymatic technique in tube. There is no statistic significant correlation between the pre-operative rate of CEA and the localisation of the tumor and its histologic type; in contrast, it was significantly correlated with the ganglionnary metastasis. A significant relationship between the pre-operative rate of CEA and the Dukes stage was found for a reference value of 10 ng/ml but not for a reference value of 5 ng/ml. We calculated the specificity of the CEA for the cancers of colon and rectum which was at 76.98% with a reference value of 5 ng/ml and 86% with a reference value of 10 ng/ml.

  8. Novel flow cytometric analysis of the progress and route of internalization of a monoclonal anti-carcinoembryonic antigen (CEA) antibody.

    PubMed

    Ford, C H; Tsaltas, G C; Osborne, P A; Addetia, K

    1996-03-01

    A flow cytometric method of studying the internalization of a monoclonal antibody (Mab) directed against carcinoembryonic antigen (CEA) has been compared with Western blotting, using three human colonic cancer cell lines which express varying amounts of the target antigen. Cell samples incubated for increasing time intervals with fluoresceinated or unlabelled Mab were analyzed using flow cytometry or polyacrylamide gel electrophoresis and Western blotting. SDS/PAGE analysis of cytosolic and membrane components of solubilized cells from the cell lines provided evidence of non-degraded internalized anti-CEA Mab throughout seven half hour intervals, starting at 5 min. Internalized anti-CEA was detected in the case of high CEA expressing cell lines (LS174T, SKCO1). Very similar results were obtained with an anti-fluorescein flow cytometric assay. Given that these two methods consistently provided comparable results, use of flow cytometry for the detection of internalized antibody is suggested as a rapid alternative to most currently used methods for assessing antibody internalization. The question of the endocytic route followed by CEA-anti-CEA complexes was addressed by using hypertonic medium to block clathrin mediated endocytosis.

  9. Analgesic Effects of Duloxetine on Formalin-Induced Hyperalgesia and Its Underlying Mechanisms in the CeA

    PubMed Central

    Zhang, Lie; Yin, Jun-Bin; Hu, Wei; Zhao, Wen-Jun; Fan, Qing-Rong; Qiu, Zhi-Chun; He, Ming-Jie; Ding, Tan; Sun, Yan; Kaye, Alan D.; Wang, En-Ren

    2018-01-01

    In rodents, the amygdala has been proposed to serve as a key center for the nociceptive perception. Previous studies have shown that extracellular signal-regulated kinase (ERK) signaling cascade in the central nucleus of amygdala (CeA) played a functional role in inflammation-induced peripheral hypersensitivity. Duloxetine (DUL), a serotonin and noradrenaline reuptake inhibitor, produced analgesia on formalin-induced spontaneous pain behaviors. However, it is still unclear whether single DUL pretreatment influences formalin-induced hypersensitivity and what is the underlying mechanism. In the current study, we revealed that systemic pretreatment with DUL not only dose-dependently suppressed the spontaneous pain behaviors, but also relieved mechanical and thermal hypersensitivity induced by formalin hindpaw injection. Consistent with the analgesic effects of DUL on the pain behaviors, the expressions of Fos and pERK that were used to check the neuronal activities in the spinal cord and CeA were also dose-dependently reduced following DUL pretreatment. Meanwhile, no emotional aversive behaviors were observed at 24 h after formalin injection. The concentration of 5-HT in the CeA was correlated with the dose of DUL in a positive manner at 24 h after formalin injection. Direct injecting 5-HT into the CeA suppressed both the spontaneous pain behaviors and hyperalgesia induced by formalin injection. However, DUL did not have protective effects on the formalin-induced edema of hindpaw. In sum, the activation of CeA neurons may account for the transition from acute pain to long-term hyperalgesia after formalin injection. DUL may produce potent analgesic effects on the hyperalgesia and decrease the expressions of p-ERK through increasing the concentration of serotonin in the CeA. PMID:29692727

  10. Analgesic Effects of Duloxetine on Formalin-Induced Hyperalgesia and Its Underlying Mechanisms in the CeA.

    PubMed

    Zhang, Lie; Yin, Jun-Bin; Hu, Wei; Zhao, Wen-Jun; Fan, Qing-Rong; Qiu, Zhi-Chun; He, Ming-Jie; Ding, Tan; Sun, Yan; Kaye, Alan D; Wang, En-Ren

    2018-01-01

    In rodents, the amygdala has been proposed to serve as a key center for the nociceptive perception. Previous studies have shown that extracellular signal-regulated kinase (ERK) signaling cascade in the central nucleus of amygdala (CeA) played a functional role in inflammation-induced peripheral hypersensitivity. Duloxetine (DUL), a serotonin and noradrenaline reuptake inhibitor, produced analgesia on formalin-induced spontaneous pain behaviors. However, it is still unclear whether single DUL pretreatment influences formalin-induced hypersensitivity and what is the underlying mechanism. In the current study, we revealed that systemic pretreatment with DUL not only dose-dependently suppressed the spontaneous pain behaviors, but also relieved mechanical and thermal hypersensitivity induced by formalin hindpaw injection. Consistent with the analgesic effects of DUL on the pain behaviors, the expressions of Fos and pERK that were used to check the neuronal activities in the spinal cord and CeA were also dose-dependently reduced following DUL pretreatment. Meanwhile, no emotional aversive behaviors were observed at 24 h after formalin injection. The concentration of 5-HT in the CeA was correlated with the dose of DUL in a positive manner at 24 h after formalin injection. Direct injecting 5-HT into the CeA suppressed both the spontaneous pain behaviors and hyperalgesia induced by formalin injection. However, DUL did not have protective effects on the formalin-induced edema of hindpaw. In sum, the activation of CeA neurons may account for the transition from acute pain to long-term hyperalgesia after formalin injection. DUL may produce potent analgesic effects on the hyperalgesia and decrease the expressions of p-ERK through increasing the concentration of serotonin in the CeA.

  11. Gfr Core Neutronics Studies at CEA

    NASA Astrophysics Data System (ADS)

    Bosq, J. C.; Brun-Magaud, V.; Rimpault, G.; Tommasi, J.; Conti, A.; Garnier, J. C.

    2006-04-01

    The Gas cooled Fast Reactor (GFR) is a high priority in the CEA R&D program on Future Nuclear Energy Systems. After preliminary neutronics and thermo-aerolic studies, a first He-cooled 2400MWth core design based on a series of carbide CERCER plates arranged in an hexagonal wrapper were selected. Although GFR subassembly and core design studies are still at an early stage of development, it is nonetheless possible to identify a number of nuclear data needs that could have some impact on the actual design: new materials, decay heat contributors….

  12. Simplifying CEA through Excel, VBA, and Subeq

    NASA Technical Reports Server (NTRS)

    Foster, Ryan

    2004-01-01

    Many people use compound equilibrium programs for very different reasons, varying from refrigerators to light bulbs to rockets. A commonly used equilibrium program is CEA. CEA can take various inputs such as pressure, temperature, and volume along with numerous reactants and run them through equilibrium equations to obtain valuable output information, including products formed and their relative amounts. A little over a year ago, Bonnie McBride created the program subeq with the goal to simplify the calling of CEA. Subeq was also designed to be called by other programs, including Excel, through the use of Visual Basic for Applications (VBA). The largest advantage of using Excel is that it allows the user to input the information in a colorful and user-friendly environment while allowing VBA to run subeq, which is in the form of a FORTRAN DLL (Dynamic Link Library). Calling subeq in this form makes it much faster than if it were converted to VBA. Since subeq requires such large lists of reactant and product names, all of which can't be passed in as an array, subeq had to be changed to accept very long strings of reactants and products. To pass this string and adjust the transfer of input and output parameters, the subeq DLL had to be changed. One program that does this is Compaq Visual FORTRAN, which allows DLLs to be edited, debugged, and compiled. Compaq Visual FORTRAN uses FORTRAN 90/95, which has additional features to that of FORTRAN 77. My goals this summer include finishing up the excel spreadsheet of subeq, which I started last summer, and putting it on the Internet so that others can use it without having to download my spreadsheet. To finish up the spreadsheet I will need to work on debugging current options and problems. I will also work on making it as robust as possible, so that all errors that may arise will be clearly communicated to the user. New features will be added old ones will be changed as I receive comments from people using the spreadsheet

  13. Comparison of the CEAS and Williams-type barley yield models for North Dakota and Minnesota

    NASA Technical Reports Server (NTRS)

    Leduc, S. (Principal Investigator)

    1982-01-01

    The CEAS and Williams type models were compared based on specified selection criteria which includes a ten year bootstrap test (1970-1979). Based on this, the models were quite comparable; however, the CEAS model was slightly better overall. The Williams type model seemed better for the 1974 estimates. Because that year spring wheat yield was particularly low, the Williams type model should not be excluded from further consideration.

  14. Dexamethasone minimizes the risk of cranial nerve injury during CEA.

    PubMed

    Regina, Guido; Angiletta, Domenico; Impedovo, Giovanni; De Robertis, Giovanni; Fiorella, Marialuisa; Carratu', Maria Rosaria

    2009-01-01

    The incidence of cranial and cervical nerve injury during carotid endarterectomy (CEA) ranges from less than 7.6% to more than 50%. Lesions are mainly due to surgical maneuvers such as traction, compression, tissue electrocoagulation, clamping, and extensive dissections. The use of dexamethasone (DEX) and its beneficial effects in spinal cord injuries have already been described. We investigated whether DEX could also be beneficial to minimize the incidence of cranial and cervical nerve injury during CEA. To evaluate whether dexamethasone is able to reduce the incidence of cranial nerve injuries. From March 1999 through April 2006, 1126 patients undergoing CEA because of high-grade carotid stenosis were enrolled and randomized by predetermined randomization tables into two groups. The first group, "A", included 586 patients that all received an intravenous administration of dexamethasone following a therapeutic scheme. The second group, "B", included 540 control subjects that received the standard pre- and postoperative therapy. All patients were submitted to a deep cervical plexus block, eversion carotid endarterectomy, and selective shunting. Three days after the operation, an independent neurologist and otorhinolaryngologist evaluated the presence of cranial nerve deficits. All patients (group A and group B) showing nerve injuries continued the treatment (8 mg of dexamethasone once in the morning) for 7 days and were re-evaluated after 2 weeks, 30 days, and every 3 months for 1 year. Recovery time took from 2 weeks to 12 months, with a mean time of 3.6 months. The chi(2) test was used to compare the two groups and to check for statistical significance. The incidence of cranial nerve dysfunction was higher in group B and the statistical analysis showed a significant effect of dexamethasone in preventing the neurological damage (P = .0081). The incidence of temporary lesions was lower in group A and the chi(2) test yielded a P value of .006. No statistically

  15. Installation and first operation of the International Fusion Materials Irradiation Facility injector at the Rokkasho site

    NASA Astrophysics Data System (ADS)

    Gobin, Raphael; Bogard, Daniel; Bolzon, Benoit; Bourdelle, Gilles; Chauvin, Nicolas; Chel, Stéphane; Girardot, Patrick; Gomes, Adelino; Guiho, Patrice; Harrault, Francis; Loiseau, Denis; Lussignol, Yves; Misiara, Nicolas; Roger, Arnaud; Senée, Franck; Valette, Matthieu; Cara, Philippe; Duglué, Daniel; Gex, Dominique; Okumura, Yoshikazu; Marcos Ayala, Juan; Knaster, Juan; Marqueta, Alvaro; Kasugai, Atsushi; O'Hira, Shigeru; Shinto, Katsuhiro; Takahashi, Hiroki

    2016-02-01

    The International Fusion Materials Irradiation Facility (IFMIF) linear IFMIF prototype accelerator injector dedicated to high intensity deuteron beam production has been designed, built, and tested at CEA/Saclay between 2008 and 2012. After the completion of the acceptance tests at Saclay, the injector has been fully sent to Japan. The re-assembly of the injector has been performed between March and May 2014. Then after the check-out phase, the production of the first proton beam occurred in November 2014. Hydrogen and deuteron beam commissioning is now in progress after having proceeded with the final tests on the entire injector equipment including high power diagnostics. This article reports the different phases of the injector installation pointing out the safety and security needs, as well as the first beam production results in Japan and chopper tests. Detailed operation and commissioning results (with H+ and D+ 100 keV beams) are reported in a second article.

  16. Detection of CEA in human serum using surface-enhanced Raman spectroscopy coupled with antibody-modified Au and γ-Fe₂O₃@Au nanoparticles.

    PubMed

    Lin, Yan; Xu, Guanhong; Wei, Fangdi; Zhang, Aixia; Yang, Jing; Hu, Qin

    2016-03-20

    In this present work, a rapid and simple method to detect carcinoembryonic antigen (CEA) was developed by using surface-enhanced Raman spectroscopy (SERS) coupled with antibody-modified Au and γ-Fe2O3@Au nanoparticles. First, Au@Raman reporter and γ-Fe2O3@Au were prepared, and then modified with CEA antibody. When CEA was present, the immuno-Au@Raman reporter and immuno-γ-Fe2O3@Au formed a complex through antibody-antigen-antibody interaction. The selective and sensitive detection of CEA could be achieved by SERS after magnetic separation. Under the optimal conditions, a linear relationship was observed between the Raman peak intensity and the concentration of CEA in the range of 1-50 ng mL(-1) with an excellent correlation coefficient of 0.9942. The limit of detection based on two times ratio of signal to noise was 0.1 ng/mL. The recoveries of CEA standard solution spiked with human serum samples were in the range of 88.5-105.9% with the relative standard deviations less than 17.4%. The method built was applied to the detection of CEA in human serum, and the relative deviations of the analysis results between the present method and electrochemiluminescence immunoassay were all less than 16.6%. The proposed method is practical and has a potential for clinic test of CEA. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Environmental Profiles of Paper vs. Electronic UC-CEAS Annual Reports

    EPA Science Inventory

    In 2010, the University of Cincinnati College of Engineering and Applied Sciences (UC-CEAS) created a new electronic format for the Annual Report that could be distributed through the college’s website to replace the prior print version. In order to determine the environmental co...

  18. Calculation to experiment comparison of SPND signals in various nuclear reactor environments

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

    Barbot, Loic; Radulovic, Vladimir; Fourmentel, Damien

    2015-07-01

    In the perspective of irradiation experiments in the future Jules Horowitz Reactor (JHR), the Instrumentation Sensors and Dosimetry Laboratory of CEA Cadarache (France) is developing a numerical tool for SPND design, simulation and operation. In the frame of the SPND numerical tool qualification, dedicated experiments have been performed both in the Slovenian TRIGA Mark II reactor (JSI) and very recently in the French CEA Saclay OSIRIS reactor, as well as a test of two detectors in the core of the Polish MARIA reactor (NCBJ). A full description of experimental set-ups and neutron-gamma calculations schemes are provided in the first partmore » of the paper. Calculation to experiment comparison of the various SPNDs in the different reactors is thoroughly described and discussed in the second part. Presented comparisons show promising final results. (authors)« less

  19. An Information Building on Radioactivity and Nuclear Energy for the French CEA Cadarache Research Center - 13492

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

    Brunel, Guy; Denis, Dominique; Boulet, Alain

    The CEA Cadarache research center is one of the 10 research centers of the French Alternative Energies and Atomic Energy Commission (CEA). Distributed throughout various research platforms, it focuses on nuclear fission, nuclear fusion, new energy technologies (hydrogen, solar, biomass) and fundamental research in the field of vegetal biology. It is the most important technological research and development centers for energy in Europe. Considering the sensitive nature of nuclear activities, the questions surrounding the issue of radioactive waste, the nuclear energy and the social, economic and environmental concerns for present and future generations, the French Government asked nuclear actors tomore » open communication and to give all the information asked by the Local Information Commission (CLI) and the public [1]. In this context, the CEA Cadarache has decided to better show and explain its expertise and experience in the area of nuclear energy and nuclear power plant design, and to make it available to stakeholders and to the public. CEA Cadarache receives each year more than 9000 visitors. To complete technical visits of the research facilities and laboratories, a scientific cultural center has been built in 2011 to inform the public on CEA Cadarache research activities and to facilitate the acceptance of nuclear energy in a way suited to the level of knowledge of the visitors. A modern interactive exhibition of 150 m{sup 2} allows visitors to find out more about energy, CEA Cadarache research programs, radioactive waste management and radiological impact on the research center activities. It also offers an auditorium for group discussions and for school groups to discover science through enjoyment. This communication center has received several thousand visitors since its opening on October 2011; the initial results of this experience are now available. It's possible to explain the design of this exhibition, to give some statistics on the number of the

  20. [Clinical value of combined detection of LDH, TPS, CEA and beta2-MG in patients with non- Hodgkin's lymphoma].

    PubMed

    Chen, Wei; Luo, Rong-cheng; Fan, Wei-wen; Ma, Shu-dong

    2006-02-01

    To study the clinical value of combined detection of 4 tumor markers, namely lactic dehydrogenate (LDH), tissue polypeptide specific antigen (TPS), carcinoembryonic antigen (CEA) and beta2-microglobulin (beta2-MG) in patients with non-Hodgkin's lymphoma (NHL). The serum level of LDH was determined with automatic biochemical analyzer and TPS, CEA and beta2-MG levels were determined by enzyme-linked immumosorbent assay (ELISA) in 59 patients with NHL and 40 healthy adults. The levels of the 4 tumor markers were significantly higher in NHL patients than in the healthy control subjects (P<0.05). After chemotherapy, the serum levels of TPS and beta2-MG were significantly lowered in the patients who showed favorable response to the treatment (P<0.05), but the levels of LDH and CEA showed no significant change (P>0.05). The serum levels of LDH, TPS, CEA and beta2-MG in the patients in a stable or progressive phase did had no significant changes after chemotherapy (P>0.05). Combined detection of LDH, TPS, CEA and beta2-MG can be helpful to assist diagnosis of NHL and treatment evaluation.

  1. Ex vivo PD-L1/PD-1 pathway blockade reverses dysfunction of circulating CEA specific T cells in pancreatic cancer patients

    PubMed Central

    Chen, Y; Xue, SA; Behboudi, S; Mohammad, GH; Pereira, SP; Morris, EC

    2017-01-01

    Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer (PC). In this study, we have characterised the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2 restricted peptide, pCEA691–699, isolated from the peripheral T cell repertoire of PC patients and sought to determine if ex vivo PD-L1 & TIM3 blockade could enhance CTL function. CD8+ T cell lines were generated from peripheral blood mononuclear cells (PBMCs) of 18 HLA-A2+ patients with PC and from 15 healthy controls. In vitro peptide specific responses were evaluated by flow cytometry after staining for intracellular cytokine production and CSFE cytotoxicity assays using pancreatic cancer cell lines as targets. Cytokine secreting functional CEA691-specific CTL lines were successfully generated from 10 of 18PC patients, with two CTL lines able to recognise and kill both CEA691 peptide-loaded T2 cells and CEA+ HLA-A2+ pancreatic cancer cell lines. In the presence of ex vivo PD-L1 blockade, functional CEA691-specific CD8+ T cell responses, including IFN-γ secretion and proliferation, were enhanced and this effect was more pronounced on Ag-specific T cells isolated from tumor draining lymph nodes. These data demonstrate that CEA691-specific CTL can be readily expanded from the self-restricted T cell repertoire of PC patients and that their function can be enhanced by PD-L1 blockade. PMID:28710313

  2. Aeroacoustics research in Europe: The CEAS-ASC report on 2013 highlights

    NASA Astrophysics Data System (ADS)

    Bennett, G. J.; Kennedy, J.; Meskell, C.; Carley, M.; Jordan, P.; Rice, H.

    2015-03-01

    The Council of European Aerospace Societies (CEAS) Aeroacoustics Specialists Committee (ASC) supports and promotes the interests of the scientific and industrial aeroacoustics community on an European scale and European aeronautics activities internationally. In this context, "aeroacoustics" encompasses all aerospace acoustics and related areas. Each year the committee highlights some of the research and development projects in Europe. This paper is a report on highlights of aeroacoustics research in Europe in 2013, compiled from information provided to the ASC of the CEAS. During 2013, a number of research programmes involving aeroacoustics were funded by the European Commission. Some of the highlights from these programmes are summarised in this paper, as well as highlights from other programmes funded by national programmes or by industry. Furthermore, a concise summary of the CEAS-ASC workshop "Atmospheric and Ground Effects on Aircraft Noise" held in Seville, Spain in September 2013 is included in this report. Enquiries concerning all contributions should be addressed to the authors who are given at the end of each subsection. This issue of the "highlights" paper is dedicated to the memory of Prof. John A. Fitzpatrick, Professor of Mechanical Engineering, Trinity College Dublin, and a valued member of the Aeroacoustics Specialists Committee. John passed away in September 2012 and is fondly missed across the globe by the friends he made in the Aeroacoustics Community. This paper is edited by PhD graduates and colleagues of John's who conduct research in aeroacoustics, inspired by his thirst for knowledge.

  3. The preliminary study of the quench protection of an MgB2

    NASA Astrophysics Data System (ADS)

    Juster, F. P.; Berriaud, C.; Bonelli, A.; Pasquet, R.; Przybilski, H.; Schild, T.; Scola, L.

    2014-01-01

    In the framework of general studies currently carried out at CEA/Saclay in collaboration with Sigmaphi Company on dry MgB2 magnet operating at 10 K and medium range field, 1 T up to 4 T., we plan to build a prototype-coil with a commercial MgB2 wire. This coil, the nominal axial magnetic field of which is 1 tesla, will be placed in a 3 teslas background field generated by a classical NbTi coil. This paper deals with the preliminary quench protection studies including stability and quench propagation modeling.

  4. Cellules solaires photovoltaïques plastiques enjeux et perspectives

    NASA Astrophysics Data System (ADS)

    Sicot, L.; Dumarcher, V.; Raimond, P.; Rosilio, C.; Sentein, C.; Fiorini, C.

    2002-04-01

    Après avoir détaillé le fonctionnement d'une cellule photovoltaïque plastique et les paramètres photovoltaïques permettant de caractéiser son efficacité, un état de l'art des technologies de fabrication des cellules est présenté. Des moyens d'amélioration des performances des cellules photovoltaïques organiques sont ensuite illustrés par l'étude de dispositifs développés au Laboratoire Composants Organiques (LCO) du CEA Saclay.

  5. Aeroacoustics research in Europe: The CEAS-ASC report on 2012 highlights

    NASA Astrophysics Data System (ADS)

    Bodén, H.; Efraimsson, G.

    2013-12-01

    The Council of European Aerospace Societies (CEAS) Aeroacoustics Specialists Committee (ASC) supports and promotes the interests of the scientific and industrial aeroacoustics community on an European scale and European aeronautics activities internationally. In this context, "aeroacoustics" encompasses all aerospace acoustics and related areas. Each year the committee highlights some of the research and development projects in Europe. This paper is a report on highlights of aeroacoustics research in Europe in 2012, compiled from information provided to the ASC of the CEAS. During 2012, a number of research programmes involving aeroacoustics were funded by the European Commission. Some of the highlights from these programmes are summarized in this paper, as well as highlights from other programmes funded by national programmes or by industry. Enquiries concerning all contributions should be addressed to the authors who are given at the end of each subsection.

  6. Thymidine kinase 1 combined with CEA, CYFRA21-1 and NSE improved its diagnostic value for lung cancer.

    PubMed

    Jiang, Z F; Wang, M; Xu, J L

    2018-02-01

    Thymidine kinase 1 (TK1) is a tumor biomarker in human malignancies. The purpose of this study was to evaluate the diagnostic efficiency of this marker for lung cancer using the combined analysis of carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1), neuron specific enolase (NSE) and TK1. From 2013 to 2014, 147 patients with lung cancer and 228 patients with lung benign diseases who were admitted to our hospital were reviewed. Peripheral blood samples were collected for the detection of TK1, CEA, CYFRA21-1 and NSE. The diagnostic value of each marker was analyzed using receiver operating characteristic (ROC) curves and logistic regression equations. The serum levels of TK1, CEA, CYFRA21-1 and NSE were significantly higher than those in patients with lung benign diseases (all P<0.05). The TK1 concentration was dependent on TNM stage (P=0.005). The ROC curve analyses showed that the diagnostic value of TK1 combined with CEA, CYFRA21-1 and NSE in lung cancer was significantly higher than that of each biomarker alone (all P<0.0001). In addition, TK1 combined with CEA, CYFRA21-1, or NSE could also improve the diagnosis of the squamous cell carcinoma, adenocarcinoma and small cell lung cancer subtypes, respectively. The combined detection of TK1 and the other three markers significantly improved the diagnosis of lung cancer. Furthermore, the detection of TK1 combined with that of CYFRA21-1, CEA or NSE increased the diagnostic value of TK1 for lung squamous cell carcinoma, adenocarcinoma and SCLC, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Efficient induction of anti-tumor immunity by a TAT-CEA fusion protein vaccine with poly(I:C) in a murine colorectal tumor model.

    PubMed

    Park, Jung-Sun; Kim, Hye-Sung; Park, Hye-Mi; Kim, Chang-Hyun; Kim, Tai-Gyu

    2011-11-03

    Protein vaccines may be a useful strategy for cancer immunotherapy because recombinant tumor antigen proteins can be produced on a large scale at relatively low cost and have been shown to be safe for clinical application. However, protein vaccines have historically exhibited poor immunogenicity; thus, an improved strategy is needed for successful induction of immune responses. TAT peptide is a protein transduction domain composed of an 11-amino acid peptide (TAT(47-57): YGRKKRRQRRR). The positive charge of this peptide allows protein antigen fused with it to improve cell penetration. Poly(I:C) is a synthetic double-stranded RNA that is negatively charged and favors interaction with the cationic TAT peptide. Poly(I:C) has been reported on adjuvant role in tumor vaccine through promotion of immune responses. Therefore, we demonstrated that vaccine with a mixture of TAT-CEA fusion protein and poly(I:C) can induce anti-tumor immunity in a murine colorectal tumor model. Splenocytes from mice vaccinated with a mixture of TAT-CEA fusion protein and poly(I:C) effectively induced CEA-specific IFN-γ-producing T cells and showed cytotoxic activity specific for MC-38-cea2 tumor cells expressing CEA. Vaccine with a mixture of TAT-CEA fusion protein and poly(I:C) delayed tumor growth in MC-38-cea-2 tumor-bearing mice. Depletion of CD8(+) T cells and NK cells reversed the inhibition of tumor growth in an MC-38-cea2-bearing mice, indicating that CD8(+) T cells and NK cells are responsible for anti-tumor immunity by vaccine with a mixture of TAT-CEA fusion protein and poly(I:C). Taken together, these results suggest that poly(I:C) could be used as a potent adjuvant to induce the anti-tumor immunity of a TAT-CEA fusion protein vaccine in a murine colorectal tumor model. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Deterministic Role of CEA and MSI Status in Predicting Outcome of CRC Patients: a Perspective Study Amongst Hospital Attending Eastern Indian Populations.

    PubMed

    Koyel, Banerjee; Priyabrata, Das; Rittwika, Bhattacharya; Swati, Dasgupta; Soma, Mukhopadhyay; Jayasri, Basak; Ashis, Mukhopadhyay

    2017-12-01

    Carcinoembryonic antigen (CEA) is an important deterministic factor in predicting colorectal carcinoma (CRC) progression. It is also evident that microsatellite instability (MSI) which results in a hypermutable phenotype of genomic DNA is common in CRC. Owing to the scarcity of reports from India, our aim of this study was to understand the clinicopathological correlations of CEA status with surgery and chemotherapy, correlate the same with socio-demographic status of the patients, determine the MSI status amongst them and understand the prognostic implications of CEA and MSI as CRC progression marker amongst patients. The serum CEA level was estimated by chemiluminescence assay (CLIA). Serum liver enzyme assay was carried out following the manufacturer's instructions using auto-analysers (E. Merck and Sera mol. Health Care, India). MSI analysis was carried out by PCR-SSCP. From our study, most frequently detected colorectal cancer was in 40-49 years age group (25.26%) with 61.05% male and 38.95% females. CEA showed a significant association with higher TNM staging, tumour size, smoking habit and MSI status ( p  < 0.05) but not with sex and site of cancer ( p  > 0.05). After surgery and chemotherapy, CEA and WBCs were decreased significantly ( p  < 0.05), while liver enzymes did not change significantly ( p  > 0.05). Overall, microsatellite instability was observed in approximately 40% of the populations. From our study, it was also evident that for both, MSI and abnormal CEA level predicted poor prognosis for the patient (by using Kaplan-Meier survival analysis; p  = 0.04). Thus, CEA and initial MSI status can be used as prognostic markers of CRC.

  9. [Usefulness of evaluation of carcinoembryonic antigen (CEA) and soluble fragments of cytokeratin 18-th (TPS) in postoperative monitoring of patients with colorectal cancer].

    PubMed

    Sandelewski, Artur; Kokocińska, Danuta; Partyka, Robert; Kocot, Jacek; Starzewski, Jacek; Chanek, Izabela; Jałowiecki, Przemysław

    2005-06-01

    The aim of this study is to diagnose the evaluation of concentration of CEA and TPS in postoperative monitoring of patients with colorectal cancer. We measured 178 consecutive patients with histopathologically confirmed colorectal cancer: 101 men and 78 women ages 22-86 (average age 54.7). Markers' CEA nad TPS concentration were evaluated before operation and every month after operation during the first 3 months and then every 3 months during 2 years. Relapse was detected in 47 patients. In postoperative period in non-relapse group the mean (the average) concentration of CEA was 1.92+/-2.03 ng/ml and TPS 65.54+/-33.96 U/l and respectively in relapse group for CEA was 1.92+/-2.03 ng/ml and for TPS 65.54+/-33.96 U/l. The obtained results in investigated group show significantly statistical. The relapse was confirmed by using CEA concentration in 42 patients (89.4%). In case of TPS concentration relapse was confirmed in 38 patients (80.85%). The relapse was detected in 45 patients (95.74) if increase in CEA or TPS concentration was treated as a way of detecting relapse. TPS markers point out that the increase of TPS concentartion may be ahead of relapse symptoms at about 2-6 months. TPS is a useful marker in postoperative monitoring of patients with colorectal cancer. The evaluation of TPS concentration allow to diagnose the recurrence of colorectal cancer earlier than by using burden markers--CEA. Common evaluation of TPS and CEA increase sensitivity in detection of relapse in patients with colorectal cancer.

  10. C.-E.A. Winslow Day: Proceedings of the June 3, 1977 Centenary Celebration

    PubMed Central

    Viseltear, Arthur J.

    1977-01-01

    Sponsored by Yale University, the City of New Haven, and the John B. Pierce Foundation, the C.-E.A. Winslow Day program consisted of speeches by Mr. Leonard Woodcock, President Emeritus, U.A.W., the Honorable Kenneth Gibson, Mayor of Newark, and Dr. Hector Acuña, Director, Pan American Health Organization; reminiscences of Ira Hiscock, Anna M.R. Lauder Professor Emeritus of Public Health, Mary Elizabeth Tennant, Associate Professor Emeritus of Nursing (Public Health), A. Pharo Gagge, Emeritus Fellow, John B. Pierce Foundation, and Mrs. Harriet Welch, Former President of the VNA of New Haven. The proceedings also included the presentation of gifts and the official C.-E.A. Winslow Day Proclamation. PMID:345631

  11. Combination of preoperative NLR, PLR and CEA could increase the diagnostic efficacy for I-III stage CRC.

    PubMed

    Peng, Hong-Xin; Yang, Lin; He, Bang-Shun; Pan, Yu-Qin; Ying, Hou-Qun; Sun, Hui-Ling; Lin, Kang; Hu, Xiu-Xiu; Xu, Tao; Wang, Shu-Kui

    2017-09-01

    Inflammation plays an important role in the development and progression of CRC. The members of inflammatory biomarkers, preoperative NLR and PLR, have been proved by numerous studies to be promising prognostic biomarkers for CRC. However, the diagnostic value of the two biomarkers in CRC remains unknown, and no study reported the combined diagnostic efficacy of NLR, PLR and CEA. Five hundred and fifty-nine patients with I-III stage CRC undergoing surgical resection and 559 gender- and age-matched healthy controls were enrolled in this retrospective study. NLR and PLR were calculated from preoperative peripheral blood cell count detected using white blood cell five classification by Sysmex XT-1800i Automated Hematology System and serum CEA were measured by electrochemiluminescence by ELECSYS 2010. The diagnostic performance of NLR, PLR and CEA for CRC was evaluated by ROC curve. Levels of NLR and PLR in the cases were significantly higher than them in the healthy controls. ROC curves comparison analyses showed that the diagnostic efficacy of NLR (AUC=.755, 95%CI=.728-.780) alone for CRC was significantly higher than PLR (AUC=.723, 95%CI=.696-.749, P=.037) and CEA (AUC=.690, 95%CI=.662-.717, P=.002) alone. In addition, the diagnostic efficacy of the combination of NLR, PLR and CEA(AUC=.831, 95%CI=.807-.852)for CRC was not only significantly higher than NLR alone but also higher than any combinations of the two of these three biomarkers (P<.05). Moreover, the NLR and PLR in the patients with TNM stage I/II was higher than that in the healthy controls, and patients with stage III had a higher NLR and PLR than those with stage I/II, but no significant difference was observed. Our study indicated that preoperative NLR could be a CRC diagnostic biomarker, even for early stage CRC, and the combination of NLR, PLR and CEA could significantly improve the diagnostic efficacy. © 2016 Wiley Periodicals, Inc.

  12. [A case of brain metastasis discovered after surgery for lung cancer based on changes in CEA, in which long-term survival was obtained by repeated gammaknife irradiation].

    PubMed

    Kakeya, Hiroshi; Inoue, Yuichi; Sawai, Toyomitsu; Ikuta, Yasushi; Ohno, Hideaki; Yanagihara, Katsunori; Higashiyama, Yasuhito; Miyazaki, Yoshitsugu; Soda, Hiroshi; Tashiro, Takayoshi; Kohno, Shigeru

    2005-12-01

    A 58-year-old man underwent right lower lobectomy for lung adenocarcinoma in June 1998. Since a high level of tumor marker CEA persisted after surgery, chemotherapy was additionally performed, and the CEA level subsequently normalized. However, the CEA level increased in April 1999, and brain metastasis was found in the left occipital lobe, and the first gammaknife irradiation was performed. Multiple brain metastases were found when CEA increased again in August 1999, and the second gammaknife irradiation was performed. Moreover, brain metastases were found in the left frontal and occipital lobes in February 2000, and the third gammaknife irradiation was performed. CEA normalized thereafter, but increased in February 2001. Brain metastasis was found in the right occipital lobe, and the fourth gammaknife irradiation was performed. CEA has remained within the normal range for about 4 years thereafter. Long-term survival was possible by repeated gammaknife irradiation for brain metastases. Monitoring of CEA played an important role in finding recurrent brain metastasis in this patient.

  13. Comparison of CEAS and Williams-type models for spring wheat yields in North Dakota and Minnesota

    NASA Technical Reports Server (NTRS)

    Barnett, T. L. (Principal Investigator)

    1982-01-01

    The CEAS and Williams-type yield models are both based on multiple regression analysis of historical time series data at CRD level. The CEAS model develops a separate relation for each CRD; the Williams-type model pools CRD data to regional level (groups of similar CRDs). Basic variables considered in the analyses are USDA yield, monthly mean temperature, monthly precipitation, and variables derived from these. The Williams-type model also used soil texture and topographic information. Technological trend is represented in both by piecewise linear functions of year. Indicators of yield reliability obtained from a ten-year bootstrap test of each model (1970-1979) demonstrate that the models are very similar in performance in all respects. Both models are about equally objective, adequate, timely, simple, and inexpensive. Both consider scientific knowledge on a broad scale but not in detail. Neither provides a good current measure of modeled yield reliability. The CEAS model is considered very slightly preferable for AgRISTARS applications.

  14. A risk prediction model for determining appropriateness of CEA in patients with asymptomatic carotid artery stenosis.

    PubMed

    Conrad, Mark F; Kang, Jeanwan; Mukhopadhyay, Shankha; Patel, Virendra I; LaMuraglia, Glenn M; Cambria, Richard P

    2013-10-01

    The benefit of carotid endarterectomy (CEA) over medical therapy in patients with asymptomatic carotid artery stenosis is predicated upon a life expectancy of at least 5 years after the procedure. The goal of this study was to create a scoring system for prediction of 5-year survival after CEA that can be used to triage patients with ACAS. All patients who underwent CEA for severe asymptomatic carotid stenosis from 1989 to 2005 were identified. Long-term survival was determined by a review of hospital records and the social security death index. Because all patients had at least 5-year follow-up, a logistic regression of predictors of survival at 5 years was performed and the odds ratios associated with particular significant comorbidities were used to create a scoring system to predict survival. The scoring system was then validated within the cohort using the Hosmer-Lemeshow Test and a derivation/validation receiver operating characteristic (ROC) curve. There were 2004 CEA performed in 1791 patients. The average follow-up was 130 ± 49 months. The clinical profile of the cohort data included 84% hypertension, 56% coronary artery disease (CAD), 24% diabetes, and 71% on statins. The 30-day stroke rate was 1.1% and the death rate was 0.7%. The actual 5-year survival was 73%. Logistic regression yielded the following predictors of mortality: age (by decade) (odds ratio [OR] = 1.8, P < 0.0001), CAD (OR = 1.5, P = 0.0007), chronic obstructive pulmonary disease (OR = 2.5; P < 0.0001), diabetes (OR = 1.7, P < 0.0001), neck radiation (OR = 2.6, P = 0.005), no statin (OR = 2.1, P < 0.0001), and creatinine more than 1.5 (OR = 2.6, P < 0.0001). These variables were then assigned a hierarchal point scoring system in accordance with the OR value. The 5-year survival based on the scoring system was as follows: 0 to 5 points = 92.5%, 6 to 8 points = 83.6%, 9 to 11 points = 63.7%, 12 to 14 points = 46.5%, and more than 15 points = 33.8%. The Hosmer-Lemeshow test validated the

  15. Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

    PubMed

    Metildi, Cristina A; Kaushal, Sharmeela; Luiken, George A; Talamini, Mark A; Hoffman, Robert M; Bouvet, Michael

    2014-04-01

    The aim of this study was to evaluate a new fluorescently labeled chimeric anti-CEA antibody for improved detection and resection of colon cancer. Frozen tumor and normal human tissue samples were stained with chimeric and mouse antibody-fluorophore conjugates for comparison. Mice with patient-derived orthotopic xenografts (PDOX) of colon cancer underwent fluorescence-guided surgery (FGS) or bright-light surgery (BLS) 24 hr after tail vein injection of fluorophore-conjugated chimeric anti-CEA antibody. Resection completeness was assessed using postoperative images. Mice were followed for 6 months for recurrence. The fluorophore conjugation efficiency (dye/mole ratio) improved from 3-4 to >5.5 with the chimeric CEA antibody compared to mouse anti-CEA antibody. CEA-expressing tumors labeled with chimeric CEA antibody provided a brighter fluorescence signal on frozen human tumor tissues (P = 0.046) and demonstrated consistently lower fluorescence signals in normal human tissues compared to mouse antibody. Chimeric CEA antibody accurately labeled PDOX colon cancer in nude mice, enabling improved detection of tumor margins for more effective FGS. The R0 resection rate increased from 86% to 96% with FGS compared to BLS. Improved conjugating efficiency and labeling with chimeric fluorophore-conjugated antibody resulted in better detection and resection of human colon cancer in an orthotopic mouse model. © 2013 Wiley Periodicals, Inc.

  16. A dye-sensitized solar cell acting as the electrical reading box of an immunosensor: Application to CEA determination.

    PubMed

    Truta, Liliana A A N A; Moreira, Felismina T C; Sales, M Goreti F

    2018-06-01

    Monitoring cancer biomarkers in biological fluids has become a key tool for disease diagnosis, which should be of easy access anywhere in the world. The possibility of reducing basic requirements in the field of electrochemical biosensing may open doors in this direction. This work proposes for this purpose an innovative electrochemical immunosensing system using a photovoltaic cell as an electrical reading box. Immunosensing ensures accuracy, the electrochemical-ground of the device ensures sensitivity and detectability, and the photovoltaic cell drives the system towards electrical autonomy. As proof-of-concept, Carcinoembryonic antigen (CEA) was used herein, a cancer biomarker of clinical relevance. In brief, a conductive glass with a fluorine doped tin oxide film was used as conductive support and modified with anti-CEA by means of a bottom-up approach. All stages involved in the biochemical modification of the FTO surface were followed by electrochemical techniques, namely electrochemical impedance spectroscopy and cyclic voltammetry. This electrode acted as counter electrode of a dye-sensitized solar cells, and the electrical output of this cell was monitored for the different concentrations of CEA. Under optimized conditions, the device displayed a linear behaviour against CEA concentration, from 5 pg/mL to 15 ng/mL. The immunosensor was applied to the analysis of CEA in urine from healthy individual and spiked with the antigen. Overall, the presented approach demonstrates that photovoltaic cells may be employed as an electrical reading box of electrochemical biosensors, yielding a new direction towards autonomous electrochemical biosensing. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  17. The concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid can be useful indicators for diagnosis of meningeal carcinomatosis of lung cancer.

    PubMed

    Wang, Peng; Piao, Yingzhe; Zhang, Xiaohui; Li, Wenliang; Hao, Xishan

    2013-01-01

    We aimed to investigate the concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid (CSF) and to explore their clinical value in the meningeal carcinomatosis (MC) of lung cancer. So that, sensitive and specificity of CSF examination can be improved in the initial diagnosis of MC. A total of 35 lung cancer patients and 35 patients with benign brain tumor in the same period enrolled in this study. The concentrations of tumor markers CEA, CYFRA 21-1 and NSE in CSF and peripheral blood were examined. The concentrations of three tumor markers of CYFRA 21-1, NSE and CEA in blood serum and CSF were obviously higher than that of benign disease group. In MC patients, the concentrations of three tumor markers of CYFRA 21-1, NSE and CEA in blood serum were significant lower than that in CSF. The maximum of Youden's index was identified as the cutoff value of indicator of MC in three tumor markers in CSF which were CEA > 4.7 μg/L, NSE > 14.6 μg/L and CYFRA21-1 > 5.5 μg/L respectively. Based on the cutoff values, the CEA had the highest sensitivity while the CYFRA21-1 had the highest specificitiy. Three tumor markers in the CSF had higher positive rate than those in blood serum. We combined the levels of CEA, NSE and CYFRA21-1 in CSF to diagnosis of MC. Positive of CEA or CYFRA21-1 had the greatest sensitivity of 100% while the specificity of 91.4%; the positive of both CEA and CYFRA21-1 had the highest specificity of 100% while the sensitivity of 74.3%. Both positive predictive value and negative predictive value were 100% when combination positive were confirmed when the all three markers were positive. The combination of CEA and CYFRA21-1 can be recommended in early screening of meningeal carcinoma. Especially, for the patient who was difficult to be diagnosed by CSF histology and MRI, it will be a useful auxiliary marker in diagnosis of MC. The combination of CEA, NSE and CYFRA21-1 can be an effective clinically confirmation and exclusively diagnose indictor of

  18. CEA SMAD 2016 Digitizer Evaluation.

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

    Merchant, Bion J.

    Sandia National Laboratories has tested and evaluated an updated SMAD digitizer, developed by the French Alternative Energies and Atomic Energy Commission (CEA). The SMAD digitizers are intended to record sensor output for seismic and infrasound monitoring applications. The purpose of this digitizer evaluation is to measure the performance characteristics in such areas as power consumption, input impedance, sensitivity, full scale, self-noise, dynamic range, system noise, response, passband, and timing. The SMAD digitizers have been updated since their last evaluation by Sandia to improve their performance when recording at a sample rate of 20 Hz for infrasound applications and 100 Hzmore » for hydro-acoustic seismic stations. This evaluation focuses primarily on the 20 Hz and 100 Hz sample rates. The SMAD digitizers are being evaluated for potential use in the International Monitoring System (IMS) of the Comprehensive Nuclear Test- Ban-Treaty Organization (CTBTO).« less

  19. [Clinical value of combined determination of serum and pleural effusion level of CEA,CYFRA21-1, TPS in the diagnosis of lung cancer].

    PubMed

    Huang, Fang; Wang, Xiao-li; Yang, Lian; Yin, Bin-xia; Geng, Yan; Li, Ting-ting

    2008-04-01

    To study the clinical value of combined determination of carcinoembryonic antigen (CEA), cytokeratin-19-fragments (CYFRA21-1) and tissue polypeptide specific antigen (TPS) levels in both serum and pleural effusion in the diagnosis of lung cancer. The levels of CEA, CYFRA21-1 and TPS in serum and pleural effusion were measured in 78 patients with lung cancer and 45 patients with benign lung disease by using electrochemiluminescence and ELISA methods respectively. The levels of CEA, CYFRA21-1 and TPS in pleural effusion of patients with lung cancer were much higher than those with benign lung disease (P<0.01). The levels of CEA and TPS in serum of patients with lung cancer were much higher than those with benign lung disease (P<0.05, P<0.01). It was also found that the levels of these tumor markers in pleural effusion were higher and more sensitive than those in sera, especially TPS. TPS showed the highest sensitivity in single tumor marker detection, and TPS+CYFRA21-1+ CEA showed the highest sensitivity and accuracy in combined tumor marker detection for diagnosis of lung cancer in pleural effusion. The combined detection of CEA, CYFRA21-1 and TPS in pleural effusion showed higher sensitivity, better accuracy and higher clinical value than those in serum for diagnosis of lung cancer.

  20. Combination of a poxvirus-based vaccine with a cyclooxygenase-2 inhibitor (celecoxib) elicits antitumor immunity and long-term survival in CEA.Tg/MIN mice.

    PubMed

    Zeytin, Hasan E; Patel, Arti C; Rogers, Connie J; Canter, Daniel; Hursting, Stephen D; Schlom, Jeffrey; Greiner, John W

    2004-05-15

    The present study was designed to determine whether: (a) chronic administration of dietary celecoxib (Celebrex), a potent nonsteroidal anti-inflammatory drug, which targets the cyclooxygenase-2 (COX-2) enzyme, negatively impacts host immunity; and (b) celecoxib can be coupled with a poxvirus-based vaccine to impact tumor burden in a murine tumor model of spontaneous adenomatous polyposis coli. Naive mice fed the celecoxib-supplemented diets developed eosinophilia with lowered plasma prostaglandin E(2) levels and reduced COX-2 mRNA expression levels in their splenic T cells. Responses of splenic T, B, and natural killer cells to broad-based and antigen-specific stimuli were, for the most part, unchanged in those mice as well as COX-2 knockout mice; exceptions included: (a) reduced IFN-gamma production by concanavalin A- or antigen-stimulated T cells; and (b) heightened lipopolysaccharide response of naive B cells from mice fed a diet supplemented with 1000 ppm of celecoxib. When transgenic mice that express the human carcinoembryonic antigen (CEA) gene (CEA transgenic) were bred with mice bearing a mutation in the Apc(Delta850) gene (multiple intestinal neoplasia mice), the progeny (CEA transgenic/multiple intestinal neoplasia) spontaneously develop multiple intestinal neoplasms that overexpress CEA and COX-2. Beginning at 30 days of age, the administration of a diversified prime/boost recombinant CEA-poxvirus-based vaccine regimen or celecoxib (1000 ppm)-supplemented diet reduced the number of intestinal neoplasms by 54% and 65%, respectively. Combining the CEA-based vaccine with the celecoxib-supplemented diet reduced tumor burden by 95% and significantly improved overall long-term survival. Both tumor reduction and improved overall survival were achieved without any evidence of autoimmunity directed at CEA-expressing or other normal tissues. Celecoxib is prescribed for the treatment of familial adenomatous polyposis in humans, and the CEA-based vaccines have been

  1. Comparing Hp(3) evaluated from the conversion coefficients from air kerma to personal dose equivalent for eye lens dosimetry calibrated on a new cylindrical PMMA phantom

    NASA Astrophysics Data System (ADS)

    Esor, J.; Sudchai, W.; Monthonwattana, S.; Pungkun, V.; Intang, A.

    2017-06-01

    Based on a new occupational dose limit recommended by ICRP (2011), the annual dose limit for the lens of the eye for workers should be reduced from 150 mSv/y to 20 mSv/y averaged over 5 consecutive years in which no single year exceeding 50 mSv. This new dose limit directly affects radiologists and cardiologists whose work involves high radiation exposure over 20 mSv/y. Eye lens dosimetry (Hp(3)) has become increasingly important and should be evaluated directly based on dosimeters that are worn closely to the eye. Normally, Hp(3) dose algorithm was carried out by the combination of Hp(0.07) and Hp(10) values while dosimeters were calibrated on slab PMMA phantom. Recently, there were three reports from European Union that have shown the conversion coefficients from air kerma to Hp(3). These conversion coefficients carried out by ORAMED, PTB and CEA Saclay projects were performed by using a new cylindrical head phantom. In this study, various delivered doses were calculated using those three conversion coefficients while nanoDot, small OSL dosimeters, were used for Hp(3) measurement. These calibrations were performed with a standard X-ray generator at Secondary Standard Dosimetry Laboratory (SSDL). Delivered doses (Hp(3)) using those three conversion coefficients were compared with Hp(3) from nanoDot measurements. The results showed that percentage differences between delivered doses evaluated from the conversion coefficient of each project and Hp(3) doses evaluated from the nanoDots were found to be not exceeding -11.48 %, -8.85 % and -8.85 % for ORAMED, PTB and CEA Saclay project, respectively.

  2. Use of integral experiments for the assessment of a new 235U IRSN-CEA evaluation

    NASA Astrophysics Data System (ADS)

    Ichou, Raphaëlle; Leclaire, Nicolas; Leal, Luiz; Haeck, Wim; Morillon, Benjamin; Romain, Pascal; Duarte, Helder

    2017-09-01

    The Working Party on International Nuclear Data Evaluation Co-operation (WPEC) subgroup 29 (SG 29) was established to investigate an issue with the 235U capture cross-section in the energy range from 0.1 to 2.25 keV, due to a possible overestimation of 10% or more. To improve the 235U capture crosssection, a new 235U evaluation has been proposed by the Institut de Radioprotection et de Sûreté Nucléaire (IRSN) and the CEA, mainly based on new time-of-flight 235U capture cross-section measurements and recent fission cross-section measurements performed at the n_TOF facility from CERN. IRSN and CEA Cadarache were in charge of the thermal to 2.25 keV energy range, whereas the CEA DIF was responsible of the high energy region. Integral experiments showing a strong 235U sensitivity are used to assess the new evaluation, using Monte-Carlo methods. The keff calculations were performed with the 5.D.1 beta version of the MORET 5 code, using the JEFF-3.2 library and the new 235U evaluation, as well as the JEFF-3.3T1 library in which the new 235U has been included. The benchmark selection allowed highlighting a significant improvement on keff due to the new 235U evaluation. The results of this data testing are presented here.

  3. [Clinical value of serum TPS, CEA, Pro-GRP and CYFRA21-1 in patients with lung cancer].

    PubMed

    Wang, Jinghui; Shi, Guangli; Zhang, Shucai; Wang, Qunhui; Yang, Xinjie; Li, Xi; Wang, Haiyong; Zhang, Hui; Song, Changxing

    2010-05-01

    Serum tumor markers play important roles in diagnosis, response and prognosis monitoring for lung cancer. The clinical significance of serum level of tissue polypeptide specific antigen (TPS) was investigated in diagnosis, response monitoring and prognosis in patients with lung cancer, compared with carcinoembryonic antigen (CEA), precursor of gastrin-releasing peptide (Pro-GRP) and cytokeratin-19-fragments (CYFRA21-1). Blood samples of eighty-two patients with lung cancer before treatment and some after chemotherapy were measured by ELISA for four tumor markers. Compared with lung benign diseases group and health control group, the positive rates and levels of TPS, CEA and Pro-GRP in patients with lung cancer were higher, with statistically significant difference. TPS in extensive-small cell lung cancer was significant higher than that in limited-small cell lung cancer. The positive rates and levels of TPS, CEA and Pro-GRP in patients after treatment had significant decreases compared with before treatment. TPS was an independent prognostic factor of non-small cell lung cancer. TPS is valuable to diagnosis, response monitoring for patients with lung cancer, moreover, it maybe a useful factor of prognosis of non-small cell lung cancer.

  4. [CEA, CA-19-9 and il-8, sTNFRII and sil-2R in persons at high risk of colorectal cancer].

    PubMed

    Grotowski, Maciej; Wojtuń, Stanisław

    2003-04-01

    The aim of the study was to determine whether elevated concentrations of CEA, CA19-9, IL-8, sTNFRII and sIL-2R occur in persons at high risk of colorectal cancer. A group of 37 persons at high risk of colorectal cancer and 40 healthy subjects (control group) were included into this study. In both groups IL-8, sTNFRII and sIL-2R concentrations were measured by ELISA method (R&D Systems Minneapolis, USA). In the group of persons at high risk of colorectal cancer CEA and CA19-9 concentrations were determined using MEIA kits (Abbott Laboratories, USA). Using the 95th percentiles of the distribution in the control group the upper normal limits of IL-8, sTN-FRII and sIL-2R values were calculated. The cut-off value for CEA was 3 ng/ml and that for CA 19-9 was 37 U/ml. The incidence of elevated concentrations of the studied factors and concentrations of CEA and CA19-9 was compared. The association was assessed of elevated concentrations of the studied factors and CEA and CA19-9 with the results of histological examination of pathological changes in the colon and rectum. In the group of persons at high risk of colorectal cancer only CEA concentration was elevated in 2.7%. The percentages of persons with elevated concentrations of IL-8, sIL-2R and sTNFRII were 29.7, 8.1 and 18.9%, respectively. The percentage of persons with elevated concentrations of IL-8 and sTNFRII was higher in comparison with the percentage of persons with elevated concentrations of CEA and CA19-9 (p < 0.05). Pathological lesions in the colon and rectum were detected in 16 persons (43.2%). High-grade dysplasia was detected in 11 cases. Elevated concentration of IL-8 always accompanied high-grade dysplasia in ulcerative colitis. The concentrations of IL-8 were significantly higher in high-grade dysplasia (23.7 pg/ml, SD +/- 7.53) than in cases of its absence (18.9 pg/ml, SD +/- 3.53) (p < 0.05). The obtained results of preliminary studies with IL-8 in persons at high risk of colorectal cancer require a

  5. The diagnostic value of serum tumor markers CEA, CA19-9, CA125, CA15-3, and TPS in metastatic breast cancer.

    PubMed

    Wang, Weigang; Xu, Xiaoqin; Tian, Baoguo; Wang, Yan; Du, Lili; Sun, Ting; Shi, Yanchun; Zhao, Xianwen; Jing, Jiexian

    2017-07-01

    This study aims to understand the diagnostic value of serum tumor markers carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), cancer antigen 15-3 (CA15-3), and tissue polypeptide-specific antigen (TPS) in metastatic breast cancer (MBC). A total of 164 metastatic breast cancer patients in Shanxi Cancer Hospital were recruited between February 2016 and July 2016. 200 breast cancer patients without metastasis in the same period were randomly selected as the control group. The general characteristics, immunohistochemical, and pathological results were investigated between the two groups, and tumor markers were determined. There were statistical differences in the concentration and the positive rates of CEA, CA19-9, CA125, CA15-3, and TPS between the MBC and control group (P<0.05). The highest sensitivity was in CEA and the highest specificity was in CA125 for the diagnosis of MBC when using a single tumor marker at 56.7% and 97.0%, respectively. In addition, two tumor markers were used for the diagnosis of MBC and the CEA and TPS combination had the highest diagnostic sensitivity with 78.7%, while the CA15-3 and CA125 combination had the highest specificity of 91.5%. Analysis of tumor markers of 164 MBC found that there were statistical differences in the positive rates of CEA and CA15-3 between bone metastases and other metastases (χ 2 =6.00, P=0.014; χ 2 =7.32, P=0.007, respectively). The sensitivity and specificity values of the CEA and CA15-3 combination in the diagnosis of bone metastases were 77.1% and 45.8%, respectively. The positive rate of TPS in the lung metastases group was lower than in other metastases (χ 2 =8.06, P=0.005).There were significant differences in the positive rates of CA15-3 and TPS between liver metastases and other metastases (χ 2 =15.42, P<0.001; χ 2 =9.72, P=0.002, respectively). The sensitivity and specificity of the CA15-3 and TPS combination in the diagnosis of liver metastases were 92.3% and

  6. Enhanced power generation and energy conversion of sewage sludge by CEA-microbial fuel cells.

    PubMed

    Abourached, Carole; Lesnik, Keaton Larson; Liu, Hong

    2014-08-01

    The production of methane from sewage sludge through the use of anaerobic digestion has been able to effectively offset energy costs for wastewater treatment. However, significant energy reserves are left unrecovered and effluent standards are not met necessitating secondary processes such as aeration. In the current study a novel cloth-electrode assembly microbial fuel cell (CEA-MFC) was used to generate electricity from sewage sludge. Fermentation pretreatment of the sludge effectively increased the COD of the supernatant and improved reactor performance. Using the CEA-MFC design, a maximum power density of 1200 mW m(-2) was reached after a fermentation pre-treatment time of 96 h. This power density represents a 275% increase over those previously observed in MFC systems. Results indicate continued improvements are possible and MFCs may be a viable modification to existing wastewater treatment infrastructure. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. [Clinical and prognostic significance of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer].

    PubMed

    Chen, Yan; Zheng, Yu-hong; Lin, Ying-ying; Hu, Min-hua; Chen, Yan-song

    2011-11-01

    To investigate the clinical and prognostic values of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer. A total of 386 hospitalized patients with stage I ∼ IV breast cancer from Nov 1998 to Feb 2009 were followed up, and their clinicopathological data were analyzed retrospectively to determine the factors affecting their prognosis. First, preoperative serum CA153 expression level was significantly associated with the age of onset and tumor size (P < 0.05), the expression of serum CEA was correlated with tumor size (P < 0.05), and the expression of serum tissue polypeptide specific antigen (TPS) was correlated with tumor size and lymph node metastases (P < 0.05). Second, the overall survival was significantly shorter among patients with elevated serum CA153, CEA or TPS, respectively (P < 0.05 for overall). Finally, multivariate Cox regression analysis indicated that estrogen receptor status (ER) and elevated preoperative values of CA 153 are independent prognostic factors for overall survival (P < 0.05), and CA 153 is a risk factor but estrogen receptor status is a protective factor for overall survival. Higher preoperative expression of serum CA153, CEA or TPS is closely correlated with clinicopathological characteristics and overall survival. The prognosis is poorer in primary breast cancer patients with higher CA15-3 expression level, and pre-treatment CA153 expression level can be used as an independent prognostic parameter in patients with primarily breast cancer.

  8. [Diagnostic values of type III Procollagen N-terminal peptide and combination assay of type III procollagen N-terminal peptide with CEA and CA 19-9 in gastric cancer].

    PubMed

    Akazawa, S; Harada, A; Futatsuki, K

    1984-07-01

    It is known that interstitial collagens are initially synthesized as precursors (procollagen), which possess extra peptide segments at both ends of the molecules. The authors attempted to detect the aminoterminal peptide of type III procollagen (type III-N-peptide) and also to measure the carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) together in sera of patients with gastric cancer. The results showed that: (1) mean serum levels and positive ratios of the type III-N-peptide increased as the clinical stage of the patients with gastric cancer advanced; (2) serum levels of the type III-N-peptide were not correlated either with those of CEA or CA 19-9; (3) positive ratios of type III-N-peptide, CEA and CA 19-9 were 51.7%, 44.8% and 48.3%, respectively: (4) positive ratio in combination of the type III-N-peptide with CEA was 69.3% and that in combination of the type III-N-peptide with CEA and CA 19-9 was 72.4%. These results suggest that type III-N-peptide is available for diagnosis of gastric cancer and, that the combination assay of type III-N-peptide with CEA and CA 19-9 is more effective than a single assay for diagnosis.

  9. The Nucifer Experiment

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

    Cucoanes, A.S., E-mail: cucoanes@subatech.in2p3.fr

    In nuclear reactors, a large number of antineutrinos are generated in the decay chains of the fission products; thus a survey of the antineutrino flux could provide valuable information related to the uranium and plutonium content of the core. This application generated interest by the IAEA in using antineutrino detectors as a potential safeguard tool. Here we present the Nucifer experiment, developed in France, by CEA and CNRS/IN2P3. The design of this new antineutrino detector has focused on safety, size reduction, reliability and high detection efficiency with a good background rejection. The Nucifer detector is currently taking data at themore » OSIRIS research reactor, inside CEA-Saclay. Presently, the ongoing analyses are considering the main sources of background for the antineutrino detection; the first antineutrino result is expected in 2013. A possible contribution to the understanding of the so called “reactor antineutrino anomaly” is also discussed. Finally, we present a brief description of the proposed experiments at very short baselines (VSBL) from reactors in France.« less

  10. NARMER-1: a photon point-kernel code with build-up factors

    NASA Astrophysics Data System (ADS)

    Visonneau, Thierry; Pangault, Laurence; Malouch, Fadhel; Malvagi, Fausto; Dolci, Florence

    2017-09-01

    This paper presents an overview of NARMER-1, the new generation of photon point-kernel code developed by the Reactor Studies and Applied Mathematics Unit (SERMA) at CEA Saclay Center. After a short introduction giving some history points and the current context of development of the code, the paper exposes the principles implemented in the calculation, the physical quantities computed and surveys the generic features: programming language, computer platforms, geometry package, sources description, etc. Moreover, specific and recent features are also detailed: exclusion sphere, tetrahedral meshes, parallel operations. Then some points about verification and validation are presented. Finally we present some tools that can help the user for operations like visualization and pre-treatment.

  11. PyOperators: Operators and solvers for high-performance computing

    NASA Astrophysics Data System (ADS)

    Chanial, P.; Barbey, N.

    2012-12-01

    PyOperators is a publicly available library that provides basic operators and solvers for small-to-very large inverse problems ({http://pchanial.github.com/pyoperators}). It forms the backbone of the package PySimulators, which implements specific operators to construct an instrument model and means to conveniently represent a map, a timeline or a time-dependent observation ({http://pchanial.github.com/pysimulators}). Both are part of the Tamasis (Tools for Advanced Map-making, Analysis and SImulations of Submillimeter surveys) toolbox, aiming at providing versatile, reliable, easy-to-use, and optimal map-making tools for Herschel and future generation of sub-mm instruments. The project is a collaboration between 4 institutes (ESO Garching, IAS Orsay, CEA Saclay, Univ. Leiden).

  12. Study of Background Rejection Systems for the IXO Mission.

    NASA Astrophysics Data System (ADS)

    Laurent, Philippe; Limousin, O.; Tatischeff, V.

    2009-01-01

    The scientific performances of the IXO mission will necessitate a very low detector background level. This will imply thorough background simulations, and efficient background rejection systems. It necessitates also a very good knowledge of the detectors to be shielded. In APC, Paris, and CEA, Saclay, we got experience on these activities by conceiving and optimising in parallel the high energy detector and the active and passive background rejection system of the Simbol-X mission. Considering that this work may be naturally extended to other X-ray missions, we have initiated with CNES a R&D project on the study of background rejection systems mainly in view the IXO project. We will detail this activity in the poster.

  13. Spanish Pre-University Students' Use of English: CEA Results from the University Entrance Examination

    ERIC Educational Resources Information Center

    Diez-Bedmar, Maria Belen

    2011-01-01

    In this paper an updated overview of the main errors that Spanish students make when writing the English exam in the University Entrance Examination is provided. To do so, a Computer-aided Error Analysis (CEA) (Dagneaux, Denness & Granger, 1998) was conducted on a representative sample of the students who took the exam in June 2008 in Jaen,…

  14. Comparative study of CEA and CA19-9 in esophageal, gastric and colon cancers individually and in combination (ROC curve analysis).

    PubMed

    Bagaria, Bhawna; Sood, Sadhna; Sharma, Rameshwaram; Lalwani, Soniya

    2013-09-01

    To determine the clinical serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), individually and in combination, for the diagnosis of 50 healthy subjects and 150 cases of esophageal, gastric, and colon cancers. The sensitivities of the two markers were compared individually and in combination, with specificity set at 100%. Receiver operating characteristic (ROC) curves were plotted. Serum CEA levels were significantly higher in cancer patients than in the control group. The sensitivity of CEA was determined: in esophageal cancer, sensitivity=28%, negative predictive value (NPV)=61.72%, and AUC=0.742 
(SE=0.05), with a significance level of P<0.0001; in gastric cancer, sensitivity=30%, NPV=58.82%, and AUC=0.734 (SE=0.05), with a significance level of P<0.0001; in colon cancer, sensitivity=74%, NPV=79.36%, and AUC=0.856 
(SE=0.04), with a significance level of P<0.0001. The sensitivity of CA19-9 was also evaluated: in esophageal cancer, sensitivity=18%, NPV=54.94%, and AUC=0.573 (SE =0.05), with a significance level of P=0.2054. In gastric cancer, sensitivity=42%, NPV=63.29%, and AUC=0.679 (SE =0.05), with a significance level of P<0.0011. In colon cancer, sensitivity=26%, NPV=57.47%, and AUC=0.580 (SE =0.05), with a significance level of P=0.1670. The following were the sensitivities of CEA/CA19-9 combined: in esophageal cancer, sensitivity=42%, NPV=63.29%, SE=0.078 (95% CI: 0.0159-0.322); gastric cancer, sensitivity=58%, NPV=70.42%, SE=0.072 (95% CI: -0.0866-0.198); and colon cancer, sensitivity=72%, NPV=78.12%, SE=0.070 (95% CI: 0.137-0.415). CEA exhibited the highest sensitivity for colon cancer, and CA19-9 exhibited the highest sensitivity for gastric cancer. Combined analysis indicated an increase in diagnostic sensitivity in esophageal and gastric cancer compared with that in colon cancer.

  15. Application of boronated anti-CEA immunoliposome to tumour cell growth inhibition in in vitro boron neutron capture therapy model.

    PubMed Central

    Yanagië, H.; Tomita, T.; Kobayashi, H.; Fujii, Y.; Takahashi, T.; Hasumi, K.; Nariuchi, H.; Sekiguchi, M.

    1991-01-01

    An immunoliposome containing a 10B-compound has been examined as a selective drug delivery system in boron neutron-capture therapy. Liposomes, conjugated with monoclonal antibodies specific for carcinoembryonic antigen (CEA) were shown to bind selectively to cells bearing CEA on their surface. The immunoliposomes attached to tumour cells suppressed growth in vitro upon thermal neutron irradiation and suppression was dependent upon the concentration of the 10B-compound in the liposomes and on the density of antibody conjugated to the liposomes. The results suggest that immunoliposomes containing the 10B-compound could act as a selective and efficient carrier of 10B atoms to target tumour cells in boron neutron-capture therapy. Images Figure 1 PMID:2021537

  16. Overview of studies and developments in cinematography, optoelectronic imaging, and photonics at CEA/DIF

    NASA Astrophysics Data System (ADS)

    Mens, Alain; Alozy, Eric; Aubert, Damien; Benier, Jacky; Bourgade, Jean-Luc; Boutin, Jean-Yves; Brunel, Patrick; Charles, Gilbert; Chollet, Clement; Desbat, Laurent; Gontier, Dominique; Jacquet, Henri-Patrick; Jasmin, Serge; Le Breton, Jean-Pierre; Marchet, Bruno; Masclet-Gobin, Isabelle; Mercier, Patrick; Millier, Philippe; Missault, Carole; Negre, Jean-Paul; Paul, Serge; Rosol, Rodolphe; Sommerlinck, Thierry; Veaux, Jacqueline; Veron, Laurent; Vincent de Araujo, Manuel; Jaanimagi, Paul; Pien, Greg

    2003-07-01

    This paper gives an overview of works undertaken at CEA/DIF in high speed cinematography, optoelectronic imaging and ultrafast photonics for the needs of the CEA/DAM experimental programs. We have developed a new multichannel velocimeter, and a new probe for shock breakout timing measurements in detonics experiments. A brief description and a recall of their main performances will be made. We have implemented three new optoelectronic imaging systems, in order to observe dynamic scenes in the ranges of 50 - 100 keV and 4 MeV. These systems are described, their main specifications and performances are given. Then we describe our contribution to the ICF program: after recalling the specifications of LIL plasma diagnostics, we describe the features and performances of visible streak tubes, X-ray streak tubes, visible and X-ray framing cameras and the associated systems developed to match these specifications. At last we introduce the subject of components and systems vulnerability in the LMJ target area, the principles identified to mitigate this problem and the first results of studies (image relay, response of streak tube phosphors, MCP image intensifiers and CCDs to fusion neutrons) related to this subject. Results obtained so far are presented.

  17. Joint modelling of longitudinal CEA tumour marker progression and survival data on breast cancer

    NASA Astrophysics Data System (ADS)

    Borges, Ana; Sousa, Inês; Castro, Luis

    2017-06-01

    This work proposes the use of Biostatistics methods to study breast cancer in patients of Braga's Hospital Senology Unit, located in Portugal. The primary motivation is to contribute to the understanding of the progression of breast cancer, within the Portuguese population, using a more complex statistical model assumptions than the traditional analysis that take into account a possible existence of a serial correlation structure within a same subject observations. We aim to infer which risk factors aect the survival of Braga's Hospital patients, diagnosed with breast tumour. Whilst analysing risk factors that aect a tumour markers used on the surveillance of disease progression the Carcinoembryonic antigen (CEA). As survival and longitudinal processes may be associated, it is important to model these two processes together. Hence, a joint modelling of these two processes to infer on the association of these was conducted. A data set of 540 patients, along with 50 variables, was collected from medical records of the Hospital. A joint model approach was used to analyse these data. Two dierent joint models were applied to the same data set, with dierent parameterizations which give dierent interpretations to model parameters. These were used by convenience as the ones implemented in R software. Results from the two models were compared. Results from joint models, showed that the longitudinal CEA values were signicantly associated with the survival probability of these patients. A comparison between parameter estimates obtained in this analysis and previous independent survival[4] and longitudinal analysis[5][6], lead us to conclude that independent analysis brings up bias parameter estimates. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary. Results indicate that the longitudinal progression of CEA is signicantly associated with the probability of survival of these patients. Hence, an assumption of

  18. Advances in Monte-Carlo code TRIPOLI-4®'s treatment of the electromagnetic cascade

    NASA Astrophysics Data System (ADS)

    Mancusi, Davide; Bonin, Alice; Hugot, François-Xavier; Malouch, Fadhel

    2018-01-01

    TRIPOLI-4® is a Monte-Carlo particle-transport code developed at CEA-Saclay (France) that is employed in the domains of nuclear-reactor physics, criticality-safety, shielding/radiation protection and nuclear instrumentation. The goal of this paper is to report on current developments, validation and verification made in TRIPOLI-4 in the electron/positron/photon sector. The new capabilities and improvements concern refinements to the electron transport algorithm, the introduction of a charge-deposition score, the new thick-target bremsstrahlung option, the upgrade of the bremsstrahlung model and the improvement of electron angular straggling at low energy. The importance of each of the developments above is illustrated by comparisons with calculations performed with other codes and with experimental data.

  19. Big Data solution for CTBT monitoring: CEA-IDC joint global cross correlation project

    NASA Astrophysics Data System (ADS)

    Bobrov, Dmitry; Bell, Randy; Brachet, Nicolas; Gaillard, Pierre; Kitov, Ivan; Rozhkov, Mikhail

    2014-05-01

    Waveform cross-correlation when applied to historical datasets of seismic records provides dramatic improvements in detection, location, and magnitude estimation of natural and manmade seismic events. With correlation techniques, the amplitude threshold of signal detection can be reduced globally by a factor of 2 to 3 relative to currently standard beamforming and STA/LTA detector. The gain in sensitivity corresponds to a body wave magnitude reduction by 0.3 to 0.4 units and doubles the number of events meeting high quality requirements (e.g. detected by three and more seismic stations of the International Monitoring System (IMS). This gain is crucial for seismic monitoring under the Comprehensive Nuclear-Test-Ban Treaty. The International Data Centre (IDC) dataset includes more than 450,000 seismic events, tens of millions of raw detections and continuous seismic data from the primary IMS stations since 2000. This high-quality dataset is a natural candidate for an extensive cross correlation study and the basis of further enhancements in monitoring capabilities. Without this historical dataset recorded by the permanent IMS Seismic Network any improvements would not be feasible. However, due to the mismatch between the volume of data and the performance of the standard Information Technology infrastructure, it becomes impossible to process all the data within tolerable elapsed time. To tackle this problem known as "BigData", the CEA/DASE is part of the French project "DataScale". One objective is to reanalyze 10 years of waveform data from the IMS network with the cross-correlation technique thanks to a dedicated High Performance Computer (HPC) infrastructure operated by the Centre de Calcul Recherche et Technologie (CCRT) at the CEA of Bruyères-le-Châtel. Within 2 years we are planning to enhance detection and phase association algorithms (also using machine learning and automatic classification) and process about 30 terabytes of data provided by the IDC to

  20. CEA, CA 15-3, and TPS as Prognostic Factors in the Follow-up Monitoring of Patients After Radical Surgery for Breast Cancer.

    PubMed

    Svobodova, Sarka; Kucera, Radek; Fiala, Ondrej; Marie, Karlikova; Narsanska, Andrea; Zedníková, Ilona; Treska, Vladislav; Slouka, David; Milena, Rousarova; Topolcan, Ondrej; Finek, Jindrich

    2018-01-01

    The aim of this study was to evaluate the ability of tissue polypeptide-specific antigen (TPS), carcinoembryonic antigen (CEA), and cancer antigen 15-3 (CA 15-3) to predict relapse in breast cancer patients, when the measurement of biomarkers is performed within 6 months after surgery. Four hundred and seventy-two patients with breast cancer were evaluated. TPS, CEA, and CA 15-3 were measured in months 1, 3, and 6, after surgery. Disease recurrence was recorded between 7-12 months after surgery. Disease recurrence occurred in 60 patients, while 412 patients remained in recurrence-free status. TPS levels of the recurrence group differed statistically significantly in the first and sixth month after surgery compared to recurrence-free group (p=0.0339, AUC=0.6056; p<0.0001, AUC=0.7196). CEA and CA 15-3 measurements did not achieve a statistically significant difference for any month examined. TPS level in the sixth month after surgery is the best candidate biomarker to predict disease recurrence. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Enhanced peroxidase-like properties of Au@Pt DNs/NG/Cu2+ and application of sandwich-type electrochemical immunosensor for highly sensitive detection of CEA.

    PubMed

    Lv, Hui; Li, Yueyun; Zhang, Xiaobo; Gao, Zengqiang; Zhang, Chunyan; Zhang, Shuan; Dong, Yunhui

    2018-07-30

    Effective treatment of cancer depends upon the early detection of the tumor marker. Here, we report on the development of a new immunosensor for early detection of carcinoembryonic antigen (CEA). Cubic Au@Pt dendritic nanomaterials functionalized nitrogen-doped graphene loaded with copper ion (Au@Pt DNs/NG/Cu 2+ ) with enhanced peroxidase-like properties was synthesized as labels to effectively capture and immobilize secondary anti-CEA. The Au@Pt DNs with more active surface area could efficiently enhance electrocatalysis for reduction of hydrogen peroxide (H 2 O 2 ). Meanwhile, with good conductivity and large specific surface area, NG can immobilize a large amount of Au@Pt DNs. Furthermore, after adsorbed Cu 2+ can further promote the redox of H 2 O 2 and amplify the signal of the immunosensor. For the immobilization of primary antibodies, Au nanoparticles functionalized polydopamine (Au@PDA) were used as transducing materials to modify glassy carbon electrodes and enhance the electron transfer efficiently. Under optimal conditions, the immunosensor exhibited a satisfactory response to CEA with a limit detection of 0.167 pg/mL and linear detection range from 0.5 pg/mL to 50 ng/mL. Based on the high sensitivity and specificity of the immunosensor, we propose this multiple amplified biosensor for early detection of CEA. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Neuropeptide Y (NPY) in the central nucleus of the amygdala (CeA) does not affect ethanol-reinforced responding in binge-drinking, nondependent rats.

    PubMed

    Henderson, Angela N; Czachowski, Cristine L

    2012-03-01

    The central nucleus of the amygdala (CeA) has been implicated as having a significant role in mediating alcohol-drinking behavior. Neuropeptide Y (NPY) has been investigated as a potential pharmacotherapeutic due to its ability to attenuate ethanol intake, particularly when administered into the CeA. Previous research suggests, though the evidence is somewhat conflicting, that the efficacy of NPY is contingent upon genetic background and/or prior history of ethanol dependence in rats. However, studies looking at the effects of NPY in nonselected animals lacking a history of ethanol dependence have two factors that could impact the interpretation of the results: ethanol history/selection AND relatively low baseline ethanol intakes as compared to ethanol-dependent and/or genetically selected controls. The purpose of the present study was to generate higher baseline ethanol intakes upon which to examine the effects of NPY on ethanol and sucrose drinking in nonselected rats using a binge drinking model. Long Evans rats were trained to complete a single response requirement resulting in access to either 2% sucrose (Sucrose Group) or 2% sucrose/10% ethanol (Ethanol Group) for a 20-min drinking session. On treatment days, rats were bilaterally microinjected into the CeA with aCSF or one of three doses of NPY (0.25μg, 0.50μg, or 1.00μg/.5μL). Subjects in the Ethanol Group were consuming an average of 1.2g/kg of ethanol (yielding BELs of ~90mg%) during the 20min access period following aCSF treatments. The results revealed that NPY had no effect on either sucrose or ethanol consumption or on appetitive responding (latency to respond). Overall, the findings indicate that even a history of binge-like ethanol consumption is not sufficient to recruit CeA NPY activity, and are consistent with previous studies showing that the role of NPY in regulating ethanol reinforcement in the CeA may be contingent upon a prior history of ethanol dependence. Copyright © 2011 Elsevier Inc

  3. [Relation between the level of TPS, NSE, CEA and beta2-mG in the serum and the biological behavior of small cell lung cancer].

    PubMed

    Chen, Ming-sheng; Xu, Yan; Ma, Jing; Wu, Chang-gui; Hao, Xiao-ke; Lu, Bao-bi; Liu, Tian

    2007-08-01

    To study the relation between the level of tissue polypeptide specific antigen (TPS), neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and beta(2)-microglobulin (beta(2)-mG) in serum and the biological behavior of lung cancer for the more scientific diagnosis of lung cancer. To detect the level of TPS, NSE, CEA and beta(2)-mG in the serum of 94 patients with small cell lung cancer (SCLC), 86 patients with benign pulmonary diseases (BPD) and 89 patients in normal control group, the level of serum were examined by ELISA and immunoradiometric assay. The level of TPS and NSE in the serum of SCLC group [(437.8+/-516.6) U/L, (76.8+/-91.4) microg/L] were much higher than those in BPD group [(143.6+/-78.7) U/L, (13.3+/-10.8) microg/L] and normal group [(98.4+/-58.9) U/L, (10.1+/-5.7) microg/L, P<0.01)], and the level of CEA and beta(2)-mG in the serum of SCLC group were also obviously higher than those in normal group and BPD group (P<0.01). The sensitivity, specificity and accuracy of SCLC'S diagnosis by an indicator of TPS and NSE were 84.4%, 87.8%, 83.6% and 79.3%, 93.7%, 88.3%, respectively, and were much higher than CEA and beta(2)-Mg. In addition, the level of TPS and NSE in the patients' serum with metastatic SCLC were markedly higher than those in the patients with SCLC without metastasis, increased with the number of metastatic focuses. In clinical practice, the possibility of smokers suffering from lung cancer disease is 8 to 10 times higher than that of no-smokers, and 10 to 24 times higher of the people who smoked 30 to 40 cigarettes per day. From this comparison, the amount of smoking was closely related to the occurrence of lung cancer. TPS, NSE, CEA and beta(2)-mG in serum are useful for early diagnosis of lung cancer. There is complementarity in the combined detection of the level of TPS, NSE, CEA and beta(2)-MG. Their levels have close correlation with lung cancer, histological grades and lymphoid nodule metastasis.

  4. [Comparison of TPS, CEA, CYFRA21-1 and STNFR in diagnosis of lung cancer].

    PubMed

    Liao, Qiulin; Li, Lianhua; Chen, Mingsheng

    2005-08-20

    In recent years, new progress has been made in research of tumor markers. And namely tissue polypeptide specific antigen (TPS), cytokeratin 19-fragments (CYFRA21-1) and soluble tumor necrosis factor receptor (STNFR) are new tumor markers that have been used in clinical application. The aim of this study is to determine and compare the diagnostic value of 4 kinds of tumor markers, TPS, carcinoembryonic antigen (CEA), CYFRA21-1 and STNFR in patients with lung cancer. The serum levels of TPS, CEA, CYFRA21-1 and STNFR were determined in 72 patients with lung cancer, 54 patients with pulmonary benign diseases and 32 healthy adults by enzyme-linked immunosorbent assay (ELISA). The levels of the four tumor markers in lung cancer group were significantly higher than those in benign disease group (P < 0.005) and healthy control group (P < 0.001). Among the four markers, STNFR had the highest sensitivity (81.9%), CYFRA21-1 had the highest specificity (91.5%) and TPS had the highest accuracy (83.5%). TPS, CYFRA21-1 and STNFR can be used as very useful and sensitive tumor markers in the diagnosis of lung cancer, in which CYFRA21-1 may be the most useful tumor marker for clinical application.

  5. Space cryogenics at CEA-SBT

    NASA Astrophysics Data System (ADS)

    Duband, Lionel; Charles, Ivan; Duval, Jean-Marc; Ercolani, Eric; Gully, Philippe; Luchier, Nicolas; Prouve, Thomas; Thibault, Pierre

    2017-11-01

    The "Service des Basses Températures" (SBT) of CEA Grenoble has been involved in space cryogenics for over 20 years now. In fact a dedicated laboratory was created within SBT to carry out these developments, the "Cryocoolers and Space Cryogenics" group, which comprises about 20 persons as of today. Various cryocoolers have been developed in the past and our fields of activity focus now on four main technologies: sorption coolers, multistage pulse tubes, adiabatic demagnetization refrigerators (ADR), and cryogenic loop heat pipes. In addition work on two new concepts for ground based dilution refrigerators is also ongoing. Finally developments on various key technologies such as the heat switches, the suspension or structural systems are also carried out. These developments are mainly funded by the European Space Agency (ESA) or by the Centre National d'Etudes Spatiales (CNES). For most of these systems the common feature is the absence of any moving parts or any friction, which guarantees a very good reliability and make them very good candidates for space borne instruments requiring cryogenic temperatures. In this paper we give an overview of these developments with a particular focus on the sub Kelvin coolers. Based on the HERSCHEL heritage for which we developed the flight sorption coolers, we are now proposing an original concept featuring the association of a 300 mK sorption unit with a miniature adiabatic demagnetization refrigerator. This combination will allow to provide temperature as low as 50 mK with a system weighting less than 5 kg. This development may have direct application for the XEUS and SPICA missions.

  6. Advanced uncooled infrared focal plane development at CEA/LETI

    NASA Astrophysics Data System (ADS)

    Tissot, Jean-Luc; Mottin, Eric; Martin, Jean-Luc; Yon, Jean-Jacques; Vilain, Michel

    2017-11-01

    LETI/LIR has been involved for a few year in the field of uncooled detectors and has chosen amorphous silicon for its microbolometer technology development. Uncooled IR detectors pave the way to reduced weight systems aboard satellites. The silicon compatibility of our thermometer is a key parameter which has enabled a very fast technology development and transfer to industry. This competitive technology is now able to provide a new approach for IR detectors for space applications. This paper presents the main characteristics of the CEA / LETI technology which is based on a monolithically integrated structure over a fully completed readout circuit from a commercially available 0.5 μm design rules CMOS line. The technology maturity will be illustrated by the results obtained at LETI/LIR and SOFRADIR on a 320 x 240 with a pitch of 45 μm. First improvement on device reliability and characterization results will be presented.

  7. Imaging of a parapharyngeal hemangiopericytoma. Radioimmunoscintigraphy (SPECT) with indium-111-labeled anti-CEA antibody, and comparison to digital subtraction angiography, computed tomography, and immunohistochemistry

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

    Kairemo, K.J.; Hopsu, E.V.; Melartin, E.J.

    1991-01-01

    A 27-year-old male patient with a parapharyngeal hemangiopericytoma was investigated radiologically with orthopantomography, computed tomography, and digital subtraction angiography before the operation. Because a malignancy was suspected, the patient was imaged with gamma camera using radiolabeled monoclonal anticarcinoembryonal antigen antibody including single photon emission computed tomography. The radioantibody accumulated strongly into the neoplasm. Tumor to background ratio was 2.2. Samples of the excised tumor were stained immunohistochemically for desmin, vimentin, muscle actin, cytokeratin, CEA (carcinoembryonic antigen), and factor VIII. They showed that the antibody uptake was of unspecific nature and not due to CEA expression in the tumor.

  8. Multi-arm Cost-Effectiveness Analysis (CEA) comparing different durations of adjuvant trastuzumab in early breast cancer, from the English NHS payer perspective

    PubMed Central

    Hunter, Rachael M.; Shemilt, Ian; Serra-Sastre, Victoria

    2017-01-01

    Background Trastuzumab improves survival in HER2+ breast cancer patients, with some evidence of adverse cardiac side effects. Current recommendations are to give adjuvant trastuzumab for one year or until recurrence, although trastuzumab treatment for only 9 or 10 weeks has shown similar survival rates to 12-month treatment. We present here a multi-arm joint analysis examining the relative cost-effectiveness of different durations of adjuvant trastuzumab. Methods and findings Network meta-analysis (NMA) was used to examine which trials’ data to include in the cost-effectiveness analysis (CEA). A network using FinHer (9 weeks vs. zero) and BCIRG006 (12 months vs. zero) trials offered the only jointly randomisable network so these trials were used in the CEA. The 3-arm CEA compared costs and quality-adjusted life-years (QALYs) associated with zero, 9-week and 12-month adjuvant trastuzumab durations in early breast cancer, using a decision tree followed by a Markov model that extrapolated the results to a lifetime time horizon. Pairwise incremental cost-effectiveness ratios (ICERs) were also calculated for each pair of regimens and used in budget impact analysis, and the Bucher method was used to check face validity of the findings. Addition of the PHARE trial (6 months vs. 12 months) to the network, in order to create a 4-arm CEA including the 6-month regimen, was not possible as late randomisation in this trial resulted in recruitment of a different patient population as evidenced by the NMA findings. The CEA results suggest that 9 weeks’ trastuzumab is cost-saving and leads to more QALYs than 12 months’, i.e. the former dominates the latter. The cost-effectiveness acceptability frontier (CEAF) favours zero trastuzumab at willingness-to-pay levels below £2,500/QALY and treatment for 9 weeks above this threshold. The combination of the NMA and Bucher investigations suggests that the 9-week duration is as efficacious as the 12-month duration for distant

  9. Multi-arm Cost-Effectiveness Analysis (CEA) comparing different durations of adjuvant trastuzumab in early breast cancer, from the English NHS payer perspective.

    PubMed

    Clarke, Caroline S; Hunter, Rachael M; Shemilt, Ian; Serra-Sastre, Victoria

    2017-01-01

    Trastuzumab improves survival in HER2+ breast cancer patients, with some evidence of adverse cardiac side effects. Current recommendations are to give adjuvant trastuzumab for one year or until recurrence, although trastuzumab treatment for only 9 or 10 weeks has shown similar survival rates to 12-month treatment. We present here a multi-arm joint analysis examining the relative cost-effectiveness of different durations of adjuvant trastuzumab. Network meta-analysis (NMA) was used to examine which trials' data to include in the cost-effectiveness analysis (CEA). A network using FinHer (9 weeks vs. zero) and BCIRG006 (12 months vs. zero) trials offered the only jointly randomisable network so these trials were used in the CEA. The 3-arm CEA compared costs and quality-adjusted life-years (QALYs) associated with zero, 9-week and 12-month adjuvant trastuzumab durations in early breast cancer, using a decision tree followed by a Markov model that extrapolated the results to a lifetime time horizon. Pairwise incremental cost-effectiveness ratios (ICERs) were also calculated for each pair of regimens and used in budget impact analysis, and the Bucher method was used to check face validity of the findings. Addition of the PHARE trial (6 months vs. 12 months) to the network, in order to create a 4-arm CEA including the 6-month regimen, was not possible as late randomisation in this trial resulted in recruitment of a different patient population as evidenced by the NMA findings. The CEA results suggest that 9 weeks' trastuzumab is cost-saving and leads to more QALYs than 12 months', i.e. the former dominates the latter. The cost-effectiveness acceptability frontier (CEAF) favours zero trastuzumab at willingness-to-pay levels below £2,500/QALY and treatment for 9 weeks above this threshold. The combination of the NMA and Bucher investigations suggests that the 9-week duration is as efficacious as the 12-month duration for distant-disease-free survival and overall survival

  10. CEA to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with colorectal cancer peritoneal carcinomatosis undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study.

    PubMed

    Kozman, Mathew A; Fisher, Oliver M; Rebolledo, Bree-Anne J; Parikh, Roneil; Valle, Sarah J; Arrowaili, Arief; Alzahrani, Nayef; Liauw, Winston; Morris, David L

    2018-03-01

    Serum tumor markers are prognostic in patients with colorectal cancer peritoneal carcinomatosis (CRPC) undergoing cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). Assessment of the ratio of tumor marker to volume, as depicted by peritoneal carcinomatosis index (PCI), and how this may affect overall (OS) and recurrence free survival (RFS) has not been reported. Survival effect of this ratio was analyzed in patients with CRPC managed from 1996 to 2016 with CRS and IPC. Of 260 patients included, those with low CEA/PCI ratio (<2.3) had longer median OS (56 vs 24 months, P = 0.001) and RFS (13 vs 9 months, P = 0.02). The prognostic impact of CEA/PCI ratio was most pronounced in patients with PCI ≤ 10 (OS of 72 vs 30 months, P < 0.001; RFS of 21 vs 10 months, P = 0.002). In multivariable analysis, elevated CEA/PCI ratio was independently associated with poorer OS (adjusted HR 1.85, 95%CI 1.11-3.10, P = 0.02) and RFS (adjusted HR 1.58, 95%CI 1.04-2.41, P = 0.03). CEA/PCI ratio is an independent prognostic factor for OS and RFS in CRPC. This novel approach allows both tumor activity and volume to be accounted for in one index, thus potentially providing a more accurate indication of tumor biological behavior. © 2017 Wiley Periodicals, Inc.

  11. XMM-Newton observation of the Coma Galaxy cluster. The temperature structure in the central region

    NASA Astrophysics Data System (ADS)

    Arnaud, M.; Aghanim, N.; Gastaud, R.; Neumann, D. M.; Lumb, D.; Briel, U.; Altieri, B.; Ghizzardi, S.; Mittaz, J.; Sasseen, T. P.; Vestrand, W. T.

    2001-01-01

    We present a temperature map and a temperature profile of the central part (r < 20' or 1/4 virial radius) of the Coma cluster. We combined 5 overlapping pointings made with XMM/EPIC/MOS and extracted spectra in boxes of 3.5'x3.5'. The temperature distribution around the two central galaxies is remarkably homogeneous (r<10'), contrary to previous ASCA results, suggesting that the core is actually in a relaxed state. At larger distance from the cluster center we do see evidence for recent matter accretion. We confirm the cool area in the direction of NGC 4921, probably due to gas stripped from an infalling group. We find indications of a hot front in the South West, in the direction of NGC 4839, probably due to an adiabatic compression. Based on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and the USA (NASA). EPIC was developed by the EPIC Consortium led by the Principal Investigator, Dr. M. J. L. Turner. The consortium comprises the following Institutes: University of Leicester, University of Birmingham, (UK); CEA/Saclay, IAS Orsay, CESR Toulouse, (France); IAAP Tuebingen, MPE Garching, (Germany); IFC Milan, ITESRE Bologna, IAUP Palermo, Italy. EPIC is funded by: PPARC, CEA, CNES, DLR and ASI.

  12. TPS, CA 19-9, VEGF-A, and CEA as diagnostic and prognostic factors in patients with mass lesions in the pancreatic head.

    PubMed

    Sandblom, Gabriel; Granroth, Sofie; Rasmussen, Ib Christian

    2008-01-01

    Although numerous tumour markers are available for periampullary tumours, including pancreatic cancer, their specificity and sensitivity have been questioned. To assess the diagnostic and prognostic values of tissue polypeptide specific antigen (TPS), carbohydrate antigen 19-9 (CA 19-9), vascular endothelial growth factor (VEGF-A), and carcinoembryonic antigen (CEA) we took serum samples in 56 patients with mass lesions in the pancreatic head. Among these patients, further investigations revealed pancreatic cancer in 20 patients, other malignant diseases in 12 and benign conditions in 24. Median CEA in all patients was 3.4 microg/L (range 0.5-585.0), median CA 19-9 was105 kU/L (range 0.6-1 300 00), median TPS 123.5 U/L (range 15.0-3350) and median VEGF-A 132.5 ng/L (range 60.0-4317). Area under the curve was 0.747, standard error (standard error [SE] =0.075) for CEA, 0.716 (SE=0.078) for CA 19-9 and 0.822 (SE=0.086) for TPS in ROC plots based on the ability of the tumours to distinguish between benign and malignant conditions. None of the markers significantly predicted survival in the subgroup of patients with pancreatic cancer. Our study shows that the markers may be used as fairly reliable diagnostic tools, but cannot be used to predict survival.

  13. Flexible attosecond beamline for high harmonic spectroscopy and XUV/near-IR pump probe experiments requiring long acquisition times

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

    Weber, S. J., E-mail: sebastien.weber@cea.fr; Manschwetus, B.; Billon, M.

    2015-03-15

    We describe the versatile features of the attosecond beamline recently installed at CEA-Saclay on the PLFA kHz laser. It combines a fine and very complete set of diagnostics enabling high harmonic spectroscopy (HHS) through the advanced characterization of the amplitude, phase, and polarization of the harmonic emission. It also allows a variety of photo-ionization experiments using magnetic bottle and COLTRIMS (COLd Target Recoil Ion Momentum Microscopy) electron spectrometers that may be used simultaneously, thanks to a two-foci configuration. Using both passive and active stabilization, special care was paid to the long term stability of the system to allow, using bothmore » experimental approaches, time resolved studies with attosecond precision, typically over several hours of acquisition times. As an illustration, applications to multi-orbital HHS and electron-ion coincidence time resolved spectroscopy are presented.« less

  14. Fluorescent humanized anti-CEA antibody specifically labels metastatic pancreatic cancer in a patient-derived orthotopic xenograft (PDOX) mouse model

    NASA Astrophysics Data System (ADS)

    Lwin, Thinzar M.; Miyake, Kentaro; Murakami, Takashi; DeLong, Jonathan C.; Yazaki, Paul J.; Shivley, John E.; Clary, Bryan; Hoffman, Robert M.; Bouvet, Michael

    2018-03-01

    Specific tumor targeting can result in selective labeling of cancer in vivo for surgical navigation. In the present study, we show that the use of an anti-CEA antibody conjugated to the near-infrared (NIR) fluorescent dye, IRDye800CW, can selectively target and label pancreatic cancer and its metastases in a clinically relevant patient derived xenograft mouse model.

  15. A sensitive label-free amperometric CEA immunosensor based on graphene-nafion nanocomposite film as an enhanced sensing platform.

    PubMed

    Li, Yan; Yang, Wei-Kang; Fan, Man-Qi; Liu, Ao

    2011-01-01

    A novel approach to fabricate a label-free amperometric immunosensor for the detection of carcinoembryonic antigen (CEA) was described. Herein, methylene blue (MB), gold nanoparticles (AuNPs) and carcinoembryonic antibody (anti-CEA) were layer-by-layer assembled on the graphene-Nafion nanocomposite film-modified electrode by means of a self-assembling technique and the opposite-charged adsorption. Subsequently, the stepwise self-assembling procedure of the immunosensor was further characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The factors influencing the performance of the resulting immunosensor were studied in detail. The developed procedure showed improved features, including larger amount and higher immunoactivity of the immobilized antibody and repeatable regeneration of the sensor, as well as direct, rapid and simple determination for the antigen without multiple separation and labeling steps. The immunosensor could detect the target protein in a range of 0.5 to 120 ng/mL with a limit of 0.17 ng/mL (at 3σ). Finally, the immunosensing system was evaluated on several clinical samples. Analytical results were found to be in satisfactory agreement with those detected by the enzyme-linked immunosorbent assay (ELISA) method, indicating that this new method was a promising alternative tool for clinical diagnosis.

  16. The CEA Second-Look Trial: a randomised controlled trial of carcinoembryonic antigen prompted reoperation for recurrent colorectal cancer

    PubMed Central

    Treasure, Tom; Monson, Kathryn; Fiorentino, Francesca; Russell, Christopher

    2014-01-01

    Objective In patients who have undergone a potentially curative resection of colorectal cancer, does a ‘second-look’ operation to resect recurrence, prompted by monthly monitoring of carcinoembryonic antigen, confer a survival benefit? Design A randomised controlled trial recruiting patients from 1982 to 1993 was recovered under the Restoring Invisible and Abandoned Trials (RIAT) initiative. Setting 58 hospitals in the UK. Participants From 1982 to 1993, 1447 patients were enrolled. Of these 216 met the criteria for carcinoembryonic antigen (CEA) elevation and were randomised to ‘Aggressive’ or ‘Conventional’ arms. Interventions ‘Second-look’ surgery with intention to remove any recurrence discovered. Primary outcome measure Survival. Results By February 1993, 91/108 patients had died in the ‘Aggressive arm’ and 88/108 in the ‘Conventional’ arm (relative risk=1.16, 95% CI 0.87 to 1.37). By 2011 a further 25 randomised patients had died. Kaplan-Meier analysis showed no difference in long-term survival. Conclusions The trial was closed in 1993 following a recommendation from the Data Monitoring Committee that it was highly unlikely that any survival advantage would be demonstrated for CEA prompted second-look surgery. This conclusion was confirmed by repeat analysis of survival times after 20 years. Trial registration number ISRCTN76694943. PMID:24823671

  17. Operation and commissioning of IFMIF (International Fusion Materials Irradiation Facility) LIPAc injector.

    PubMed

    Okumura, Y; Gobin, R; Knaster, J; Heidinger, R; Ayala, J-M; Bolzon, B; Cara, P; Chauvin, N; Chel, S; Gex, D; Harrault, F; Ichimiya, R; Ihara, A; Ikeda, Y; Kasugai, A; Kikuchi, T; Kitano, T; Komata, M; Kondo, K; Maebara, S; Marqueta, A; O'Hira, S; Perez, M; Phillips, G; Pruneri, G; Sakamoto, K; Scantamburlo, F; Senée, F; Shinto, K; Sugimoto, M; Takahashi, H; Usami, H; Valette, M

    2016-02-01

    The objective of linear IFMIF prototype accelerator is to demonstrate 125 mA/CW deuterium ion beam acceleration up to 9 MeV. The injector has been developed in CEA Saclay and already demonstrated 140 mA/100 keV deuterium beam [R. Gobin et al., Rev. Sci. Instrum. 85, 02A918 (2014)]. The injector was disassembled and delivered to the International Fusion Energy Research Center in Rokkasho, Japan. After reassembling the injector, commissioning has started in 2014. Up to now, 100 keV/120 mA/CW hydrogen and 100 keV/90 mA/CW deuterium ion beams have been produced stably from a 10 mm diameter extraction aperture with a low beam emittance of 0.21 π mm mrad (rms, normalized). Neutron production by D-D reaction up to 2.4 × 10(9) n/s has been observed in the deuterium operation.

  18. Evaluation of the CEAS model for barley yields in North Dakota and Minnesota

    NASA Technical Reports Server (NTRS)

    Barnett, T. L. (Principal Investigator)

    1981-01-01

    The CEAS yield model is based upon multiple regression analysis at the CRD and state levels. For the historical time series, yield is regressed on a set of variables derived from monthly mean temperature and monthly precipitation. Technological trend is represented by piecewise linear and/or quadriatic functions of year. Indicators of yield reliability obtained from a ten-year bootstrap test (1970-79) demonstrated that biases are small and performance as indicated by the root mean square errors are acceptable for intended application, however, model response for individual years particularly unusual years, is not very reliable and shows some large errors. The model is objective, adequate, timely, simple and not costly. It considers scientific knowledge on a broad scale but not in detail, and does not provide a good current measure of modeled yield reliability.

  19. Running and testing GRID services with Puppet at GRIF- IRFU

    NASA Astrophysics Data System (ADS)

    Ferry, S.; Schaer, F.; Meyer, JP

    2015-12-01

    GRIF is a distributed Tiers 2 centre, made of 6 different centres in the Paris region, and serving many VOs. The sub-sites are connected with 10 Gbps private network and share tools for central management. One of the sub-sites, GRIF-IRFU held and maintained in the CEA- Saclay centre, moved a year ago, to a configuration management using Puppet. Thanks to the versatility of Puppet/Foreman automation, the GRIF-IRFU site maintains usual grid services, with, among them: a CREAM-CE with a TORQUE+Maui (running a batch with more than 5000 jobs slots), a DPM storage of more than 2 PB, a Nagios monitoring essentially based on check_mk, as well as centralized services for the French NGI, like the accounting, or the argus central suspension system. We report on the actual functionalities of Puppet and present the last tests and evolutions including a monitoring with Graphite, a HT-condor multicore batch accessed with an ARC-CE and a CEPH storage file system.

  20. Featured Image: The Cosmic Velocity Web

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2017-09-01

    You may have heard of the cosmic web, a network of filaments, clusters and voids that describes the three-dimensional distribution of matter in our universe. But have you ever considered the idea of a cosmic velocity web? In a new study led by Daniel Pomarde (IRFU CEA-Saclay, France), a team of scientists has built a detailed 3D view of the flows in our universe, showing in particular motions along filaments and in collapsing knots. In the image above (click for the full view), surfaces of knots (red) are embedded within surfaces of filaments (grey). The rainbow lines show the flow motion, revealing acceleration (redder tones) toward knots and retardation (bluer tones) beyond them. You can learn more about Pomarde and collaborators work and see their unusual and intriguing visualizationsin the video they produced, below. Check out the original paper for more information.CitationDaniel Pomarde et al 2017 ApJ 845 55. doi:10.3847/1538-4357/aa7f78

  1. C.-E.A. Winslow and the later years of public health at Yale, 1940-1945.

    PubMed Central

    Viseltear, A. J.

    1987-01-01

    This paper is one of a series of papers in which I consider contemporary Yale medical education in general and the Yale Department of Epidemiology and Public Health in particular. It tells of the retirement in 1945 of C.-E.A. Winslow, Professor and Chairman of the Yale Department of Public Health since its inception in 1915; of the committees established by the dean of the School of Medicine and the president of the University, charged with determining the future direction of the department; and of the outcome, which, in 1945, proved favorable to Winslow's public health philosophy in contrast to the medical school's clinical needs and desires. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 PMID:3321724

  2. BAGHEERA: A new experimental facility at CEA / Valduc for actinides studies under high dynamic loading

    NASA Astrophysics Data System (ADS)

    Roy, G.; Llorca, F.; Lanier, G.; Lamalle, S.; Beaulieu, J.; Antoine, P.; Martinuzzi, P.

    2006-08-01

    This paper is a technical presentation about a new experimental facility recently developed at CEA/Valduc, BAGHEERA, a French acronym for “Hopkinson And High Speed Experiments Glove Box”. This facility is used since mid-2003 to characterize the physical and mechanical behaviour of actinides under high dynamic loadings. For this purpose, four basic experimental devices are confined inside a single glove box: a 50 mm bore diameter single stage light gas gun, two compression and torsion split Hopkinson bars (SHPB and TSHB respectively) and a Taylor test device (TTD). Design and technical data on the experimental equipment are addressed, with a particular emphasis on the gas gun specific features due to actinide applications.

  3. CeasIng Cpap At standarD criteriA (CICADA): predicting a successful outcome.

    PubMed

    Yin, Yue; Broom, Margaret; Wright, Audrey; Hovey, Donna; Abdel-Latif, Mohamed E; Shadbolt, Bruce; Todd, David A

    2016-01-01

    This is a retrospective analysis of a multicentre randomised controlled trial (RCT) where we concluded that CeasIng Cpap At standerD criteriA (CICADA) in premature babies (PBs) <30 weeks gestational age (GA) was the significantly better method of ceasing CPAP. To identify factors that may influence the number of attempts to cease CPAP, we reviewed the records of 50 PBs from the RCT who used the CICADA method. PBs were grouped according to number of attempts to cease CPAP (fast group ≤2 attempts and slow group >2 attempts to cease CPAP). There were 26 (fast group) and 24 (slow group) PBs included in the analysis. Results showed significant differences in mean GA (27.8 ± 0.3 vs 26.9 ± 0.3 [weeks ± SE], p = 0.03) and birth weight ([Bwt]; 1080 ± 48.8 vs 899 ± 45.8 [grams ± SE], p = 0.01) between groups. Significantly fewer PBs in the fast group had a patent ductus arteriosus (PDA) compared to the slow group (5/26 (19.2%) vs 13/24 (54.2 %), p = 0.02). Bwt was a significant negative predictor of CPAP duration (r = -0.497, p = 0.03) and CPAP ceasing attempts (r = -0.290, p = 0.04). PBs with a higher GA and Bwt without a PDA ceased CPAP earlier using the CICADA method. Bwt was better than GA for predicting CPAP duration and attempts to cease CPAP. Our previous studies showed that CeasIng Cpap At standarD criteriA (CICADA) significantly reduces CPAP time, oxygen requirements and caffeine use. Some PBs however using the CICADA method required >2 attempts to cease CPAP ('slow CICADA' group). PBs in the 'fast CICADA' group (<3 attempts to cease CPAP) (a) have longer gestational age and higher birth weight, (b) shorter mechanical ventilation and (c) lower incidence of patent ductus arteriosus. Attempts to cease CPAP decreased by 0.5 times per 1 week increase in GA and 0.3 times per 100-g increase in birth weight for PBs <30 weeks gestation.

  4. The NGC 4839 group falling into the Coma cluster observed by XMM-Newton

    NASA Astrophysics Data System (ADS)

    Neumann, D. M.; Arnaud, M.; Gastaud, R.; Aghanim, N.; Lumb, D.; Briel, U. G.; Vestrand, W. T.; Stewart, G. C.; Molendi, S.; Mittaz, J. P. D.

    2001-01-01

    We present here the first analysis of the XMM-Newton EPIC-MOS data of the galaxy group around NGC 4839, which lies at a projected distance to the Coma cluster center of 1.6h50-1 Mpc. In our analysis, which includes imaging, spectro-imaging and spectroscopy we find compelling evidence for the sub group being on its first infall onto the Coma cluster. The complex temperature structure around NGC 4839 is consistent with simulations of galaxies falling into a cluster environment. We see indications of a bow shock and of ram pressure stripping around NGC 4839. Furthermore our data reveal a displacement between NGC 4839 and the center of the hot gas in the group of about 300h50-1 kpc. With a simple approximation we can explain this displacement by the pressure force originating from the infall, which acts much stronger on the group gas than on the galaxies. Based on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and the USA (NASA). EPIC was developed by the EPIC Consortium led by the Principal Investigator, Dr. M. J. L. Turner. The consortium comprises the following Institutes: University of Leicester, University of Birmingham, (UK); CEA/Saclay, IAS Orsay, CESR Toulouse, (France); IAAP Tuebingen, MPE Garching, (Germany); IFC Milan, ITESRE Bologna, IAUP Palermo, Italy. EPIC is funded by: PPARC, CEA, CNES, DLR and ASI.

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

    Fain, D.E.

    The conference was an excellent initial forum for coordinating international communication about the rapidly emerging field of inorganic membranes. It was well organized and held in an excellent new conference facility. There were about 300 conferees representing 26 countries, including most of the best known researchers in the field. The quality of the papers was excellent. Many of then presented very new and sophisticated work at the cutting edge of the technology. In Europe and Japan there is a broad awareness of these technologies and techniques for fabricating membranes with a broad range of properties and potential commercial uses. Inmore » his opening plenary paper, J. Charpin, with the Commissariat a L'Energie Atomic (CEA) at Saclay, gave the CEA credit for creating the new generation of inorganic membranes through its technology transfer from their nuclear energy programs. I met and talked with most of the best known people in the field. Our paper was extremely well received. Jacques Gillot hardly spoke to me before the paper. After presenting the paper, he approached me everywhere I went. The visits to the two best known membrane laboratories in Europe were worth the trip alone. Professor Cot's lab in Montpellier is rather modest, but doing some interesting and sophisticated work. Professor Burggraaf's lab in Enschede, Netherlands is extremely well equipped and staffed (63 people), and I believe this lab is doing the most advanced work.« less

  6. CEAS/AIAA/ICASE/NASA Langley International Forum on Aeroelasticity and Structural Dynamics 1999. Pt. 2

    NASA Technical Reports Server (NTRS)

    Whitlow, Jr., Woodrow (Editor); Todd, Emily N. (Editor)

    1999-01-01

    The proceedings of a workshop sponsored by the Confederation of European Aerospace Societies (CEAS), the American Institute of Aeronautics and Astronautics (AIAA), the National Aeronautics and Space Administration (NASA), Washington, D.C., and the Institute for Computer Applications in Science and Engineering (ICASE), Hampton, Virginia, and held in Williamsburg, Virginia June 22-25, 1999 represent a collection of the latest advances in aeroelasticity and structural dynamics from the world community. Research in the areas of unsteady aerodynamics and aeroelasticity, structural modeling and optimization, active control and adaptive structures, landing dynamics, certification and qualification, and validation testing are highlighted in the collection of papers. The wide range of results will lead to advances in the prediction and control of the structural response of aircraft and spacecraft.

  7. Polyethylene Glycol (PEG) Linked to Near Infrared (NIR) Dyes Conjugated to Chimeric Anti-Carcinoembryonic Antigen (CEA) Antibody Enhances Imaging of Liver Metastases in a Nude-Mouse Model of Human Colon Cancer

    PubMed Central

    Maawy, Ali A.; Hiroshima, Yukihiko; Zhang, Yong; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

    2014-01-01

    We report here that polyethylene glycol (PEG) linked to near infrared dyes conjugated to chimeric mouse-human anti-carcinoembryonic antigen (CEA) antibody greatly improves imaging of liver metastases in a nude mouse model of colon-cancer experimental metastases. PEGylated and non-PEGylated DyLight 650 and 750 dyes were conjugated to the chimeric anti-CEA antibody. The dyes were initially injected intravenously into nude mice without tumors. Tissue biodistribution was determined by tissue sonication and analyzing tissue dye concentration profiles over time. PEGylated dyes had significantly lower accumulation in the liver (p = 0.03 for the 650 dyes; p = 0.002 for the 750 dyes) compared to non-PEGylated dyes. In an experimental liver metastasis model of HT-29 colon cancer, PEGylated dyes conjugated to the anti-CEA antibody showed good labeling of metastatic tumors with high contrast between normal and malignant tissue which was not possible with the non-PEGylated dyes since there was so much non-specific accumulation in the liver. PEGylation of the DyLight 650 and 750 NIR dyes significantly altered tissue biodistribution, allowing brighter tissue labeling, decreased accumulation in normal organs, particularly the liver. This enabled high fidelity and high contrast imaging of liver metastases. PMID:24859320

  8. Delayed Gamma Measurements in Different Nuclear Research Reactors Bringing Out the Importance of the Delayed Contribution in Gamma Flux Calculations

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

    Fourmentel, D.; Radulovic, V.; Barbot, L.

    Neutron and gamma flux levels are key parameters in nuclear research reactors. In Material Testing Reactors, such as the future Jules Horowitz Reactor, under construction at the French Alternative Energies and Atomic Energy Commission (CEA Cadarache, France), the expected gamma flux levels are very high (nuclear heating is of the order of 20 W/g at 100 MWth). As gamma rays deposit their energy in the reactor structures and structural materials it is important to take them into account when designing irradiation devices. There are only a few sensors which allow measurements of the nuclear heating ; a recent development atmore » the CEA Cadarache allows measurements of the gamma flux using a miniature ionization chamber (MIC). The measured MIC response is often compared with calculation using modern Monte Carlo (MC) neutron and photon transport codes, such as TRIPOLI-4 and MCNP6. In these calculations only the production of prompt gamma rays in the reactor is usually modelled thus neglecting the delayed gamma rays. Hence calculations and measurements are usually in better accordance for the neutron flux than for the gamma flux. In this paper we study the contribution of delayed gamma rays to the total MIC signal in order to estimate the systematic error in gamma flux MC calculations. In order to experimentally determine the delayed gamma flux contributions to the MIC response, we performed gamma flux measurements with CEA developed MIC at three different research reactors: the OSIRIS reactor (MTR - 70 MWth at CEA Saclay, France), the TRIGA MARK II reactor (TRIGA - 250 kWth at the Jozef Stefan Institute, Slovenia) and the MARIA reactor (MTR - 30 MWth at the National Center for Nuclear Research, Poland). In order to experimentally assess the delayed gamma flux contribution to the total gamma flux, several reactor shut down (scram) experiments were performed specifically for the purpose of the measurements. Results show that on average about 30 % of the MIC signal is

  9. A Pilot Study to Evaluate the Safety and Clinical Outcomes of Vaccination with Recombinant CEA-MUC-1-TRICOM (PANVAC) Poxviral-based Vaccines in Patients with Metastatic Carcinoma

    PubMed Central

    Gulley, James L.; Arlen, Philip M.; Tsang, Kwong-Yok; Yokokawa, Junko; Palena, Claudia; Poole, Diane J.; Remondo, Cinzia; Cereda, Vittore; Jones, Jacquin L.; Pazdur, Mary P.; Higgins, Jack P.; Hodge, James W.; Steinberg, Seth M.; Kotz, Herbert; Dahut, William L.; Schlom, Jeffrey

    2009-01-01

    Purpose: Poxviral vectors have a proven safety record and can be used to incorporate multiple transgenes. Prior clinical trials with poxviral vaccines have shown that immunologic tolerance to self-antigens can be broken. Carcinoembryonic antigen (CEA) and MUC-1 are overexpressed in a substantial proportion of common solid carcinomas. The primary endpoint of this study was vaccine safety, with immunologic and clinical responses as secondary endpoints. Experimental Design: We report here a pilot study of 25 patients treated with a poxviral vaccine regimen consisting of the genes for CEA and MUC-1, along with a triad of costimulatory molecules (TRICOM, composed of B7.1, ICAM-1, and LFA-3) engineered into vaccinia (PANVAC-V) as a prime and fowlpox (PANVAC-F) as booster vaccinations. Results: The vaccine was well-tolerated. Apart from injection-site reaction, no grade II or greater toxicity was seen in more than 2% of the cycles. Immune responses to MUC-1 and/or CEA were seen following vaccine in 9 of 16 patients tested. A patient with clear cell ovarian cancer and symptomatic ascites had a durable (18-month) clinical response radiographically and biochemically, and one breast cancer patient had a confirmed decrease of > 20% in the size of large liver metastasis. Conclusions: This vaccine strategy appears to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this agent, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted. PMID:18483372

  10. Systems assessment of water savings impact of controlled environment agriculture (CEA) utilizing wirelessly networked Sense•Decide•Act•Communicate (SDAC) systems.

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

    Campbell, Jonathan T.; Baynes, Edward E., Jr.; Aguirre,Carlos

    Reducing agricultural water use in arid regions while maintaining or improving economic productivity of the agriculture sector is a major challenge. Controlled environment agriculture (CEA, or, greenhouse agriculture) affords advantages in direct resource use (less land and water required) and productivity (i.e., much higher product yield and quality per unit of resources used) relative to conventional open-field practices. These advantages come at the price of higher operating complexity and costs per acre. The challenge is to implement and apply CEA such that the productivity and resource use advantages will sufficiently outweigh the higher operating costs to provide for overall benefitmore » and viability. This project undertook an investigation of CEA for livestock forage production as a water-saving alternative to open-field forage production in arid regions. Forage production is a large consumer of fresh water in many arid regions of the world, including the southwestern U.S. and northern Mexico. With increasing competition among uses (agriculture, municipalities, industry, recreation, ecosystems, etc.) for limited fresh water supplies, agricultural practice alternatives that can potentially maintain or enhance productivity while reducing water use warrant consideration. The project established a pilot forage production greenhouse facility in southern New Mexico based on a relatively modest and passive (no active heating or cooling) system design pioneered in Chihuahua, Mexico. Experimental operations were initiated in August 2004 and carried over into early-FY05 to collect data and make initial assessments of operational and technical system performance, assess forage nutrition content and suitability for livestock, identify areas needing improvement, and make initial assessment of overall feasibility. The effort was supported through the joint leveraging of late-start FY04 LDRD funds and bundled CY2004 project funding from the New Mexico Small Business

  11. Proceedings of the 1989 CESAR/CEA (Center for Engineering Systems Advanced Research/Commissariat a l'Energie Atomique) workshop on autonomous mobile robots (May 30--June 1, 1989)

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

    Harber, K.S.; Pin, F.G.

    1990-03-01

    The US DOE Center for Engineering Systems Advanced Research (CESAR) at the Oak Ridge National Laboratory (ORNL) and the Commissariat a l'Energie Atomique's (CEA) Office de Robotique et Productique within the Directorat a la Valorization are working toward a long-term cooperative agreement and relationship in the area of Intelligent Systems Research (ISR). This report presents the proceedings of the first CESAR/CEA Workshop on Autonomous Mobile Robots which took place at ORNL on May 30, 31 and June 1, 1989. The purpose of the workshop was to present and discuss methodologies and algorithms under development at the two facilities in themore » area of perception and navigation for autonomous mobile robots in unstructured environments. Experimental demonstration of the algorithms and comparison of some of their features were proposed to take place within the framework of a previously mutually agreed-upon demonstration scenario or base-case.'' The base-case scenario described in detail in Appendix A, involved autonomous navigation by the robot in an a priori unknown environment with dynamic obstacles, in order to reach a predetermined goal. From the intermediate goal location, the robot had to search for and locate a control panel, move toward it, and dock in front of the panel face. The CESAR demonstration was successfully accomplished using the HERMIES-IIB robot while subsets of the CEA demonstration performed using the ARES robot simulation and animation system were presented. The first session of the workshop focused on these experimental demonstrations and on the needs and considerations for establishing benchmarks'' for testing autonomous robot control algorithms.« less

  12. Clinical significance and diagnostic capacity of serum TK1, CEA, CA 19-9 and CA 72-4 levels in gastric and colorectal cancer patients.

    PubMed

    Ning, Shufang; Wei, Wene; Li, Jilin; Hou, Bingbing; Zhong, Jianhong; Xie, Yuxuan; Liu, Haizhou; Mo, Xianwei; Chen, Jiansi; Zhang, Litu

    2018-01-01

    Despite extensive progress in treatment for cancer in recent decades, the early diagnosis for gastric cancer (GC) and colorectal cancer (CRC) remains poor. In this study, we explore the diagnostic value of joint detection of thymidine kinase 1 (TK1), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and carbohydrate antigen 72-4 (CA 72-4) in the diagnosis of GC and CRC, and to evaluated the relationship between TK1 expression and clinical pathological characteristics in the patients. Serum TK1, CA 19-9, CA 72-4 and CEA levels were measured in 169 patients with GC, 344 patients with CRC and 75 healthy controls using electro-chemiluminescence. The TK1 concentration was significantly higher in patients with cancer than in healthy controls and patients with clinical stage Ⅲ+Ⅳ had higher TK1 levels than clinical stage Ⅰ+Ⅱ ( P <0.05). The levels of TK1 is significantly associated with tumor stage, lymph node metastasis, distant metastasis, tumor differentiation and age ( P <0.05). When the tumor markers (TK1, CA 19-9 and CA 72-4) were detected respectively, the area under receiver operating characteristics curve (AUC) of TK1 for three cancers was the highest (0.823-0.895). However, the combination of AUC was higher than that for each tumor marker detected respectively (0.934-0.953), and the Hosmer-Lemeshow test showed an adequate model of calibration (P>0.05). Moreover, the AUCs varied significantly between the combination tests and single biomarker tests (Z test, P <0.01). In conclusion, serum TK1 may be an independent tumor marker for GC and CRC patients, and the combination of TK1, CA 19-9 and CA 72-4 and CEA performed even better. This study suggests that combination detection of four tumor markers may prove to be useful for the diagnosis of GC and CRC.

  13. Investigation of ion beam space charge compensation with a 4-grid analyzer

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

    Ullmann, C., E-mail: c.ullmann@gsi.de; Adonin, A.; Berezov, R.

    2016-02-15

    Experiments to investigate the space charge compensation of pulsed high-current heavy ion beams are performed at the GSI ion source text benches with a 4-grid analyzer provided by CEA/Saclay. The technical design of the 4-grid analyzer is revised to verify its functionality for measurements at pulsed high-current heavy ion beams. The experimental investigation of space charge compensation processes is needed to increase the performance and quality of current and future accelerator facilities. Measurements are performed directly downstream a triode extraction system mounted to a multi-cusp ion source at a high-current test bench as well as downstream the post-acceleration system ofmore » the high-current test injector (HOSTI) with ion energies up to 120 keV/u for helium and argon. At HOSTI, a cold or hot reflex discharge ion source is used to change the conditions for the measurements. The measurements were performed with helium, argon, and xenon and are presented. Results from measurements with single aperture extraction systems are shown.« less

  14. A Micromegas-based telescope for muon tomography: The WatTo experiment

    NASA Astrophysics Data System (ADS)

    Bouteille, S.; Attié, D.; Baron, P.; Calvet, D.; Magnier, P.; Mandjavidze, I.; Procureur, S.; Riallot, M.; Winkler, M.

    2016-10-01

    This paper reports about the first Micromegas-based telescope built for applications in muon tomography. The telescope consists of four, 50×50 cm2 resistive multiplexed Micromegas with a 2D layout and a self-triggering electronics based on the Dream chip. Thanks to the multiplexing, the four detectors were readout with a single Front-End Unit. The high voltages were provided by a dedicated card using low consumption CAEN miniaturized modules. A nano-PC (Hummingboard) ensured the HV control and monitoring coupled with a temperature feedback as well as the data acquisition and storage. The overall consumption of the instrument yielded 30 W only, i.e. the equivalent of a standard bulb. The telescope was operated outside during 3.5 months to image the water tower of the CEA-Saclay research center, including a 1.5-month campaign with solar panels. The development of autonomous, low consumption muon telescopes with unprecedented accuracy opens new applications in imaging as well as in the field of muon metrology.

  15. Treatment of G1 Baskets at the CEA Marcoule Site - 12027

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

    Fourquet, Line; Boya, Didier

    2012-07-01

    In the dismantling program for the first-generation French reactors in accordance with the nonproliferation treaty, the CEA is in charge of cleanup and dismantling operations for the facilities at Marcoule, including the decladding units. The G1 decladding was built between 1955 and 1957 in order to de-clad spent fuel elements from the G1 plutonium-producing reactor and prepare them for dissolution. The facility was also used for interim storage of G1, G2 and G3 fuel dissolution baskets, which had been used during plant operation for transfer (from the decladding facility to the UP1 plant) and/or dissolution of spent fuel elements. Onemore » of the cleanup projects involves recovery of the baskets, which will be cut up, sorted, and conditioned in metal bins. The bins will be immobilized with cement grout, then transferred to the onsite solid waste conditioning facility (CDS) and to the repository operated by the French National Radioactive Waste Management Agency (ANDRA). The project is now in progress, after special safety permits were issued and measurement stations and dedicated tools were developed to handle all types of baskets (which differed according to their origin and use). The disposal of all the baskets is scheduled to last 2 years and will produce 55 metal waste bins. (authors)« less

  16. [Tumor markers p53, sFAS, FASL, CEA and CA 19-9 in evaluating the effectiveness of surgical and pharmaco nutritional treatment of patients with gastric cancer].

    PubMed

    Bluvshteĭn, G A; Lysenko, V G; Zakharova, N B; Kitaev, I V

    2012-01-01

    The objective of this study is to develop a marker panel of abnormalities of immune regulatory systems and cell genome in patients with gastric cancer for assessment of efficacy of surgical treatment in combination with pharmaco-nutritional therapy in early postoperative period. Expression of p53, sFAS, FASL, CEA, and CA 19-9, nutritial status, as well as incidence of purulent-septic complications in early postoperative period were determined in 40 patients with gastric cancer (21 patients--the test group and 19 patients--the comparative group) prior to a curative surgical intervention, postoperative days 1 and 7, while the pharmaco-nutritional therapy (the test group) or partial parenteral nutrition (the comparative group) has been performed. The pharmaco-nutritional therapy significantly decreases in activity of tumor suppressing genome, lymphocyte apoptosis, expression of oncology-associated markers, incidence of purulent-septic complications, as well as exacerbation risk for hypotrophy in patients with gastric cancer in early postoperative period. To assess the efficacy of the surgical intervention performed in patients with gastric cancer, an expression of mutant p53 and markers of lymphocyte apoptosis (sFAS/FASL) is reasonable to be evaluated together with determination of oncomarkers (CEA and CA 19-9).

  17. Terahertz Real-Time Imaging Uncooled Arrays Based on Antenna-Coupled Bolometers or FET Developed at CEA-Leti

    NASA Astrophysics Data System (ADS)

    Simoens, François; Meilhan, Jérôme; Nicolas, Jean-Alain

    2015-10-01

    Sensitive and large-format terahertz focal plane arrays (FPAs) integrated in compact and hand-held cameras that deliver real-time terahertz (THz) imaging are required for many application fields, such as non-destructive testing (NDT), security, quality control of food, and agricultural products industry. Two technologies of uncooled THz arrays that are being studied at CEA-Leti, i.e., bolometer and complementary metal oxide semiconductor (CMOS) field effect transistors (FET), are able to meet these requirements. This paper reminds the followed technological approaches and focuses on the latest modeling and performance analysis. The capabilities of application of these arrays to NDT and security are then demonstrated with experimental tests. In particular, high technological maturity of the THz bolometer camera is illustrated with fast scanning of large field of view of opaque scenes achieved in a complete body scanner prototype.

  18. The 400W at 1.8K Test Facility at CEA-Grenoble

    NASA Astrophysics Data System (ADS)

    Roussel, P.; Girard, A.; Jager, B.; Rousset, B.; Bonnay, P.; Millet, F.; Gully, P.

    2006-04-01

    A new test facility with a cooling capacity respectively of 400W at 1.8K or 800W at 4.5K, is now under nominal operation in SBT (Low Temperature Department) at CEA Grenoble. It has been recently used for thermohydraulic studies of two phase superfluid helium in autumn 2004. In the near future, this test bench will allow: - to test industrial components at 1.8K (magnets, cavities of accelerators) - to continue the present studies on thermohydraulics of two phase superfluid helium - to develop and simulate new cooling loops for ITER Cryogenics, and other applications such as high Reynolds number flows This new facility consists of a cold box connected to a warm compressor station (one subatmospheric oil ring pump in series with two screw compressors). The cold box, designed by AIR LIQUIDE, comprises two centrifugal cold compressors, a cold turbine, a wet piston expander, counter flow heat exchangers and two phase separators at 4.5K and 1.8K. The new facility uses a Programmable Logic Controller (PLC) connected to a bus for the measurements. The design is modular and will allow the use of saturated fluid flow (two phase flow at 1.8K or 4.5K) or single phase fluid forced flow. Experimental results and cooling capacity in different operation modes are detailed.

  19. Pulsations in the late-type Be star HD 50 209 detected by CoRoT

    NASA Astrophysics Data System (ADS)

    Diago, P. D.; Gutiérrez-Soto, J.; Auvergne, M.; Fabregat, J.; Hubert, A.-M.; Floquet, M.; Frémat, Y.; Garrido, R.; Andrade, L.; de Batz, B.; Emilio, M.; Espinosa Lara, F.; Huat, A.-L.; Janot-Pacheco, E.; Leroy, B.; Martayan, C.; Neiner, C.; Semaan, T.; Suso, J.; Catala, C.; Poretti, E.; Rainer, M.; Uytterhoeven, K.; Michel, E.; Samadi, R.

    2009-10-01

    Context: The presence of pulsations in late-type Be stars is still a matter of controversy. It constitutes an important issue to establish the relationship between non-radial pulsations and the mass-loss mechanism in Be stars. Aims: To contribute to this discussion, we analyse the photometric time series of the B8IVe star HD 50 209 observed by the CoRoT mission in the seismology field. Methods: We use standard Fourier techniques and linear and non-linear least squares fitting methods to analyse the CoRoT light curve. In addition, we applied detailed modelling of high-resolution spectra to obtain the fundamental physical parameters of the star. Results: We have found four frequencies which correspond to gravity modes with azimuthal order m=0,-1,-2,-3 with the same pulsational frequency in the co-rotating frame. We also found a rotational period with a frequency of 0.679 cd-1 (7.754 μHz). Conclusions: HD 50 209 is a pulsating Be star as expected from its position in the HR diagram, close to the SPB instability strip. Based on observations made with the CoRoT satellite, with FEROS at the 2.2 m telescope of the La Silla Observatory under the ESO Large Programme LP178.D-0361 and with Narval at the Télescope Bernard Lyot of the Pic du Midi Observatory. Current address: Valencian International University (VIU), José Pradas Gallen s/n, 12006 Castellón, Spain. Current address: Laboratoire AIM, CEA/DSM-CNRS-Université Paris Diderot; CEA, IRFU, SAp, centre de Saclay, 91191 Gif-sur-Yvette, France.

  20. The Diagnostic and Prognostic Value of Tumor Markers (CEA, SCC, CYFRA 21-1, TPS) in Head and Neck Cancer Patients.

    PubMed

    Barak, Vivian; Meirovitz, Amichay; Leibovici, Vera; Rachmut, Jacob; Peretz, Tamar; Eliashar, Ron; Gross, Menachem

    2015-10-01

    Establishing prognostic factors is very important in the management of cancer patients. Our aim was to evaluate the clinical significance of a panel of tumor markers, including CEA (Carcino Embryonic Antigen), SCC (Squamous Cell Carcinoma Antigen), TPS (Tissue Polypeptide Specific Antigen) and CYFRA 21-1 in head and neck cancer patients, for assessing treatment response and prognosis of patients. We evaluated 312 blood samples from 143 head and neck cancer patients, from several sub-groups: 82 Larynx Carcinoma pre- and 38 post-therapy, 46 Oral Cavity pre and 29 post-therapy, 12 nasopharynx, 16 parotid and other salivary gland patients. Blood tumor markers levels were evaluated by conventional ELISA assays. Correlations of marker levels to stage of disease, lymph node involvement and therapy, were performed. Serum levels of all four tumor markers were higher before therapy and decreased thereafter in all patients. The decrease in TPS level following therapy was significant (p=0.03). Significantly higher levels of TPS and similarly higher levels of the other tumor markers were demonstrated in advanced disease (stages III and IV) patients, as opposed to early disease (stages I and II) patients (p=0.012). Node positive patients had significantly higher TPS levels as compared to node negative (p=0.02). The same trend was shown by the other markers as well, but did not reach statistical significance. TPS was best correlated to survival of patients; those having low levels had the best clinical outcome and longer survival. CEA, SCC, TPS and CYFRA 21-1 can all serve as useful tumor markers in HNC patients. They assessed response to therapy and were prognostic for recurrence. TPS proved to be the most sensitive predictor of advanced disease and poor prognosis. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy

    PubMed Central

    Pan, Haitao; Liu, Jiayu; Deng, Wentong; Xing, Jieyu; Li, Qing; Wang, Zhong

    2018-01-01

    Introduction Bispecific antibodies that engage immune cells to kill cancer cells are actively pursued in cancer immunotherapy. Different types of bispecific antibodies, including single-chain fragments, Fab fragments, nanobodies, and immunoglobulin Gs (IgGs), have been studied. However, the low molecular weight of bispecific antibodies with single-chain or Fab fragments generally leads to their rapid clearance in vivo, which limits the therapeutic potential of these bispecific antibodies. Materials and methods In this study, we used a site-specific PEGylation strategy to modify the bispecific single-domain antibody-linked Fab (S-Fab), which was designed by linking an anticarcinoembryonic antigen (anti-CEA) nanobody with an anti-CD3 Fab. Results The half-life (t1/2) of PEGylated S-Fab (polyethylene glycol-S-Fab) was increased 12-fold in vivo with a slightly decreased tumor cell cytotoxicity in vitro as well as more potent tumor growth inhibition in vivo compared to S-Fab. Conclusion This study demonstrated that PEGylation is an effective approach to enhance the antitumor efficacy of bispecific antibodies. PMID:29881272

  2. Decontamination of Nuclear Liquid Wastes Status of CEA and AREVA R and D: Application to Fukushima Waste Waters - 12312

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

    Fournel, B.; Barre, Y.; Lepeytre, C.

    2012-07-01

    Liquid wastes decontamination processes are mainly based on two techniques: Bulk processes and the so called Cartridges processes. The first technique has been developed for the French nuclear fuel reprocessing industry since the 60's in Marcoule and La Hague. It is a proven and mature technology which has been successfully and quickly implemented by AREVA at Fukushima site for the processing of contaminated waters. The second technique, involving cartridges processes, offers new opportunities for the use of innovative adsorbents. The AREVA process developed for Fukushima and some results obtained on site will be presented as well as laboratory scale resultsmore » obtained in CEA laboratories. Examples of new adsorbents development for liquid wastes decontamination are also given. A chemical process unit based on co-precipitation technique has been successfully and quickly implemented by AREVA at Fukushima site for the processing of contaminated waters. The asset of this technique is its ability to process large volumes in a continuous mode. Several chemical products can be used to address specific radioelements such as: Cs, Sr, Ru. Its drawback is the production of sludge (about 1% in volume of initial liquid volume). CEA developed strategies to model the co-precipitation phenomena in order to firstly minimize the quantity of added chemical reactants and secondly, minimize the size of co-precipitation units. We are on the way to design compact units that could be mobilized very quickly and efficiently in case of an accidental situation. Addressing the problem of sludge conditioning, cementation appears to be a very attractive solution. Fukushima accident has focused attention on optimizations that should be taken into account in future studies: - To better take account for non-typical aqueous matrixes like seawater; - To enlarge the spectrum of radioelements that can be efficiently processed and especially short lives radioelements that are usually less present

  3. Five common tumor biomarkers and CEA for diagnosing early gastric cancer: A protocol for a network meta-analysis of diagnostic test accuracy.

    PubMed

    Shen, Minghui; Wang, Hui; Wei, Kongyuan; Zhang, Jianling; You, Chongge

    2018-05-01

    Although surgical resection is the recommended treatment for the patients with gastric cancer, lots of patients show advanced or metastatic gastric cancer at the time of diagnosis. Detection of gastric cancer at early stages is a huge challenge because of lack of appropriate detection tests. Unfortunately, existing clinical guidelines focusing on early diagnosis of gastric cancer do not provide consistent and prudent evidence. Serum carcinoembryonic antigen was considered as a complementary test, although it is not good enough to diagnose early gastric cancer. There are no other tumor markers recommended for diagnosing early gastric cancer. This study aims to evaluate and compare the diagnostic accuracy of 5 common tumor biomarkers (CA19-9, CA125, PG, IncRNA, and DNA methylation) and CEA and their combinations for diagnosing gastric cancer through network meta-analysis method, and to rank these tests using a superiority index. PubMed, EMBASE.com, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched from their inception to March 2018. We will include diagnostic tests which assessed the accuracy of the above-mentioned tumor biomarkers and CEA for diagnosing gastric cancer. The risk of bias for each study will be independently assessed as low, moderate, or high using criteria adapted from Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Network meta-analysis will be performed using STATA 12.0 and R 3.4.1 software. The competing diagnostic tests will be ranked by a superiority index. This study is ongoing and will be submitted to a peer-reviewed journal for publication. This study will provide systematically suggestions to select different tumor biomarkers for detecting the early gastric cancer.

  4. Novel Micromegas trackers

    NASA Astrophysics Data System (ADS)

    Sabatie, Franck

    2017-09-01

    The latest development in Micromegas trackers includes the Micromegas Vertex Tracker (MVT) soon to be installed in Jefferson Lab Hall B, in the CLAS12 central tracking system. The MVT is composed of 6 cylindrical layers and 6 flat disks of resistive bulk Micromegas detectors. They have been designed to withstand the high particle flux environment and the high magnetic field using a low material budget of less than 0.5% of a radiation length per detector. The MVT is read out using front-end electronics based on the ``Dream'' Asic developed at CEA Saclay/Irfu. The low material budget requirements and very stringent space restrictions of the central tracking system surrounded by a 5T solenoid prevent the use of on-detector frontend electronics. The ability of the Dream chip to work with high-capacitance detectors allows deploying the electronics some 2 m away using flat micro-coaxial cables. After a short introduction to Micromegas detectors and the state-of-the-art achievements in this technology, I will focus on the CLAS12 MVT detector system, from the fabrication techniques to the readout electronics. Possible future developments will briefly be presented as well.

  5. Physics Program at The RIBF with MINOS

    NASA Astrophysics Data System (ADS)

    Obertelli, Alexandre; Doornenbal, Pieter; Corsi, Anna; Kondo, Yosuke; Kubota, Yuki; Lee, Jenny; Nakamura, Takashi; Orr, Nigel; Sakurai, Hiroyoshi; Sasano, Masaki; Uesaka, Tomohiro

    MINOS is a new device composed of a thick hydrogen target and a vertex tracker [1]. It has been primarily conceived for the spectroscopy of rare isotopes produced at fragmentation facilities such as the RIKEN Radioactive Isotope Beam Facility. In the near future, MINOS in association with other detectors and spectrometers should contribute to exciting physics programs at the RIBF focusing on nuclei produced by hydrogen-induced secondary knockout reactions. The full detector and its electronics have been finalized at CEA Saclay and validated in Japan at the end of 2013. Among foreseen experiments, a scientific program named SEASTAR dedicated to the study of shell evolution and measurement of new 2+ state energies in medium-mass unstable nuclei has been initiated at the RIBF. SEASTAR aims at exploiting the unique opportunities offered by the RIBF and the association of the high-efficiency DALI2 gamma array [2] and MINOS. The first campaign was held in May 2014. In this communication, a brief presentation of the MINOS detection system is presented as well as the intended physics program at the RIBF. A report on the first SEASTAR campaign foreseen this spring is given.

  6. High intensity proton injector for facility of antiproton and ion research

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

    Berezov, R., E-mail: r.berezov@gsi.de; Brodhage, R.; Fils, J.

    The high current ion source with the low energy beam transport (LEBT) will serve as injector into the proton LINAC to provide primary proton beam for the production of antiprotons. The pulsed ion source developed and built in CEA/Saclay operates with a frequency of 2.45 GHz based on ECR plasma production with two coils with 87.5 mT magnetic field necessary for the electron cyclotron resonance. The compact LEBT consists of two solenoids with a maximum magnetic field of 500 mT including two integrated magnetic steerers to adjust the horizontal and vertical beam positions. The total length of the compact LEBTmore » is 2.3 m and was made as short as possible to reduced emittance growth along the beam line. To measure ion beam intensity behind the pentode extraction system, between solenoids and at the end of the beam line, two current transformers and a Faraday cup are installed. To get information about the beam quality and position, the diagnostic chamber with different equipment will be installed between the two solenoids. This article reports the current status of the proton injector for the facility of antiproton and ion research.« less

  7. Tests and foreseen developments of fibered-OSLD gamma heating measurements in low-power reactors

    NASA Astrophysics Data System (ADS)

    Gruel, A.; Guillou, M. Le; Blaise, P.; Destouches, C.; Magne, S.

    2018-01-01

    In this paper are presented test measurements of a fibered-OSLD system performed during a dedicated experimental phase in EOLE zero-power reactor. The measurement setup consists of an OSLD crystal connected onto the extremity of an optical fiber and a laser stimulation system, manufactured by the CEA/LIST in Saclay. The OSL sensor is remotely stimulated via an optical fiber using a diode-pumped solid-state laser. The OSL light is collected and guided back along the same fiber to a photomultiplier tube. Results obtained using this system are compared to usual gamma heating measurement protocol using OSLD pellets. The presence of induced radio-luminescence in the OSLD during the irradiation was also observed and could be used to monitor the gamma flux. The feasibility of remote measurements is achieved, whereas further developments could be conducted to improve this technique since the readout procedure still requires to withdraw the OSLD off the gamma flux (hence from the core) on account of the dose rate (around a few Gy.h-1), and the readout time remains quite long for on-line applications. Several improvements are foreseen, and will be tested in the forthcoming years.

  8. Design, test, and calibration of an electrostatic beam position monitor

    NASA Astrophysics Data System (ADS)

    Cohen-Solal, Maurice

    2010-03-01

    The low beta of proton or ion beams favors an electrostatic pickup to measure the transverse beam centroid position. Often papers on beam position monitors (BPM) are focused on a particular aspect of the problem; however, it is important to consider all various issues of a position measurement system. Based on our experience at the IPHI (high intensity injector proton) facility at CEA-Saclay, this paper will address all aspects to design, test, and calibrate a BPM for proton linear accelerators, while emphasizing the determination of the absolute beam position. We present details of the readout electronics, and describe the calibration of the BPM using a test station. For calculation and simulation of the electrical signals we developed a Mathematica script. The error analysis presented, on the basis of six BPMs installed in the high energy section of IPHI, demonstrates the expected accuracy of the position measurement. These studies also identify the parameters that could improve the performance of the beam position control. The experience from these developments is currently being used for the BPM design and test stand dedicated to the Spiral2 accelerator at Ganil-Caen which will deliver heavy ion beams.

  9. Dye sensitized photoelectrochemical immunosensor for the tumor marker CEA by using a flower-like 3D architecture prepared from graphene oxide and MoS2.

    PubMed

    Song, Kaijing; Ding, Chuanmin; Zhang, Bing; Chang, Honghong; Zhao, Zhihuan; Wei, Wenlong; Wang, Junwen

    2018-06-01

    The authors describe a dye-sensitized photoelectrochemical immunoassay for the tumor marker carcinoembryonic antigen (CEA). The method employs the rhodamine dye Rh123 with red color and absorption maximum at 500 nm for spectral sensitization, and a 3D nanocomposite prepared from graphene oxide and MoS 2 acting as the photoelectric conversion layer. The nanocomposite with flower-like 3D architectures was characterized by transmission electron microscopy, scanning electron microscopy, X-ray powder diffraction, and UV-vis diffuse reflectometry. A photoelectrochemical sandwich immunoassay was developed that is based on the use of the nanocomposite and based on the specific binding of antibody and antigen, and by using a secondary antibody labeled with Rh123 and CdS (Ab 2 -Rh123@CdS). Under optimal conditions and at a typical working voltage of 0 V (vs. Hg/HgCl 2 ), the photocurrent increases linearly 10 pg mL -1 to 80 ng mL -1 CEA concentration range, with a 3.2 pg mL -1 detection limit. Graphical abstract Flower-like GO-MoS 2 complex with high efficiency of electron transport was synthesized to construct photoelectrochemical platform. The sandwich-type immunoassay was built on this platform based on specific binding of antigen and antibody. Carcinoembryonic antigen in sample was detected sensitively by using sensitization of rhodamine dye Rh123 as signal amplification strategy.

  10. A novel classifier based on three preoperative tumor markers predicting the cancer-specific survival of gastric cancer (CEA, CA19-9 and CA72-4).

    PubMed

    Guo, Jing; Chen, Shangxiang; Li, Shun; Sun, Xiaowei; Li, Wei; Zhou, Zhiwei; Chen, Yingbo; Xu, Dazhi

    2018-01-12

    Several studies have highlighted the prognostic value of the individual and the various combinations of the tumor markers for gastric cancer (GC). Our study was designed to assess establish a new novel model incorporating carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4). A total of 1,566 GC patients (Primary cohort) between Jan 2000 and July 2013 were analyzed. The Primary cohort was randomly divided into Training set (n=783) and Validation set (n=783). A three-tumor marker classifier was developed in the Training set and validated in the Validation set by multivariate regression and risk-score analysis. We have identified a three-tumor marker classifier (including CEA, CA19-9 and CA72-4) for the cancer specific survival (CSS) of GC (p<0.001). Consistent results were obtained in the both Training set and Validation set. Multivariate analysis showed that the classifier was an independent predictor of GC (All p value <0.001 in the Training set, Validation set and Primary cohort). Furthermore, when the leave-one-out approach was performed, the classifier showed superior predictive value to the individual or two of them (with the highest AUC (Area Under Curve); 0.618 for the Training set, and 0.625 for the Validation set), which ascertained its predictive value. Our three-tumor marker classifier is closely associated with the CSS of GC and may serve as a novel model for future decisions concerning treatments.

  11. Cold hybrid electronics for CIRS-Cassini

    NASA Astrophysics Data System (ADS)

    Picault, Robert; Royer, Michel; Vannier, Patrice; De Antoni, Philippe; Lapegue, Jacques; Quatrehomme, Franck

    1995-09-01

    Cassini/Huygens is a joint NASA/ESA planetary mission to the Saturnian system. Titan, the largest Saturn moon, is the major target of the mission. Cassini is the Saturn orbiter provided by NASA to be launched on October 1997. To reach planet Saturn in 2004 and to study the rings, the planet and its satellites, the Cassini/Huygens planetary mission, a NASA-JPL project, includes among 12 instruments, the composite infrared spectrometer (CIRS) with GSFC as prime contractor of this instrument. The French participants are the Service d'Astrophysique (SAp) of CEA-Saclay and the DESPA-Observatoire de Meudon. CEA/SAp is in charge of the focal plane 4 electronics (detector, cold preamplifier, and analog processing electronic). SAT has developed under a CEA-SAp contract the hybrid micro-circuit which ensures the preamplifying function. These transimpedance amplifiers operate at 170 K and consist of 10 channels. The input current from the detector is up to 60 nA (mainly background current, modulated by a signal in the pA-nA range) and is converted into voltage up to 1.2 V through a 20 M(Omega) feedback resistor. The noise is < 15 nV/(root)Hz. The stability of the resistors is expected to be 0.1% for a duration of 16 years. The lifetime reuqirement consists of: 1) ground storage: 3-4 years, 2) transfer orbit: 7 years (instrument not operating), 3) Saturnian orbit: 4-5 years (instrument operating) and more than 40 Saturn-centered orbits. The preamplifier hybrid is an operational amplifier using a resistor multichip substrate designed, manufactured, and selected according to ESA PSS and MIL applicable documents. This amplifier integrated circuit has been chosen taking into account its cold temperature electrical performance and on the basis of its radiation resistance to 100 krad (at 170 K and operating). The model philosophy includes 2 main deliveries: engineering models and flight/spare models. The evaluation program consists of the electrical testing of all component

  12. Cost-Effectiveness Analysis (CEA) of Four Interventions for Adolescents with a Substance Use Disorder

    PubMed Central

    French, Michael T.; Zavala, Silvana K.; McCollister, Kathryn E.; Waldron, Holly B.; Turner, Charles W.; Ozechowski, Timothy J.

    2008-01-01

    Alcohol, tobacco, and illicit drug use among adolescents in the U.S. continues to be a serious public health challenge. A variety of outpatient treatments for adolescent substance use disorders have been developed and evaluated. Although no specific treatment modality is effective in all settings, a number of promising adolescent interventions have emerged. As policy makers try to prioritize which programs to fund with limited public resources, the need for systematic economic evaluations of these programs is critical. The present study attempted a cost-effectiveness analysis (CEA) of four interventions, including family-based, individual, and group cognitive behavioral approaches, for adolescents with a substance use disorder. The results indicated that treatment costs varied substantially across the four interventions. Moreover, family therapy showed significantly better substance use outcome compared to group treatment at the 4-month assessment, but group treatment was similar to the other interventions for substance use outcome at the 7-month assessment and for delinquency outcome at both the 4-month and 7-month assessments. These findings over a relatively short follow-up period suggest that the least expensive intervention (group) was the most cost effective. However, this study encountered numerous data and methodological challenges in trying to supplement a completed clinical trial with an economic evaluation. These challenges are explained and recommendations are proposed to guide future economic evaluations in this area. PMID:17600651

  13. Key Performance Criteria Affecting the Most the Safety of a Nuclear Waste Long Term Storage : A Case Study Commissioned by CEA

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

    Marvy, A.; Lioure, A; Heriard-Dubreuil, G.

    2003-02-24

    As part of the work scope set in the French law on high level long lived waste R&D passed in 1991, CEA is conducting a research program to establish the scientific basis and assess the feasibility of long term storage as an option for the safe management of nuclear waste for periods as long as centuries. This goal is a significant departure from the current industrial practice where storage facilities are usually built to last only a few decades. From a technical viewpoint such an extension in time seems feasible provided care and maintenance is exercised. Considering such long periodsmore » of time, the risk for Society of loosing oversight and control of such a facility is real, which triggers the question of whether and how long term storage safety can be actually achieved. Therefore CEA commissioned a study (1) in which MUTADIS Consultants (2) and CEPN (3) were both involved. The case study looks into several past and actual human enterprises conducted over significant periods o f time, one of them dating back to the end of the 18th century, and all identified out of the nuclear field. Then-prevailing societal behavior and organizational structures are screened out to show how they were or are still able to cope with similar oversight and control goals. As a result, the study group formulated a set of performance criteria relating to issues like responsibility, securing funds, legal and legislative implications, economic sustainable development, all being areas which are not traditionally considered as far as technical studies are concerned. These criteria can be most useful from the design stage onward, first in an attempt to define the facility construction and operating guiding principles, and thereafter to substantiate the safety case for long term storage and get geared to the public dialogue on that undertaking should it become a reality.« less

  14. Evaluation of the CEAS trend and monthly weather data models for soybean yields in Iowa, Illinois, and Indiana

    NASA Technical Reports Server (NTRS)

    French, V. (Principal Investigator)

    1982-01-01

    The CEAS models evaluated use historic trend and meteorological and agroclimatic variables to forecast soybean yields in Iowa, Illinois, and Indiana. Indicators of yield reliability and current measures of modeled yield reliability were obtained from bootstrap tests on the end of season models. Indicators of yield reliability show that the state models are consistently better than the crop reporting district (CRD) models. One CRD model is especially poor. At the state level, the bias of each model is less than one half quintal/hectare. The standard deviation is between one and two quintals/hectare. The models are adequate in terms of coverage and are to a certain extent consistent with scientific knowledge. Timely yield estimates can be made during the growing season using truncated models. The models are easy to understand and use and are not costly to operate. Other than the specification of values used to determine evapotranspiration, the models are objective. Because the method of variable selection used in the model development is adequately documented, no evaluation can be made of the objectivity and cost of redevelopment of the model.

  15. Performance assessment of imaging plates for the JHR transfer Neutron Imaging System

    NASA Astrophysics Data System (ADS)

    Simon, E.; Guimbal, P. AB(; )

    2018-01-01

    The underwater Neutron Imaging System to be installed in the Jules Horowitz Reactor (JHR-NIS) is based on a transfer method using a neutron activated beta-emitter like Dysprosium. The information stored in the converter is to be offline transferred on a specific imaging system, still to be defined. Solutions are currently under investigation for the JHR-NIS in order to anticipate the disappearance of radiographic films commonly used in these applications. We report here the performance assessment of Computed Radiography imagers (Imaging Plates) performed at LLB/Orphée (CEA Saclay). Several imaging plate types are studied, in one hand in the configuration involving an intimate contact with an activated dysprosium foil converter: Fuji BAS-TR, Fuji UR-1 and Carestream Flex XL Blue imaging plates, and in the other hand by using a prototypal imaging plate doped with dysprosium and thus not needing any contact with a separate converter foil. The results for these imaging plates are compared with those obtained with gadolinium doped imaging plate used in direct neutron imaging (Fuji BAS-ND). The detection performances of the different imagers are compared regarding resolution and noise. The many advantages of using imaging plates over radiographic films (high sensitivity, linear response, high dynamic range) could palliate its lower intrinsic resolution.

  16. An innovative acoustic sensor for first in-pile fission gas release determination - REMORA 3 experiment

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

    Rosenkrantz, E.; Ferrandis, J. Y.; Augereau, F.

    2011-07-01

    A fuel rod has been instrumented with a new design of an acoustic resonator used to measure in a non destructive way the internal rod plenum gas mixture composition. This ultrasonic sensor has demonstrated its ability to operate in pile during REMORA 3 irradiation experiment carried out in the OSIRIS Material Testing Reactor (CEA Saclay, France). Due to very severe experimental conditions such as temperature rising up to 150 deg.C and especially, high thermal fluence level up to 3.5 10{sup 19} n.cm{sup 2}, the initial sensor gas speed of sound efficiency measurement was strongly reduced due to the irradiation effectsmore » on the piezo-ceramic properties. Nevertheless, by adding a differential signal processing method to the initial data analysis procedure validated before irradiation, the gas resonance peaks were successfully extracted from the output signal. From these data, the molar fractions variations of helium and fission gas were measured from an adapted Virial state equation. Thus, with this sensor, the kinetics of gas release inside fuel rods could be deduced from the in-pile measurements and specific calculations. These data will also give information about nuclear reaction effect on piezo-ceramics sensor under high neutron and gamma flux. (authors)« less

  17. The effect of high level natural ionizing radiation on expression of PSA, CA19-9 and CEA tumor markers in blood serum of inhabitants of Ramsar, Iran.

    PubMed

    Heidari, Mohammad Hassan; Porghasem, Mohsen; Mirzaei, Nazanin; Mohseni, Jafar Hesam; Heidari, Matine; Azargashb, Eznollah; Movafagh, Abolfazl; Heidari, Reihane; Molouki, Aidin; Larijani, Leila

    2014-02-01

    Since several high level natural radiation areas (HLNRAs) exist on our planet, considerable attention has been drawn to health issues that may develop as the result of visiting or living in such places. City of Ramsar in Iran is an HNLRA, and is a tourist attraction mainly due to its hot spas. However, the growing awareness over its natural radiation sources has prompted widespread scientific investigation at national level. In this study, using an ELISA method, the level of expression of three tumor markers known as carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and carcino antigen 19-9 (CA19-9) in blood serum of 40 local men of Ramsar (subject group) was investigated and compared to 40 men from the city of Noshahr (control group). Noshahr was previously identified as a normal level natural radiation area (NLNRA) that is some 85 km far from Ramsar. According to statistical analysis, there was a significant difference in the levels of PSA and CA19-9 markers between the two groups (p < 0.001) with those of Ramsar being considerably higher. CEA level did not show any difference. Although some of the volunteers tested positive to the markers, they were in good health as confirmed by the physician. Moreover, the high number of positive markers in Noshahr was considerable. Therefore, future study is needed to further validate this result and to determine the level of positivity to tumor markers in both cities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. A preoperative serum signature of CEA+/CA125+/CA19-9 ≥ 1000 U/mL indicates poor outcome to pancreatectomy for pancreatic cancer.

    PubMed

    Liu, Liang; Xu, Huaxiang; Wang, Wenquan; Wu, Chuntao; Chen, Yong; Yang, Jingxuan; Cen, Putao; Xu, Jin; Liu, Chen; Long, Jiang; Guha, Sushovan; Fu, Deliang; Ni, Quanxing; Jatoi, Aminah; Chari, Suresh; McCleary-Wheeler, Angela L; Fernandez-Zapico, Martin E; Li, Min; Yu, Xianjun

    2015-05-01

    Pancreatectomy is associated with significant morbidity and unpredictable outcome, with few diagnostic tools to determine, which patients gain the most benefit from this treatment, especially before the operation. This study aimed to define a preoperative signature panel of serum markers to indicate response to pancreatectomy for pancreatic cancer. Over 1000 patients with pancreatic cancer treated at two independent high-volume institutions were included in this study and were divided into three groups, including resected, locally advanced and metastatic. Eight serum tumor markers most commonly used in gastrointestinal cancers were analyzed for patient outcome. Preoperative CA19-9 independently indicated surgical response in pancreatic cancer. Patients with CA19-9 ≥1000 U/mL generally had a poor surgical benefit. However, a subset of these patients still achieved a survival advantage when CA19-9 levels decreased postoperatively. CEA and CA125 in the presence of CA19-9 ≥1000 U/mL could independently predict the non-decrease of CA19-9 postoperatively. The combination of the three markers was useful for predicting a worse surgical outcome with a median survival of 5.1 months vs. 23.0 months (p < 0.001) for the training cohort and 7.0 months vs. 18.2 months (p < 0.001) for the validation cohort and also suggested a higher prevalence of early distant metastasis after surgery. Resected patients with this proposed signature showed no survival advantage over patients in the locally advanced group who did not receive pancreatectomy. Therefore, a preoperative serum signature of CEA(+)/CA125(+)/CA19-9 ≥1000 U/mL is associated with poor surgical outcome and can be used to select appropriate patients with pancreatic cancer for pancreatectomy. © 2014 UICC.

  19. An immunohistochemical study of primary signet-ring cell carcinoma of the stomach and colorectum: III. expressions of EMA, CEA, CA19-9, CDX-2, p53, Ki-67 antigen, TTF-1, vimentin, and p63 in normal mucosa and in 42 cases

    PubMed Central

    Terada, Tadashi

    2013-01-01

    There have no comprehensive immunohistochemical studies of primary signet ring cell carcinoma (SRCC) in the stomach and colorectum. The author examined the expression of nine common antigens (EMA, CEA, CA19-9, CDX-2, p53, Ki-67 antigen, TTF-1, vimentin, and p63) in the non-tumorous normal epithelium of the stomach and colorectum and in 42 cases of primary SRCC of the stomach (30 cases) and colorectum (12 cases). The normal epithelium of the stomach and colon consistently (100%) expressed EMA, CEA, CA19-9, CDX-2, and Ki-67 (labeling <15%). Normal epithelium of these locations never expressed p53, TTF-1, vimentin, and p63. In the primary gastric SRCC, the expression percentage of EMA was 57% (17/30), CEA 100% (30/30), CA19-9 100% (30/30), CDX-2 43% (13/30), p53 83% (25/30), Ki-67 100% (30/30) (labeling index= 36 ± 23 %), TTF-1 0% (0/30), vimentin 0% (0/30), and p63 0% (0/30). In primary colorectal SRCC, the expression percentage of EMA was 25% (3/12), CEA 100% (12/12), CA19-9 100% (12/12), CDX-2 93% (28/30), p53 75% (9/12), Ki-67 100% (30/30) (labeling index= 47% ± 26 %), TTF-1 0% (0/12), vimentin 0% (0/12), and p63 0% (0/12). A comparative statistical analysis showed significant difference in EMA (gastric SRCC 57% vs colorectal SRCC 25%) and CDX-2 (43% vs 93%). There were no significant differences in the other seven antigens’ expression between primary gastric SRCC and primary colorectal SRCC. These findings provide much knowledge of primary SRCC of the stomach and colorectum. The data indicated primary gastric SRCC frequently express EMA but not CDX-2 whereas primary colorectal SRCC frequently express CDX-2 but not EMA. These findings also suggest that EMA and CDX-2 are down-regulated during the gastric SRCC carcinogenesis. This down regulations may be associated with the malignant transformation of gastric SRCC. The data of colorectal SRCC suggest EMA is markedly down-regulated and also suggest that this EMA down-regulation may be associated with the

  20. Performance in the vertical test of the 832 nine-cell 1.3 GHz cavities for the European X-ray Free Electron Laser

    NASA Astrophysics Data System (ADS)

    Reschke, D.; Gubarev, V.; Schaffran, J.; Steder, L.; Walker, N.; Wenskat, M.; Monaco, L.

    2017-04-01

    The successful production and associated vertical testing of over 800 superconducting 1.3 GHz accelerating cavities for the European X-ray Free Electron Laser (XFEL) represents the culmination of over 20 years of superconducting radio-frequency R&D. The cavity production took place at two industrial vendors under the shared responsibility of INFN Milano-LASA and DESY. Average vertical testing rates at DESY exceeded 10 cavities per week, peaking at up to 15 cavities per week. The cavities sent for cryomodule assembly at Commissariat à l'énergie atomique (CEA) Saclay achieved an average maximum gradient of approximately 33 MV /m , reducing to ˜30 MV /m when the operational specifications on quality factor (Q) and field emission were included (the so-called usable gradient). Only 16% of the cavities required an additional surface retreatment to recover their low performance (usable gradient less than 20 MV /m ). These cavities were predominantly limited by excessive field emission for which a simple high pressure water rinse (HPR) was sufficient. Approximately 16% of the cavities also received an additional HPR, e.g. due to vacuum problems before or during the tests or other reasons, but these were not directly related to gradient performance. The in-depth statistical analyses presented in this report have revealed several features of the series produced cavities.

  1. CdTe Based Hard X-ray Imager Technology For Space Borne Missions

    NASA Astrophysics Data System (ADS)

    Limousin, Olivier; Delagnes, E.; Laurent, P.; Lugiez, F.; Gevin, O.; Meuris, A.

    2009-01-01

    CEA Saclay has recently developed an innovative technology for CdTe based Pixelated Hard X-Ray Imagers with high spectral performance and high timing resolution for efficient background rejection when the camera is coupled to an active veto shield. This development has been done in a R&D program supported by CNES (French National Space Agency) and has been optimized towards the Simbol-X mission requirements. In the latter telescope, the hard X-Ray imager is 64 cm² and is equipped with 625µm pitch pixels (16384 independent channels) operating at -40°C in the range of 4 to 80 keV. The camera we demonstrate in this paper consists of a mosaic of 64 independent cameras, divided in 8 independent sectors. Each elementary detection unit, called Caliste, is the hybridization of a 256-pixel Cadmium Telluride (CdTe) detector with full custom front-end electronics into a unique 1 cm² component, juxtaposable on its four sides. Recently, promising results have been obtained from the first micro-camera prototypes called Caliste 64 and will be presented to illustrate the capabilities of the device as well as the expected performance of an instrument based on it. The modular design of Caliste enables to consider extended developments toward IXO type mission, according to its specific scientific requirements.

  2. Joint tests at INL and CEA of a transient hot wire needle probe for in-pile thermal conductivity measurement

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

    Daw, J.E.; Knudson, D.L.; Villard, J.F.

    2015-07-01

    for both room temperature proof-of-concept evaluations and high temperature testing. Evaluations have been performed jointly by the INL and the French Alternative Energies and Atomic Energy Commission (CEA), both in Idaho Falls (USA) and in Cadarache (France), in the framework of a collaborative program for instrumentation of Material Testing Reactors. Initial tests were conducted on samples with a large range of thermal conductivities and temperatures ranging from 20 deg. C to 600 deg. C. Particularly, tests were recently performed on a sample having thermal conductivity and dimensions similar to UO{sub 2} and MOX nuclear fuels, in order to validate the ability of this sensor to operate for in-pile characterization of Light Water Reactors fuels. The results of the tests already completed at INL and CEA indicate that the Transient Hot Wire Needle Probe offers an enhanced method for in-pile detection of thermal conductivity. (authors)« less

  3. ESA's Integral solves thirty-year old gamma-ray mystery

    NASA Astrophysics Data System (ADS)

    Integral solves mystery hi-res Size hi-res: 60 kb Credits: Credit: ESA, F. Lebrun (CEA-Saclay). ESA's Integral solves thirty-year old gamma-ray mystery The central regions of our galaxy, the Milky Way, as seen by Integral in gamma rays. With its superior ability to see faint details, Integral correctly reveals the individual sources that comprised the foggy, gamma-ray background seen by previous observatories. The brightest 91 objects seen in this image were classified by Integral as individual sources, while the others appear too faint to be properly characterized at this stage. During the spring and autumn of 2003, Integral observed the central regions of our Galaxy, collecting some of the perpetual glow of diffuse low-energy gamma rays that bathe the entire Galaxy. These gamma rays were first discovered in the mid-1970s by high-flying balloon-borne experiments. Astronomers refer to them as the 'soft' Galactic gamma-ray background, with energies similar to those used in medical X-ray equipment. Initially, astronomers believed that the glow was caused by interactions involving the atoms of the gas that pervades the Galaxy. Whilst this theory could explain the diffuse nature of the emission, since the gas is ubiquitous, it failed to match the observed power of the gamma rays. The gamma rays produced by the proposed mechanisms would be much weaker than those observed. The mystery has remained unanswered for decades. Now Integral's superb gamma-ray telescope IBIS, built for ESA by an international consortium led by Principal Investigator Pietro Ubertini (IAS/CNR, Rome, Italy), has seen clearly that, instead of a fog produced by the interstellar medium, most of the gamma-rays are coming from individual celestial objects. In the view of previous, less sensitive instruments, these objects appeared to merge together. In a paper published today in "Nature", Francois Lebrun (CEA Saclay, Gif sur Yvette, France) and his collaborators report the discovery of 91 gamma

  4. Negative serum carcinoembryonic antigen has insufficient accuracy for excluding recurrence from patients with Dukes C colorectal cancer: analysis with likelihood ratio and posttest probability in a follow-up study.

    PubMed

    Hara, Masayasu; Kanemitsu, Yukihide; Hirai, Takashi; Komori, Koji; Kato, Tomoyuki

    2008-11-01

    This study was designed to determine the efficacy of carcinoembryonic antigen (CEA) monitoring for screening patients with colorectal cancer by using posttest probability of recurrence. For this study, 348 (preoperative serum CEA level elevated: CEA+, n = 119; or normal: CEA-, n = 229) patients who had undergone potentially curative surgery for colorectal cancer were enrolled. After five-year follow-up with measurements of serum CEA levels and imaging workup, posttest probabilities of recurrence were calculated. Recurrence was observed in 39 percent of CEA+ patients and 30 percent in CEA- patients, and CEA levels were elevated in 33.3 percent of CEA+ patients and 17.5 percent of CEA- patients. With obtained sensitivity (68.4 percent, CEA+; 41 percent, CEA-), specificity (83 percent, CEA+; 91 percent, CEA-) and likelihood ratio (test positive: 4.0, CEA+; 4.4, CEA-; and test negative: 0.38, CEA+; 0.66, CEA-), posttest probability given the presence of CEA elevation in the CEA+ and CEA- was 72.2 and 65.5 percent, respectively, and that given the absence of CEA elevation was 20 and 22.2 percent, respectively. Whereas postoperative CEA elevation indicates recurrence with high probability, a normal postoperative CEA is not useful for excluding the probability of recurrence.

  5. Design of the helium cooled lithium lead breeding blanket in CEA: from TBM to DEMO

    NASA Astrophysics Data System (ADS)

    Aiello, G.; Aubert, J.; Forest, L.; Jaboulay, J.-C.; Li Puma, A.; Boccaccini, L. V.

    2017-04-01

    The helium cooled lithium lead (HCLL) blanket concept was originally developed in CEA at the beginning of 2000: it is one of the two European blanket concepts to be tested in ITER in the form of a test blanket module (TBM) and one of the four blanket concepts currently being considered for the DEMOnstration reactor that will follow ITER. The TBM is a highly optimized component for the ITER environment that will provide crucial information for the development of the DEMO blanket, but its design needs to be adapted to the DEMO reactor. With respect to the TBM design, reduction of the steel content in the breeding zone (BZ) is sought in order to maximize tritium breeding reactions. Different options are being studied, with the potential of reaching tritium breeding ratio (TBR) values up to 1.21. At the same time, the design of the back supporting structure (BSS), which is a DEMO specific component that has to support the blanket modules inside the vacuum vessel (VV), is ongoing with the aim of maximizing the shielding power and minimizing pumping power. This implies a re-engineering of the modules’ attachment system. Design changes however, will have an impact on the manufacturing and assembly sequences that are being developed for the HCLL-TBM. Due to the differences in joint configurations, thicknesses to be welded, heat dissipation and the various technical constraints related to the accessibility of the welding tools and implementation of non-destructive examination (NDE), the manufacturing procedure should be adapted and optimized for DEMO design. Laser welding instead of TIG could be an option to reduce distortions. The time-of-flight diffraction (TOFD) technique is being investigated for NDE. Finally, essential information expected from the HCLL-TBM program that will be needed to finalize the DEMO design is discussed.

  6. Seeing the NICE side of cost-effectiveness analysis: a qualitative investigation of the use of CEA in NICE technology appraisals.

    PubMed

    Bryan, Stirling; Williams, Iestyn; McIver, Shirley

    2007-02-01

    Resource scarcity is the raison d'être for the discipline of economics. Thus, the primary purpose of economic analysis is to help decision-makers when addressing problems arising due to the scarcity problem. The research reported here was concerned with how cost-effectiveness information is used by the National Institute for Health & Clinical Excellence (NICE) in national technology coverage decisions in the UK, and how its impact might be increased. The research followed a qualitative case study methodology with semi-structured interviews, supported by observation and analysis of secondary sources. Our research highlights that the technology appraisal function of NICE represents an important progression for the UK health economics community: new cost-effectiveness work is commissioned for each technology and that work directly informs national health policy. However, accountability in policy decisions necessitates that the information upon which decisions are based (including cost-effectiveness analysis, CEA) is accessible. This was found to be a serious problem and represents one of the main ongoing challenges. Other issues highlighted include perceived weaknesses in analysis methods and the poor alignment between the health maximisation objectives assumed in economic analyses and the range of other objectives facing decision-makers in reality. Copyright (c) 2006 John Wiley & Sons, Ltd.

  7. Education and training in the field of nuclear instrumentation and measurement: CEA/INSTN (National Institute for Nuclear Sciences and Technologies) strategy to improve and develop new pedagogical tools and methods

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

    Vitart, Xavier; Foulon, Francois; Bodineau, Jean Christophe

    Part of the French Alternative Energies and Atomic Energy Commission (CEA), the National Institute for Nuclear Science and Technology (INSTN) is a higher education institution whose mission is to provide students and professionals a high level of scientific and technological qualification in all disciplines related to nuclear energy applications. In this frame, INSTN carries out education and training (E and T) programs in nuclear instrumentation and radioprotection. Its strategy has always been to complete theoretical courses by training courses and laboratory works carried out on an extensive range of training tools that includes a large panel of nuclear instrumentation asmore » well as software applications. Since its creation in 1956, the INSTN has conducted both education and vocational programs on ionizing radiation detection. An extensive range of techniques have commonly been used during practical works with students and employees of companies who need to get the knowledge and specialization in this field. Today, the INSTN is mainly equipped with usual detectors and electronics in large numbers in order to be able to accommodate up to 48 trainees at the same time in two classrooms, with only two trainees for one workstation in order to optimize their learning. In the field of the neutron detection systems, the INSTN has strongly developed its offer taking advantage of the use of research reactors, such as ISIS reactor (700 kW) at Saclay. The implementation of neutron detection systems specific to the courses offers a unique way of observing and analysing the signal coming from neutron detectors, as well as learning how to set the parameters of the detection system in real conditions. Providing the trainees with an extensive overview of each part of the neutron monitoring instrumentation apply to a nuclear reactor, hands-on measurements on the ISIS reactor play a major role in ensuring a practical and comprehensive understanding of the neutron detection

  8. Minister unveils new nanotech centres

    NASA Astrophysics Data System (ADS)

    Dumé, Belle

    2009-06-01

    Three new nanotechnology research centres are to be set up in France as part of a €70m government plan to help French companies in the sector. Researchers at the new centres, which will be located in Grenoble, Saclay (near Paris) and Toulouse, will be encouraged to collaborate with industry to develop new nanotech-based products. Dubbed NANO-INNOV, the new plan includes €46m for two new buildings at Saclay, with the rest being used to buy new equipment at the three centres and to fund grant proposals from staff to the French National Research Agency (ANR).

  9. A Drift Chamber to Measure Charged Particles at COMPASS-II

    NASA Astrophysics Data System (ADS)

    Heitz, Robert; Compass Collaboration

    2013-10-01

    A new drift chamber (DC05) will be constructed to replace two tracking detector stations based on straw tubes, ST02 and ST03 in the COMPASS spectrometer. DC05 uses the designs from DC04, a previous drift chamber designed at CEA-Saclay, France, but adds the addition of more wires for improved acceptance. In addition to more wires DC05 will also change its front end electronics using a new pre-amplifier-discriminator chip (CMAD). DC05 consists of 8 layers of anode planes and 21 layers of G-10 material frames carrying cathode planes and gas windows. The wires are orientated with two layers in the vertical x-direction, two layers in the horizontal y-direction, two layers offset +10 deg of the vertical x-direction, and two layers offset -10 deg of the vertical x-direction. The wires in parallel directions are offset half a pitch to resolve left-right ambiguities. The purpose for different wire orientations is to reconstruct the 3D space particle trajectory to fit a particle track. Each layer of wires is covered on the top and bottom by a cathode plane of carbon coated mylar. All these layers are sandwiched between two steel stiffening frames for support and noise reduction. A future drift chamber, DC06, is also being designed based off of DC05. Research funded by NSF-PHY-12-05-671 Medium Energy Nuclear Physics.

  10. Association of Preoperative and Postoperative Serum Carcinoembryonic Antigen and Colon Cancer Outcome.

    PubMed

    Konishi, Tsuyoshi; Shimada, Yoshifumi; Hsu, Meier; Tufts, Lauren; Jimenez-Rodriguez, Rosa; Cercek, Andrea; Yaeger, Rona; Saltz, Leonard; Smith, J Joshua; Nash, Garrett M; Guillem, José G; Paty, Philip B; Garcia-Aguilar, Julio; Gonen, Mithat; Weiser, Martin R

    2018-03-01

    Guidelines recommend measuring preoperative carcinoembryonic antigen (CEA) in patients with colon cancer. Although persistently elevated CEA after surgery has been associated with increased risk for metastatic disease, prognostic significance of elevated preoperative CEA that normalized after resection is unknown. To investigate whether patients with elevated preoperative CEA that normalizes after colon cancer resection have a higher risk of recurrence than patients with normal preoperative CEA. This retrospective cohort analysis was conducted at a comprehensive cancer center. Consecutive patients with colon cancer who underwent curative resection for stage I to III colon adenocarcinoma at the center from January 2007 to December 2014 were identified. Patients were grouped into 3 cohorts: normal preoperative CEA, elevated preoperative but normalized postoperative CEA, and elevated preoperative and postoperative CEA. Three-year recurrence-free survival (RFS) and hazard function curves over time were analyzed. A total of 1027 patients (461 [50.4%] male; median [IQR] age, 64 [53-75] years) were identified. Patients with normal preoperative CEA had 7.4% higher 3-year RFS (n = 715 [89.7%]) than the combined cohorts with elevated preoperative CEA (n = 312 [82.3%]) (P = .01) but had RFS similar to that of patients with normalized postoperative CEA (n = 142 [87.9%]) (P = .86). Patients with elevated postoperative CEA had 14.9% lower RFS (n = 57 [74.5%]) than the combined cohorts with normal postoperative CEA (n = 857 [89.4%]) (P = .001). The hazard function of recurrence for elevated postoperative CEA peaked earlier than for the other cohorts. Multivariate analyses confirmed that elevated postoperative CEA (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5), but not normalized postoperative CEA (HR, 0.77; 95% CI, 0.45-1.30), was independently associated with shorter RFS. Elevated preoperative CEA that normalizes after resection is not an indicator of

  11. Clinical studies of type-I procollagen carboxyterminal peptide in serum of patients with gastric cancer: comparison with CEA and CA19-9.

    PubMed

    Ogawa, K; Naritaka, Y; Katsube, T; Ohtani, Y; Yagawa, H; Kajiwara, T

    1994-06-01

    The serum level of a newly developed monoclonal antibody against type-I procollagen carboxyterminal peptide (P-1-P) was determined in patients with gastric cancer. The location of P-1-P in gastric cancer tissue was also investigated. We found that: (1) The serum P-1-P level and the positivity rate in patients with gastric cancer were similar to those in patients with other malignant or benign GI diseases and healthy individuals. (2) In patients with gastric cancer, the P-1-P positivity rate was significantly lower than that of CEA or CA19-9. (3) In patients with gastric cancer, the P-1-P positivity rate increased as the disease stage advanced. (4) Among patients with gastric cancer, the P-1-P positivity rate was significantly higher in those with scirrhous type than in those with medullary or intermediate type. (5) P-1-P was detected in the cytoplasm of cancer cells. P-1-P staining was stronger in scirrhous type and histologically undifferentiated gastric cancer. These results show that P-1-P can serve as a good marker for scirrhous type gastric cancer. The production of collagen by cancer cells themselves seems to be involved in collagen production in scirrhous type gastric cancer.

  12. Effect of heterogeneity of carcinoembryonic antigen on liver cell membrane binding and its kinetics of removal from circulation.

    PubMed

    Byrn, R A; Medrek, P; Thomas, P; Jeanloz, R W; Zamcheck, N

    1985-07-01

    Carcinoembryonic antigen (CEA) is a glycoprotein metabolized primarily by the liver. Subcellular fractions of rat liver were examined for CEA binding activity. Hepatocyte plasma membrane and microsome fractions bound CEA, and this binding shared the calcium requirement, neuraminidase sensitivity, and carbohydrate specificity of the hepatocyte asialoglycoprotein receptor. CEA had previously been shown to react with this galactose-specific receptor, in vivo, only following neuraminidase treatment. Galactose receptor binding of CEA was measured in three different purified CEA preparations. The fraction of CEA capable of binding to excess levels of galactose receptor on membranes varied (46.5%, 40.2%, and 4.7% for CEA-1, -2, and -3, respectively). These CEAs were shown to be 2.3%, 7.9%, and 0.7% as effective, respectively, as asialo-alpha 1-acid glycoprotein in inhibiting the binding of radiolabeled asialo-alpha 1-acid glycoprotein to liver cell membranes. Each of the three CEA preparations showed different clearance kinetics from the circulation of mice. Coinjection of asialo-alpha 1-acid glycoprotein with the CEAs revealed differing inhibition of the clearances. These results show that differences in the carbohydrate components of purified CEA preparations affect their rate of removal from circulation and thus possibly the relationship between CEA production and observed plasma levels in patients. The possible origin of these CEA differences is discussed with their clinical implications.

  13. The characterization of radioactive waste: a critical review of techniques implemented or under development at CEA, France

    NASA Astrophysics Data System (ADS)

    Pérot, Bertrand; Jallu, Fanny; Passard, Christian; Gueton, Olivier; Allinei, Pierre-Guy; Loubet, Laurent; Estre, Nicolas; Simon, Eric; Carasco, Cédric; Roure, Christophe; Boucher, Lionel; Lamotte, Hervé; Comte, Jérôme; Bertaux, Maïté; Lyoussi, Abdallah; Fichet, Pascal; Carrel, Frédérick

    2018-03-01

    This review paper describes the destructive and non-destructive measurements implemented or under development at CEA, in view to perform the most complete radioactive waste characterization. First, high-energy photon imaging (radiography, tomography) brings essential information on the waste packages, such as density, position and shape of the waste inside the container and in the possible binder, quality of coating and blocking matrices, presence of internal shields or structures, presence of cracks, voids, or other defects in the container or in the matrix, liquids or other forbidden materials, etc. Radiological assessment is then performed using a series of non-destructive techniques such as gamma-ray spectroscopy, which allows characterizing a wide range of radioactive and nuclear materials, passive neutron coincidence counting and active neutron interrogation with the differential die-away technique, or active photon interrogation with high-energy photons (photofission), to measure nuclear materials. Prompt gamma neutron activation analysis (PGNAA) can also be employed to detect toxic chemicals or elements which can greatly influence the above measurements, such as neutron moderators or absorbers. Digital auto-radiography can also be used to detect alpha and beta contaminated waste. These non-destructive assessments can be completed by gas measurements, to quantify the radioactive and radiolysis gas releases, and by destructive examinations such as coring homogeneous waste packages or cutting the heterogeneous ones, in view to perform visual examination and a series of physical, chemical, and radiochemical analyses on samples. These last allow for instance to check the mechanical and containment properties of the package envelop, or of the waste binder, to measure toxic chemicals, to assess the activity of long-lived radionuclides or pure beta emitters, to determine the isotopic composition of nuclear materials, etc.

  14. Number and cost of claims linked to minor cervical trauma in Europe: results from the comparative study by CEA, AREDOC and CEREDOC.

    PubMed

    Chappuis, Guy; Soltermann, Bruno

    2008-10-01

    Comparative epidemiological study of minor cervical spine trauma (frequently referred to as whiplash injury) based on data from the Comité Européen des Assurances (CEA) gathered in ten European countries. To determine the incidence and expenditure (e.g., for assessment, treatment or claims) for minor cervical spine injury in the participating countries. Controversy still surrounds the basis on which symptoms following minor cervical spine trauma may develop. In particular, there is considerable disagreement with regard to a possible contribution of psychosocial factors in determining outcome. The role of compensation is also a source of constant debate. The method followed here is the comparison of the data from different areas of interest (e.g., incidence of minor cervical spine trauma, percentage of minor cervical spine trauma in relationship to the incidence of bodily trauma, costs for assessment or claims) from ten European countries. Considerable differences exist regarding the incidence of minor cervical spine trauma and related costs in participating countries. France and Finland have the lowest and Great Britain the highest incidence of minor cervical spine trauma. The number of claims following minor cervical spine trauma in Switzerland is around the European average; however, Switzerland has the highest expenditure per claim at an average cost of 35,000.00 euros compared to the European average of 9,000.00 euros. Furthermore, the mandatory accident insurance statistics in Switzerland show very large differences between German-speaking and French- or Italian-speaking parts of the country. In the latter the costs for minor cervical spine trauma expanded more than doubled in the period from 1990 to 2002, whereas in the German-speaking part they rose by a factor of five. All the countries participating in the study have a high standard of medical care. The differences in claims frequency and costs must therefore reflect a social phenomenon based on the

  15. Quantitative analysis of antigen for the induction of tolerance in carcinoembryonic antigen transgenic mice.

    PubMed Central

    Hasegawa, T; Isobe, K; Nakashima, I; Shimokata, K

    1992-01-01

    In order to analyse the amounts of antigen in the thymus for the induction of tolerance, several carcinoembryonic antigen (CEA) transgenic lines were established which expressed human CEA antigen with different amounts. The chimeric KSN nude mice transplanted with the thymus of the B601 line (in which CEA mRNA and CEA protein could be detected in various tissues) to kidney capsule showed tolerance to human CEA. On the other hand, the chimeric KSN nude mice transplanted with the thymus of the B602 or BC60 line (in which neither CEA mRNA nor CEA protein could be detected by Northern blot analysis and flow cytometry analysis) or normal C57BL/6 (B6) did not develop the tolerance to human CEA. However, the chimeric KSN nude mice transplanted simultaneously with thymus of the B6 and spleen of the B601 line became tolerant to human CEA antigen. In the case of systemic immunization with cells which had CEA antigen, the B601 line was tolerant to human CEA. Surprisingly, the B602 and BC60 lines were also tolerant to CEA molecule. These results indicate that not only the antigen present in the thymus but also the antigen which flows from the peripheral organs to the thymus may be necessary for the induction of CEA tolerance. Images Figure 1 PMID:1493931

  16. Innovations for In-Pile Measurements in the Framework of the CEA-SCK•CEN Joint Instrumentation Laboratory

    NASA Astrophysics Data System (ADS)

    Villard, Jean-Francois; Schyns, Marc

    2010-12-01

    Optimizing the life cycle of nuclear systems under safety constraints requires high-performance experimental programs to reduce uncertainties on margins and limits. In addition to improvement in modeling and simulation, innovation in instrumentation is crucial for analytical and integral experiments conducted in research reactors. The quality of nuclear research programs relies obviously on an excellent knowledge of their experimental environment which constantly calls for better online determination of neutron and gamma flux. But the combination of continuously increasing scientific requirements and new experimental domains -brought for example by Generation IV programsnecessitates also major innovations for in-pile measurements of temperature, dimensions, pressure or chemical analysis in innovative mediums. At the same time, the recent arising of a European platform around the building of the Jules Horowitz Reactor offers new opportunities for research institutes and organizations to pool their resources in order to face these technical challenges. In this situation, CEA (French Nuclear Energy Commission) and SCK'CEN (Belgian Nuclear Research Centre) have combined their efforts and now share common developments through a Joint Instrumentation Laboratory. Significant progresses have thus been obtained recently in the field of in-pile measurements, on one hand by improvement of existing measurement methods, and on the other hand by introduction in research reactors of original measurement techniques. This paper highlights the state-of-the-art and the main requirements regarding in-pile measurements, particularly for the needs of current and future irradiation programs performed in material testing reactors. Some of the main on-going developments performed in the framework of the Joint Instrumentation Laboratory are also described, such as: - a unique fast neutron flux measurement system using fission chambers with 242Pu deposit and a specific online data processing

  17. FOREWORD: 3rd Symposium on Large TPCs for Low Energy Event Detection

    NASA Astrophysics Data System (ADS)

    Irastorza, Igor G.; Colas, Paul; Gorodetzky, Phillippe

    2007-05-01

    organization of the Symposium was made possible by the contribution of the members of the organizating Committee and International Advisory Committee. I want to thank in particular the session chairmen, G. Wormser, S. Katsanevas, J. Timmermans, S. Andriamonje, G. Chardin, T. Ebisuzaki, J.-E. Augustin and E. Delagnes for their contribution to the smooth running of the workshop. The symposium was free of fees and was made possible thanks to the financial support from DAPNIA-CEA and IN2P3-CNRS, the two major French research organizations that are gratefully acknowledged. Finally I want to thank the speakers for the high quality of their talks and all participants for coming to Paris and actively contributing in the meeting. The symposium was dedicated to the memory of Mike Ronan who left us a few months before. Mike was organizing in Berkeley a similar series of TPC workshops. David Nygren reviewed Mike Ronan's contribution to physics and especially to the development of new TPCs. Ioannis Giomataris Chair of the Organizing Committee International Advisory Committee Bouchez J. jacques.bouchez@cea.frNygren D-R. DRNygren@lbl.gov Charpak G. charpak@emse.frPaschos E. paschos@physik.uni-dortmund.de Collar J. collar@uchicago.eduShipsey I. shipsey@physics.purdue.edu Garwin R. RSA@watson.ibm.comSinclair D. D.sinclair@physics.carleton.ca Iliopoulos J. ilio@lpt.ens.frSpiro M. mspiro@admin.in2p3.fr Katsanevas S. katsan@admin.in2p3.frSpooner N. n.spooner@sheffield.ac.uk Mansoulié B. bruno.mansoulie@cea.frVergados J-D. vergados@cc.uoi.gr Morales J. jmorales@unizar.esVignaud D. vignaud@cdf.in2p3.fr Local Organizing Committee Busto J. busto@cppm.in2p3.frGiomataris I. ioa@hep.saclay.cea.fr (chairman) Colas P. paul.colas@cea.frGorodetzky Ph. philippe.gorodetzky@cern.ch Coudray Lydia (secretary)Irastorza I.G. Igor.Irastorza@cern.ch Fauvel Patricia (secretary)Vuilleumier J-L. jean-Luc.vuilleumier@unine.ch

  18. Experimental study of Large-scale cryogenic Pulsating Heat Pipe

    NASA Astrophysics Data System (ADS)

    Barba, Maria; Bruce, Romain; Bonelli, Antoine; Baudouy, Bertrand

    2017-12-01

    Pulsating Heat Pipes (PHP) are passive two-phase heat transfer devices consisting of a long capillary tube bent into many U-turns connecting the condenser part to the evaporator part. They are thermally driven by an oscillatory flow of liquid slugs and vapor plugs coming from phase changes and pressure differences along the tube. The coupling of hydrodynamic and thermodynamic effects allows high heat transfer performances. Three closed-loop pulsating heat pipes have been developed by the DACM (Department of Accelerators, Cryogenics and Magnetism) of CEA Paris-Saclay, France. Each PHP measures 3.7 meters long (0.35 m for the condenser and the evaporator and 3 m for the adiabatic part), being almost 20 times longer than the longest cryogenic PHP tested. These PHPs have 36, 22 and 12 parallel channels. Numerous tests have been performed in horizontal position (the closest configuration to non-gravity) using nitrogen as working fluid, operating between 75 and 90 K. The inner and outer diameters of the stainless steel capillary tubes are 1.5 and 2 mm respectively. The PHPs were operated at different filling ratios (20 to 90 %), heat input powers (3 to 20 W) and evaporator and condenser temperatures (75 to 90 K). As a result, the PHP with 36 parallel channels achieves a certain level of stability during more than thirty minutes with an effective thermal conductivity up to 200 kW/m.K at 10 W heat load and during forty minutes with an effective thermal conductivity close to 300 kW/m.K at 5 W heat load.

  19. Detection of carcinoembryonic antigen messenger RNA in blood using quantitative real-time reverse transcriptase-polymerase chain reaction to predict recurrence of gastric adenocarcinoma

    PubMed Central

    2010-01-01

    Background The existence of circulating tumor cells (CTCs) in peripheral blood as an indicator of tumor recurrence has not been clearly established, particularly for gastric cancer patients. We conducted a retrospective analysis of the relationship between CTCs in peripheral blood at initial diagnosis and clinicopathologic findings in patients with gastric carcinoma. Methods Blood samples were obtained from 123 gastric carcinoma patients at initial diagnosis. mRNA was extracted and amplified for carcinoembryonic antigen (CEA) mRNA detection using real-time RT-PCR. Periodic 3-month follow-up examinations included serum CEA measurements and imaging. Results The minimum threshold for corrected CEA mRNA score [(CEA mRNA/GAPDH mRNA) × 106] was set at 100. Forty-five of 123 patients (36.6%) were positive for CEA mRNA expression. CEA mRNA expression significantly correlated with T stage and postoperative recurrence status (P = 0.001). Recurrent disease was found in 44 of 123 cases (35.8%), and 25 of these (56.8%) were positive for CEA mRNA. Of these patients, CEA mRNA was more sensitive than serum CEA in indicating recurrence. Three-year disease-free survival of patients positive for CEA mRNA was significantly poorer than of patients negative for CEA mRNA (P < 0.001). Only histological grade and CEA mRNA positivity were independent factors for disease-free survival using multivariate analysis. Conclusions CEA mRNA copy number in peripheral blood at initial diagnosis was significantly associated with disease recurrence in gastric adenocarcinoma patients. Real-time RT-PCR detection of CEA mRNA levels at initial diagnosis appears to be a promising predictor for disease recurrence in gastric adenocarcinoma patients. PMID:21040522

  20. Detection of carcinoembryonic antigen messenger RNA in blood using quantitative real-time reverse transcriptase-polymerase chain reaction to predict recurrence of gastric adenocarcinoma.

    PubMed

    Qiu, Miao-Zhen; Li, Zhuang-Hua; Zhou, Zhi-Wei; Li, Yu-Hong; Wang, Zhi-Qiang; Wang, Feng-Hua; Huang, Peng; Aziz, Fahad; Wang, Dao-Yuan; Xu, Rui-Hua

    2010-10-31

    The existence of circulating tumor cells (CTCs) in peripheral blood as an indicator of tumor recurrence has not been clearly established, particularly for gastric cancer patients. We conducted a retrospective analysis of the relationship between CTCs in peripheral blood at initial diagnosis and clinicopathologic findings in patients with gastric carcinoma. Blood samples were obtained from 123 gastric carcinoma patients at initial diagnosis. mRNA was extracted and amplified for carcinoembryonic antigen (CEA) mRNA detection using real-time RT-PCR. Periodic 3-month follow-up examinations included serum CEA measurements and imaging. The minimum threshold for corrected CEA mRNA score [(CEA mRNA/GAPDH mRNA) × 106] was set at 100. Forty-five of 123 patients (36.6%) were positive for CEA mRNA expression. CEA mRNA expression significantly correlated with T stage and postoperative recurrence status (P = 0.001). Recurrent disease was found in 44 of 123 cases (35.8%), and 25 of these (56.8%) were positive for CEA mRNA. Of these patients, CEA mRNA was more sensitive than serum CEA in indicating recurrence. Three-year disease-free survival of patients positive for CEA mRNA was significantly poorer than of patients negative for CEA mRNA (P < 0.001). Only histological grade and CEA mRNA positivity were independent factors for disease-free survival using multivariate analysis. CEA mRNA copy number in peripheral blood at initial diagnosis was significantly associated with disease recurrence in gastric adenocarcinoma patients. Real-time RT-PCR detection of CEA mRNA levels at initial diagnosis appears to be a promising predictor for disease recurrence in gastric adenocarcinoma patients.

  1. Divergent functions of the left and right central amygdala in visceral nociception

    PubMed Central

    Sadler, Katelyn E.; McQuaid, Neal A.; Cox, Abigail C.; Behun, Marissa N.; Trouten, Allison M.; Kolber, Benedict J.

    2017-01-01

    The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2–mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase–activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2–mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain–like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries. PMID:28225716

  2. Divergent functions of the left and right central amygdala in visceral nociception.

    PubMed

    Sadler, Katelyn E; McQuaid, Neal A; Cox, Abigail C; Behun, Marissa N; Trouten, Allison M; Kolber, Benedict J

    2017-04-01

    The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2-mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase-activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2-mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain-like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries.

  3. Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

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

    Bajenova, Olga, E-mail: o.bazhenova@spbu.ru; Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034; Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178

    2014-06-10

    Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA andmore » beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein.« less

  4. Prognostic Role of Carcinoembryonic Antigen Level after Preoperative Chemoradiotherapy in Patients with Rectal Cancer.

    PubMed

    Huh, Jung Wook; Yun, Seong Hyeon; Kim, Seok Hyung; Park, Yoon Ah; Cho, Yong Beom; Kim, Hee Cheol; Lee, Woo Yong; Park, Hee Chul; Choi, Doo Ho; Park, Joon Oh; Park, Young Suk; Chun, Ho-Kyung

    2018-05-29

    The prognostic role of post-chemoradiotherapy (CRT) carcinoembryonic antigen (CEA) level is not clear. We evaluated the prognostic significance of post-CRT CEA level in patients with rectal cancer after preoperative CRT. We reviewed 659 consecutive patients who underwent preoperative CRT and total mesorectal excision for non-metastatic rectal cancer. Patients were categorized into two groups according to post-CRT serum CEA level: low CEA (< 5 ng/mL) and high CEA (≥ 5 ng/mL). Median post-CRT CEA level was 1.7 ng/mL (range, 0.1-207.0). A high post-CRT level was significantly associated with ypStage, ypT category, tumor regression grade, and pre-CRT CEA level. The 5-year overall survival rate of the 659 patients was 87.8% with a median follow-up period of 57.0 months (range, 1.4-176.4). When the post-CRT CEA groups were divided into groups according to pre-CRT CEA level, the 5-year overall survival rates were significantly different (P < 0.001 and P = 0.001, respectively). Post-CRT CEA level was an independent prognostic factor for overall survival. Multivariate analysis revealed that operation method, differentiation, perineural invasion, postoperative chemotherapy, tumor regression grade, and post-CRT CEA level were independent prognostic factors for overall survival. The level of serum CEA after preoperative CRT was an independent prognostic factor for overall survival in patients with rectal cancer.

  5. Neem leaf glycoprotein enhances carcinoembryonic antigen presentation of dendritic cells to T and B cells for induction of anti-tumor immunity by allowing generation of immune effector/memory response.

    PubMed

    Sarkar, Koustav; Goswami, Shyamal; Roy, Soumyabrata; Mallick, Atanu; Chakraborty, Krishnendu; Bose, Anamika; Baral, Rathindranath

    2010-08-01

    Vaccination with neem leaf glycoprotein matured carcinoembryonic antigen (CEA) pulsed dendritic cells (DCs) enhances antigen-specific humoral and cellular immunity against CEA and restricts the growth of CEA(+) murine tumors. NLGP helps better CEA uptake, processing and presentation to T/B cells. This vaccination (DCNLGPCEA) elicits mitogen induced and CEA specific T cell proliferation, IFN gamma secretion and induces specific cytotoxic reactions to CEA(+) colon tumor cells. In addition to T cell response, DCNLGPCEA vaccine generates anti-CEA antibody response, which is principally IgG2a in nature. This antibody participates in cytotoxicity of CEA(+) cells in antibody-dependent manner. This strong anti-CEA cellular and humoral immunity protects mice from tumor development and these mice remained tumor free following second tumor inoculation, indicating generation of effector memory response. Evaluation of underlying mechanism suggests vaccination generates strong CEA specific CTL and antibody response that can completely prevent the tumor growth following adoptive transfer. In support, significant upregulation of CD44 on the surface of lymphocytes from DCNLGPCEA immunized mice was noticed with a substantial reduction in L-selectin (CD62L). (c) 2010 Elsevier B.V. All rights reserved.

  6. Molecular Mechanism Underlying the Entomotoxic Effect of Colocasia esculenta Tuber Agglutinin against Dysdercus cingulatus

    PubMed Central

    Roy, Amit; Das, Sampa

    2015-01-01

    Colocasia esculenta tuber agglutinin (CEA), a mannose binding lectin, exhibits insecticidal efficacy against different hemipteran pests. Dysdercus cingulatus, red cotton bug (RCB), has also shown significant susceptibility to CEA intoxication. However, the molecular basis behind such entomotoxicity of CEA has not been addressed adequately. The present study elucidates the mechanism of insecticidal efficacy of CEA against RCB. Confocal and scanning electron microscopic analyses documented CEA binding to insect midgut tissue, resulting in an alteration of perimicrovillar membrane (PMM) morphology. Internalization of CEA into insect haemolymph and ovary was documented by western blotting analyses. Ligand blot followed by mass spectrometric identification revealed the cognate binding partners of CEA as actin, ATPase and cytochrome P450. Deglycosylation and mannose inhibition assays indicated the interaction to probably be mannose mediated. Bioinformatic identification of putative glycosylation or mannosylation sites in the binding partners further supports the sugar mediated interaction. Correlating entomotoxicity of CEA with immune histological and binding assays to the insect gut contributes to a better understanding of the insecticidal potential of CEA and endorses its future biotechnological application.

  7. Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate

    PubMed Central

    Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

    2017-01-01

    The central extended amygdala (CEA) has been conceptualized as a ‘macrosystem’ that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the ‘limbic-associative’ striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning. PMID:28220796

  8. Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

    PubMed

    Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

    2017-07-01

    The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

  9. Concordance of Carcinoembryonic Antigen Ratio and Response Evaluation Criteria in Solid Tumors as Prognostic Surrogate Indicators of Metastatic Colorectal Cancer Patients Treated with Chemotherapy.

    PubMed

    Huang, Sheng-Chieh; Lin, Jen-Kou; Lin, Tzu-Chen; Chen, Wei-Shone; Yang, Shung-Haur; Wang, Huann-Sheng; Lan, Yuan-Tzu; Lin, Chun-Chi; Jiang, Jeng-Kai; Chang, Shih-Ching

    2015-07-01

    Carcinoembryonic antigen (CEA) is widely used as a tumor marker in colorectal cancer (CRC). This study aimed to evaluate the role of the degree of change in CEA levels during the treatment period and found that the degree of change highly correlated with disease survival and Response Evaluation Criteria in Solid Tumors (RECIST) criteria in evaluating therapy response. A total of 447 metastatic CRC patients treated with surgery of the primary tumor followed by systemic therapy at a single center from the year 2000 through 2011 were reviewed. The degree of change in CEA levels was expressed as the CEA ratio (post-CEA/pre-CEA) and classified into four groups during the treatment period for further evaluation. The imaging change of the same population was also compared with the CEA ratio during the treatment period. The CEA ratio was significantly correlated with different chemotherapy regimens (p < 0.001), pre-treatment CEA level (p < 0.001), lymphovascular invasion (p = 0.006), and tumor differentiation (p = 0.018). CEA ratio and imaging change according to RECIST criteria were both correlated with overall survival (p < 0.001). These two methods for evaluating treatment response were highly correlated (p < 0.001). CEA ratio was found to be a reliable prognostic factor in stage IV CRC, and was highly correlated with the imaging survey according to RECIST criteria. Further prospective studies are essential to validate these findings.

  10. Carcinoembryonic antigen-stimulated THP-1 macrophages activate endothelial cells and increase cell-cell adhesion of colorectal cancer cells.

    PubMed

    Aarons, Cary B; Bajenova, Olga; Andrews, Charles; Heydrick, Stanley; Bushell, Kristen N; Reed, Karen L; Thomas, Peter; Becker, James M; Stucchi, Arthur F

    2007-01-01

    The liver is the most common site for metastasis by colorectal cancer, and numerous studies have shown a relationship between serum carcinoembryonic antigen (CEA) levels and metastasis to this site. CEA activates hepatic macrophages or Kupffer cells via binding to the CEA receptor (CEA-R), which results in the production of cytokines and the up-regulation of endothelial adhesion molecules, both of which are implicated in hepatic metastasis. Since tissue macrophages implicated in the metastatic process can often be difficult to isolate, the aim of this study was to develop an in vitro model system to study the complex mechanisms of CEA-induced macrophage activation and metastasis. Undifferentiated, human monocytic THP-1 (U-THP) cells were differentiated (D-THP) to macrophages by exposure to 200 ng/ml phorbol myristate acetate (PMA) for 18 h. Immunohistochemistry showed two CEA-R isoforms present in both U- and D-THP cells. The receptors were localized primarily to the nucleus in U-THP cells, while a significant cell-surface presence was observed following PMA-differentiation. Incubation of D-THP-1 cells with CEA resulted in a significant increase in tumor necrosis factor-alpha (TNF-alpha) release over 24 h compared to untreated D-THP-1 or U-THP controls confirming the functionality of these cell surface receptors. U-THP cells were unresponsive to CEA. Attachment of HT-29 cells to human umbilical vein endothelial cells significantly increased at 1 h after incubation with both recombinant TNF-alpha and conditioned media from CEA stimulated D-THP cells by six and eightfold, respectively. This study establishes an in vitro system utilizing a human macrophage cell line expressing functional CEA-Rs to study activation and signaling mechanisms of CEA that facilitate tumor cell attachment to activated endothelial cells. Utilization of this in vitro system may lead to a more complete understanding of the expression and function of CEA-R and facilitate the design of anti-CEA

  11. Standard duplex criteria overestimate the degree of stenosis after eversion carotid endarterectomy.

    PubMed

    Benzing, Travis; Wilhoit, Cameron; Wright, Sharee; McCann, P Aaron; Lessner, Susan; Brothers, Thomas E

    2015-06-01

    The eversion technique for carotid endarterectomy (eCEA) offers an alternative to longitudinal arteriotomy and patch closure (pCEA) for open carotid revascularization. In some reports, eCEA has been associated with a higher rate of >50% restenosis of the internal carotid when it is defined as peak systolic velocity (PSV) >125 cm/s by duplex imaging. Because the conformation of the carotid bifurcation may differ after eCEA compared with native carotid arteries, it was hypothesized that standard duplex criteria might not accurately reflect the presence of restenosis after eCEA. In a case-control study, the outcomes of all patients undergoing carotid endarterectomy by one surgeon during the last 10 years were analyzed retrospectively, with a primary end point of PSV >125 cm/s. Duplex flow velocities were compared with luminal diameter measurements for any carotid computed tomography arteriography or magnetic resonance angiography study obtained within 2 months of duplex imaging, with the degree of stenosis calculated by the methodology used in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST) as well as cross-sectional area (CSA) reduction. Simulations were generated and analyzed by computational model simulations of the eCEA and pCEA arteries. Eversion and longitudinal arteriotomy with patch techniques were used in 118 and 177 carotid arteries, respectively. Duplex follow-up was available in 90 eCEA arteries at a median of 16 (range, 2-136) months and in 150 pCEA arteries at a median of 41 (range, 3-115) months postoperatively. PSV >125 cm/s was present at some time during follow-up in 31% of eCEA and pCEA carotid arteries, each, and in the most recent duplex examination in 7% after eCEA and 21% after pCEA (P = .003), with no eCEA and two pCEA arteries occluding completely during follow-up (P = .29). In 19 carotid arteries with PSV >125 cm/s after angle correction (median, 160 cm/s; interquartile range

  12. [A study of growth and malignancy grading of stomach and colorectal cancers by serial serum carcinoembryonic antigen levels analysis].

    PubMed

    Umehara, Y; Miyahara, T; Yoshida, M; Isobe, S; Oba, N; Harada, Y

    1990-06-01

    Changes in serum CEA levels were analyzed on a time-course basis in 33 patients with stomach cancer and 20 patients with colorectal cancer. A linear relationship between log CEA and time could be evaluated and individual CEA doubling time (CEA D.T.) was calculated. The results obtained are as follows. 1) The CEA D.T. was not constant from the onset of the disease to death in stomach cancer and colorectal cancer. 2) The CEA D.T. was distributed widely with 5 to 140 days in stomach cancer and 8 to 134 days in colorectal cancer. It tended to be shortened at the terminal stage in both tumors. 3) In terms of age, sex and histology, the CEA D.T. tended to be short in the young, female and poorly differentiated cancer. These background appeared to have an influence on the growth of tumor. 4) The CEA D.T. was well correlated with the period of survival of the patients with gastric cancer (r = 0.636, p less than 0.001). The analysis of serial CEA levels on a time-course basis is considered useful in studying the relationship between tumor-bearing hosts and malignancy of the tumor.

  13. The U.S. Forest Service's analysis of cumulative effects to wildlife: A study of legal standards, current practice, and ongoing challenges on a National Forest

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

    Schultz, Courtney A., E-mail: courtney.schultz@colostate.edu

    Cumulative effects analysis (CEA) allows natural resource managers to understand the status of resources in historical context, learn from past management actions, and adapt future activities accordingly. U.S. federal agencies are required to complete CEA as part of environmental impact assessment under the National Environmental Policy Act (NEPA). Past research on CEA as part of NEPA has identified significant deficiencies in CEA practice, suggested methodologies for handling difficult aspects of CEA, and analyzed the rise in litigation over CEA in U.S. courts. This article provides a review of the literature and legal standards related to CEA as it is donemore » under NEPA and then examines current practice on a U.S. National Forest, utilizing qualitative methods in order to provide a detailed understanding of current approaches to CEA. Research objectives were to understand current practice, investigate ongoing challenges, and identify impediments to improvement. Methods included a systematic review of a set of NEPA documents and semi-structured interviews with practitioners, scientists, and members of the public. Findings indicate that the primary challenges associated with CEA include: issues of both geographic and temporal scale of analysis, confusion over the purpose of the requirement, the lack of monitoring data, and problems coordinating and disseminating data. Improved monitoring strategies and programmatic analyses could support improved CEA practice.« less

  14. Regulation of gene expression in plasmid ColE1: delayed expression of the kil gene.

    PubMed Central

    Zhang, S P; Yan, L F; Zubay, G

    1988-01-01

    cea, imm, and kil are a cluster of three functionally related genes of the plasmid ColE1. The cea and kil genes are in the same inducible operon, with transcription being initiated from a promoter adjacent to the cea gene. The imm gene is located between the cea and kil genes, but it is transcribed in the opposite direction. Complementary interaction between the imm mRNA and the anti-imm sequences in the middle of the cea-kil transcript causes a pronounced delay in expression of the kil gene when the cea-kil operon is induced. A segment in the overlapping region between the cea and imm genes causes delayed expression of the kil gene in the absence of imm gene transcription. This delay effect increases the yields of colicin synthesized in induced cells. Images PMID:3142845

  15. The carcinoembryonic antigen IgV-like N domain plays a critical role in the implantation of metastatic tumor cells.

    PubMed

    Abdul-Wahid, Aws; Huang, Eric H-B; Cydzik, Marzena; Bolewska-Pedyczak, Eleonora; Gariépy, Jean

    2014-03-01

    The human carcinoembryonic antigen (CEA) is a cell adhesion molecule involved in both homotypic and heterotypic interactions. The aberrant overexpression of CEA on adenocarcinoma cells correlates with their increased metastatic potential. Yet, the mechanism(s) by which its adhesive properties can lead to the implantation of circulating tumor cells and expansion of metastatic foci remains to be established. In this study, we demonstrate that the IgV-like N terminal domain of CEA directly participates in the implantation of cancer cells through its homotypic and heterotypic binding properties. Specifically, we determined that the recombinant N terminal domain of CEA directly binds to fibronectin (Fn) with a dissociation constant in the nanomolar range (K(D) 16 ± 3 nM) and interacts with itself (K(D) 100 ± 17 nM) and more tightly to the IgC-like A(3) domain (K(D) 18 ± 3 nM). Disruption of these molecular associations through the addition of antibodies specific to the CEA N or A(3)B(3) domains, or by adding soluble recombinant forms of the CEA N, A(3) or A(3)B(3) domains or a peptide corresponding to residues 108-115 of CEA resulted in the inhibition of CEA-mediated intercellular aggregation and adherence events in vitro. Finally, pretreating CEA-expressing murine colonic carcinoma cells (MC38.CEA) with rCEA N, A3 or A(3)B(3) modules blocked their implantation and the establishment of tumor foci in vivo. Together, these results suggest a new mechanistic insight into how the CEA IgV-like N domain participates in cellular events that can have a macroscopic impact in terms of cancer progression and metastasis. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  16. Stenting versus endarterectomy for restenosis following prior ipsilateral carotid endarterectomy: an individual patient data meta-analysis.

    PubMed

    Fokkema, Margriet; Vrijenhoek, Joyce E P; Den Ruijter, Hester M; Groenwold, Rolf H H; Schermerhorn, Marc L; Bots, Michiel L; Pasterkamp, Gerard; Moll, Frans L; De Borst, Gert Jan

    2015-03-01

    To study perioperative results and restenosis during follow-up of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) for restenosis after prior ipsilateral CEA in an individual patient data (IPD) meta-analysis. The optimal treatment strategy for patients with restenosis after CEA remains unknown. A comprehensive search of electronic databases (Medline, Embase) until July 1, 2013, was performed, supplemented by a review of references. Studies were considered for inclusion if they reported procedural outcome of CAS or CEA after prior ipsilateral CEA of a minimum of 5 patients. IPD were combined into 1 data set and an IPD meta-analysis was performed. The primary endpoint was perioperative stroke or death and the secondary endpoint was restenosis greater than 50% during follow-up, comparing CAS and CEA. In total, 13 studies were included, contributing to 1132 unique patients treated by CAS (10 studies, n = 653) or CEA (7 studies; n = 479). Among CAS and CEA patients, 30% versus 40% were symptomatic, respectively (P < 0.01). After adjusting for potential confounders, the primary endpoint did not differ between CAS and CEA groups (2.3% vs 2.7%, adjusted odds ratio 0.8, 95% confidence interval (CI): 0.4-1.8). Also, the risk of restenosis during a median follow-up of 13 months was similar for both groups (hazard ratio 1.4, 95% (CI): 0.9-2.2). Cranial nerve injury (CNI) was 5.5% in the CEA group, while CAS was in 5% associated with other procedural related complications. In patients with restenosis after CEA, CAS and CEA showed similar low rates of stroke, death, and restenosis at short-term follow-up. Still, the risk of CNI and other procedure-related complications should be taken into account.

  17. Linkages between childhood emotional abuse and marital satisfaction: The mediating role of empathic accuracy for hostile emotions

    PubMed Central

    Maneta, E.K.; Cohen, S.; Schulz, M.S.; Waldinger, R.J.

    2014-01-01

    Research linking childhood emotional abuse (CEA) and adult marital satisfaction has focused on individuals without sufficient attention to couple processes. Less attention has also been paid to the effects of CEA on the ability to read other’s emotions, and how this may be related to satisfaction in intimate relationships. In this study, 156 couples reported on histories of CEA, marital satisfaction and empathic accuracy of their partners’ positive and hostile emotions during discussion of conflicts in their relationships. Actor-Partner Interdependence Modeling was used to examine links between CEA and marital satisfaction, with empathic accuracy as a potential mediator. Both men’s and women’s CEA histories were linked not only with their own lower marital satisfaction but also with their partners’ lower satisfaction. Empathic accuracy for hostile emotions mediated the link between women’s CEA and their satisfaction and their partners’ satisfaction in the relationship. Findings suggest that a history of CEA is associated with difficulties with empathic accuracy, and that empathic inaccuracy in part mediates the association between CEA and adult marital dissatisfaction. PMID:25151303

  18. Linkages between childhood emotional abuse and marital satisfaction: The mediating role of empathic accuracy for hostile emotions.

    PubMed

    Maneta, E K; Cohen, S; Schulz, M S; Waldinger, R J

    2015-06-01

    Research linking childhood emotional abuse (CEA) and adult marital satisfaction has focused on individuals without sufficient attention to couple processes. Less attention has also been paid to the effects of CEA on the ability to read other's emotions, and how this may be related to satisfaction in intimate relationships. In this study, 156 couples reported on histories of CEA, marital satisfaction and empathic accuracy of their partners' positive and hostile emotions during discussion of conflicts in their relationships. Actor-Partner Interdependence Modeling was used to examine links between CEA and marital satisfaction, with empathic accuracy as a potential mediator. Both men's and women's CEA histories were linked not only with their own lower marital satisfaction but also with their partners' lower satisfaction. Empathic accuracy for hostile emotions mediated the link between women's CEA and their satisfaction and their partners' satisfaction in the relationship. Findings suggest that a history of CEA is associated with difficulties with empathic accuracy, and that empathic inaccuracy in part mediates the association between CEA and adult marital dissatisfaction. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Polyaniline modified flexible conducting paper for cancer detection

    NASA Astrophysics Data System (ADS)

    Kumar, Saurabh; Sen, Anindita; Kumar, Suveen; Augustine, Shine; Yadav, Birendra K.; Mishra, Sandeep; Malhotra, Bansi D.

    2016-05-01

    We report results of studies relating to the fabrication of a flexible, disposable, and label free biosensing platform for detection of the cancer biomarker (carcinoembryonic antigen, CEA). Polyaniline (PANI) has been electrochemically deposited over gold sputtered paper (Au@paper) for covalent immobilization of monoclonal carcinoembryonic antibodies (anti-CEA). The bovine serum albumin (BSA) has been used for blocking nonspecific binding sites at the anti-CEA conjugated PANI/Au@Paper. The PANI/Au@Paper, anti-CEA/PANI/Au@Paper, and BSA/anti-CEA/PANI/Au@Paper platforms have been characterized using scanning electron microscopy, X-ray diffraction, Fourier transmission infrared spectroscopy, chronoamperometry, and electrochemical impedance techniques. The results of the electrochemical response studies indicate that this BSA/anti-CEA/PANI/Au@paper electrode has sensitivity of 13.9 μA ng-1 ml cm2, shelf life of 22 days, and can be used to estimate CEA in the range of 2-20 ng ml-1. This paper sensor has been validated by detection of CEA in serum samples of cancer patients via immunoassay technique.

  20. Hidden Costs: the ethics of cost-effectiveness analyses for health interventions in resource-limited settings

    PubMed Central

    Rutstein, Sarah E.; Price, Joan T.; Rosenberg, Nora E.; Rennie, Stuart M.; Biddle, Andrea K.; Miller, William C.

    2017-01-01

    Cost-effectiveness analysis (CEA) is an increasingly appealing tool for evaluating and comparing health-related interventions in resource-limited settings. The goal is to inform decision-makers regarding the health benefits and associated costs of alternative interventions, helping guide allocation of limited resources by prioritizing interventions that offer the most health for the least money. Although only one component of a more complex decision-making process, CEAs influence the distribution of healthcare resources, directly influencing morbidity and mortality for the world’s most vulnerable populations. However, CEA-associated measures are frequently setting-specific valuations, and CEA outcomes may violate ethical principles of equity and distributive justice. We examine the assumptions and analytical tools used in CEAs that may conflict with societal values. We then evaluate contextual features unique to resource-limited settings, including the source of health-state utilities and disability weights; implications of CEA thresholds in light of economic uncertainty; and the role of external donors. Finally, we explore opportunities to help align interpretation of CEA outcomes with values and budgetary constraints in resource-limited settings. The ethical implications of CEAs in resource-limited settings are vast. It is imperative that CEA outcome summary measures and implementation thresholds adequately reflect societal values and ethical priorities in resource-limited settings. PMID:27141969

  1. Hidden costs: The ethics of cost-effectiveness analyses for health interventions in resource-limited settings.

    PubMed

    Rutstein, Sarah E; Price, Joan T; Rosenberg, Nora E; Rennie, Stuart M; Biddle, Andrea K; Miller, William C

    2017-10-01

    Cost-effectiveness analysis (CEA) is an increasingly appealing tool for evaluating and comparing health-related interventions in resource-limited settings. The goal is to inform decision-makers regarding the health benefits and associated costs of alternative interventions, helping guide allocation of limited resources by prioritising interventions that offer the most health for the least money. Although only one component of a more complex decision-making process, CEAs influence the distribution of health-care resources, directly influencing morbidity and mortality for the world's most vulnerable populations. However, CEA-associated measures are frequently setting-specific valuations, and CEA outcomes may violate ethical principles of equity and distributive justice. We examine the assumptions and analytical tools used in CEAs that may conflict with societal values. We then evaluate contextual features unique to resource-limited settings, including the source of health-state utilities and disability weights, implications of CEA thresholds in light of economic uncertainty, and the role of external donors. Finally, we explore opportunities to help align interpretation of CEA outcomes with values and budgetary constraints in resource-limited settings. The ethical implications of CEAs in resource-limited settings are vast. It is imperative that CEA outcome summary measures and implementation thresholds adequately reflect societal values and ethical priorities in resource-limited settings.

  2. Parvalbumin Interneurons of Central Amygdala Regulate the Negative Affective States and the Expression of Corticotrophin-Releasing Hormone During Morphine Withdrawal

    PubMed Central

    Wang, Li; Shen, Minjie; Jiang, Changyou

    2016-01-01

    Background: The central nucleus of the amygdala (CeA) is a crucial component of the neuronal circuitry mediating aversive emotion. Its role in the negative affective states during drug withdrawal includes changes in opioidergic, GABAergic, and corticotropin-releasing factor neurotransmission. However, the modulation of the neurobiological interconnectivity in the CeA and its effects in the negative reinforcement of drug dependents are poorly understood. Method: We performed electrophysiological recordings to assess the membrane excitability of parvalbumin (PV)+ interneurons in the CeA during chronic morphine withdrawal. We tested the morphine withdrawal–induced negative affective states, such as the aversive (assessed by conditioned place aversion), anxiety (assessed by elevated plus maze), and anhedonic-like (assessed by saccharin preference test) behaviors, as well as the mRNA level of corticotropin-releasing hormone (CRH) via optogenetic inhibition or activation of PV+ interneurons in the CeA. Result: Chronic morphine withdrawal increased the firing rate of CeA PV+ interneurons. Optogenetic inhibition of the activity of CeA PV+ interneurons attenuated the morphine withdrawal–induced negative affective states, such as the aversive, anxiety, and anhedonic-like behaviors, while direct activation of CeA PV+ interneurons could trigger those negative affective-like behaviors. Optogenetic inhibition of the CeA PV+ interneurons during the morphine withdrawal significantly attenuated the elevated CRH mRNA level in the CeA. Conclusion: The activity of PV+ interneurons in the CeA was up-regulated during chronic morphine withdrawal. The activation of PV+ interneurons during morphine withdrawal was crucial for the induction of the negative emotion and the up-regulation of CRH mRNA levels in the CeA. PMID:27385383

  3. Monolithic Active Pixel Sensors

    NASA Astrophysics Data System (ADS)

    Lutz, P.

    In close collaboration with the group from Strasbourg, Saclay has been developing fast monolithic active pixel sensors for future vertex detectors. This presentation gives some recent results from the MIMOSA serie, emphazising the participation of the group.

  4. CeasIng Cpap At standarD criteriA (CICADA): impact on weight gain, time to full feeds and caffeine use.

    PubMed

    Broom, Margaret; Ying, Lei; Wright, Audrey; Stewart, Alice; Abdel-Latif, Mohamed E; Shadbolt, Bruce; Todd, David A

    2014-09-01

    In our previous randomised controlled trial (RCT), we have shown in preterm babies (PBs) <30 weeks gestation that CeasIng Cpap At standarD criteriA (CICADA (method 1)) compared with cycling off continuous positive airway pressure (CPAP) gradually (method 2) or cycling off CPAP gradually with low flow air/oxygen during periods off CPAP (method 3) reduces CPAP cessation time in PBs <30 weeks gestation. This retrospective study reviewed weight gain, time to reach full feeds and time to cease caffeine in PBs previously enrolled in the RCT. Data were collected from 162 of the 177 PBs, and there was no significant difference in the projected weight gain between the three methods. Based on intention to treat, the time taken to reach full feeds for all three methods showed no significant difference. However, post hoc analysis showed the CICADA method compared with cycling off gradually just failed significance (30.3±1.6 vs 31.1±2.4 (weeks corrected gestational age (Wks CGA±SD)), p=0.077). Analysis of time to cease caffeine showed there was a significant difference between the methods with PBs randomised to the CICADA method compared with the cycling off method ceasing caffeine almost a week earlier (33.6±2.4 vs 34.5±2.8 (Wks CGA±SD), p=0.02). This retrospective study provides evidence to substantiate the optimum method of ceasing CPAP; the CICADA method, does not adversely affect weight gain, time to reach full feeds and may reduce time to cease caffeine in PBs <30 weeks gestation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Polyaniline modified flexible conducting paper for cancer detection

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

    Kumar, Saurabh; Sen, Anindita; Kumar, Suveen

    We report results of studies relating to the fabrication of a flexible, disposable, and label free biosensing platform for detection of the cancer biomarker (carcinoembryonic antigen, CEA). Polyaniline (PANI) has been electrochemically deposited over gold sputtered paper (Au@paper) for covalent immobilization of monoclonal carcinoembryonic antibodies (anti-CEA). The bovine serum albumin (BSA) has been used for blocking nonspecific binding sites at the anti-CEA conjugated PANI/Au@Paper. The PANI/Au@Paper, anti-CEA/PANI/Au@Paper, and BSA/anti-CEA/PANI/Au@Paper platforms have been characterized using scanning electron microscopy, X-ray diffraction, Fourier transmission infrared spectroscopy, chronoamperometry, and electrochemical impedance techniques. The results of the electrochemical response studies indicate that this BSA/anti-CEA/PANI/Au@paper electrodemore » has sensitivity of 13.9 μA ng{sup −1} ml cm{sup 2}, shelf life of 22 days, and can be used to estimate CEA in the range of 2–20 ng ml{sup −1}. This paper sensor has been validated by detection of CEA in serum samples of cancer patients via immunoassay technique.« less

  6. Age-dependent effects of carotid endarterectomy or stenting on cognitive performance.

    PubMed

    Wasser, Katrin; Hildebrandt, Helmut; Gröschel, Sonja; Stojanovic, Tomislav; Schmidt, Holger; Gröschel, Klaus; Pilgram-Pastor, Sara M; Knauth, Michael; Kastrup, Andreas

    2012-11-01

    Although evidence is accumulating that age modifies the risk of carotid angioplasty and stenting (CAS) versus endarterectomy (CEA) for patients with significant carotid stenosis, the impact of age on cognition after either CEA or CAS remains unclear. In this study, we analyzed the effects of age on cognitive performance after either CEA or CAS using a comprehensive neuropsychological test battery with parallel test forms and a control group to exclude a learning effect. The neuropsychological outcomes after revascularization were determined in 19 CAS and 27 CEA patients with severe carotid stenosis. The patients were subdivided according to their median age (<68 years and ≥68 years); 27 healthy subjects served as a control group. In all patients clinical examinations, MRI scans and a neuropsychological test battery that assessed four major cognitive domains were performed immediately before, within 72 h, and 3 months after CEA or CAS. While patients <68 years of age showed no significant cognitive alteration after either CEA or CAS, a significant cognitive decline was observed in patients ≥68 years in both treatment groups (p = 0.001). Notably, this cognitive deterioration persisted in patients after CEA, whereas it was only transient in patients treated with CAS. These results demonstrate an age-dependent effect of CEA and CAS on cognitive functions. In contrast to the recently observed increased clinical complication rates in older subjects after CAS compared with CEA, CEA appears to be associated with a greater, persistent decline in cognitive performance than CAS in this subgroup of patients.

  7. Increased mortality associated with elevated carcinoembryonic antigen in insurance applicants.

    PubMed

    Stout, Robert L; Fulks, Michael; Dolan, Vera F; Magee, Mark E; Suarez, Luis

    2007-01-01

    Determine the relationship between the carcinoembryonic antigen (CEA) value and all-cause mortality in life insurance applicants aged 50 years and over. By use of the Social Security Master Death Index, mortality was examined in 115,590 insurance applicants aged 50 and up for whom blood samples for CEA were submitted to the Clinical Reference Laboratory. Results were stratified by CEA value (<5 ng/mL, 5 to 9.9 ng/mL, 10+ ng/mL), smoking status, and age groups (50-59 years, 60-69 years, and 70 years and up). Relative mortality is increased at CEA values between 5 and 9.9 ng/mL and further increased at 10+ ng/mL for all age groups, with the most dramatic increase at the youngest ages. Excess mortality appears to last at least 3 to 4 years after the elevated result. Five-year all-cause mortality in applicants with CEA values of 10+ ng/mL is 25.2% with a mortality ratio relative to those with a CEA <5 ng/mL of 1156%. This study shows that CEA can detect the risk of early excess mortality in life insurance applicants; CEA levels of 5 ng/mL and over may be of concern. CEA testing beginning at age 50 years for life insurance applicants could capture 4.6% of early mortality if the threshold for further evaluation was set at 10 ng/mL. Only 0.4% of all applicants aged 50 and over have CEA values at or above this threshold.

  8. The Central Nucleus of the Amygdala and Corticotropin-Releasing Factor: Insights into Contextual Fear Memory

    PubMed Central

    Pitts, Matthew W.; Todorovic, Cedomir; Blank, Thomas; Takahashi, Lorey K.

    2009-01-01

    The central nucleus of the amygdala (CeA) has been traditionally viewed in fear conditioning to serve as an output neural center that transfers conditioned information formed in the basolateral amygdala to brain structures that generate emotional responses. Recent studies suggest that the CeA may also be involved in fear memory consolidation. In addition, corticotropin-releasing factor systems were shown to facilitate memory consolidation in the amygdala, which contains a high density of CRF immunoreactive cell bodies and fibers in the lateral part of the CeA (CeAl). However, the involvement of CeA CRF in contextual fear conditioning remains poorly understood. Therefore, we first conducted a series of studies using fiber-sparing lesion and reversible inactivation methods to assess the general role of the CeA in contextual fear. We then used identical training and testing procedures to compare and evaluate the specific function of CeA CRF using CRF antisense oligonucleotides (CRF ASO). Rats microinjected with ibotenic acid, muscimol, or a CRF ASO into the CeA prior to contextual fear conditioning showed typical levels of freezing during acquisition training but exhibited significant reductions in contextual freezing in a retention test 48 h later. Furthermore, CeA inactivation induced by either muscimol or CRF ASO administration immediately prior to retention testing did not impair freezing, suggesting that the previously observed retention deficits were due to inhibition of consolidation rather than fear expression. Collectively, our results suggest CeA involvement in the consolidation of contextual fear memory and specifically implicate CeA CRF as an important mediator. PMID:19494159

  9. Degranulation and shrinkage of dark cells in eccrine glands and elevated serum carcinoembryonic antigen in patients with acquired idiopathic generalized anhidrosis.

    PubMed

    Sano, K; Asahina, M; Uehara, T; Matsumoto, K; Araki, N; Okuyama, R

    2017-12-01

    Acquired idiopathic generalized anhidrosis (AIGA) is characterized by anhidrosis/hypohidrosis without other autonomic and neurological dysfunctions. Pathologically, AIGA is considered to usually present no significant morphological alterations in eccrine glands, the secretory portion which consists of clear cells, dark cells, and myoepithelial cells. AIGA patients recently have been reported to show high serum concentrations of carcinoembryonic antigen (CEA). Our aim is to reveal morphological abnormalities of dark cells and investigate their relationship with serum CEA. We performed comparative analysis of eccrine glands between sweat-preserved and non-sweating skin in four AIGA patients. Serum CEA concentrations in 22 cases with AIGA were measured with healthy volunteers. Furthermore, we semiquantitatively investigated dermcidin, FoxA1 and CEA expression in eccrine glands of 12 cases with AIGA and 5 cases with non-AIGA. Marked degranulation and shrinkage of dark cells consistently occurred in AIGA. Furthermore, high serum CEA concentrations were found in 14 of 22 AIGA patients (over 60%), but serum CEA levels were not correlated with CEA expression in eccrine glands. Dermcidin expression in dark cells apparently decreased in AIGA patients, severely in those with high serum CEA and moderately in those with low serum CEA, while well-preserved expression was found in non-AIGA subjects. Our study suggests morphological damage and molecular dysregulation of dark cells, leading to impairment of their functions in AIGA patients. Severely damaged dark cells correspond to high serum CEA. Accordingly, these pathological changes in eccrine dark cells may be involved in anhidrosis/hypohidrosis of AIGA. © 2017 European Academy of Dermatology and Venereology.

  10. Cost-effectiveness Analysis Appraisal and Application: An Emergency Medicine Perspective.

    PubMed

    April, Michael D; Murray, Brian P

    2017-06-01

    Cost-effectiveness is an important goal for emergency care delivery. The many diagnostic, treatment, and disposition decisions made in the emergency department (ED) have a significant impact upon healthcare resource utilization. Cost-effectiveness analysis (CEA) is an analytic tool to optimize these resource allocation decisions through the systematic comparison of costs and effects of alternative healthcare decisions. Yet few emergency medicine leaders and policymakers have any formal training in CEA methodology. This paper provides an introduction to the interpretation and use of CEA with a focus on application to emergency medicine problems and settings. It applies a previously published CEA to the hypothetical case of a patient presenting to the ED with chest pain who requires risk stratification. This paper uses a widely cited checklist to appraise the CEA. This checklist serves as a vehicle for presenting basic CEA terminology and concepts. General topics of focus include measurement of costs and outcomes, incremental analysis, and sensitivity analysis. Integrated throughout the paper are recommendations for good CEA practice with emphasis on the guidelines published by the U.S. Panel on Cost-Effectiveness in Health and Medicine. Unique challenges for emergency medicine CEAs discussed include the projection of long-term outcomes from emergent interventions, costing ED services, and applying study results to diverse patient populations across various ED settings. The discussion also includes an overview of the limitations inherent in applying CEA results to clinical practice to include the lack of incorporation of noncost considerations in CEA (e.g., ethics). After reading this article, emergency medicine leaders and researchers will have an enhanced understanding of the basics of CEA critical appraisal and application. The paper concludes with an overview of economic evaluation resources for readers interested in conducting ED-based economic evaluation

  11. The use of cultured epithelial autograft in the treatment of major burn injuries: a critical review of the literature.

    PubMed

    Wood, F M; Kolybaba, M L; Allen, P

    2006-06-01

    The need to achieve rapid wound closure in patients with massive burns and limited skin donor sites led to the investigation of in vitro cellular expansion of keratinocytes. The use of cultured epithelial autografts (CEA) was first reported in the treatment of major burns in 1981. Since that time, support for the use of CEA has varied, ranging from 'a useful agent' to having 'no demonstrable effect on the outcome of extensively burned patients'. This critical review of the literature examines issues associated with the use of CEA and the introduction of the technology into clinical practice. The factors potentially limiting the use of cultured CEA are the time necessary to culture CEA sheets, the reliability of 'take', vulnerability of grafts on the newly healed surface, long-term durability and the cost implications of such treatment. The available literature was located and critically evaluated using the Australian National Health and Medical Research Council Guidelines. In the identified literature, the level of evidence to support the use of CEA in major burn injures is limited and often restricted to case studies and case series with no Level 1 evidence currently available. The main question arising 'Does CEA have a role in the treatment of major burns?' has proven difficult to answer due to the wide variation in both the quality of study design and the findings. At best, the literature review has highlighted areas of concern that have hindered the successful use of CEA. Our review critically evaluates the use of CEA and explores the advances in techniques towards attempting to improve reliable clinical implementation of CEA. The need for higher level research into the use of CEA is emphasised by this review.

  12. Processing of carcinoembryonic antigen by Kupffer cells: recognition of a penta-peptide sequence.

    PubMed

    Gangopadhyay, A; Thomas, P

    1996-10-01

    Carcinoembryonic antigen (CEA) binds to an 80-kDa cell surface receptor on Kupffer cells via the peptide sequence PELPK (residues 108-112) located at the hinge region between the N and Al immunoglobulin-like domains. This study is aimed at analyzing the specificity of the peptide binding, determining biodistribution of 80-kDa receptor, and processing of CEA by this receptor. We synthesized a number of bovine serum albumin (BSA) derivatives carrying PELPK and related sequences. A series of peptides (YPELPK, YPDLPK, YPDLPR, and YPELGK) were conjugated to bovine serum albumin using N-hydroxysuccinimidyl-4-azidobenzoate. When 125I peptide conjugates, CEA, and BSA were injected intravenously into rats CEA and the PELPK-albumin conjugate were cleared rapidly. The other peptide conjugates and BSA cleared at a much slower rate. Activity of 125I-labeled CEA and PELPK-albumin conjugate per gram of tissue was highest for the liver and spleen. Clearance of 125I-CEA was inhibited by the presence of higher concentrations of the PELPK-albumin conjugate. With isolated rat Kupffer cells, only CEA and the PELPK-albumin conjugate were bound and internalized in vitro and CEA binding was inhibited by higher concentrations of the PELPK-albumin conjugate. Similarly, binding of the PELPK-albumin conjugate was inhibited by the presence of unlabeled CEA. Use of a heterobifunctional cross linking agent demonstrated reaction of the PELPK-albumin with an 80-kDa protein on the Kupffer cell surface by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). This semisynthetic ligand (PELPK-albumin) allows us to examine the function of the 80-kDa receptor without interference due to other properties of CEA including its ability to bind lectins and to cause homotypic aggregation of cells. The consequences of CEA binding to the 80-kDa receptor may have implications in the development of hepatic metastasis from colorectal cancer.

  13. Ethanol produces corticotropin releasing factor receptor-dependent enhancement of spontaneous glutamatergic transmission in the mouse central amygdala

    PubMed Central

    Silberman, Yuval; Fetterly, Tracy L.; Awad, Elias K.; Milano, Elana J.; Usdin, Ted B.; Winder, Danny G.

    2015-01-01

    Background Ethanol modulation of Central Amygdala (CeA) neurocircuitry plays a key role in the development of alcoholism via activation of the corticotropin releasing factor (CRF) receptor system. Previous work has predominantly focused on ethanol/CRF interactions on the CeA GABA circuitry; however our lab recently showed that CRF enhances CeA glutamatergic transmission. Therefore, this study sought to determine if ethanol modulates CeA glutamate transmission via activation of CRF signaling. Methods The effects of ethanol on spontaneous excitatory postsynaptic currents (sEPSCs) and basal resting membrane potentials were examined via standard electrophysiology methods in adult male C57BL/6J mice. Local ablation of CeA CRF neurons (CRFCeAhDTR) was achieved by targeting the human diphtheria toxin receptor (hDTR) to CeA CRF neurons with an adeno-associated virus. Ablation was quantified post-hoc with confocal microscopy. Genetic targeting of the diphtheria toxin active subunit to CRF neurons (CRFDTA mice) ablated CRF neurons throughout the CNS, as assessed by qRT-PCR quantification of CRF mRNA. Results Acute bath application of ethanol significantly increased sEPSC frequency in a concentration dependent manner in CeA neurons, and this effect was blocked by pretreatment of co-applied CRF receptor 1 and CRF receptor 2 antagonists. In experiments utilizing a CRF-tomato reporter mouse, ethanol did not significantly alter the basal membrane potential of CeA CRF neurons. The ability of ethanol to enhance CeA sEPSC frequency was not altered in CRFCeAhDTR mice despite a ~78% reduction in CeA CRF cell counts. The ability of ethanol to enhance CeA sEPSC frequency was also not altered in the CRFDTA mice despite a three-fold reduction in CRF mRNA levels. Conclusion These findings demonstrate that ethanol enhances spontaneous glutamatergic transmission in the CeA via a CRF receptor dependent mechanism. Surprisingly, our data suggest that this action may not require endogenous CRF

  14. A systematic review on the quality, validity and usefulness of current cost-effectiveness studies for treatments of neovascular age-related macular degeneration.

    PubMed

    Elshout, Mari; Webers, Carroll A B; van der Reis, Margriet I; Schouten, Jan S A G

    2018-06-04

    Ophthalmologists increasingly depend on new drugs to advance their treatment options. These options are limited by restraints on reimbursements for new and expensive drugs. These restraints are put in place through health policy decisions based on cost-effectiveness analyses (CEA). Cost-effectiveness analyses need to be valid and of good quality to support correct decisions to create new treatment opportunities. In this study, we report the quality, validity and usefulness of CEAs for therapies for nAMD. A systematic review in PubMed, EMBASE and Cochrane was performed to include CEAs. Quality and validity assessment was based on current general quality criteria and on elements that are specific to the field of ophthalmology. Forty-eight CEAs were included in the review. Forty-four CEAs did not meet four basic model quality and validity criteria specific to CEAs in the field of ophthalmology (both eyes analysed instead of one; a time horizon extending beyond 4 years; extrapolating VA and treatment intervals beyond trial data realistically; and including the costs of low-vision). Four CEAs aligned with the quality and validity criteria. In two of these CEAs bevacizumab as-needed (PRN) was more cost-effective than bevacizumab monthly; aflibercept (VIEW); or ranibizumab monthly or PRN. In two CEAs, ranibizumab (PRN or treat and extent) was dominant over aflibercept. In two other CEAs, aflibercept was either more cost-effective or dominant over ranibizumab monthly or PRN. Two of the CEAs of sufficient quality and validity show that bevacizumab PRN is the most cost-effective treatment. Comparing ranibizumab and aflibercept, either treatment can be more cost-effective depending on the assumptions used for drug prices and treatment frequencies. The majority of the published CEAs are of insufficient quality and validity. They wrongly inform decision-makers at the cost of opportunities for ophthalmologists to treat patients. As such, they may negatively influence overall

  15. Contralateral occlusion is not a clinically important reason for choosing carotid artery stenting for patients with significant carotid artery stenosis.

    PubMed

    Brewster, Luke P; Beaulieu, Robert; Kasirajan, Karthik; Corriere, Matthew A; Ricotta, Joseph J; Patel, Siddharth; Dodson, Thomas F

    2012-11-01

    Contralateral carotid artery occlusion by itself carries an increased risk of stroke. Carotid endarterectomy (CEA) in the presence of contralateral carotid artery occlusion has high reported rates of perioperative morbidity and mortality. Our objective was to determine if there is a clinical benefit to patients who receive carotid artery stenting (CAS) compared to CEA in the presence of contralateral carotid artery occlusion. We conducted a retrospective medical chart review over a 4.5-year institutional experience of persons with contralateral carotid artery occlusion and ipsilateral carotid artery stenosis who underwent CAS or CEA. The main outcome measures were 30-day cardiac, stroke, and mortality rate, and midterm mortality. Of a total of 713 patients treated for carotid artery stenosis during this time period, 57 had contralateral occlusion (~8%). Thirty-nine of these patients were treated with CAS, and 18 with CEA. The most common indications for CAS were prior neck surgery (18), contralateral internal carotid occlusion (nine), and prior neck radiation (seven). The average age was 70 ± 8.5 for CEA and 66.7 ± 9.3 for CAS (P = .20). Both groups were predominantly men (CEA 12 of 18; CAS 28 of 39; P = .76), with similar prevalence of symptomatic lesions (CEA 8 of 18, CAS 20 of 39; P = .77). Two patients died within 30 days in the CAS group (5%). No deaths occurred within 30 days in the CEA group (P = .50); the mortality rate for CAS and CEA combined was 3.5%. No perioperative strokes or myocardial infarction occurred in either group. Two transient ischemic attacks occurred after CAS. At mean follow-up of 29.4 ± 16 months (CEA) and 28 ± 14.4 months (CAS; range, 1.5-48.5 months), seven deaths occurred in the CAS group and one in the CEA group (17.9% vs 5.5%; P = .40). There were two reinterventions in the CAS group for in-stent restenosis and there were no reoperations in the CEA group. Although CEA and CAS can both be performed with good perioperative results

  16. Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine

    PubMed Central

    2017-01-01

    Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting that higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats' motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target. SIGNIFICANCE STATEMENT In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing central

  17. CEA blood test

    MedlinePlus

    Carcinoembryonic antigen blood test ... A blood sample is needed . ... When the needle is inserted to draw blood, some people feel moderate pain. Others feel only a prick or stinging. Afterward, there may be some throbbing or a slight bruise. This ...

  18. Application of the cultured epidermal autograft "JACE(®") for treatment of severe burns: Results of a 6-year multicenter surveillance in Japan.

    PubMed

    Matsumura, Hajime; Matsushima, Asako; Ueyama, Masashi; Kumagai, Norio

    2016-06-01

    In the 1970s, Green et al. developed a method that involved culturing keratinocyte sheets and used for treatment of burns. Since then, the take rate of cultured epidermal autograft (CEA) onto fascia, granulation tissue, or allografts has been extensively reported, while that on an artificial dermis in a large case series is not. Moreover, the contribution of CEA to patient survival has not been analyzed in a multicenter study. We conducted a 6-year multicenter surveillance on the application of the CEA "JACE(®") for treatment of burns >30% total body surface area (TBSA) across 118 Japanese hospitals. This surveillance included 216 patients and 718 graft sites for efficacy analysis. The CEA take rate at 4 weeks after grafting was evaluated, and safety was monitored until 52 weeks. In addition, the survival curve obtained in this study and the data obtained from the Tokyo Burn Unit Association (TBUA) were compared. The mean CEA take rates at week 4 were 66% (sites) and 68% (patients), and the rate on the artificial dermis was 65% for 226 sites. CEA application combined with wide split-thickness auto or patch autograft increased the CEA take rate. On comparison with the data obtained from the TBUA, which included data on individuals with burns of the same severity, CEA application was found to contribute to patient survival until 7 weeks after burn. We reported the take rate of CEA based on a 6-year multicenter surveillance. From our results, we found that the application of CEA is a useful treatment for the patients with extensive burns. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  19. AT1 receptor blockade in the central nucleus of the amygdala attenuates the effects of muscimol on sodium and water intake.

    PubMed

    Hu, B; Qiao, H; Sun, B; Jia, R; Fan, Y; Wang, N; Lu, B; Yan, J Q

    2015-10-29

    The blockade of the central nucleus of the amygdala (CeA) with the GABAA receptor agonist muscimol significantly reduces hypertonic NaCl and water intake by sodium-depleted rats. In the present study we investigated the effects of previous injection of losartan, an angiotensin II type-1 (AT1) receptor antagonist, into the CeA on 0.3M NaCl and water intake reduced by muscimol bilaterally injected into the same areas in rats submitted to water deprivation-partial rehydration (WD-PR) and in rats treated with the diuretic furosemide (FURO). Male Sprague-Dawley rats with stainless steel cannulas bilaterally implanted into the CeA were used. Bilateral injections of muscimol (0.2 nmol/0.5 μl, n=8 rats/group) into the CeA in WD-PR-treated rats reduced 0.3M NaCl intake and water intake, and pre-treatment of the CeA with losartan (50 μg/0.5 μl) reversed the inhibitory effect of muscimol. The negative effect of muscimol on sodium and water intake could also be blocked by pretreatment with losartan microinjected into the CeA in rats given FURO (n=8 rats/group). However, bilateral injections of losartan (50 μg/0.5 μl) alone into the CeA did not affect the NaCl or water intake. These results suggest that the deactivation of CeA facilitatory mechanisms by muscimol injection into the CeA is promoted by endogenous angiotensin II acting on AT1 receptors in the CeA, which prevents rats from ingesting large amounts of hypertonic NaCl and water. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. A Prospective Examination of the Relations between Emotional Abuse and Anxiety: Moderation by Distress Tolerance

    PubMed Central

    Banducci, Anne N.; Lejuez, C.W.; Dougherty, Lea R.; MacPherson, Laura

    2016-01-01

    Objective Anxiety, the most common and impairing psychological problem experienced by youth, is associated with numerous individual and environmental factors. Two such factors include childhood emotional abuse (CEA) and low distress tolerance (DT). The current study aimed to understand how CEA and low DT impacted anxiety symptoms measured annually across five years among a community sample of youth. We hypothesized DT would moderate the relationship between CEA and anxiety, such that youth with higher levels of CEA and lower levels of DT would have elevated anxiety over time. Method Community youth (N = 244) were annually assessed across five years using the Revised Child Anxiety and Depression Scale, Childhood Trauma Questionnaire, and Behavioral Indicator of Resiliency to Distress. Results Higher CEA at baseline was associated with higher anxiety at baseline, higher anxiety at each annual assessment, and with greater overall decreases in anxiety over time. Lower DT was associated with higher anxiety at baseline, but did not predict changes in anxiety over time. Baseline DT significantly moderated the relationship between baseline CEA and anxiety, such that youth with both higher CEA and lower DT had the highest anxiety at each annual assessment. Conclusions Youth with lower DT and higher CEA scores had the highest level of anxiety symptoms across time. PMID:27501698

  1. A Prospective Examination of the Relations Between Emotional Abuse and Anxiety: Moderation by Distress Tolerance.

    PubMed

    Banducci, Anne N; Lejuez, C W; Dougherty, Lea R; MacPherson, Laura

    2017-01-01

    Anxiety, the most common and impairing psychological problem experienced by youth, is associated with numerous individual and environmental factors. Two such factors include childhood emotional abuse (CEA) and low distress tolerance (DT). The current study aimed to understand how CEA and low DT impacted anxiety symptoms measured annually across 5 years among a community sample of youth. We hypothesized DT would moderate the relationship between CEA and anxiety, such that youth with higher levels of CEA and lower levels of DT would have elevated anxiety over time. Community youth (N = 244) were annually assessed across 5 years using the Revised Child Anxiety and Depression Scale, Childhood Trauma Questionnaire, and Behavioral Indicator of Resiliency to Distress. Higher CEA at baseline was associated with higher anxiety at baseline, higher anxiety at each annual assessment, and with greater overall decreases in anxiety over time. Lower DT was associated with higher anxiety at baseline, but did not predict changes in anxiety over time. Baseline DT significantly moderated the relationship between baseline CEA and anxiety, such that youth with both higher CEA and lower DT had the highest anxiety at each annual assessment. Youth with lower DT and higher CEA scores had the highest level of anxiety symptoms across time.

  2. Gender Differences in Treatment of Severe Carotid Stenosis After TIA

    PubMed Central

    Poisson, Sharon N.; Johnston, S. Claiborne; Sidney, Stephen; Klingman, Jeffrey G.; Nguyen-Huynh, Mai N.

    2010-01-01

    Background and Purpose Gender differences in carotid endarterectomy (CEA) rates after transient ischemic attack (TIA) are not well studied, though some reports suggest that eligible men are more likely to have CEA than women after stroke. Methods We retrospectively identified all patients diagnosed with TIA and ≥70% carotid stenosis on ultrasound in 2003-2004 from 19 emergency departments. Medical records were abstracted for clinical data, 90-day follow-up events including stroke, cardiovascular events or death, CEA within 6 months, and post-operative 30-day outcomes. We assessed gender as a predictor of CEA and its complications, adjusting for demographic and clinical variables, as well as time to CEA between groups. Results Of 299 patients identified, 47% were women. Women were older with higher presenting SBP and less likely to smoke or to have CAD or diabetes. Fewer women (36.4%) had CEA than men (53.8%) (p=0.004). Reasons for withholding surgical treatment were similar in women and men, and there were no differences in follow-up stroke, CV event, postoperative complications or death. Time to CEA was also significantly delayed in women. Conclusions Women with severe carotid stenosis and recent TIA are less likely to undergo CEA than men, and surgeries are more delayed. PMID:20651270

  3. A peptide sequence on carcinoembryonic antigen binds to a 80kD protein on Kupffer cells.

    PubMed

    Thomas, P; Petrick, A T; Toth, C A; Fox, E S; Elting, J J; Steele, G

    1992-10-30

    Clearance of carcinoembryonic antigen (CEA) from the circulation is by binding to Kupffer cells in the liver. We have shown that CEA binding to Kupffer cells occurs via a peptide sequence YPELPK representing amino acids 107-112 of the CEA sequence. This peptide sequence is located in the region between the N-terminal and the first immunoglobulin like loop domain. Using native CEA and peptides containing this sequence complexed with a heterobifunctional crosslinking agent and ligand blotting with biotinylated CEA and NCA we have shown binding to an 80kD protein on the Kupffer cell surface. This binding protein may be important in the development of hepatic metastases.

  4. A chimeric anti-CEA antibody with heavy interchain disulfide bonds deleted: molecular characterization and biodistributions in normal and tumor bearing mice.

    PubMed

    Neumaier, M; Gaida, F J; Lewis, M R; Hefta, L J; Shively, L E; Raubitschek, A; Shively, J E

    1999-01-01

    We have deleted the interchain disulfide bonds in a chimeric anti-CEA antibody (chT84.66) by mutating two cysteines in the heavy chain to glycine residues. The resulting antibody delta SSchT84.66 was expressed in high yield in a bioreactor and purified to homogeneity in a single step on an anti-idiotypic antibody affinity column. The molecular size of the antibody was 150 kDa as judged by gel filtration, SDS gel electrophoresis under non-reducing conditions, and MALDI-TOF/MS. The 150 kDa antibody had nearly identical kinetic (Kon = 1.53 x 10(6) M-1 s-1, .koff = 1.14 x 10(-5) s-1) and affinity constants (Kaff = 1.34 x 10(11) M-1) compared to the parent murine (Kaff = 1.25 x 10(11) M-1) and chimeric (Kaff = 1.16 x 10(11) M-1) antibodies when tested on biosensor chips. When delta SSchT84.66 was conjugated to the isothiocynato derivative of DTPA, radiolabeled with 111In, and injected into either normal or nude mice bearing tumor xenografts, it gave nearly identical biodistributions to chT84.66. delta SSchT84.66 and chT84.66 antibodies gave a maximum tumor uptake of 48 and 74% ID/g, and tumor to blood ratios of 5.3 and 6.2 at 48 h, respectively. We conclude that delta SSchT84.66 irreversibly associates into H2L2 dimers after concentration, that the dimers are stable under both the in vitro and in vivo conditions used in this study, and the properties of the antibody are virtually indistinguishable from the parent chT84.66 antibody.

  5. Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine.

    PubMed

    Warlow, Shelley M; Robinson, Mike J F; Berridge, Kent C

    2017-08-30

    Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting that higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats' motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target. SIGNIFICANCE STATEMENT In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing central

  6. Stroke/Death Rates Following Carotid Artery Stenting and Carotid Endarterectomy in Contemporary Administrative Dataset Registries: A Systematic Review.

    PubMed

    Paraskevas, K I; Kalmykov, E L; Naylor, A R

    2016-01-01

    Randomised trials have reported higher stroke/death rates after carotid artery stenting (CAS) versus carotid endarterectomy (CEA). Despite this, the 2011 American Heart Association (AHA) guidelines expanded CAS indications, partly because of the Carotid Revascularization Endarterectomy versus Stenting Trial, but also because of improving outcomes in industry sponsored CAS Registries. The aim of this systematic review was: (i) to compare stroke/death rates after CAS/CEA in contemporary dataset registries, (ii) to examine whether published stroke/death rates after CAS fall within AHA thresholds, and, (iii) to see if there had been a decline (over time) in procedural risk after CAS/CEA. PubMed/Medline, Embase, and Cochrane databases were systematically searched according to the recommendations of the PRISMA statement from January 1, 2008 until February 23, 2015 for administrative dataset registries reporting outcomes after both CEA and CAS. Twenty-one registries reported outcomes involving more than 1,500,000 procedures. Stroke/death after CAS was significantly higher than after CEA in 11/21 registries (52%) involving "average risk for CEA" asymptomatic patients and in 11/18 registries (61%) involving "average risk for CEA" symptomatic patients. In another five registries, CAS was associated with higher stroke/death rates than CEA for both symptomatic and asymptomatic patients, but formal statistical comparison was not reported. CAS was associated with stroke/death rates that exceeded risk thresholds recommended by the AHA in 9/21 registries (43%) involving "average risk for CEA" asymptomatic patients and in 13/18 registries (72%) involving "average risk for CEA" symptomatic patients. In 5/18 registries (28%), the procedural risk after CAS in "average risk" symptomatic patients exceeded 10%. Data from contemporary administrative dataset registries suggest that stroke/death rates following CAS remain significantly higher than after CEA and often exceed accepted AHA

  7. First experience using cultured epidermal autografts in Taiwan for burn victims of the Formosa Fun Coast Water Park explosion, as part of Japanese medical assistance.

    PubMed

    Matsumura, Hajime; Harunari, Nobuyuki; Ikeda, Hiroto

    2016-05-01

    On June 27, 2015, a flammable starch-based powder exploded at Formosa Fun Coast in Taipei, Taiwan, injuring 499 people, and more than 200 people were in critical condition with severe burns. Although a cultured epidermal autograft (CEA) was not approved or used in clinical practice, the Taiwan Food and Drug Administration requested a Japanese CEA manufacturer to donate CEA for the burn victims as part of international medical assistance. The authors cooperated in this project and participated in the patient selection, wound bed management for CEA, and technical assistance for CEA use. Here, we provide an overview of the project. Nine patients were enrolled, and two patients were excluded from the skin biopsy; seven skin biopsies were collected approximately 1 month after the disaster. The average TBSA% burned was 81.0%, and the mean age was 20.1 years. CEA was grafted in five patients; wound closure had been obtained in one patient, and one patient was severely ill at the time of grafting. The CEA was combined with a wide split auto mesh graft or patch graft. The mean re-epithelization rate at 4 weeks after the grafting was 84.2% by patient, and all of the patients survived. Although this project had many obstacles to overcome, CEA grafting was successful and contributed to wound closure and survival. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  8. Optogenetic Excitation of Central Amygdala Amplifies and Narrows Incentive Motivation to Pursue One Reward Above Another

    PubMed Central

    Warlow, Shelley M.; Berridge, Kent C.

    2014-01-01

    Choosing one reward above another is important for achieving adaptive life goals. Yet hijacked into excessive intensity in disorders such as addiction, single-minded pursuit becomes maladaptive. Here, we report that optogenetic channelrhodopsin stimulation of neurons in central nucleus of amygdala (CeA), paired with earning a particular sucrose reward in rats, amplified and narrowed incentive motivation to that single reward target. Therefore, CeA rats chose and intensely pursued only the laser-paired sucrose reward while ignoring an equally good sucrose alternative. In contrast, reward-paired stimulation of basolateral amygdala did not hijack choice. In a separate measure of incentive motivation, CeA stimulation also increased the progressive ratio breakpoint or level of effort exerted to obtain sucrose reward. However, CeA stimulation by itself failed to support behavioral self-stimulation in the absence of any paired external food reward, suggesting that CeA photo-excitation specifically transformed the value of its external reward (rather than adding an internal reinforcement state). Nor did CeA stimulation by itself induce any aversive state that motivated escape. Finally, CeA stimulation also failed to enhance ‘liking’ reactions elicited by sucrose taste and did not simply increase the general motivation to eat. This pattern suggests that CeA photo-excitation specifically enhances and narrows incentive motivation to pursue an associated external reward at the expense of another comparable reward. PMID:25505310

  9. The Physiology of Fear: Reconceptualizing the Role of the Central Amygdala in Fear Learning

    PubMed Central

    Keifer, Orion P.; Hurt, Robert C.; Ressler, Kerry J.

    2015-01-01

    The historically understood role of the central amygdala (CeA) in fear learning is to serve as a passive output station for processing and plasticity that occurs elsewhere in the brain. However, recent research has suggested that the CeA may play a more dynamic role in fear learning. In particular, there is growing evidence that the CeA is a site of plasticity and memory formation, and that its activity is subject to tight regulation. The following review examines the evidence for these three main roles of the CeA as they relate to fear learning. The classical role of the CeA as a routing station to fear effector brain structures like the periaqueductal gray, the lateral hypothalamus, and paraventricular nucleus of the hypothalamus will be briefly reviewed, but specific emphasis is placed on recent literature suggesting that the CeA 1) has an important role in the plasticity underlying fear learning, 2) is involved in regulation of other amygdala subnuclei, and 3) is itself regulated by intra- and extra-amygdalar input. Finally, we discuss the parallels of human and mouse CeA involvement in fear disorders and fear conditioning, respectively. PMID:26328883

  10. Cost-effectiveness modelling in diagnostic imaging: a stepwise approach.

    PubMed

    Sailer, Anna M; van Zwam, Wim H; Wildberger, Joachim E; Grutters, Janneke P C

    2015-12-01

    Diagnostic imaging (DI) is the fastest growing sector in medical expenditures and takes a central role in medical decision-making. The increasing number of various and new imaging technologies induces a growing demand for cost-effectiveness analysis (CEA) in imaging technology assessment. In this article we provide a comprehensive framework of direct and indirect effects that should be considered for CEA in DI, suitable for all imaging modalities. We describe and explain the methodology of decision analytic modelling in six steps aiming to transfer theory of CEA to clinical research by demonstrating key principles of CEA in a practical approach. We thereby provide radiologists with an introduction to the tools necessary to perform and interpret CEA as part of their research and clinical practice. • DI influences medical decision making, affecting both costs and health outcome. • This article provides a comprehensive framework for CEA in DI. • A six-step methodology for conducting and interpreting cost-effectiveness modelling is proposed.

  11. Study of the influence of heat sources on the out-of-pile calibration curve of calorimetric cells used for nuclear energy deposition quantification

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

    De Vita, C.; Brun, J.; Reynard-Carette, C.

    2015-07-01

    At present the Jules Horowitz Reactor is under construction in Cadarache research center of CEA 'French Alternative Energies and Atomic Energy Commission' center located in the south-east of France. This new Material Testing Reactor (MTR) will be operational in late 2019 and will allow the generation of a new experimental potential (up to 20 irradiation devices simultaneously) and new harsh conditions such as higher neutron fluxes (5.10{sup 14} n.cm{sup -2}.s{sup -1} for E≥1 MeV), faster material ageing and higher nuclear heating (up to 20 W/g for nominal capacity of 100 MW). In nuclear research field, the control and the measurementmore » of the nuclear heating (energy deposition rate per mass unit induced by the interactions of radiations with matter) is crucial to carry out accurate studies on ageing of materials and on the behavior of nuclear fuels under irradiation. Several experiments need to know precisely this key parameter in order to establish dedicated thermal conditions. The measurement of the nuclear heating inside MTRs is realized by three kinds of sensors: single-cell calorimeter, differential calorimeter and gamma thermometer. One scientific objective of the IN-CORE program, between CEA and Aix-Marseille University in 2009, is to improve the nuclear heating measurement. In this context a new multi-sensor device, called CARMEN, was made. This device contains in particular a differential calorimeter which was designed to measure the nuclear heating in the periphery of OSIRIS reactor (a MTR located at Saclay, France) up to 2 W/g and tested during two irradiation campaigns. Results obtained during these campaigns showed that temperatures reached inside the calorimeter are higher than ones obtained during the preliminary out-of-pile calibration experiments. For instance for 1.74 W/g, the in-pile temperature of the calorimeter rod is equal to 305 deg. C against 225 deg. C in laboratory conditions by simulating the nuclear heating by Joule Effect

  12. Keratin, luminal epithelial antigen and carcinoembryonic antigen in human urinary bladder carcinomas. An immunohistochemical study.

    PubMed

    Nathrath, W B; Arnholdt, H; Wilson, P D

    1982-01-01

    14 urinary bladder carcinomas of all main types were investigated with antisera to "broad spectrum keratin" (aK), "luminal epithelial antigen" (aLEA) and carcinoembryonic antigen (aCEA), using an indirect immunoperoxidase method on formalin fixed paraffin embedded sections. Keratin and LEA were both present in normal transitional epithelium, papilloma and carcinoma in situ whereas CEA was absent. Transitional cell carcinomas reacted with both aK and aLEA whereas CEA was seen only in a few foci. In squamous metaplasia and squamous carcinoma reaction with aK was particularly strong, while LEA was almost lacking and CEA was present in necrotic centres. In adenocarcinomas aK and aLEA reacted equally while aCEA reacted only on the surface.

  13. Identity and relatedness as mediators between child emotional abuse and adult couple adjustment in women.

    PubMed

    Bigras, Noémie; Godbout, Natacha; Hébert, Martine; Runtz, Marsha; Daspe, Marie-Ève

    2015-12-01

    The empirical literature indicates that childhood emotional abuse (CEA) produces long lasting impairments in interpersonal relatedness and identity, often referred to as self-capacities. CEA has also been shown to negatively impact couple functioning. This study examined the role of identity and interpersonal conflicts in mediating the relationship between CEA and women's report of couple adjustment among 184 French Canadian women from the general population. Path analysis revealed that CEA was related to poorer couple adjustment through its impact on dysfunctional self-capacities and the experience of greater conflicts in relationships. Findings highlight the importance of assessing CEA to better explain couple adjustment in women with relationship difficulties and provide potential intervention targets based on the self-capacities framework. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. A filamentous bacteriophage targeted to carcinoembryonic antigen induces tumor regression in mouse models of colorectal cancer.

    PubMed

    Murgas, Paola; Bustamante, Nicolás; Araya, Nicole; Cruz-Gómez, Sebastián; Durán, Eduardo; Gaete, Diana; Oyarce, César; López, Ernesto; Herrada, Andrés Alonso; Ferreira, Nicolás; Pieringer, Hans; Lladser, Alvaro

    2018-02-01

    Colorectal cancer is a deadly disease, which is frequently diagnosed at advanced stages, where conventional treatments are no longer effective. Cancer immunotherapy has emerged as a new form to treat different malignancies by turning-on the immune system against tumors. However, tumors are able to evade antitumor immune responses by promoting an immunosuppressive microenvironment. Single-stranded DNA containing M13 bacteriophages are highly immunogenic and can be specifically targeted to the surface of tumor cells to trigger inflammation and infiltration of activated innate immune cells, overcoming tumor-associated immunosuppression and promoting antitumor immunity. Carcinoembryonic antigen (CEA) is highly expressed in colorectal cancers and has been shown to promote several malignant features of colorectal cancer cells. In this work, we targeted M13 bacteriophage to CEA, a tumor-associated antigen over-expressed in a high proportion of colorectal cancers but largely absent in normal cells. The CEA-targeted M13 bacteriophage was shown to specifically bind to purified CEA and CEA-expressing tumor cells in vitro. Both intratumoral and systemic administration of CEA-specific bacteriophages significantly reduced tumor growth of mouse models of colorectal cancer, as compared to PBS and control bacteriophage administration. CEA-specific bacteriophages promoted tumor infiltration of neutrophils and macrophages, as well as maturation dendritic cells in tumor-draining lymph nodes, suggesting that antitumor T-cell responses were elicited. Finally, we demonstrated that tumor protection provided by CEA-specific bacteriophage particles is mediated by CD8 + T cells, as depletion of circulating CD8 + T cells completely abrogated antitumor protection. In summary, we demonstrated that CEA-specific M13 bacteriophages represent a potential immunotherapy against colorectal cancer.

  15. Cerebral hyperperfusion following carotid endarterectomy: diagnostic utility of intraoperative transcranial Doppler ultrasonography compared with single-photon emission computed tomography study.

    PubMed

    Ogasawara, Kuniaki; Inoue, Takashi; Kobayashi, Masakazu; Endo, Hidehoko; Yoshida, Kenji; Fukuda, Takeshi; Terasaki, Kazunori; Ogawa, Akira

    2005-02-01

    Cerebral hyperperfusion syndrome is a rare but serious complication of carotid endarterectomy (CEA). The aim of the present study was to determine whether intraoperative blood flow velocity (BFV) monitoring in the middle cerebral artery (MCA) by using transcranial Doppler ultrasonography (TCD) could be used as a reliable technique to detect cerebral hyperperfusion following CEA by comparing findings with those of brain single photon emission CT (SPECT). Intraoperative BFV monitoring was attempted in 67 patients undergoing CEA for treatment of ipsilateral internal carotid artery (ICA) stenosis (> or =70%). Cerebral blood flow (CBF) was also assessed using SPECT, which was performed before and immediately after CEA. Intraoperative BFV monitoring was achieved in 60 patients. Of the 60 patients, post-CEA hyperperfusion (CBF increase > or =100%, compared with preoperative values) was observed in six patients. The sensitivity, specificity, and positive predictive value of the BFV increases immediately after declamping of the ICA for detecting post-CEA hyperperfusion was 100%, 94% and 67%, respectively, with a cut-off point 2.0-fold that of preclamping BFV. The sensitivity and specificity of the BFV increases at the end of the procedure for detecting post-CEA hyperperfusion were 100% for both parameters, with cut-off points of 2.0- to 2.2-fold BFV of preclamping value. Hyperperfusion syndrome developed in two patients with post-CEA hyperperfusion, but intracerebral hemorrhage did not occur. In one of these two patients, BFV monitoring was not possible because of failure to obtain an adequate bone window. Intraoperative MCA BFV monitoring by using TCD is a less reliable method to detect cerebral hyperperfusion following CEA than postoperative MCA BFV monitoring, provided adequate monitoring can be achieved.

  16. Multicenter experience on eversion versus conventional carotid endarterectomy in symptomatic carotid artery stenosis: observations from the Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE-1) trial.

    PubMed

    Demirel, Serdar; Attigah, Nicolas; Bruijnen, Hans; Ringleb, Peter; Eckstein, Hans-Henning; Fraedrich, Gustav; Böckler, Dittmar

    2012-07-01

    Carotid endarterectomy (CEA) is beneficial in patients with symptomatic carotid artery stenosis. However, randomized trials have not provided evidence concerning the optimal CEA technique, conventional or eversion. The outcome of 563 patients within the surgical randomization arm of the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE-1) trial was analyzed by surgical technique subgroups: eversion endarterectomy versus conventional endarterectomy with patch angioplasty. The primary end point was ipsilateral stroke or death within 30 days after surgery. Secondary outcome events included perioperative adverse events and the 2-year risk of restenosis, stroke, and death. Both groups were similar in terms of demographic and other baseline clinical variables. Shunt frequency was higher in the conventional CEA group (65% versus 17%; P<0.0001). The risk of ipsilateral stroke or death within 30 days after surgery was significantly greater with eversion CEA (9% versus 3%; P=0.005). There were no statistically significant differences in the rate of perioperative secondary outcome events with the exception of a significantly higher risk of intraoperative ipsilateral stroke rate in the eversion CEA group (4% versus 0.3%; P=0.0035). The 2-year risk of ipsilateral stroke occurring after 30 days was significantly higher in the conventional CEA group (2.9% versus 0%; P=0.017). In patients with symptomatic carotid artery stenosis, conventional CEA appears to be associated with better periprocedural neurological outcome than eversion CEA. Eversion CEA, however, may be more effective for long-term prevention of ipsilateral stroke. These findings should be interpreted with caution noting the limitations of the post hoc, nonrandomized nature of the analysis.

  17. National variation in preoperative imaging, carotid duplex ultrasound criteria, and threshold for surgery for asymptomatic carotid artery stenosis.

    PubMed

    Arous, Edward J; Simons, Jessica P; Flahive, Julie M; Beck, Adam W; Stone, David H; Hoel, Andrew W; Messina, Louis M; Schanzer, Andres

    2015-10-01

    Carotid endarterectomy (CEA) for asymptomatic carotid artery stenosis is among the most common procedures performed in the United States. However, consensus is lacking regarding optimal preoperative imaging, carotid duplex ultrasound criteria, and ultimately, the threshold for surgery. We sought to characterize national variation in preoperative imaging, carotid duplex ultrasound criteria, and threshold for surgery for asymptomatic CEA. The Society for Vascular Surgery Vascular Quality Initiative (VQI) database was used to identify all CEA procedures performed for asymptomatic carotid artery stenosis between 2003 and 2014. VQI currently captures 100% of CEA procedures performed at >300 centers by >2000 physicians nationwide. Three analyses were performed to quantify the variation in (1) preoperative imaging, (2) carotid duplex ultrasound criteria, and (3) threshold for surgery. Of 35,695 CEA procedures in 33,488 patients, the study cohort was limited to 19,610 CEA procedures (55%) performed for asymptomatic disease. The preoperative imaging modality used before CEA varied widely, with 57% of patients receiving a single preoperative imaging study (duplex ultrasound imaging, 46%; computed tomography angiography, 7.5%; magnetic resonance angiography, 2.0%; cerebral angiography, 1.3%) and 43% of patients receiving multiple preoperative imaging studies. Of the 16,452 asymptomatic patients (89%) who underwent preoperative duplex ultrasound imaging, there was significant variability between centers in the degree of stenosis (50%-69%, 70%-79%, 80%-99%) designated for a given peak systolic velocity, end diastolic velocity, and internal carotid artery-to-common carotid artery ratio. Although 68% of CEA procedures in asymptomatic patients were performed for an 80% to 99% stenosis, 26% were performed for a 70% to 79% stenosis, and 4.1% were performed for a 50% to 69% stenosis. At the surgeon level, the range in the percentage of CEA procedures performed for a <80% asymptomatic

  18. 76 FR 41375 - Retail Foreign Exchange Transactions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-14

    ... retail customers. The rule also describes various requirements with which national banks, Federal... section 2(c)(2)(B)(i)(I) of the CEA with a retail customer \\5\\ except pursuant to a rule or regulation of... the CEA. \\3\\ The CEA defines ``financial institution'' as including ``a depository institution (as...

  19. Capillary electrophoresis-chemiluminescence detection for carcino-embryonic antigen based on aptamer/graphene oxide structure.

    PubMed

    Zhou, Zi-Ming; Feng, Zhe; Zhou, Jun; Fang, Bi-Yun; Qi, Xiao-Xiao; Ma, Zhi-Ya; Liu, Bo; Zhao, Yuan-Di; Hu, Xue-Bin

    2015-02-15

    A new strategy is proposed for determination of carcino-embryonic antigen (CEA) based on aptamer/graphene oxide (Apt/GO) by capillary electrophoresis-chemiluminescence (CE-CL) detection system. CEA aptamer conjugated with horseradish peroxidase (HRP) firstly mixes with GO, and the CL will be quenched because the stack of HRP-Apt on GO leads to chemiluminescence resonance energy transfer (CRET). When CEA exists, the specific combination of HRP-Apt and CEA can form HRP-Apt-CEA complex, which dissociates from GO. Then, the CL catalyzed by HRP-Apt-CEA complex can be detected without any CRET, and the content of CEA can be estimated by the CL intensity. It has been proved that the interference issue resulted from free HRP-Apt is solved well by mixing GO firstly with HRP-Apt, which blocks the free HRP-Apt's CL signal due to CL quenching effect of GO; and the interference resulted from GO to CL is also solved by CE, then the sensitivity and accuracy can be greatly improved. Results also showed that the CL intensity had a linear relationship with the concentration of CEA in the range from 0.0654 to 6.54 ng/mL, and the limit of detection was approximately 4.8 pg/mL (S/N = 3). This proposed method with high specificity offers a new way for separation and determination of biomolecule, and has good potential in application of biochemistry and bioanalysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Optogenetic excitation of central amygdala amplifies and narrows incentive motivation to pursue one reward above another.

    PubMed

    Robinson, Mike J F; Warlow, Shelley M; Berridge, Kent C

    2014-12-10

    Choosing one reward above another is important for achieving adaptive life goals. Yet hijacked into excessive intensity in disorders such as addiction, single-minded pursuit becomes maladaptive. Here, we report that optogenetic channelrhodopsin stimulation of neurons in central nucleus of amygdala (CeA), paired with earning a particular sucrose reward in rats, amplified and narrowed incentive motivation to that single reward target. Therefore, CeA rats chose and intensely pursued only the laser-paired sucrose reward while ignoring an equally good sucrose alternative. In contrast, reward-paired stimulation of basolateral amygdala did not hijack choice. In a separate measure of incentive motivation, CeA stimulation also increased the progressive ratio breakpoint or level of effort exerted to obtain sucrose reward. However, CeA stimulation by itself failed to support behavioral self-stimulation in the absence of any paired external food reward, suggesting that CeA photo-excitation specifically transformed the value of its external reward (rather than adding an internal reinforcement state). Nor did CeA stimulation by itself induce any aversive state that motivated escape. Finally, CeA stimulation also failed to enhance 'liking' reactions elicited by sucrose taste and did not simply increase the general motivation to eat. This pattern suggests that CeA photo-excitation specifically enhances and narrows incentive motivation to pursue an associated external reward at the expense of another comparable reward. Copyright © 2014 the authors 0270-6474/14/3416567-14$15.00/0.

  1. VISIR upgrade overview and status

    NASA Astrophysics Data System (ADS)

    Kerber, Florian; Käufl, Hans Ulrich; Baksai, Pedro; Dobrzycka, Danuta; Finger, Gert; Ives, Derek; Jakob, Gerd; Lagadec, Eric; Lundin, Lars; Mawet, Dimitri; Mehrgan, Leander; Moerchen, Margaret; Momany, Yazan; Moreau, Vincent; Pantin, Eric; Riquelme, Miguel; Siebenmorgen, Ralf; Silber, Armin; Smette, Alain; Taylor, Julian; van den Ancker, Mario; Venema, Lars; Weilenmann, Ueli; Yegorova, Irina

    2012-09-01

    We present an overview of the VISIR upgrade project. VISIR is the mid-infrared imager and spectrograph at ESO's VLT. The project team is comprised of ESO staff and members of the original VISIR consortium: CEA Saclay and ASTRON. The project plan is based on input from the ESO user community with the goal of enhancing the scientific performance and efficiency of VISIR by a combination of measures: installation of improved hardware, optimization of instrument operations and software support. The cornerstone of the upgrade is the 1k by 1k Si:As Aquarius detector array (Raytheon) which has demonstrated very good performance (sensitivity, stability) in the laboratory IR detector test facility (modified TIMMI 2 instrument). A prism spectroscopic mode will cover the N-band in a single observation. New scientific capabilities for high resolution and high-contrast imaging will be offered by sub-aperture mask (SAM) and phase-mask coronagraphic (4QPM/AGPM) modes. In order to make optimal use of favourable atmospheric conditions a water vapour monitor has been deployed on Paranal, allowing for real-time decisions and the introduction of a userdefined constraint on water vapour. Improved pipelines based on the ESO Reflex concept will provide better support to astronomers. The upgraded VISIR will be a powerful instrument providing background limited performance for diffraction-limited observations at an 8-m telescope. It will offer synergy with facilities such as ALMA, JWST, VLTI and SOFIA, while a wealth of targets is available from survey work (e.g. VISTA, WISE). In addition it will bring confirmation of the technical readiness and scientific value of several aspects of potential mid-IR instrumentation at Extremely Large Telescopes. The intervention on VISIR and installation of hardware has been completed in July and commissioning will take place during July and August. VISIR is scheduled to be available to the users starting Oct 2012.

  2. Commissioning of the ECR ion source of the high intensity proton injector of the Facility for Antiproton and Ion Research (FAIR)

    NASA Astrophysics Data System (ADS)

    Tuske, O.; Chauvin, N.; Delferriere, O.; Fils, J.; Gauthier, Y.

    2018-05-01

    The CEA at Saclay is in charge of developing and building the ion source and the low energy line of the proton linac of the FAIR (Facility for Antiproton and Ion Research) accelerator complex located at GSI (Darmstadt) in Germany. The FAIR facility will deliver stable and rare isotope beams covering a huge range of intensities and beam energies for experiments in the fields of atomic physics, plasma physics, nuclear physics, hadron physics, nuclear matter physics, material physics, and biophysics. A significant part of the experimental program at FAIR is dedicated to antiproton physics that requires an ultimate number 7 × 1010 cooled pbar/h. The high-intensity proton beam that is necessary for antiproton production will be delivered by a dedicated 75 mA/70 MeV proton linac. A 2.45 GHz microwave ion source will deliver a 100 mA H+ beam pulsed at 4 Hz with an energy of 95 keV. A 2 solenoids low energy beam transport line allows the injection of the proton beam into the radio frequency quadrupole (RFQ) within an acceptance of 0.3π mm mrad (norm. rms). An electrostatic chopper system located between the second solenoid and the RFQ is used to cut the beam macro-pulse from the source to inject 36 μs long beam pulses into the RFQ. At present time, a Ladder-RFQ is under construction at the University of Frankfurt. This article reports the first beam measurements obtained since mid of 2016. Proton beams have been extracted from the ECR ion source and analyzed just after the extraction column on a dedicated diagnostic chamber. Emittance measurements as well as extracted current and species proportion analysis have been performed in different configurations of ion source parameters, such as magnetic field profile, radio frequency power, gas injection, and puller electrode voltage.

  3. Risk factor analysis of new brain lesions associated with carotid endarterectmy.

    PubMed

    Lee, Jae Hoon; Suh, Bo Yang

    2014-01-01

    Carotid endarterectomy (CEA) is the standard treatment for carotid artery stenosis. New brain ischemia is a major concern associated with CEA and diffusion weighted imaging (DWI) is a good imaging modality for detecting early ischemic brain lesions. We aimed to investigate the surgical complications and identify the potential risk factors for the incidence of new brain lesions (NBL) on DWI after CEA. From January 2006 to November 2011, 94 patients who had been studied by magnetic resonance imaging including DWI within 1 week after CEA were included in this study. Data were retrospectively investigated by review of vascular registry protocol. Seven clinical variables and three procedural variables were analyzed as risk factors for NBL after CEA. The incidence of periprocedural NBL on DWI was 27.7%. There were no fatal complications, such as ipsilateral disabling stroke, myocardial infarction or mortality. A significantly higher incidence of NBL was found in ulcer positive patients as opposed to ulcer negative patients (P = 0.029). The incidence of NBL after operation was significantly higher in patients treated with conventional technique than with eversion technique (P = 0.042). Our data shows CEA has acceptable periprocedural complication rates and the existence of ulcerative plaque and conventional technique of endarterectomy are high risk factors for NBL development after CEA.

  4. The Physiology of Fear: Reconceptualizing the Role of the Central Amygdala in Fear Learning.

    PubMed

    Keifer, Orion P; Hurt, Robert C; Ressler, Kerry J; Marvar, Paul J

    2015-09-01

    The historically understood role of the central amygdala (CeA) in fear learning is to serve as a passive output station for processing and plasticity that occurs elsewhere in the brain. However, recent research has suggested that the CeA may play a more dynamic role in fear learning. In particular, there is growing evidence that the CeA is a site of plasticity and memory formation, and that its activity is subject to tight regulation. The following review examines the evidence for these three main roles of the CeA as they relate to fear learning. The classical role of the CeA as a routing station to fear effector brain structures like the periaqueductal gray, the lateral hypothalamus, and paraventricular nucleus of the hypothalamus will be briefly reviewed, but specific emphasis is placed on recent literature suggesting that the CeA 1) has an important role in the plasticity underlying fear learning, 2) is involved in regulation of other amygdala subnuclei, and 3) is itself regulated by intra- and extra-amygdalar input. Finally, we discuss the parallels of human and mouse CeA involvement in fear disorders and fear conditioning, respectively. ©2015 Int. Union Physiol. Sci./Am. Physiol. Soc.

  5. Suppression of Murine Colitis and its Associated Cancer by Carcinoembryonic Antigen-Specific Regulatory T Cells

    PubMed Central

    Blat, Dan; Zigmond, Ehud; Alteber, Zoya; Waks, Tova; Eshhar, Zelig

    2014-01-01

    The adoptive transfer of regulatory T cells (Tregs) offers a promising strategy to combat pathologies that are characterized by aberrant immune activation, including graft rejection and autoinflammatory diseases. Expression of a chimeric antigen receptor (CAR) gene in Tregs redirects them to the site of autoimmune activity, thereby increasing their suppressive efficiency while avoiding systemic immunosuppression. Since carcinoembryonic antigen (CEA) has been shown to be overexpressed in both human colitis and colorectal cancer, we treated CEA-transgenic mice that were induced to develop colitis with CEA-specific CAR Tregs. Two disease models were employed: T-cell-transfer colitis as well as the azoxymethane–dextran sodium sulfate model for colitis-associated colorectal cancer. Systemically administered CEA-specific (but not control) CAR Tregs accumulated in the colons of diseased mice. In both model systems, CEA-specific CAR Tregs suppressed the severity of colitis compared to control Tregs. Moreover, in the azoxymethane–dextran sodium sulfate model, CEA-specific CAR Tregs significantly decreased the subsequent colorectal tumor burden. Our data demonstrate that CEA-specific CAR Tregs exhibit a promising potential in ameliorating ulcerative colitis and in hindering colorectal cancer development. Collectively, this study provides a proof of concept for the therapeutic potential of CAR Tregs in colitis patients as well as in other autoimmune inflammatory disorders. PMID:24686242

  6. The Central Amygdala Projection to the Substantia Nigra Reflects Prediction Error Information in Appetitive Conditioning

    ERIC Educational Resources Information Center

    Lee, Hongjoo J.; Gallagher, Michela; Holland, Peter C.

    2010-01-01

    The central amygdala nucleus (CeA) plays a critical role in cognitive processes beyond fear conditioning. For example, intact CeA function is essential for enhancing attention to conditioned stimuli (CSs). Furthermore, this enhanced attention depends on the CeA's connections to the nigrostriatal system. In the current study, we examined the role…

  7. Kappa Opioid Receptor-Mediated Dysregulation of GABAergic Transmission in the Central Amygdala in Cocaine Addiction

    PubMed Central

    Kallupi, Marsida; Wee, Sunmee; Edwards, Scott; Whitfield, Tim W.; Oleata, Christopher S.; Luu, George; Schmeichel, Brooke E.; Koob, George F.; Roberto, Marisa

    2013-01-01

    Background Studies have demonstrated an enhanced dynorphin/kappa-opioid receptor (KOR) system following repeated cocaine exposure, but few reports have focused on neuroadaptations within the central amygdala (CeA). Methods We identified KOR-related physiological changes in the CeA following escalation of cocaine self-administration in rats. We used in vitro slice electrophysiological (intracellular and whole-cell recordings) methods to assess whether differential cocaine access in either 1h (short access, ShA) or 6h (long access, LgA) sessions induced plasticity at CeA GABAergic synapses, or altered the sensitivity of these synapses to KOR agonism (U50488) or antagonism (nor-BNI). We then determined the functional effects of CeA KOR blockade in cocaine-related behaviors. Results Baseline evoked GABAergic transmission was enhanced in the CeA from ShA and LgA rats compared to cocaine-naïve rats. Acute cocaine (1 uM) application significantly decreased GABA release in all groups (naïve, ShA, and LgA rats). Application of U50488 (1 uM) significantly decreased GABAergic transmission in the CeA from naïve rats, but increased it in LgA rats. Conversely, nor-BNI (200 nM) significantly increased GABAergic transmission in the CeA from naïve rats, but decreased it in LgA rats. Nor-BNI did not alter the acute cocaine-induced inhibition of GABAergic responses. Finally, CeA microinfusion of nor-BNI blocked cocaine-induced locomotor sensitization and attenuated the heightened anxiety-like behavior observed during withdrawal from chronic cocaine exposure in the defensive burying paradigm. Conclusion Together these data demonstrate that CeA dynorphin/KOR systems are dysregulated following excessive cocaine exposure and suggest KOR antagonism as a viable therapeutic strategy for cocaine addiction. PMID:23751206

  8. Conceptual and methodological challenges to integrating SEA and cumulative effects assessment

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

    Gunn, Jill, E-mail: jill.gunn@usask.c; Noble, Bram F.

    The constraints to assessing and managing cumulative environmental effects in the context of project-based environmental assessment are well documented, and the potential benefits of a more strategic approach to cumulative effects assessment (CEA) are well argued; however, such benefits have yet to be clearly demonstrated in practice. While it is widely assumed that cumulative effects are best addressed in a strategic context, there has been little investigation as to whether CEA and strategic environmental assessment (SEA) are a 'good fit' - conceptually or methodologically. This paper identifies a number of conceptual and methodological challenges to the integration of CEA andmore » SEA. Based on results of interviews with international experts and practitioners, this paper demonstrates that: definitions and conceptualizations of CEA are typically weak in practice; approaches to effects aggregation vary widely; a systems perspective lacks in both SEA and CEA; the multifarious nature of SEA complicates CEA; tiering arrangements between SEA and project-based assessment are limited to non-existing; and the relationship of SEA to regional planning remains unclear.« less

  9. Kinetics of anti-carcinoembryonic antigen antibody internalization: effects of affinity, bivalency, and stability

    PubMed Central

    Schmidt, Michael M.; Thurber, Greg M.

    2010-01-01

    Theoretical analyses suggest that the cellular internalization and catabolism of bound antibodies contribute significantly to poor penetration into tumors. Here we quantitatively assess the internalization of antibodies and antibody fragments against the commonly targeted antigen carcinoembryonic antigen (CEA). Although CEA is often referred to as a non-internalizing or shed antigen, anti-CEA antibodies and antibody fragments are shown to be slowly endocytosed by LS174T cells with a half-time of 10–16 h, a time scale consistent with the metabolic turnover rate of CEA in the absence of antibody. Anti-CEA single chain variable fragments (scFvs) with significant differences in affinity, stability against protease digestion, and valency exhibit similar uptake rates of bound antibody. In contrast, one anti-CEA IgG exhibits unique binding and trafficking properties with twice as many molecules bound per cell at saturation and significantly faster cellular internalization after binding. The internalization rates measured herein can be used in simple computational models to predict the microdistribution of these antibodies in tumor spheroids. PMID:18408925

  10. Nanogold-enwrapped graphene nanocomposites as trace labels for sensitivity enhancement of electrochemical immunosensors in clinical immunoassays: Carcinoembryonic antigen as a model.

    PubMed

    Zhong, Zhaoyang; Wu, Wei; Wang, Dong; Wang, Dan; Shan, Jinlu; Qing, Yi; Zhang, Zhimin

    2010-06-15

    A new, highly sensitive electrochemical immunosensor with a sandwich-type immunoassay format was designed to quantify carcinoembryonic antigen (CEA), as a model tumor marker, using nanogold-enwrapped graphene nanocomposites (NGGNs) as trace labels in clinical immunoassays. The device consisted of a glassy carbon electrode coated with Prussian Blue (PB) on whose surface gold nanoparticles were electrochemically deposited to the further modified with the specific analyte-capturing molecule, anti-CEA antibodies. The immunoassay was performed using horseradish peroxidase (HRP)-conjugated anti-CEA as secondary antibodies attached on the NGGN surface (HRP-anti-CEA-NGGN). The method using HRP-anti-CEA-NGGNs as detection antibodies shows high signal amplification, and exhibits a dynamic working range of 0.05-350 ng/mL with a low detection limit of 0.01 ng/mL CEA (at 3s). The assayed results of serum samples with the sensor received an acceptable agreement with the reference values. Importantly, the methodology provides a promising ultrasensitive assay strategy for clinical applications. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Diagnostic Accuracy of Combinations of Tumor Markers for Malignant Pleural Effusion: An Updated Meta-Analysis.

    PubMed

    Yang, Yuan; Liu, Ya-Lan; Shi, Huan-Zhong

    2017-01-01

    The role of combinations of tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a fragment of cytokeratin 19) in diagnosing malignant pleural effusion (MPE) has not been clearly established. This meta-analysis was performed to establish the overall diagnostic accuracies of combinations of these pleural fluid tumor markers for MPE. The PubMed, Ovid, Embase, Web of Science, and Cochrane bibliographic databases were searched. Sensitivity, specificity, and other measures of the accuracy of combinations of pleural CEA, CA 125, CA 15-3, CA 19-9, and CYFRA 21-1 in the diagnosis of MPE were pooled after a systematic review of English-language studies. Twenty studies met the inclusion criteria. For pleural fluid tumor marker combinations including more than 3 studies, the summary estimates of the sensitivity/specificity for diagnosing MPE were as follows: CEA + CA 125, 0.65/0.98; CEA + CA 15-3, 0.64/0.98; CEA + CA 19-9, 0.58/0.98; CEA + CYFRA 21-1, 0.82/0.92; and CA 15-3 + CYFRA 21-1, 0.88/0.94. In patients with undiagnosed pleural effusion, the combinations of positive pleural CEA + CA 15-3 and CEA + CA 19-9 are highly suspicious for pleural malignancy, but the sensitivity of these tests is poor. Therefore, their routine role in the diagnostic algorithm of these patients is questionable, and management decisions should depend on positive cytological or biopsy results from the pleura. © 2017 S. Karger AG, Basel.

  12. Short-Term Results of Carotid Endarterectomy and Stenting After the Introduction of Carotid Magnetic Resonance Imaging: A Single-Institution Retrospective Study.

    PubMed

    Fukumitsu, Ryu; Yoshida, Kazumichi; Kurosaki, Yoshitaka; Torihashi, Koichi; Sadamasa, Nobutake; Koyanagi, Masaomi; Narumi, Osamu; Sato, Tsukasa; Chin, Masaki; Handa, Akira; Yamagata, Sen; Miyamoto, Susumu

    2017-05-01

    Although carotid artery stenting (CAS) has been gaining popularity as an alternative to carotid endarterectomy (CEA), perioperative stroke rate following contemporary CAS remains significantly higher than stroke rate after CEA. The purpose of this study was to assess perioperative (within 30 days) therapeutic results in patients with carotid stenosis (CS) after introduction of preoperative carotid magnetic resonance imaging plaque evaluation in a single center performing both CEA and CAS. Based on prospectively collected data for patients with CS who were scheduled for carotid revascularization, retrospective analysis was conducted of 295 consecutive patients with CS. An intervention was selected after consideration of periprocedural risks for both CEA and CAS. Concerning risk factors for CAS, results of magnetic resonance imaging plaque evaluation were emphasized with a view toward reducing embolic complications. CAS was performed in 114 patients, and CEA was performed in 181 patients. Comparing baseline characteristics of the 295 patients, age, T1 signal intensity of plaque, symptomatic CS, urgent intervention, and diabetes mellitus differed significantly between CAS and CEA groups. Among patients who underwent CAS, new hyperintense lesions on diffusion-weighted imaging were confirmed in 47 patients. New hyperintense lesions on diffusion-weighted imaging were recognized in 21.4% of patients who underwent CEA (n = 39), significantly less frequent than in patients who underwent CAS. The overall short-term outcome of CEA and CAS is acceptable. Preoperative carotid magnetic resonance imaging evaluation of plaque might contribute to low rates of ischemic complications in CAS. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Value of combining serum carcinoembryonic antigen and PET/CT in predicting EGFR mutation in non-small cell lung cancer.

    PubMed

    Gu, Jincui; Xu, Siqi; Huang, Lixia; Li, Shaoli; Wu, Jian; Xu, Junwen; Feng, Jinlun; Liu, Baomo; Zhou, Yanbin

    2018-02-01

    We sought to investigate the associations between pretreatment serum Carcinoembryonic antigen (CEA) level, 18 F-Fluoro-2-deoxyglucose ( 18 F-FDG) uptake value of primary tumor and epidermal growth factor receptor ( EGFR ) mutation status in non-small cell lung cancer (NSCLC). We retrospectively reviewed medical records of 210 NSCLC patients who underwent EGFR mutation test and 18 F-FDG positron emission tomography/computed tomography (PET/CT) scan before anti-tumor therapy. The associations between EGFR mutations and patients' characteristics, serum CEA, PET/CT imaging characteristics maximal standard uptake value (SUVmax) of the primary tumor were analyzed. Receiver-operating characteristic (ROC) curve was used to assess the predictive value of these factors. EGFR mutations were found in 70 patients (33.3%). EGFR mutations were more common in high CEA group (CEA ≥7.0 ng/mL) than in low CEA group (CEA <7.0 ng/mL) (40.4% vs . 27.6%; P=0.05). Females (P<0.001), non-smokers (P<0.001), patients with adenocarcinoma (P<0.001) and SUVmax <9.0 (P=0.001) were more likely to be EGFR mutation-positive. Multivariate analysis revealed that gender, tumor histology, pretreatment serum CEA level, and SUVmax were the most significant predictors for EGFR mutations. The ROC curve revealed that combining these four factors yielded a higher calculated AUC (0.80). Gender, histology, pretreatment serum CEA level and SUVmax are significant predictors for EGFR mutations in NSCLC. Combining these factors in predicting EGFR mutations has a moderate diagnostic accuracy, and is helpful in guiding anti-tumor treatment.

  14. Deep brain stimulation in the central nucleus of the amygdala decreases 'wanting' and 'liking' of food rewards.

    PubMed

    Ross, Shani E; Lehmann Levin, Emily; Itoga, Christy A; Schoen, Chelsea B; Selmane, Romeissa; Aldridge, J Wayne

    2016-10-01

    We investigated the potential of deep brain stimulation (DBS) in the central nucleus of the amygdala (CeA) in rats to modulate functional reward mechanisms. The CeA is the major output of the amygdala with direct connections to the hypothalamus and gustatory brainstem, and indirect connections with the nucleus accumbens. Further, the CeA has been shown to be involved in learning, emotional integration, reward processing, and regulation of feeding. We hypothesized that DBS, which is used to treat movement disorders and other brain dysfunctions, might block reward motivation. In rats performing a lever-pressing task to obtain sugar pellet rewards, we stimulated the CeA and control structures, and compared stimulation parameters. During CeA stimulation, animals stopped working for rewards and rejected freely available rewards. Taste reactivity testing during DBS exposed aversive reactions to normally liked sucrose tastes and even more aversive taste reactions to normally disliked quinine tastes. Interestingly, given the opportunity, animals implanted in the CeA would self-stimulate with 500 ms trains of stimulation at the same frequency and current parameters as continuous stimulation that would stop reward acquisition. Neural recordings during DBS showed that CeA neurons were still active and uncovered inhibitory-excitatory patterns after each stimulus pulse indicating possible entrainment of the neural firing with DBS. In summary, DBS modulation of CeA may effectively usurp normal neural activity patterns to create an 'information lesion' that not only decreased motivational 'wanting' of food rewards, but also blocked 'liking' of rewards. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Atmospheric trace element concentrations in total suspended particles near Paris, France

    NASA Astrophysics Data System (ADS)

    Ayrault, Sophie; Senhou, Abderrahmane; Moskura, Mélanie; Gaudry, André

    2010-09-01

    To evaluate today's trace element atmospheric concentrations in large urban areas, an atmospheric survey was carried out for 18 months, from March 2002 to September 2003, in Saclay, nearby Paris. The total suspended particulate matter (TSP) was collected continuously on quartz fibre filters. The TSP contents were determined for 36 elements (including Ag, Bi, Mo and Sb) using two analytical methods: Instrumental Neutron Activation Analysis (INAA) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The measured concentrations were in agreement within the uncertainties with the certified values for the polycarbonate reference material filter SRM-2783 (National Institute for Standard Technology NIST, USA). The measured concentrations were significantly lower than the recommended atmospheric concentrations. In 2003, the Pb atmospheric level at Saclay was 15 ng/m 3, compared to the 500 ng/m 3 guideline level and to the 200 ng/m 3 observed value in 1994. The typical urban background TSP values of 1-2, 0.2-1, 4-6, 10-30 and 3-5 ng/m 3 for As, Co, Cr, Cu and Sb, respectively, were inferred from this study and were compared with the literature data. The typical urban background TSP concentrations could not be realised for Cd, Pb and Zn, since these air concentrations are highly influenced by local features. The Zn concentrations and Zn/Pb ratio observed in Saclay represented a characteristic fingerprint of the exceptionally large extent of zinc-made roofs in Paris and its suburbs. The traffic-related origin of Ba, Cr, Cu, Pb and Sb was demonstrated, while the atmospheric source(s) of Ag was not identified.

  16. [The value of B7-H4 and carcinoembryonic antigen in diagnosing the benign and malignant pleural effusion].

    PubMed

    Wei, F; Wei, Y; Li, L F; Li, G L; Wang, G J

    2017-07-23

    Objective: To evaluate the value of combined detection of negative costimulatory molecule B7-H4 and carcinoembryonic antigen (CEA) in diagnosing malignant and benign pleural effusion. Methods: Ninety-seven pleural effusion specimen were collected, 55 of which were diagnosed as malignant pleural effusion and 42 were benign pleural effusion. Enzyme-linked immunosorbent assay(ELISA) was used to examine the concentration of B7-H4 and CEA in pleural effusion. Electro-chemiluminescence immunoassay was used to detect the CEA level in pleural effusion. Receiver operating characteristic (ROC) curve was established to analyze and evaluate the single or combined detection of B7-H4 and CEA in diagnosing malignant and benign pleural effusion. Results: The concentrations of B7-H4 and CEA in malignant pleural effusion (MPE) group were (60.08±35.04) ng/ml and (41.49±37.16) ng/ml, respectively, obviously higher than (27.26±9.55) ng/ml and (2.41±0.94) ng/ml of benign pleural effusion (BPE) group (both P <0.01). Area under curve (AUC) of B7-H4 was 0.884 in MPE groupand the diagnostic sensitivity and specificity were 81.8% and 90.5%, respectively, at the optimized cut off value of 37.25 ng/ml. Likewise, area under curve (AUC) of CEA was 0.954 and the sensitivity and specificity were 87.3% and 95.2%, respectively, at the cut off value of 4.18 ng/ml. When B7-H4 >37.25 ng/ml or CEA>4.18 ng/ml, the sensitivity of diagnosis as MPE was down-regulated to 90.9% and the specificity was elevated to 88.1%. When B7-H4 >37.25 ng/ml and CEA>4.18 ng/ml, the sensitivity of diagnosis as MPE was down-regulated to 78.2% and the specificity was elevated to 97.6%. The sensitivity and specificity of combined detection of B7-H4 and CEA to diagnose MPE were elevated to 90.9% and 97.6%, respectively. The level of B7-H4 in MPE and BPE were both positively correlated with CEA ( r =0.670, P =0.001 in MPE and r =0.002, P =0.001 in BEP). Conclusions: B7-H4 is a potential tumor marker in diagnosing the benign

  17. PREFACE: Nanosafe 2012: International Conferences on Safe Production and Use of Nanomaterials

    NASA Astrophysics Data System (ADS)

    Tardif, François

    2013-04-01

    Welcome from the organizers The rapidly developing field of nanotechnology opens up many exciting opportunities and benefits for new materials with significantly improved properties as well as some revolutionary applications in the fields of energy, environment, medicine, etc. These new materials potentially pave the way to considerable innovations in many industries of the 21st century although associated risks must be perfectly under control for workers, consumers and the environment. So, one can easily understand why Nanosafety is now considered as a specific new scientific area, gaining in importance and maturity every day. Following the successful outcome of the two past international conferences on the safe production and use of nanomaterials: Nanosafe 2008 and 2010, the organizing committee has the pleasure of welcoming again to Grenoble some of the most famous specialists of the field in the world. In addition to the standard issues addressed in previous nanosafe conferences such as Toxicology, Eco-toxicology, Expology, Detection, Life Cycle Analysis, Regulation and Standardization, new topics of great interest will be dealt with this year, concerning Governance and practical Risk Management for OSH experts and Societal issues. In order to enhance the exchanges and conviviality three debates werw organized around Nano Governance, Toxicology and Ethics. We hope that you will appreciate this new Nanosafe edition like the previous ones. This is your Nanosafe conference, please enjoy. The Nanosafe conference organisers François Tardif and Frédéric Shuster Management Vanessa Gaultier Francois TardifFrederic ShusterVanessa Gaultier François TardifFrédéric Shuster Vanessa Gaultier Local Organizing Committee Vanessa GAULTIER (CEA) François TARDIF (CEA) Dominique BAGUET (CEA) Frédédric SHUSTER (CEA) Yves SICARD (CEA) Catherine DURAND (CEA) Didier MOLKO (MINATEC) International Scientific Committee Chair: Frédéric SCHUSTER (CEA, FR) François TARDIF (CEA

  18. Comparison of carotid endarterectomy and stenting in real world practice using a regional quality improvement registry

    PubMed Central

    Nolan, Brian W.; De Martino, Randall R.; Goodney, Philip P.; Schanzer, Andres; Stone, David H.; Butzel, David; Kwolek, Christopher J.; Cronenwett, Jack L.

    2013-01-01

    Objective Carotid artery stenting (CAS) vs endarterectomy (CEA) remains controversial and has been the topic of recent randomized controlled trials. The purpose of this study was to compare the practice and outcomes of CAS and CEA in a real world setting. Methods This is a retrospective analysis of 7649 CEA and 430 CAS performed at 17 centers from 2003 to 2010 within the Vascular Study Group of New England (VSGNE). The primary outcome measures were (1) any in-hospital stroke or death and (2) any stroke, death, or myocardial infarction (MI). Patients undergoing CEA in conjunction with cardiac surgery were excluded. Multivariate logistic regression was performed to identify predictors of stroke or death in patients undergoing CAS. Results CEA was performed in 17 centers by 111 surgeons, while CAS was performed in 6 centers by 30 surgeons and 8 interventionalists. Patient characteristics varied by procedure. Patients undergoing CAS had a higher prevalence of coronary artery disease, congestive heart failure, diabetes, and prior ipsilateral CEA. Embolic protection was used in 97% of CAS. Shunts were used in 48% and patches in 86% of CEA. The overall in-hospital stroke or death rate was higher among patients undergoing CAS (2.3% vs 1.1%; P = .03). Overall stroke, death, or MI (2.8% CAS vs 2.1% CEA; P = .32) were not different. Asymptomatic patients had similar rates of stroke or death (CAS 0.73% vs CEA 0.89%; P = .78) and stroke, death, or MI (CAS 1.1% vs CEA 1.8%; P = .40). Symptomatic patients undergoing CAS had higher rates of stroke or death (5.1% vs 1.6%; P = .001), and stroke, death, or MI (5.8% vs 2.7%; P = .02). By multivariate analysis, major stroke (odds ratio, 4.5; 95% confidence interval [CI], 1.9–10.8), minor stroke (2.7; CI, 1.5–4.8), prior ipsilateral CEA (3.2, CI, 1.7–6.1), age >80 (2.1; CI, 1.3–3.4), hypertension (2.6; CI, 1.0–6.3), and a history of chronic obstructive pulmonary disease (1.6; CI, 1.0–2.4) were predictors of stroke or death

  19. Comparative Study of Carcinoembryonic Antigen Tumor Marker in Stomach and Colon Cancer Patients in Khyber Pakhtunkhwa.

    PubMed

    Ahmad, Bashir; Gul, Bushra; Ali, Sajid; Bashir, Shumaila; Mahmood, Nourin; Ahmad, Jamshed; Nawaz, Seema

    2015-01-01

    Due to the increase in morbidity and mortality rate, cancer has become an alarming threat to the human population worldwide. Since cancer is a progressive disorder, timely diagnosis would be helpful to prevent/stop cancer from progressing to severe stage. In Khyber Pakhtunkhwa, Pakistan, most of the time, tumors are diagnosed with endoscopy and biopsy; therefore rare studies exist regarding the diagnosis of gastrointestinal (GIT) carcinomas based on tumor markers, especially CEA. This study made a comparative analysis of CEA in admitted hospitalized stomach and colon cancer patients diagnosed as GIT with biopsy. In this study, a total of 66 cases were included. The level of CEA was determined in the blood of these patients using ELISA technique. Out of 66 patients, the level of CEA was high in 59.1% of the total, 60.7% in colon cancer patients and 57.9 % in stomach cancer patients. Moreover, the incidence of colorectal and stomach cancer was greater in males as compared to females. Patients were more of the age group of 40- 60 and the level of CEA was comparatively higher in patients (51.5%) with histology which was moderately differentiated, than patients with well differentiated and poorly differentiated tumor histology. CEA level was high in more than 50% of the total patients. Moreover, CEA exhibited higher sensitivity for colon than stomach cancer.

  20. Pre-clinical validation study of a miniaturized electrochemical immunoassay based on square wave voltammetry for early detection of carcinoembryonic antigen in human serum.

    PubMed

    Martínez-Mancera, Flavio Dolores; García-López, Patricia; Hernández-López, José Luis

    2015-04-15

    The ELISA format for measuring carcinoembryonic antigen (CEA) serves as a reference standard against which other assays are compared. Because the World Health Organization (WHO) increasingly recommends the use of serum CEA as a diagnostic tool for cancer, it is relevant to explore the reliability of the new decentralized CEA point-of-care-testing (POCT) technologies that are available to physicians and patients, in compliance with mandates of the clinical laboratories' regulatory agencies. Electrochemical immunoassay (ECIA) based on trace lead (Pb) analysis by anodic stripping techniques using sandwich-type immunocomplex conjugates: (MB)Ab/AgCEA/Ab(PbS), and a commercial ELISA test system with optical transmission. The ECIA provides better analytical performance than does the ELISA. The within assay precision coefficient of variance (%CVw) of the ECIA is lower than the value recommended by the Hong Kong Association of Medical Laboratories (HKAML), and the recoveries of CEA at 1.0, 5.0, 10.0, 25.0 and 50.0 ng/ml are in the range of 99-110% for control serum samples. The ECIA showed a minimal positive bias of 0.0267 ± 0.3270 ng/ml (P=0.9389). The proposed CEA screening technology can be practically employed for decentralized clinical analysis of CEA in human serum. Therefore, it can be viewed as a control method for personalized therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Clinical results of carotid artery stenting versus carotid endarterectomy

    PubMed Central

    Akinci, Tuba; Derle, Eda; Kibaroğlu, Seda; Harman, Ali; Kural, Feride; Cınar, Pınar; Kilinc, Munire; Akay, Hakki T.; Can, Ufuk; Benli, Ulku S.

    2016-01-01

    Objective: To review our results of carotid artery stenting (CAS) and carotid endarterectomy (CEA). Methods: We evaluated the medical records of patients undergoing carotid artery revascularization procedure, between 2001 and 2013 in Baskent University Hospital, Ankara, Turkey. Carotid artery stenting or CEA procedures were performed in patients with asymptomatic carotid stenosis (≥70%) or symptomatic stenosis (≥50%). Demographic data, procedural details, and clinical outcomes were recorded. Primary outcome measures were in 30-day stroke/transient ischemic attacks (TIA)/amaurosis fugax or death. Secondary outcome measures were nerve injury, bleeding complications, length of stay in hospital, stroke, restenosis (ICA patency), and all-cause death during long-term follow-up. Results: One hundred ninety-four CEA and 115 CAS procedures were performed for symptomatic and/or asymptomatic carotid artery stenosis. There is no significant differences 30-day mortality and neurologic morbidity between CAS (13%) and CEA procedures (7.7%). Length of stay in hospital were significantly longer in CEA group (p=0.001). In the post-procedural follow up, only in symptomatic patients, restenosis rate was higher in the CEA group (p=.045). The other endpoints did not differ significantly. Conclusions: Endovascular stent treatment of carotid artery atherosclerotic disease is an alternative for vascular surgery, especially for patients that are high risk for standard CEA. The increasing experience, development of cerebral protection systems and new treatment protocols increases CAS feasibility. PMID:27744460

  2. SONOlysis in prevention of Brain InfaRctions During Internal carotid Endarterectomy (SONOBIRDIE) trial - study protocol for a randomized controlled trial.

    PubMed

    Hrbáč, Tomáš; Netuka, David; Beneš, Vladimír; Nosáľ, Vladimír; Kešnerová, Petra; Tomek, Aleš; Fadrná, Táňa; Beneš, Vladimír; Fiedler, Jiří; Přibáň, Vladimír; Brozman, Miroslav; Langová, Kateřina; Herzig, Roman; Školoudík, David

    2017-01-17

    Carotid endarterectomy (CEA) is a beneficial procedure for selected patients with an internal carotid artery (ICA) stenosis. Surgical risk of CEA varies from between 2 and 15%. The aim of the study is to demonstrate the safety and effectiveness of sonolysis (continual transcranial Doppler monitoring, TCD) using a 2-MHz diagnostic probe with maximal diagnostic energy on the reduction of the incidence of stroke, transient ischemic attack (TIA) and brain infarction detected using magnetic resonance imaging (MRI) by the activation of the endogenous fibrinolytic system during CEA. Design: a multicenter, randomized, double-blind, sham-controlled trial. international, multicenter trial for patients with at least 70% symptomatic or asymptomatic ICA stenosis undergoing CEA. patients with symptomatic or asymptomatic ICA stenosis of at least 70% are candidates for CEA; a sufficient temporal bone window for TCD; aged 40-85 years, functionally independent; provision of signed informed consent. Randomization: consecutive patients will be assigned to the sonolysis or control (sham procedure) group by computer-generated 1:1 randomization. Prestudy calculations showed that a minimum of 704 patients in each group is needed to reach a significant difference with an alpha value of 0.05 (two-tailed) and a beta value of 0.8 assuming that 10% would be lost to follow-up or refuse to participate in the study (estimated 39 endpoints). the primary endpoint is the incidence of stroke or TIA during 30 days after CEA and the incidence of new ischemic lesions on brain MRI performed 24 h after CEA in the sonolysis and control groups. Secondary endpoints are occurrence of death, any stroke, or myocardial infarction within 30 days, changes in cognitive functions 1 year post procedure related to pretreatment scores, and number of new lesions and occurrence of new lesions ≥0.5 mL on post-procedural brain MRI. descriptive statistics and linear/logistic multiple regression models will be

  3. Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer.

    PubMed

    Maeda, Ryo; Suda, Takashi; Hachimaru, Ayumi; Tochii, Daisuke; Tochii, Sachiko; Takagi, Yasushi

    2017-01-01

    The objective of this study was to assess the preoperative serum carcinoembryonic antigen (CEA) level in patients with clinical stage IA non-small cell lung cancer (NSCLC) and to evaluate its clinical significance. Between January 2005 and December 2014, a total of 378 patients with clinical stage IA NSCLC underwent complete resection with systematic node dissection. The survival rate was estimated starting from the date of surgery to the date of either death or the last follow-up by the Kaplan-Meier method. Univariate analyses by log-rank tests were used to determine prognostic factors. Cox proportional hazards ratios were used to identify independent predictors of poor prognosis. Clinicopathological predictors of lymph node metastases were evaluated by logistic regression analyses. The 5-year survival rate of patients with an elevated preoperative serum CEA level was significantly lower than that of patients with a normal CEA level (75.5% vs. 87.7%; P=0.02). However, multivariate analysis did not show the preoperative serum CEA level to be an independent predictor of poor prognosis. Postoperative pathological factors, including lymphatic permeation, visceral pleural invasion, and lymph node metastases, tended to be positive in patients with an elevated preoperative serum CEA level. In addition, the CEA level was a statistically significant independent clinical predictor of lymph node metastases. The preoperative serum CEA level was not an independent predictor of poor prognosis in patients with pathological stage IA NSCLC but was an important clinical predictor of tumor invasiveness and lymph node metastases in patients with clinical stage IA NSCLC. Therefore, measurement of the preoperative serum CEA level should be considered even for patients with early-stage NSCLC.

  4. Significant Association of Annual Hospital Volume With the Risk of Inhospital Stroke or Death Following Carotid Endarterectomy but Likely Not After Carotid Stenting: Secondary Data Analysis of the Statutory German Carotid Quality Assurance Database.

    PubMed

    Kuehnl, Andreas; Tsantilas, Pavlos; Knappich, Christoph; Schmid, Sofie; König, Thomas; Breitkreuz, Thorben; Zimmermann, Alexander; Mansmann, Ulrich; Eckstein, Hans-Henning

    2016-11-01

    Associations between hospital volume and the risk of stroke or death following carotid endarterectomy (CEA) and carotid artery stenting (CAS) on a national level in Germany were analyzed. Secondary data analysis using microdata from the nationwide statutory German quality assurance database on all surgical or endovascular carotid interventions on the extracranial carotid artery between 2009 and 2014. Hospitals were categorized into empirically determined quintiles according to the annual case volume. The resulting volume thresholds were 10, 25, 46, and 79 for CEA and 2, 6, 12, and 26 for CAS procedures. The primary outcome was any stroke or death before hospital discharge. For risk-adjusted analyses, a multilevel regression model was applied. The analysis included 161 448 CEA and 17 575 CAS procedures. In CEA patients, the crude risk of stroke or death decreased monotonically from 4.2% (95% confidence interval, 3.6%-4.9%) in low-volume hospitals (first quintile 1-10 CEA per year) to 2.1% (2.0%-2.2%) in hospitals providing ≥80 CEA per year (fifth quintile; P<0.001 for trend). The overall risk of any stroke or death in CAS patients was 3.7% (3.5%-4.0%), but no trend on annual volume was seen (P=0.304). Risk-adjusted analyses confirmed a significant inverse relationship between hospital volume (categorized or continuous) and the risk of stroke or death after CEA but not CAS procedures. An inverse volume-outcome relationship in CEA-treated patients was demonstrated. No significant association between hospital volume and the risk of stroke or death was found for CAS. © 2016 American Heart Association, Inc.

  5. Evaluation of serum and pleural levels of endostatin and vascular epithelial growth factor in lung cancer patients with pleural effusion.

    PubMed

    Zhang, Yu; Yu, Li-Ke; Xia, Ning

    2012-03-01

    To evaluate the diagnostic value of endostatin (ES), vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) in both serum and pleural effusion of lung cancer patients. Levels of ES, VEGF and CEA in 52 malignant pleural effusion due to lung cancer and 50 patients with non-malignant disease were measured by using sandwich enzyme-linked immunosorbent assay and microparticle enzyme immunoassay. The ES, VEGF and CEA levels in pleural effusion and serum, and their ratio (F/S) were higher in lung cancer group than that in benign group, and the differences were statistically significant (P<0.05). The diagnostic efficiency of ES+VEGF for lung cancer was superior to either single detection. The diagnostic efficiency of ES+VEGF+CEA was superior to either ES+VEGF or ES+CEA. The results suggest that ES, VEGF and CEA might be useful in the differentiation between benign and malignant pleural effusion due to lung cancer. In comparison with either single determination of concentration in serum or pleural fluid, the combined detection of two or three markers is of important clinical significance in the diagnosis of lung cancer. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  6. Reference Intervals of Alpha-Fetoprotein and Carcinoembryonic Antigen in the Apparently Healthy Population.

    PubMed

    Zhang, Gao-Ming; Guo, Xu-Xiao; Ma, Xiao-Bo; Zhang, Guo-Ming

    2016-12-12

    BACKGROUND The aim of this study was to calculate 95% reference intervals and double-sided limits of serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) according to the CLSI EP28-A3 guideline. MATERIAL AND METHODS Serum AFP and CEA values were measured in samples from 26 000 healthy subjects in the Shuyang area receiving general health checkups. The 95% reference intervals and upper limits were calculated by using MedCalc. RESULTS We provided continuous reference intervals from 20 years old to 90 years old for AFP and CEA. The reference intervals were: AFP, 1.31-7.89 ng/ml (males) and 1.01-7.10 ng/ml (females); CEA, 0.51-4.86 ng/ml (males) and 0.35-3.45ng/ml (females). AFP and CEA were significantly positively correlated with age in both males (r=0.196 and r=0.198) and females (r=0.121 and r=0.197). CONCLUSIONS Different races or populations and different detection systems may result in different reference intervals for AFP and CEA. Continuous reference intervals of age changes are more accurate than age groups.

  7. Reference Intervals of Alpha-Fetoprotein and Carcinoembryonic Antigen in the Apparently Healthy Population

    PubMed Central

    Zhang, Gao-Ming; Guo, Xu-Xiao; Ma, Xiao-Bo; Zhang, Guo-Ming

    2016-01-01

    Background The aim of this study was to calculate 95% reference intervals and double-sided limits of serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) according to the CLSI EP28-A3 guideline. Material/Methods Serum AFP and CEA values were measured in samples from 26 000 healthy subjects in the Shuyang area receiving general health checkups. The 95% reference intervals and upper limits were calculated by using MedCalc. Results We provided continuous reference intervals from 20 years old to 90 years old for AFP and CEA. The reference intervals were: AFP, 1.31–7.89 ng/ml (males) and 1.01–7.10 ng/ml (females); CEA, 0.51–4.86 ng/ml (males) and 0.35–3.45ng/ml (females). AFP and CEA were significantly positively correlated with age in both males (r=0.196 and r=0.198) and females (r=0.121 and r=0.197). Conclusions Different races or populations and different detection systems may result in different reference intervals for AFP and CEA. Continuous reference intervals of age changes are more accurate than age groups. PMID:27941709

  8. CEA (Carcinoembryonic Antigen) Test

    MedlinePlus

    ... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin ... Transferrin Receptor Stool Culture Stool Elastase Strep ...

  9. Independent prognostic impact of preoperative serum carcinoembryonic antigen and cancer antigen 15-3 levels for early breast cancer subtypes.

    PubMed

    Imamura, Michiko; Morimoto, Takashi; Nomura, Takashi; Michishita, Shintaro; Nishimukai, Arisa; Higuchi, Tomoko; Fujimoto, Yukie; Miyagawa, Yoshimasa; Kira, Ayako; Murase, Keiko; Araki, Kazuhiro; Takatsuka, Yuichi; Oh, Koshi; Masai, Yoshikazu; Akazawa, Kouhei; Miyoshi, Yasuo

    2018-02-12

    Although the prognosis for operable breast cancers is reportedly worse if serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are above normal, the usefulness of this prognosis is limited due to the low sensitivity and specificity; in addition, the optimal cutoff levels remain unknown. A total of 1076 patients who were operated for breast cancers (test set = 608, validation set = 468) without evidence of metastasis were recruited, and their baseline and postoperative serum CEA and CA15-3 levels were analyzed. The optimal cutoff values of CEA and CA15-3 for disease-free survival (DFS) were 3.2 ng/mL and 13.3 U/mL, respectively, based on receiver operating characteristic curve and area under the curve analyses. The DFS of patients with high CEA levels (CEA-high: n = 191, 5-year DFS 70.6%) was significantly worse (p < 0.0001) than that of CEA-low patients (n = 885, 5-year DFS 87.2%). There was a significant difference in DFS (p < 0.0001) between CA15-3-high and CA15-3-low patients (n = 314 and n = 762, respectively; 5-year DFS 71.8 vs. 89.3%). Significant associations between DFS and CA15-3 levels were observed irrespective of the subtypes. Multivariable analysis indicated that tumor size, lymph node metastasis, tumor grade, and CEA (p = 0.0474) and CA15-3 (p < 0.0001) levels were independent prognostic factors (hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.005-2.245 for CEA; HR 2.088, 95% CI 1.457-2.901 for CA15-3). These findings suggest that CEA and CA15-3 levels might be useful for predicting the prognosis of patients with operable early breast cancer irrespective of the subtype. Serum levels at baseline may reflect tumor characteristics for metastatic potential even when these levels are within the normal ranges.

  10. The value of innovation under value-based pricing.

    PubMed

    Moreno, Santiago G; Ray, Joshua A

    2016-01-01

    The role of cost-effectiveness analysis (CEA) in incentivizing innovation is controversial. Critics of CEA argue that its use for pricing purposes disregards the 'value of innovation' reflected in new drug development, whereas supporters of CEA highlight that the value of innovation is already accounted for. Our objective in this article is to outline the limitations of the conventional CEA approach, while proposing an alternative method of evaluation that captures the value of innovation more accurately. The adoption of a new drug benefits present and future patients (with cost implications) for as long as the drug is part of clinical practice. Incidence patients and off-patent prices are identified as two key missing features preventing the conventional CEA approach from capturing 1) benefit to future patients and 2) future savings from off-patent prices. The proposed CEA approach incorporates these two features to derive the total lifetime value of an innovative drug (i.e., the value of innovation). The conventional CEA approach tends to underestimate the value of innovative drugs by disregarding the benefit to future patients and savings from off-patent prices. As a result, innovative drugs are underpriced, only allowing manufacturers to capture approximately 15% of the total value of innovation during the patent protection period. In addition to including the incidence population and off-patent price, the alternative approach proposes pricing new drugs by first negotiating the share of value of innovation to be appropriated by the manufacturer (>15%?) and payer (<85%?), in order to then identify the drug price that satisfies this condition. We argue for a modification to the conventional CEA approach that integrates the total lifetime value of innovative drugs into CEA, by taking into account off-patent pricing and future patients. The proposed approach derives a price that allows manufacturers to capture an agreed share of this value, thereby incentivizing

  11. Highly sensitive and selective lateral flow immunoassay based on magnetic nanoparticles for quantitative detection of carcinoembryonic antigen.

    PubMed

    Liu, Fangming; Zhang, Honglian; Wu, Zhenhua; Dong, Haidao; Zhou, Lin; Yang, Dawei; Ge, Yuqing; Jia, Chunping; Liu, Huiying; Jin, Qinghui; Zhao, Jianlong; Zhang, Qiqing; Mao, Hongju

    2016-12-01

    Carcinoembryonic antigen (CEA) is an important biomarker in cancer diagnosis. Here, we present an efficient, selective lateral-flow immunoassay (LFIA) based on magnetic nanoparticles (MNPs) for in situ sensitive and accurate point-of-care detection of CEA. Signal amplification mechanism involved linking of detection MNPs with signal MNPs through biotin-modified single-stranded DNA (ssDNA) and streptavidin. To verify the effectiveness of this modified LFIA system, the sensitivity and specificity were evaluated. Sensitivity evaluation showed a broad detection range of 0.25-1000ng/ml for CEA protein by the modified LFIA, and the limit of detection (LOD) of the modified LFIA was 0.25ng/ml, thus producing significant increase in detection threshold compared with the traditional LFIA. The modified LFIA could selectively recognize CEA in presence of several interfering proteins. In addition, this newly developed assay was applied for quantitative detection of CEA in human serum specimens collected from 10 randomly selected patients. The modified LFIA system detected minimum 0.27ng/ml of CEA concentration in serum samples. The results were consistent with the clinical data obtained using commercial electrochemiluminescence immunoassay (ECLIA) (p<0.01). In conclusion, the MNPs based LFIA system not only demonstrated enhanced signal to noise ratio, it also detected CEA with higher sensitivity and selectivity, and thus has great potential to be commercially applied as a sensitive tumor marker filtration system. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Literature review of cranial nerve injuries during carotid endarterectomy.

    PubMed

    Sajid, M S; Vijaynagar, B; Singh, P; Hamilton, G

    2007-01-01

    In the recent prospective randomised trials on carotid endarterectomy (CEA), the incidence of cranial nerve injuries (CNI) are reported to be higher than in previously published studies. The objective of this study is to review the incidence of post CEA cranial nerve injury and to discover whether it has changed in the last 25 years after many innovations in vascular surgery. Generic terms including carotid endarterectomy, cranial nerve injuries, post CEA complications and cranial nerve deficit after neck surgery were used to search a variety of electronic databases. Based on selection criteria, decisions regarding inclusion and exclusion of primary studies were made. The incidence of CNI before and after 1995 was compared. We found 31 eligible studies from the literature. Patients who underwent CEA through any approach were included in the study. All patients had cranial nerves examined both before and after surgery. The total number of patients who had CEA before 1995 was 3521 with 10.6% CNI (352 patients) and after 1995, 7324 patients underwent CEA with 8.3% CNI (614 patients). Cranial nerves XII, X and VII were most commonly involved (rarely IX and XI). Statistical analysis showed that the incidence of CNI has decreased (X(2) = 5.89 + 0.74 = 6.63 => p-value = 0.0100). CNI is still a significant postoperative complication of carotid endarterectomy. Despite increasing use of CEA, the incidence of CNI has decreased probably because of increased awareness of the possibility of cranial nerve damage.

  13. Evidence for carboxyl-terminal processing and glycolipid-anchoring of human carcinoembryonic antigen.

    PubMed

    Takami, N; Misumi, Y; Kuroki, M; Matsuoka, Y; Ikehara, Y

    1988-09-05

    We have investigated the post-translational modification of carcinoembryonic antigen (CEA) for membrane-anchoring in QGP-1 cells derived from a human pancreatic carcinoma. Pulse-chase experiments with [3H]leucine demonstrated that CEA was initially synthesized as a precursor form with Mr 150,000 having N-linked high-mannose-type oligosaccharides, which was then converted to a mature form with Mr 200,000 containing the complex type sugar chains. The mature protein thus labeled was found to be released from the cell surface by treatment with phosphatidylinositol-specific phospholipase C, suggesting that CEA is a phosphatidylinositol-linked membrane protein. This was confirmed by metabolic incorporation into CEA of 3H-labeled compounds such as ethanolamine, myo-inositol, palmitic acid, and stearic acid. The 3H-labeled fatty acids incorporated were specifically removed from the protein by nitrous acid deamination as well as by phosphatidylinositol-specific phospholipase C treatment. Since the available cDNA sequence predicts that CEA contains a single methionine residue only in its carboxyl-terminal hydrophobic domain, processing of the carboxyl terminus was examined by pulse-chase experiments with [35S]methionine. It was found that CEA with Mr 150,000 was initially labeled with [35S]methionine but its radioactivity was immediately lost with chase. Taken together, these results suggest that CEA is anchored to the membrane by simultaneously occurring proteolysis of the carboxyl terminus and replacement by the glycophospholipid immediately after the synthesis.

  14. Patient risk perceptions for carotid endarterectomy: which patients are strongly averse to surgery?

    PubMed

    Bosworth, Hayden B; Stechuchak, Karen M; Grambow, Steven C; Oddone, Eugene Z

    2004-07-01

    Patient risk perception for surgery may be central to their willingness to undergo surgery. This study examined potential factors associated with patient aversion of surgery. This is a secondary data analysis of a prospective cohort study that examined patients referred for evaluation of carotid artery stenosis at five Veterans Affairs Medical Centers. The study collected demographic, clinical, and psychosocial information related to surgery. This analysis focused on patient response to a question assessing their aversion to surgery. Among the 1065 individuals, at the time of evaluation for carotid endarterectomy (CEA), 66% of patients had no symptoms, 16% had a transient ischemic attack, and 18% had stroke. Twelve percent of patients referred for CEA evaluation were averse to surgery. In adjusted analyses, increased age, black race, no previous surgery, lower level of chance locus of control, less trust of physicians, and less social support were significantly related to greater likelihood of surgery aversion among individuals referred for CEA evaluation. Patient degree of medical comorbidity and a validated measure of preoperative risk score were not associated with increased aversion to surgery. In previous work, aversion to CEA was associated with lack of receipt of CEA even after accounting for patient clinical appropriateness for surgery. We identified important patient characteristics associated with aversion to CEA. Interventions designed to assist patient decision making should focus on these more complex factors related to CEA aversion rather than the simple explanation of clinical usefulness.

  15. Assessing the quality of online information for patients with carotid disease.

    PubMed

    Keogh, C J; McHugh, S M; Clarke Moloney, M; Hannigan, A; Healy, D A; Burke, P E; Kavanagh, E G; Grace, P A; Walsh, S R

    2014-01-01

    Controversy exists relating to carotid endarterectomy (CEA) versus carotid artery stenting (CAS). We aimed to assess the quality of online patient information relating to both. The Google search engine was searched for "carotid endarterectomy" and "carotid stenting". The first 50 webpages returned were assessed. The Gunning Fog Index (GFI) and Flesch Reading Ease Score (FRES) were calculated to assess readability. The LIDA tool (Minervation Ltd., Oxford, U.K.) was used to assess accessibility, usability and reliability. 20% (n = 10) of the webpages returned for CEA were from peer reviewed sources with 34% (n = 17) posted by hospitals or health services. Comparatively, for CAS, 40% (n = 20) were peer reviewed with 16% (n = 8) posted by hospitals or health services. GFI and FRES scores indicated webpages for both CEA and CAS had poor general readability. Webpages for CEA were easier to read than those for CAS (mean FRES difference of 6.7 (95% CI 0.51 to 12.93, p = 0.03). Median LIDA scores demonstrated acceptable reliability, accessibility and usability of information for both CEA and CAS webpages. The more readable webpages were not associated with higher LIDA scores for either CEA or CAS webpages. Webpages providing information on carotid disease management must be made more readable. Online information currently available to patients regarding CAS is more difficult to read and comprehend than CEA. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  16. Carotid Endarterectomy: Current Concepts and Practice Patterns

    PubMed Central

    Saha, Sibu P.; Saha, Subhajit; Vyas, Krishna S.

    2015-01-01

    Background Stroke is the number one cause of disability and third leading cause of death among adults in the United States. A major cause of stroke is carotid artery stenosis (CAS) caused by atherosclerotic plaques. Randomized trials have varying results regarding the equivalence and perioperative complication rates of stents versus carotid endarterectomy (CEA) in the management of CAS. Objectives We review the evidence for the current management of CAS and describe the current concepts and practice patterns of CEA. Methods A literature search was conducted using PubMed to identify relevant studies regarding CEA and stenting for the management of CAS. Results The introduction of CAS has led to a decrease in the percentage of CEA and an increase in the number of CAS procedures performed in the context of all revascularization procedures. However, the efficacy of stents in patients with symptomatic CAS remains unclear because of varying results among randomized trials, but the perioperative complication rates exceed those found after CEA. Conclusions Vascular surgeons are uniquely positioned to treat carotid artery disease through medical therapy, CEA, and stenting. Although data from randomized trials differ, it is important for surgeons to make clinical decisions based on the patient. We believe that CAS can be adopted with low complication rate in a selected subgroup of patients, but CEA should remain the standard of care. This current evidence should be incorporated into practice of the modern vascular surgeon. PMID:26417192

  17. Surface-enhanced Raman scattering study of carcinoembryonic antigen in serum from patients with colorectal cancers

    NASA Astrophysics Data System (ADS)

    Chen, Gang; Chen, Yanping; Zheng, Xiongwei; He, Cheng; Lu, Jianping; Feng, Shangyuan; Chen, Rong; Zeng, Haisan

    2013-12-01

    In this work, we developed a SERS platform for quantitative detection of carcinoembryonic antigen (CEA) in serum of patients with colorectal cancers. Anti-CEA-functionalized 4-mercaptobenzoic acid-labeled Au/Ag core-shell bimetallic nanoparticles were prepared first and then used to analyze CEA antigen solutions of different concentrations. A calibration curve was established in the range from 5 × 10-3 to 5 × 105 ng/mL. Finally, this new SERS probe was applied for quantitative detection of CEA in serum obtained from 26 colorectal cancer patients according to the calibration curve. The results were in good agreement with that obtained by electrochemical luminescence method, suggesting that SERS immunoassay has high sensitivity and specificity for CEA detection in serum. A detection limit of 5 pg/ml was achieved. This study demonstrated the feasibility and great potential for developing this new technology into a clinical tool for analysis of tumor markers in the blood.

  18. Safety of carotid endarterectomy while on clopidogrel (Plavix). Clinical article.

    PubMed

    Wait, Scott D; Abla, Adib A; Killory, Brendan D; Starke, Robert M; Spetzler, Robert F; Nakaji, Peter

    2010-10-01

    Many patients undergoing carotid endarterectomy (CEA) regularly take clopidogrel, a permanent platelet inhibitor. The authors sought to determine whether taking clopidogrel in the period before CEA leads to more bleeding or other complications. The authors performed a retrospective, institutional review board–approved review of 182 consecutive patients who underwent CEA. Clinical, radiographic, and surgical data were gleaned from hospital and clinic records. Analysis was based on the presence or absence of clopidogrel in patients undergoing CEA and was performed twice by considering clopidogrel use within 8 days and within 5 days of surgery to define the groups. Taking clopidogrel within 8 days before surgery resulted in no statistical increase in any measure of morbidity or death. Taking clopidogrel within 5 days was associated with a small but significant increase in operative blood loss and conservatively managed postoperative neck swelling. No measure of permanent morbidity or death was increased in either clopidogrel group. Findings in this study support the safety of preoperative clopidogrel in patients undergoing CEA.

  19. Diagnostic value of tumor markers for lung adenocarcinoma-associated malignant pleural effusion: a validation study and meta-analysis.

    PubMed

    Feng, Mei; Zhu, Jing; Liang, Liqun; Zeng, Ni; Wu, Yanqiu; Wan, Chun; Shen, Yongchun; Wen, Fuqiang

    2017-04-01

    Pleural effusion is one of the most common complications of lung adenocarcinoma and is diagnostically challenging. This study aimed to investigate the diagnostic performance of carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, and cancer antigen (CA) 19-9 for lung adenocarcinoma-associated malignant pleural effusion (MPE) through a validation study and meta-analysis. Pleural effusion samples were collected from 81 lung adenocarcinoma-associated MPEs and 96 benign pleural effusions. CEA, CYFRA 21-1, and CA19-9 were measured by electrochemiluminescence immunoassay. The capacity of tumor markers was assessed with receiver operating characteristic curve analyses and the area under the curve (AUC) was calculated. Standard methods for meta-analysis of diagnostic studies were used to summarize the diagnostic performance of CEA, CYFRA 21-1, and CA19-9 for lung adenocarcinoma-associated MPE. The pleural levels of CEA, CYFRA 21-1, and CA19-9 were significantly increased in lung adenocarcinoma-associated MPE compared to benign pleural effusion. The cut-off points for CEA, CYFRA 21-1, and CA19-9 were optimally set at 4.55 ng/ml, 43.10 μg/ml, and 12.89 U/ml, and corresponding AUCs were 0.93, 0.85, and 0.81, respectively. The combination of CEA, CYFRA 21-1, and CA19-9 increased the sensitivity to 95.06%, with an AUC of 0.95. Eight studies were included in this meta-analysis. CEA showed the best diagnostic performance with pooled sensitivity, specificity, positive/negative likelihood ratio, and diagnostic odds ratio of 0.75, 0.96, 16.01, 0.23, and 81.49, respectively. The AUC was 0.93. CEA, CYFRA 21-1, and CA19-9 play a role in the diagnosis of lung adenocarcinoma-associated MPE. The combination of these tumor markers increases the diagnostic accuracy.

  20. Clinical value of jointly detection serum lactate dehydrogenase/pleural fluid adenosine deaminase and pleural fluid carcinoembryonic antigen in the identification of malignant pleural effusion.

    PubMed

    Zhang, Fan; Hu, Lijuan; Wang, Junjun; Chen, Jian; Chen, Jie; Wang, Yumin

    2017-09-01

    Limited data are available for the diagnostic value, and for the diagnostic sensitivity and specificity of joint detection of serum lactate dehydrogenase (sLDH)/pleural fluid adenosine deaminase (pADA) and pleural fluid carcinoembryonic antigen (pCEA) in malignant pleural effusion (MPE). We collected 987 pleural effusion specimens (of which 318 were malignant pleural effusion, 374 were tubercular pleural effusion, and 295 were parapneumonic effusion specimens) from the First Affiliated Hospital of Wenzhou Medical University from July 2012 to March 2016. The pADA, sLDH, pleural fluid LDH (pLDH), serum C-reactive protein (sCRP), pleural fluid protein, pCEA, white blood cell (WBC), and red blood cell (RBC) were analyzed, and the clinical data of each group were collected for statistical analysis. The level of sLDH/pADA, pCEA, and RBC from the MPE group was markedly higher than the tuberculosis pleural effusion (TB) group (Mann-Whitney U=28422.000, 9278.000, 30518, P=.000, .000, .000) and the parapneumonic pleural fluid group (Mann-Whitney U=5972.500, 7113.000, 36750.500, P=.000, .000, .000). The receiver operating characteristic curve ROC showed that the area under the ROC curve (AUC) (=0.924, 0.841) of pCEA and sLDH/pADA (cutoff=4.9, 10.6) were significantly higher than other markers for the diagnosis of MPE. Thus, joint detection of pCEA and sLDH/pADA suggested that the sensitivity, specificity, and AUC was 0.94, 81.70, and 94.32 at the cutoff 0.16 and diagnostic performance was higher than pCEA or sLDH/pADA. Joint detection of sLDH/pADA and pCEA can be used as a good indicator for the identification of benign and MPE with higher sensitivity and specificity than pCEA or sLDH/pADA. © 2016 Wiley Periodicals, Inc.

  1. Visual Aids for Improving Patient Decision Making in Severe Symptomatic Carotid Stenosis.

    PubMed

    Fridman, Sebastian; Saposnik, Gustavo; Sposato, Luciano A

    2017-12-01

    Because of the large amount of information to process and the limited time of a clinical consult, choosing between carotid endarterectomy (CEA) and carotid angioplasty with stenting (CAS) can be confusing for patients with severe symptomatic internal carotid stenosis (ICA). We aim to develop a visual aid tool to help clinicians and patients in the decision-making process of selecting between CEA and CAS. Based on pooled analysis from randomized controlled trials including patients with symptomatic and severe ICA (SSICA), we generated visual plots comparing CEA with CAS for 3 prespecified postprocedural time points: (1) any stroke or death at 4 months, and (2) any stroke or death in the first 30 days and ipsilateral stroke thereafter at 5 years and (3) at 10 years. A total of 4574 participants (2393 assigned to CAS, and 2361 to CEA) were included in the analyses. For every 100 patients with SSICA, 6 would develop any stroke or death in the CEA group compared with 9 undergoing CAS at 4 months (hazard ratio [HR] 1.53; 95%CI 1.20-1.95). At 5 years, 7 patients in the CEA group would develop any periprocedural stroke or death and ipsilateral stroke thereafter versus 12 undergoing CAS (HR 1.72; 95%CI 1.24-2.39), compared with 10 patients in the CEA and 13 in the CAS groups at 10 years (HR 1.17; 95%CI 0.82-1.66). Visual aids presented in this study could potentially help patients with severe symptomatic internal carotid stenosis to better weigh the risks and benefits of CEA versus CAS as a function of time, allowing for the prioritization of personal preferences, and should be prospectively assessed. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  2. Effects of unilatral- and bilateral inhibition of rostral ventral tegmental area and central nucleus of amygdala on morphine-induced place conditioning in male Wistar rat.

    PubMed

    Mohammadian, Zahra; Sahraei, Hedayat; Meftahi, Gholam Hossein; Ali-Beik, Hengameh

    2017-03-01

    The rostral ventral tegmental area (VTAR) and central nucleus of amygdala (CeA) are considered the main regions for induction of psychological dependence on abused drugs, such as morphine. The main aim of this study was to investigate the transient inhibition of each right and left side as well as both sides of the VTAR and the CeA by lidocaine (2%) on morphine reward properties using the conditioned place preference (CPP) method. Male Wistar rats (250±20 g) 7 days after recovery from surgery and cannulation were conditioned to morphine (7.5 mg/kg) in CPP apparatus. Five minutes before morphine injection in conditioning phase, lidocaine was administered either uni- or bilaterally into the VTAR (0.25 μL/site) or CeA (0.5 μL/site). The results revealed that lidocaine administration into the left side, but not the right side of the VTAR and the CeA reduced morphine CPP significantly. The reduction was potentiated when lidocaine was injected into both sides of the VTAR and the CeA. The number of compartment crossings was reduced when lidocaine was injected into both sides of the VTAR and the CeA as well as the left side. Rearing was reduced when lidocaine was injected into the right, but not the left side of the VTAR. Sniffing and rearing increased when animals received lidocaine in the right side and reduced in the group that received lidocaine in the left side of the CeA. It was concluded that the right and the left side of VTAR and the CeA play different roles in morphine-induced activity and reward. © 2016 John Wiley & Sons Australia, Ltd.

  3. Cost-effectiveness analyses in orthopaedic sports medicine: a systematic review.

    PubMed

    Nwachukwu, Benedict U; Schairer, William W; Bernstein, Jaime L; Dodwell, Emily R; Marx, Robert G; Allen, Answorth A

    2015-06-01

    As increasing attention is paid to the cost of health care delivered in the United States (US), cost-effectiveness analyses (CEAs) are gaining in popularity. Reviews of the CEA literature have been performed in other areas of medicine, including some subspecialties within orthopaedics. Demonstrating the value of medical procedures is of utmost importance, yet very little is known about the overall quality and findings of CEAs in sports medicine. To identify and summarize CEA studies in orthopaedic sports medicine and to grade the quality of the available literature. Systematic review. A systematic review of the literature was performed to compile findings and grade the methodological quality of US-based CEA studies in sports medicine. The Quality of Health Economic Studies (QHES) instrument and the checklist by the US Panel on Cost-effectiveness in Health and Medicine were used to assess study quality. One-sided Fisher exact testing was performed to analyze the predictors of high-quality CEAs. Twelve studies met inclusion criteria. Five studies examined anterior cruciate ligament reconstruction, 3 studies examined rotator cuff repair, 2 examined autologous chondrocyte implantation, 1 study examined hip arthroscopic surgery, and 1 study examined the operative management of shoulder dislocations. Based on study findings, operative intervention in sports medicine is highly cost-effective. The quality of published evidence is good, with a mean quality score of 81.8 (range, 70-94). There is a trend toward higher quality in more recent publications. No significant predictor of high-quality evidence was found. The CEA literature in sports medicine is good; however, there is a paucity of studies, and the available evidence is focused on a few procedures. More work needs to be conducted to quantify the cost-effectiveness of different techniques and procedures within sports medicine. The QHES tool may be useful for the evaluation of future CEAs. © 2014 The Author(s).

  4. Carotid bypass: a safe and durable solution for recurrent carotid stenosis.

    PubMed

    Spinelli, Francesco; Martelli, Eugenio; Stilo, Francesco; Pipitò, Narayana; Benedetto, Filippo; Spinelli, Domenico; Squillaci, Domenico; De Caridi, Giovanni; Barillà, David

    2014-07-01

    The long-term results of carotid artery stenting (CAS) for post-carotid endarterectomy (CEA) restenosis are disappointing (4-year patency rates: ∼75%). Since 1988, our group has offered carotid bypass (CB) as an alternative to redo CEA and later also to CAS in this setting. The aim of this retrospective study was to investigate early and late outcomes associated with CB in this population. Data were collected from patients treated with CB in the year 2000-2012 for significant/symptomatic post-CEA restenosis (or intra-stent restenosis [ISR] after CAS for post-CEA restenosis). All patients had good life expectancy. CB was performed under loco-regional anesthesia. With the aid of sequential vessel clamping, the graft (great saphenous vein [GSV] or polytetrafluoroethylene) was anastomosed with the common carotid artery (side-to-end) and the distal internal carotid artery (end-to-side). Patients were followed with clinical and duplex scan assessments at 1, 3, and 6 months and yearly thereafter. The study population comprised 21 patients (mean age 67.3 years; 17 men). CB was performed for post-CEA restenosis (or ISR after CAS for post-CEA restenosis, n=3) 51.2 months (mean) after the previous operation. GSV grafts were used in half of the cases (n=11; 52.4%); temporary shunting was used in 4 (19%) patients. Intraoperative complications (none fatal) occurred in 4 (19%) patients (3 transient peripheral nerve injuries, 1 cervical hematoma). During follow-up (mean 64.8 months), there were no neurologic complications or restenoses. Overall mortality was 33.3% (6 deaths from acute myocardial infarctions, 1 from a ruptured abdominal aortic aneurysm). For post-CEA restenosis (or ISR after CAS for post-CEA restenosis), CB offers superior long-term patency rates than CAS (or redo angioplasty) and an acceptable risk of cranial nerve damage. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Measurement of the center edge angle and determination of the Severin classification using digital radiography, computer-assisted measurement tools, and a Severin algorithm: intraobserver and interobserver reliability revisited.

    PubMed

    Carroll, Kristen L; Murray, Kathleen A; MacLeod, Lynne M; Hennessey, Theresa A; Woiczik, Marcella R; Roach, James W

    2011-06-01

    Numerous studies underscore the poor intraobserver and interobserver reliability of both the center edge angle (CEA) and the Severin classification using plain film measurements. In this study, experienced observers applied a computer-assisted measurement program to determine the CEA in digital pelvic radiographs of adults who had been previously treated for dysplasia of the hip (DDH). Using a teaching aid/algorithm of the Severin classification, the observers then assigned a Severin rating to these hips. Intraobserver and interobserver errors were then calculated on both the CEA measurements and the Severin classifications. Four pediatric orthopaedic surgeons and 1 pediatric radiologist calculated the CEAs using the OrthoView TM planning system and then determined the Severin classification on 41 blinded digital pelvic radiographs. The radiographs were evaluated by each examiner twice, with evaluations separated by 2 months. All examiners reviewed a Severin classification algorithm before making their Severin assignments. The intraobserver and interobserver reliability for both the CEA and the Severin classification were calculated using the interclass correlation coefficients and Cohen and Fleiss κ scores, respectively. The intraobserver and interobserver reliability for CEA measurement was moderate to almost perfect. When we separated the Severin classification into 3 clinically relevant groups of good (Severin I and II), dysplastic (Severin III), and poor (Severin IV and above), our interobserver reliability neared almost perfect. The Severin classification is an extremely useful and oft-used radiographic measure for the success of DDH treatment. Our research found digital radiography, computer-aided measurement tools, the use of a Severin algorithm, and separating the Severin classification into 3 clinically relevant groups significantly increased the intraobserver and interobserver reliability of both the CEA and Severin classification. This finding will

  6. Carotid endarterectomy: the change in practice over 11 years in a stroke centre.

    PubMed

    Tse, Gabrielle T W; Kilkenny, Monique F; Bladin, Chris; Grigg, Michael; Dewey, Helen M

    2017-11-13

    Recent research evidence has impacted the practice of carotid endarterectomy (CEA). We aim to characterize changes in the practice and outcome of CEA over time in a single large-volume stroke centre. All patients who underwent CEA from 2004 to 2014 and carotid angioplasty and stenting (CAS) from 2003 to 2008 at an Australian metropolitan tertiary stroke centre hospital were included. Clinical data were analysed to identify time trends in choice of intervention, patient selection, preoperative imaging utilization, surgical timing and outcome. There were 510 CEAs performed during 2004-2014 and 95 CASs during 2003-2008. The proportion of patients undergoing CEA compared to CAS increased from 60% to 90% from 2004 to 2008 (P < 0.001). CAS patients were more likely to have cardiac co-morbidities. From 2004 to 2014, the proportion of CEA patients aged ≥80 years increased (P = 0.001) and the proportion of asymptomatic patients decreased (P = 0.003) over time. Median time from symptom onset to surgery decreased from 52 days (Q1: 25, Q3: 74) in 2004 to 8 days (Q1: 5, Q3: 37) in 2014 (P < 0.001). Use of preoperative ultrasonography decreased whilst CT angiography and the number of imaging modalities applied to each patient increased over time (P < 0.001). Overall, 5.9% of CEAs were complicated by death, stroke or acute myocardial infarction with no significant change over time. The trends in CEA practice at our centre align with international trends and guidelines. This study provides a representative indicator of Australian hospital practice, and illustrates how evidence from research is translated into clinical care. © 2017 Royal Australasian College of Surgeons.

  7. Use of number needed to treat in cost-effectiveness analyses.

    PubMed

    Garg, Vishvas; Shen, Xian; Cheng, Yan; Nawarskas, James J; Raisch, Dennis W

    2013-03-01

    To review the use of number needed to treat (NNT) and/or number needed to harm (NNH) values to determine their relevance in helping clinicians evaluate cost-effectiveness analyses (CEAs). PubMed and EconLit were searched from 1966 to September 2012. Reviews, editorials, non-English-language articles, and articles that did not report NNT/NNH or cost-effectiveness ratios were excluded. CEA studies reporting cost per life-year gained, per quality-adjusted life-year (QALY), or other cost per effectiveness measure were included. Full texts of all included articles were reviewed for study information, including type of journal, impact factor of the journal, focus of study, data source, publication year, how NNT/NNH values were reported, and outcome measures. A total of 188 studies were initially identified, with 69 meeting our inclusion criteria. Most were published in clinician-practice-focused journals (78.3%) while 5.8% were in policy-focused journals, and 15.9% in health-economics-focused journals. The majority (72.4%) of the articles were published in high-impact journals (impact factor >3.0). Many articles focused on either disease treatment (40.5%) or disease prevention (40.5%). Forty-eight percent reported NNT as a part of the CEA ratio per event. Most (53.6%) articles used data from literature reviews, while 24.6% used data from randomized clinical trials, and 20.3% used data from observational studies. In addition, 10% of the studies implemented modeling to perform CEA. CEA studies sometimes include NNT ratios. Although it has several limitations, clinicians often use NNT for decision-making, so including NNT information alongside CEA findings may help clinicians better understand and apply CEA results. Further research is needed to assess how NNT/NNH might meaningfully be incorporated into CEA publications.

  8. Glutamatergic transmission in the central nucleus of the amygdala is selectively altered in Marchigian Sardinian alcohol-preferring rats: alcohol and CRF effects

    PubMed Central

    Herman, Melissa A.; Varodayan, Florence P.; Oleata, Christopher S.; Luu, George; Kirson, Dean; Heilig, Markus; Ciccocioppo, Roberto; Roberto, Marisa

    2015-01-01

    The CRF system of the central nucleus of the amygdala (CeA) is important for the processing of anxiety, stress, and effects of acute and chronic ethanol. We previously reported that ethanol decreases evoked glutamate transmission in the CeA of Sprague Dawley rats and that ethanol dependence alters glutamate release in the CeA. Here, we examined the effects of ethanol, CRF and a CRF1 receptor antagonist on spontaneous and evoked glutamatergic transmission in CeA neurons from Wistar and Marchigian Sardinian Preferring (msP) rats, a rodent line genetically selected for excessive alcohol drinking and characterized by heightened activity of the CRF1 system. Basal spontaneous and evoked glutamate transmission in CeA neurons from msP rats was increased compared to Wistar rats. Ethanol had divergent effects, either increasing or decreasing spontaneous glutamate release in the CeA of Wistar rats. This bidirectional effect was retained in msP rats, but the magnitude of the ethanol-induced increase in glutamate release was significantly smaller. The inhibitory effect of ethanol on evoked glutamatergic transmission was similar in both strains. CRF also either increased or decreased spontaneous glutamate release in CeA neurons of Wistar rats, however, in msP rats CRF only increased glutamate release. The inhibitory effect of CRF on evoked glutamatergic transmission was also lost in neurons from msP rats. A CRF1 antagonist produced only minor effects on spontaneous glutamate transmission, which were consistent across strains, and no effects on evoked glutamate transmission. These results demonstrate that the genetically altered CRF system of msP rats results in alterations in spontaneous and stimulated glutamate signaling in the CeA that may contribute to both the anxiety and drinking behavioral phenotypes. PMID:26519902

  9. Nociceptin/orphanin FQ decreases glutamate transmission and blocks ethanol-induced effects in the central amygdala of naive and ethanol-dependent rats.

    PubMed

    Kallupi, Marsida; Varodayan, Florence P; Oleata, Christopher S; Correia, Diego; Luu, George; Roberto, Marisa

    2014-04-01

    The central nucleus of the amygdala (CeA) mediates several addiction-related processes and nociceptin/orphanin FQ (nociceptin) regulates ethanol intake and anxiety-like behaviors. Glutamatergic synapses, in the CeA and throughout the brain, are very sensitive to ethanol and contribute to alcohol reinforcement, tolerance, and dependence. Previously, we reported that in the rat CeA, acute and chronic ethanol exposures significantly decrease glutamate transmission by both pre- and postsynaptic actions. In this study, using electrophysiological techniques in an in vitro CeA slice preparation, we investigated the effects of nociceptin on glutamatergic transmission and its interaction with acute ethanol in naive and ethanol-dependent rats. We found that nociceptin (100-1000 nM) diminished basal-evoked compound glutamatergic receptor-mediated excitatory postsynaptic potentials (EPSPs) and spontaneous and miniature EPSCs (s/mEPSCs) by mainly decreasing glutamate release in the CeA of naive rats. Notably, nociceptin blocked the inhibition induced by acute ethanol (44 mM) and ethanol blocked the nociceptin-induced inhibition of evoked EPSPs in CeA neurons of naive rats. In neurons from chronic ethanol-treated (ethanol-dependent) rats, the nociceptin-induced inhibition of evoked EPSP amplitude was not significantly different from that in naive rats. Application of [Nphe1]Nociceptin(1-13)NH2, a nociceptin receptor (NOP) antagonist, revealed tonic inhibitory activity of NOP on evoked CeA glutamatergic transmission only in ethanol-dependent rats. The antagonist also blocked nociceptin-induced decreases in glutamatergic responses, but did not affect ethanol-induced decreases in evoked EPSP amplitude. Taken together, these studies implicate a potential role for the nociceptin system in regulating glutamatergic transmission and a complex interaction with ethanol at CeA glutamatergic synapses.

  10. Alternative forms of lethality in mitomycin C-induced bacteria carrying ColE1 plasmids

    PubMed Central

    Suit, Joan L.; Fan, M.-L. Judy; Sabik, Joseph F.; Labarre, Robert; Luria, S. E.

    1983-01-01

    We have studied the physiological effects of mitomycin C induction on cells carrying ColE1 plasmids with differing configurations of three genes: the structural gene coding for colicin (cea), a gene responsible for mitomycin C lethality (kil) that we located as part of an operon with cea, and the immunity (imm) gene, which lies near cea but is not in the same operon. kil is close to or overlaps imm. When cea+ plasmids are present mitomycin C induction results in 100-fold or greater increases in the level of colicin. Within an hour after induction more than 90% of cells carrying cea+kil+ plasmids are killed and macromolecular synthesis stops, capacity for transport of proline, thiomethyl β-D-galactoside, and α-methyl glucoside is lost, and the membrane becomes abnormally permeable as indicated by an increased accessibility of intracellular β-galactosidase to the substrate o-nitrophenyl β-D-galactoside. All of these events occur when a cea-kil+imm+ plasmid is present and none does when the plasmid is cea+kil-imm+, so the damage can be attributed solely to the Kil function and not to the presence of colicin. However, cells carrying a cea+kil-imm- plasmid are killed upon induction, apparently by action of endogenous colicin on the nonimmune cytoplasmic membrane. The pattern of accompanying physiological damage is distinguished from the kil+-associated damage by an enhancement of α-methyl glucoside uptake and accumulation and efflux of α-methyl glucoside 6-phosphate and by an absence of the alteration in membrane permeability for o-nitrophenyl β-D-galactoside. These features are typical of colicin E1 action on the membrane. The induced damage is not prevented by trypsin and occurs in cells of a strain specifically tolerant to exogenous colicin E1, indicating that the attack is from inside the cell. PMID:6403939

  11. Association between age and risk of stroke or death from carotid endarterectomy and carotid stenting: a meta-analysis of pooled patient data from four randomised trials.

    PubMed

    Howard, George; Roubin, Gary S; Jansen, Olav; Hendrikse, Jeroen; Halliday, Alison; Fraedrich, Gustav; Eckstein, Hans-Henning; Calvet, David; Bulbulia, Richard; Bonati, Leo H; Becquemin, Jean-Pierre; Algra, Ale; Brown, Martin M; Ringleb, Peter A; Brott, Thomas G; Mas, Jean-Louis

    2016-03-26

    Age was reported to be an effect-modifier in four randomised controlled trials comparing carotid artery stenting (CAS) and carotid endarterectomy (CEA), with better CEA outcomes than CAS outcomes noted in the more elderly patients. We aimed to describe the association of age with treatment differences in symptomatic patients and provide age-specific estimates of the risk of stroke and death within narrow (5 year) age groups. In this meta-analysis, we analysed individual patient-level data from four randomised controlled trials within the Carotid Stenosis Trialists' Collaboration (CSTC) involving patients with symptomatic carotid stenosis. We included only trials that randomly assigned patients to CAS or CEA and only patients with symptomatic stenosis. We assessed rates of stroke or death in 5-year age groups in the periprocedural period (between randomisation and 120 days) and ipsilateral stroke during long-term follow-up for patients assigned to CAS or CEA. We also assessed differences between CAS and CEA. All analyses were done on an intention-to-treat basis. Collectively, 4754 patients were randomly assigned to either CEA or CAS treatment in the four studies. 433 events occurred over a median follow-up of 2·7 years. For patients assigned to CAS, the periprocedural hazard ratio (HR) for stroke and death in patients aged 65-69 years compared with patients younger than 60 years was 2·16 (95% CI 1·13-4·13), with HRs of roughly 4·0 for patients aged 70 years or older. We noted no evidence of an increased periprocedural risk by age group in the CEA group (p=0·34). These changes underpinned a CAS-versus CEA periprocedural HR of 1·61 (95% CI 0·90-2·88) for patients aged 65-69 years and an HR of 2·09 (1·32-3·32) for patients aged 70-74 years. Age was not associated with the postprocedural stroke risk either within treatment group (p≥0·09 for CAS and 0·83 for CEA), or between treatment groups (p=0·84). In these RCTs, CEA was clearly superior to CAS in

  12. Cost-Effectiveness Research in Neurosurgery: We Can and We Must.

    PubMed

    Stein, Sherman C

    2018-01-05

    Rapid advancement of medical and surgical therapies, coupled with the recent preoccupation with limiting healthcare costs, makes a collision of the 2 objectives imminent. This article explains the value of cost-effectiveness analysis (CEA) in reconciling the 2 competing goals, and provides a brief introduction to evidence-based CEA techniques. The historical role of CEA in determining whether new neurosurgical strategies provide value for cost is summarized briefly, as are the limitations of the technique. Finally, the unique ability of the neurosurgical community to provide input to the CEA process is emphasized, as are the potential risks of leaving these important decisions in the hands of others. Copyright © 2018 by the Congress of Neurological Surgeons.

  13. Electronic Promoters and Semiconductor Oxidation: Alkali Metals on Si(111) Surfaces.

    DTIC Science & Technology

    1986-04-25

    SPAS, Caiimissariate a’ l’Energie Atctmique, CEN Saclay, France. 1. T. Narusawa, S. Komiya, and A. Hiraki , Appi. Phys. Lett. 20, 272 (1972). 2. J...Raisanen, and N. Troullier, Phys. Rev. B (in press). 10. K. Okuno, T. Ito, M. Iwami, and A. Hiraki , Sol. State Commun. 34, 493 (1980) and references

  14. REMORA 3: The first instrumented fuel experiment with on-line gas composition measurement by acoustic sensor

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

    Lambert, T.; Muller, E.; Federici, E.

    With the aim to improve the knowledge of nuclear fuel behaviour, the development of advanced instrumentation used during in-pile experiments in Material Testing Reactor (MTR) is necessary. To obtain data on high Burn-Up MOX fuel performance under transient operating conditions, especially in order to differentiate between the kinetics of fission gas and helium releases and to acquire data on the degradation of the fuel conductivity, a highly instrumented in-pile experiment called REMORA 3 has been conducted by CEA and IES (Southern Electronic Inst. - CNRS - Montpellier 2 Univ.). A rodlet extracted from a fuel rod base irradiated for fivemore » cycles in a French EDF commercial PWR has been re-instrumented with a fuel centerline thermocouple, a pressure transducer and an advanced acoustic sensor. This latter, patented by CEA and IES, is 1 used in addition to pressure measurement to determine the composition of the gases located in the free volume and the molar fractions of fission gas and helium. This instrumented fuel rodlet has been re-irradiated in a specific rig, GRIFFONOS, located in the periphery of the OSIRIS experimental reactor core at CEA Saclay. First of all, an important design stage and test phases have been performed before the irradiation in order to optimize the response and the accuracy of the sensors: - To control the influence of the temperature on the acoustic sensor behaviour, a thermal mock-up has been built. - To determine the temperature of the gas located in the acoustic cavity as a function of the coolant temperature, and the average temperature of the gases located in the rodlet free volume as a function of the linear heat rate, thermal calculations have been achieved. The former temperature is necessary to calculate the molar fractions of the gases and the latter is used to calculate the total amount of released gas from the internal rod pressure measurements. - At the end of the instrumented rod manufacturing, specific internal free

  15. Improvement in Cerebral and Ocular Hemodynamics Early after Carotid Endarterectomy in Patients of Severe Carotid Artery Stenosis with or without Contralateral Carotid Occlusion.

    PubMed

    Wang, Jian; Wang, Weici; Jin, Bi; Zhang, Yanrong; Xu, Ping; Xiang, Feixiang; Zheng, Yi; Chen, Juan; Sheng, Shi; Ouyang, Chenxi; Li, Yiqing

    2016-01-01

    Purpose. To investigate the alternation in cerebral and ocular blood flow velocity (BFV) in patients of carotid stenosis (CS) with or without contralateral carotid occlusion (CO) early after carotid endarterectomy (CEA). Patients and Methods. Nineteen patients underwent CEA for ≥50% CS. Fourteen patients had the unilateral CS, and five patients had the ipsilateral CS and the contralateral CO. Transcranial Doppler (TCD) and Color Doppler Imaging (CDI) were performed before and early after CEA. Results. In patients with unilateral CS, significant improvements in BFV were observed in anterior cerebral artery (ACA) and middle cerebral artery (MCA) on the ipsilateral side after CEA. In patients of ipsilateral CS and contralateral CO, significant improvements in BFV were observed in the ACA and MCA not only on the ipsilateral side but also on the contralateral side postoperatively. The ipsilateral ophthalmic artery (OA) retrograde flows in two patients were recovered to anterograde direction following CEA. The BFV in short posterior ciliary artery (SPCA) of the ipsilateral side significantly increased postoperatively irrespective of the presence of contralateral CO. Conclusions. CEA improved cerebral anterior circulation hemodynamics especially in patients of unilateral CS and contralateral CO, normalized the OA reverse flow, and increased the blood perfusion of SPCA.

  16. Cost effectiveness analysis for nursing research.

    PubMed

    Bensink, Mark E; Eaton, Linda H; Morrison, Megan L; Cook, Wendy A; Curtis, R Randall; Gordon, Deborah B; Kundu, Anjana; Doorenbos, Ardith Z

    2013-01-01

    With ever-increasing pressure to reduce costs and increase quality, nurses are faced with the challenge of producing evidence that their interventions and care provide value. Cost effectiveness analysis (CEA) is a tool that can be used to provide this evidence by comparative evaluation of the costs and consequences of two or more alternatives. The aim of this article is to introduce the essential components of CEA to nurses and nurse researchers with the protocol of a recently funded cluster randomized controlled trial as an example. This article provides (a) a description of the main concepts and key steps in CEA and (b) a summary of the background and objectives of a CEA designed to evaluate a nursing-led pain and symptom management intervention in rural communities compared with the current usual care. As the example highlights, incorporating CEA into nursing research studies is feasible. The burden of the additional data collection required is offset by quantitative evidence of the given intervention's cost and impact using humanistic and economic outcomes. At a time when U.S. healthcare is moving toward accountable care, the information provided by CEA will be an important additional component of the evidence produced by nursing research.

  17. The zebrafish maternal-effect gene cellular atoll encodes the centriolar component sas-6 and defects in its paternal function promote whole genome duplication.

    PubMed

    Yabe, Taijiro; Ge, Xiaoyan; Pelegri, Francisco

    2007-12-01

    A female-sterile zebrafish maternal-effect mutation in cellular atoll (cea) results in defects in the initiation of cell division starting at the second cell division cycle. This phenomenon is caused by defects in centrosome duplication, which in turn affect the formation of a bipolar spindle. We show that cea encodes the centriolar coiled-coil protein Sas-6, and that zebrafish Cea/Sas-6 protein localizes to centrosomes. cea also has a genetic paternal contribution, which when mutated results in an arrested first cell division followed by normal cleavage. Our data supports the idea that, in zebrafish, paternally inherited centrosomes are required for the first cell division while maternally derived factors are required for centrosomal duplication and cell divisions in subsequent cell cycles. DNA synthesis ensues in the absence of centrosome duplication, and the one-cycle delay in the first cell division caused by cea mutant sperm leads to whole genome duplication. We discuss the potential implications of these findings with regards to the origin of polyploidization in animal species. In addition, the uncoupling of developmental time and cell division count caused by the cea mutation suggests the presence of a time window, normally corresponding to the first two cell cycles, which is permissive for germ plasm recruitment.

  18. [Treatment Strategy and Results of Carotid Endarterectomy in Chronic Renal Failure Patients].

    PubMed

    Murahashi, Takeo; Kamiyama, Kenji; Osato, Toshiaki; Watanabe, Toshiichi; Ogino, Tatsuya; Sugio, Hironori; Endo, Hideki; Takahira, Kazuki; Shindo, Koichiro; Takahashi, Shuhei; Nakamura, Hirohiko

    2017-02-01

    The number of patients receiving chronic dialysis treatment in Japan currently exceeds 300,000 people. Few reports have described carotid endarterectomy(CEA)for chronic renal failure patients because of the unacceptable rate of perioperative stroke and other morbidities. A strategy for and treatment results of CEA for chronic renal failure patients in our hospital are described herein. The present study included 6 patients who underwent CEA while receiving dialysis treatment between April 2011 and November 2014. Dialysis treatment was initiated due to diabetes in 4 patients and renal sclerosis in 2 patients. All the patients were men, with a mean age of 74.0 years. Two patients were symptomatic, and four were asymptomatic. In all the patients, heart vascular lesions and arteriosclerosis risk factors were present. Postoperatively, pneumonia transient cranial neuropathy, heart failure, and pneumonia in 1 case required extensive treatment. However, by the time of discharge from hospital, no cases had deteriorated compared with their pre-CEA state. The modified Rankin scale score on discharge was 0-2 for all the patients. CEA can be performed safely in patients receiving dialysis, but further operative procedures and careful postoperative management are likely to be needed for patients with CEA who are receiving dialysis.

  19. Expression of Colocasia esculenta tuber agglutinin in Indian mustard provides resistance against Lipaphis erysimi and the expressed protein is non-allergenic.

    PubMed

    Das, Ayan; Ghosh, Prithwi; Das, Sampa

    2018-06-01

    Transgenic Brassica juncea plants expressing Colocasia esculenta tuber agglutinin (CEA) shows the non-allergenic nature of the expressed protein leading to enhanced mortality and reduced fecundity of mustard aphid-Lipaphis erysimi. Lipaphis erysimi (common name: mustard aphid) is the most devastating sucking insect pest of Indian mustard (Brassica juncea L.). Colocasia esculenta tuber agglutinin (CEA), a GNA (Galanthus nivalis agglutinin)-related lectin has previously been reported by the present group to be effective against a wide array of hemipteran insects in artificial diet-based bioassays. In the present study, efficacy of CEA in controlling L. erysimi has been established through the development of transgenic B. juncea expressing this novel lectin. Southern hybridization of the transgenic plants confirmed stable integration of cea gene. Expression of CEA in T 0 , T 1 and T 2 transgenic plants was confirmed through western blot analysis. Level of expression of CEA in the T 2 transgenic B. juncea ranged from 0.2 to 0.47% of the total soluble protein. In the in planta insect bioassays, the CEA expressing B. juncea lines exhibited enhanced insect mortality of 70-81.67%, whereas fecundity of L. erysimi was reduced by 49.35-62.11% compared to the control plants. Biosafety assessment of the transgenic B. juncea protein containing CEA was carried out by weight of evidence approach following the recommendations by FAO/WHO (Evaluation of the allergenicity of genetically modified foods: report of a joint FAO/WHO expert consultation, 22-25 Jan, Rome, http://www.fao.org/docrep/007/y0820e/y0820e00.HTM , 2001), Codex (Codex principles and guidelines on foods derived from biotechnology, Food and Agriculture Organization of the United Nations, Rome; Codex, Codex principles and guidelines on foods derived from biotechnology, Food and Agriculture Organization of the United Nations, Rome, 2003) and ICMR (Indian Council of Medical Research, guidelines for safety assessment of

  20. Systematic preoperative coronary angiography and stenting improves postoperative results of carotid endarterectomy in patients with asymptomatic coronary artery disease: a randomised controlled trial.

    PubMed

    Illuminati, G; Ricco, J-B; Greco, C; Mangieri, E; Calio', F; Ceccanei, G; Pacilè, M A; Schiariti, M; Tanzilli, G; Barillà, F; Paravati, V; Mazzesi, G; Miraldi, F; Tritapepe, L

    2010-02-01

    To evaluate the usefulness of systematic coronary angiography followed, if needed, by coronary artery angioplasty (percutaneous coronary intervention (PCI)) on the incidence of cardiac ischaemic events after carotid endarterectomy (CEA) in patients without evidence of coronary artery disease (CAD). From January 2005 to December 2008, 426 patients, candidates for CEA, with no history of CAD and with normal cardiac ultrasound and electrocardiography (ECG), were randomised into two groups. In group A (n=216) all the patients had coronary angiography performed before CEA. In group B, all the patients had CEA without previous coronary angiography. In group A, 66 patients presenting significant coronary artery lesions at angiography received PCI before CEA. They subsequently underwent surgery under aspirin (100 mg day(-1)) and clopidogrel (75 mg day(-1)). CEA was performed within a median delay of 4 days after PCI (range: 1-8 days). Risk factors, indications for CEA and surgical techniques were comparable in both groups (p>0.05). The primary combined endpoint of the study was the incidence of postoperative myocardial ischaemic events combined with the incidence of complications of coronary angiography. Secondary endpoints were death and stroke rates after CEA and incidence of cervical haematoma. Postoperative mortality was 0% in group A and 0.9% in group B (p=0.24). One postoperative stroke (0.5%) occurred in group A, and two (0.9%) in group B (p=0.62). No postoperative myocardial event was observed in group A, whereas nine ischaemic events were observed in group B, including one fatal myocardial infarction (p=0.01). Binary logistic regression analysis demonstrated that preoperative coronary angiography was the only independent variable that predicted the occurrence of postoperative coronary ischaemia after CEA. The odds ratio for coronary angiography (group A) indicated that when holding all other variables constant, a patient having preoperative coronary angiography

  1. Short-term results of a randomized trial examining timing of carotid endarterectomy in patients with severe asymptomatic unilateral carotid stenosis undergoing coronary artery bypass grafting.

    PubMed

    Illuminati, Giulio; Ricco, Jean-Baptiste; Caliò, Francesco; Pacilè, Maria Antonietta; Miraldi, Fabio; Frati, Giacomo; Macrina, Francesco; Toscano, Michele

    2011-10-01

    This study evaluated the timing of carotid endarterectomy (CEA) in the prevention of stroke in patients with asymptomatic carotid stenosis >70% receiving a coronary artery bypass graft (CABG). From January 2004 to December 2009, 185 patients with unilateral asymptomatic carotid artery stenosis >70%, candidates for CABG, were randomized into two groups. In group A, 94 patients received a CABG with previous or simultaneous CEA. In group B, 91 patients underwent CABG, followed by CEA. All patients underwent preoperative helical computed tomography scans, excluding significant atheroma of the ascending aorta or aortic arch. Baseline characteristics of the patients, type of coronary artery lesion, and preoperative myocardial function were comparable in the two groups. In group A, all patients underwent CEA under general anesthesia with the systematic use of a carotid shunt, and 79 patients had a combined procedure and 15 underwent CEA a few days before CABG. In group B, all patients underwent CEA, 1 to 3 months after CABG, also under general anesthesia and with systematic carotid shunting. Two patients (one in each group) died of cardiac failure in the postoperative period. Operative mortality was 1.0% in group A and 1.1% in group B (P = .98). No strokes occurred in group A vs seven ipsilateral ischemic strokes in group B, including three immediate postoperative strokes and four late strokes, at 39, 50, 58, and 66 days, after CABG. These late strokes occurred in patients for whom CEA was further delayed due to an incomplete sternal wound healing or because of completion of a cardiac rehabilitation program. The 90-day stroke and death rate was 1.0% (one of 94) in group A and 8.8% (eight of 91) in group B (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.01-0.91; P = .02). Logistic regression analysis showed that only delayed CEA (OR, 14.2; 95% CI, 1.32-152.0; P = .03) and duration of cardiopulmonary bypass (OR, 1.06; 95% CI, 1.02-1.11; P = .004) reliably predicted

  2. Chronic Electrical Stimulation at Acupoints Reduces Body Weight and Improves Blood Glucose in Obese Rats via Autonomic Pathway.

    PubMed

    Liu, Jiemin; Jin, Haifeng; Foreman, Robert D; Lei, Yong; Xu, Xiaohong; Li, Shiying; Yin, Jieyun; Chen, Jiande D Z

    2015-07-01

    The aim of this study was to investigate effects and mechanisms of chronic electrical stimulation at acupoints (CEA) using surgically implanted electrodes on food intake, body weight, and metabolisms in diet-induced obese (DIO) rats. Thirty-six DIO rats were chronically implanted with electrodes at acupoints ST-36 (Zusanli). Three sets of parameters were tested: electrical acupuncture (EA) 1 (2-s on, 3-s off, 0.5 ms, 15 Hz, 6 mA), EA2 (same as EA1 but continuous pulses), and EA3 (same as EA2 but 10 mA). A chronic study was then performed to investigate the effects of CEA on body weight and mechanisms involving gastrointestinal hormones and autonomic functions. EA2 significantly reduced food intake without uncomfortable behaviors. CEA at EA2 reduced body weight and epididymal fat pad weight (P < 0.05). CEA reduced both postprandial blood glucose and HbA1c (P < 0.05). CEA delayed gastric emptying (P < 0.03) and increased small intestinal transit (P < 0.02). CEA increased fasting plasma level of glucagon-like peptide-1 (GLP-1) and peptide YY (P < 0.05); the increase of GLP-1 was inversely correlated with postprandial blood glucose (R (2) = 0.89, P < 0.05); and the plasma ghrelin level remained unchanged. EA increased sympathetic activity (P < 0.01) and reduced vagal activity (P < 0.01). CEA at ST-36 reduces body weight and improves blood glucose possibly attributed to multiple mechanisms involving gastrointestinal motility and hormones via the autonomic pathway.

  3. Factors associated with parent support for condom education and availability.

    PubMed

    AugsJoost, Brett; Jerman, Petra; Deardorff, Julianna; Harley, Kim; Constantine, Norman A

    2014-04-01

    Expanding condom-related knowledge and skills and reducing barriers to condom use have the potential to help reduce pregnancies and sexually transmitted infections among youth. These goals are sometimes addressed through condom education and availability (CEA) programs as part of sexuality education in school. Parents are a key constituency in efforts to implement such programs. A representative statewide sample of households with children (N = 1,093) in California was employed to examine parent support for CEA and the potential influences of demographics (gender, age, and Hispanic ethnicity), sociodemographics (education, religious affiliation, religious service attendance, and political ideology), and condom-related beliefs (belief in condom effectiveness and belief that teens who use condoms during sex are being responsible) on parent support for CEA. The parents in our sample reported a high level of support for CEA (M = 3.23 on a 4-point scale) and believing in a high level of condom effectiveness (M = 3.36 on a 4-point scale). In addition, 84% of the parents agreed that teens who use condoms during sex are being responsible. Hierarchical regression analyses showed that parents who were younger, Hispanic, with a lower educational attainment, without a religious affiliation, less religiously observant, and politically liberal were more supportive of CEA. After controlling for these demographic and sociodemographic factors, condom effectiveness and responsibility beliefs each added independently to the predictability of parent support for CEA. These findings suggest that parent education related to condom effectiveness could help increase support for school-based CEA programs.

  4. The once and future application of cost-effectiveness analysis.

    PubMed

    Berger, M L

    1999-09-01

    Cost-effectiveness analysis (CEA) is used by payers to make coverage decisions, by providers to make formulary decisions, and by large purchasers/employers and policymakers to choose health care performance measures. However, it continues to be poorly utilized in the marketplace because of overriding financial imperatives to control costs and a low apparent willingness to pay for quality. There is no obvious relationship between the cost-effectiveness of life-saving interventions and their application. Health care decision makers consider financial impact, safety, and effectiveness before cost-effectiveness. WHY IS CEA NOT MORE WIDELY APPLIED? Most health care providers have a short-term parochial financial perspective, whereas CEA takes a long-term view that captures all costs, benefits, and hazards, regardless of to whom they accrue. In addition, a history of poor standardization of methods, unrealistic expectations that CEA could answer fundamental ethical and political issues, and society's failure to accept the need for allocating scarce resources more judiciously, have contributed to relatively little use of the method by decision makers. HOW WILL CEA FIND GREATER UTILITY IN THE FUTURE? As decision makers take a longer-term view and understand that CEA can provide a quantitative perspective on important resource allocation decisions, including the distributional consequences of alternative choices, CEA is likely to find greater use. However, it must be embedded within a framework that promotes confidence in the social justice of health care decision making through ongoing dialogue about how the value of health and health care are defined.

  5. Modern medical treatment with or without carotid endarterectomy for severe asymptomatic carotid atherosclerosis.

    PubMed

    Kolos, Igor; Troitskiy, Alexandr; Balakhonova, Tatiana; Shariya, Merab; Skrypnik, Denis; Tvorogova, Tatiana; Deev, Alexandr; Boytsov, Sergey

    2015-10-01

    This study assessed the value of modern medical treatment (MMT) with and without carotid endarterectomy (CEA) in patients with asymptomatic severe carotid artery stenosis. We conducted a randomized trial involving 55 patients with 70% to 79% carotid stenosis at three Russian centers. Between 2009 and 2013, 31 patients were randomized to undergo CEA with MMT (CEA group) and 24 to receive MMT alone. The primary end point was nonfatal ipsilateral stroke or death from any cause during a follow-up period of 5.0 years. The secondary end point was any nonfatal stroke, carotid revascularization, or death from any cause during follow-up. The trial was stopped after a median follow-up of 3.3 years (maximum, 5.0 years). There were two primary events in the CEA group and nine events in the MMT group. The 3.3-year cumulative primary event rates were 6.5% in the CEA group and 37.5% in the MMT group (hazard ratio for the MMT group, 5.06; 95% confidence interval, 1.53-16.79; P = .008). The 3.3-year cumulative secondary end point was 12.9% in the CEA group and 50.0% in the MMT group (hazard ratio for the MMT group, 4.23; 95% confidence interval, 1.55-11.53; P = .0048). CEA as an initial management strategy could reduce the risk of death and major cerebrovascular events when added to MMT. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  6. Preoperative Carcinoembryonic Antigen and Prognosis of Colorectal Cancer. An Independent Prognostic Factor Still Reliable

    PubMed Central

    Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

    2015-01-01

    To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this—to date—has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging. PMID:25875542

  7. Preoperative carcinoembryonic antigen and prognosis of colorectal cancer. An independent prognostic factor still reliable.

    PubMed

    Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

    2015-04-01

    To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this-to date-has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging.

  8. Carotid Artery Stenting Trials: Conduct, Results, Critique, and Current Recommendations

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

    Macdonald, Sumaira, E-mail: sumaira.macdonald@nuth.nhs.uk

    2012-02-15

    The carotid stenting trialists have demonstrated persistence and determination in comparing an evolving technique, carotid artery stenting (CAS), against a mature and exacting standard for carotid revascularisation, carotid endarterectomy (CEA). This review focuses on their endeavours. A total of 12 1-on-1 randomised trials comparing CAS and CEA have been reported; 6 of these can be considered major, and 5 of these reflect (in part) current CAS standards of practice and form the basis of this review. At least 18 meta-analyses seeking to compare CAS and CEA exist. These are limited by the quality and heterogeneity of the data informing themmore » (e.g., five trials were stopped prematurely such that they collectively failed to reach recruitment target by >4000 patients). The Carotid Stenting Trialists' Collaboration Publication represents a prespecified meta-analysis of European trials that were sufficiently similar to allow valid conclusions to be drawn; these trials and conclusions will be explored. When the rate of myocardial infarction (MI) is rigorously assessed, CAS and CEA are equivalent for the composite end point of stroke/death and MI, with more minor strokes for CAS and more MIs for CEA. These outcomes have a discrepant impact on quality of life and subsequent mortality. The all-stroke death outcomes for patients <70 years old are equivalent, with more minor strokes occurring in the elderly during CAS than CEA. There are significantly more severe haematomas and cranial nerve injuries after CEA. The influence of experience on outcome cannot be underestimated.« less

  9. Heterogeneous RNA-binding protein M4 is a receptor for carcinoembryonic antigen in Kupffer cells.

    PubMed

    Bajenova, O V; Zimmer, R; Stolper, E; Salisbury-Rowswell, J; Nanji, A; Thomas, P

    2001-08-17

    Here we report the isolation of the recombinant cDNA clone from rat macrophages, Kupffer cells (KC) that encodes a protein interacting with carcinoembryonic antigen (CEA). To isolate and identify the CEA receptor gene we used two approaches: screening of a KC cDNA library with a specific antibody and the yeast two-hybrid system for protein interaction using as a bait the N-terminal part of the CEA encoding the binding site. Both techniques resulted in the identification of the rat heterogeneous RNA-binding protein (hnRNP) M4 gene. The rat ortholog cDNA sequence has not been previously described. The open reading frame for this gene contains a 2351-base pair sequence with the polyadenylation signal AATAAA and a termination poly(A) tail. The mRNA shows ubiquitous tissue expression as a 2.4-kilobase transcript. The deduced amino acid sequence comprised a 78-kDa membrane protein with 3 putative RNA-binding domains, arginine/methionine/glutamine-rich C terminus and 3 potential membrane spanning regions. When hnRNP M4 protein is expressed in pGEX4T-3 vector system in Escherichia coli it binds (125)I-labeled CEA in a Ca(2+)-dependent fashion. Transfection of rat hnRNP M4 cDNA into a non-CEA binding mouse macrophage cell line p388D1 resulted in CEA binding. These data provide evidence for a new function of hnRNP M4 protein as a CEA-binding protein in Kupffer cells.

  10. Comparative Review of the Treatment Methodologies of Carotid Stenosis

    PubMed Central

    Bae, Coney; Szuchmacher, Mauricio; Chang, John B.

    2015-01-01

    The treatment of carotid stenosis entails three methodologies, namely, medical management, carotid angioplasty and stenting (CAS), as well as carotid endarterectomy (CEA). The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) have shown that symptomatic carotid stenosis greater than 70% is best treated with CEA. In asymptomatic patients with carotid stenosis greater than 60%, CEA was more beneficial than treatment with aspirin alone according to the Asymptomatic Carotid Atherosclerosis (ACAS) and Asymptomatic Carotid Stenosis Trial (ACST) trials. When CAS is compared with CEA, the CREST resulted in similar rates of ipsilateral stroke and death rates regardless of symptoms. However, CAS not only increased adverse effects in women, it also amplified stroke rates and death in elderly patients compared with CEA. CAS can maximize its utility in treating focal restenosis after CEA and patients with overwhelming cardiac risk or prior neck irradiation. When performing CEA, using a patch was equated to a more durable result than primary closure, whereas eversion technique is a new methodology deserving a spotlight. Comparing the three major treatment strategies of carotid stenosis has intrinsic drawbacks, as most trials are outdated and they vary in their premises, definitions, and study designs. With the newly codified best medical management including antiplatelet therapies with aspirin and clopidogrel, statin, antihypertensive agents, strict diabetes control, smoking cessation, and life style change, the current trials may demonstrate that asymptomatic carotid stenosis is best treated with best medical therapy. The ongoing trials will illuminate and reshape the treatment paradigm for symptomatic and asymptomatic carotid stenosis. PMID:26417191

  11. Cost-effectiveness analysis: should it be required for drug registration and beyond?

    PubMed

    Arnold, Renée J Goldberg

    2007-11-01

    Cost-effectiveness analysis (CEA) is applied in situations where trade-offs exist, typically, greater benefit for an increased cost over an alternative therapy or strategic option versus usual care. CEA is useful where a new strategy is more costly but expected to be more effective or where a new strategy is less costly but less effective. A good example for the relevance of CEA is the unanimous recommendation of a US federal vaccine advisory panel to vaccinate 11-year-old girls against cervical cancer. This recommendation was at least partly because of data showing the relative cost-effectiveness of HPV vaccine. In this era of finite budgets, CEA may facilitate drug development, drug approval, patient segmentation and pricing model development throughout the drug lifecycle continuum.

  12. Recruitment of a Neuronal Ensemble in the Central Nucleus of the Amygdala Is Required for Alcohol Dependence.

    PubMed

    de Guglielmo, Giordano; Crawford, Elena; Kim, Sarah; Vendruscolo, Leandro F; Hope, Bruce T; Brennan, Molly; Cole, Maury; Koob, George F; George, Olivier

    2016-09-07

    Abstinence from alcohol is associated with the recruitment of neurons in the central nucleus of the amygdala (CeA) in nondependent rats that binge drink alcohol and in alcohol-dependent rats. However, whether the recruitment of this neuronal ensemble in the CeA is causally related to excessive alcohol drinking or if it represents a consequence of excessive drinking remains unknown. We tested the hypothesis that the recruitment of a neuronal ensemble in the CeA during abstinence is required for excessive alcohol drinking in nondependent rats that binge drink alcohol and in alcohol-dependent rats. We found that inactivation of the CeA neuronal ensemble during abstinence significantly decreased alcohol drinking in both groups. In nondependent rats, the decrease in alcohol intake was transient and returned to normal the day after the injection. In dependent rats, inactivation of the neuronal ensemble with Daun02 produced a long-term decrease in alcohol drinking. Moreover, we observed a significant reduction of somatic withdrawal signs in dependent animals that were injected with Daun02 in the CeA. These results indicate that the recruitment of a neuronal ensemble in the CeA during abstinence from alcohol is causally related to excessive alcohol drinking in alcohol-dependent rats, whereas a similar neuronal ensemble only partially contributed to alcohol-binge-like drinking in nondependent rats. These results identify a critical neurobiological mechanism that may be required for the transition to alcohol dependence, suggesting that focusing on the neuronal ensemble in the CeA may lead to a better understanding of the etiology of alcohol use disorders and improve medication development. Alcohol dependence recruits neurons in the central nucleus of the amygdala (CeA). Here, we found that inactivation of a specific dependence-induced neuronal ensemble in the CeA reversed excessive alcohol drinking and somatic signs of alcohol dependence in rats. These results identify a

  13. Should patients with asymptomatic significant carotid stenosis undergo simultaneous carotid and cardiac surgery?

    PubMed Central

    Ogutu, Peter; Werner, Raphael; Oertel, Frank; Beyer, Michael

    2014-01-01

    A best evidence topic in cardiovascular surgery was written according to a structured protocol. The question addressed was whether patients with severe asymptomatic carotid and coronary artery diseases should undergo simultaneous carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG). A total of 624 papers were found using the reported search, of which 20 represent the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study results of these papers are tabulated. Previous cohort studies showed mixed results, while advocating for the necessity of a randomized controlled trial (RCT). A recent RCT showed that patients undergoing prophylactic or simultaneous CEA + CABG had lower rates of stroke (0%) compared with delayed CEA 1–3 months after CABG (7.7%), without significant perioperative mortality difference. This study included patients with unilateral severe (>70%) asymptomatic carotid stenosis requiring CABG. An earlier partly randomized trial also showed better outcomes for patients undergoing simultaneous procedures (P = 0.045). Interestingly, systematic reviews previously failed to show compelling evidence supporting prophylactic CEA. This could be partly due to the fact that these reviews collectively analyse different cohort qualities. Neurological studies have, however, shown reduced cognitive and phonetic quality and function in patients with unilateral and bilateral asymptomatic carotid artery stenosis. Twenty-one RCTs comparing lone carotid artery stenting (CAS) and CEA informed the American Heart Association guidelines, which declared CAS comparable with CEA for symptomatic and asymptomatic carotid stenosis (CS). However, the risk of death/stroke for CAS alone is double that for CEA alone in the acute phase following onset of symptoms, while CEA alone is associated with a doubled risk of myocardial infarction. There is

  14. The value of innovation under value-based pricing

    PubMed Central

    Moreno, Santiago G.; Ray, Joshua A.

    2016-01-01

    Objective The role of cost-effectiveness analysis (CEA) in incentivizing innovation is controversial. Critics of CEA argue that its use for pricing purposes disregards the ‘value of innovation’ reflected in new drug development, whereas supporters of CEA highlight that the value of innovation is already accounted for. Our objective in this article is to outline the limitations of the conventional CEA approach, while proposing an alternative method of evaluation that captures the value of innovation more accurately. Method The adoption of a new drug benefits present and future patients (with cost implications) for as long as the drug is part of clinical practice. Incidence patients and off-patent prices are identified as two key missing features preventing the conventional CEA approach from capturing 1) benefit to future patients and 2) future savings from off-patent prices. The proposed CEA approach incorporates these two features to derive the total lifetime value of an innovative drug (i.e., the value of innovation). Results The conventional CEA approach tends to underestimate the value of innovative drugs by disregarding the benefit to future patients and savings from off-patent prices. As a result, innovative drugs are underpriced, only allowing manufacturers to capture approximately 15% of the total value of innovation during the patent protection period. In addition to including the incidence population and off-patent price, the alternative approach proposes pricing new drugs by first negotiating the share of value of innovation to be appropriated by the manufacturer (>15%?) and payer (<85%?), in order to then identify the drug price that satisfies this condition. Conclusion We argue for a modification to the conventional CEA approach that integrates the total lifetime value of innovative drugs into CEA, by taking into account off-patent pricing and future patients. The proposed approach derives a price that allows manufacturers to capture an agreed share

  15. Préface

    NASA Astrophysics Data System (ADS)

    Ouerdane, Youcef; Laporte, Pierre

    2005-06-01

    ère sur onduleurs et 22 sur aimants de courbure. Les premiers “utilisateurs” sont prévus au printemps 2006 avec couverture de l'IR jusqu'aux X durs pour des études variées notamment dans le domaine de la matière condensée. - La LIL (ligne d'intégration laser) du LMJ fonctionne avec 4 faisceaux (de 30 kJ à 351 nm) et un ensemble de diagnostics plasma est en cours de validation (énergie, imagerie X, spectrométrie X). Un souci d'ouverture collaborative (France et étranger) est affiché. - LASERIX (LIXAM, LOA) a pour but de doter les scientifiques français d'un laser émettant en “quasi-routine” de l'émission laser X à 6 tirs/mn basée sur différents schémas collisionnels et donc différentes longueurs d'ondes, et mettant en oeuvre un laser saphir-titane ultra bref de 40 J pour la génération plasma. - Le projet Arc en Ciel (CEA, LOA) se penche sur la possibilité de mise en oeuvre d'une source de “4^ogénération”. Ces sources se veulent à la fois brillantes, cohérentes, dans la gamme des 100 femtosecondes, ce qui conduit à tourner le dos aux anneaux de stockage pour se focaliser sur la combinaison accélérateur linéaire/onduleur, complétée par un laser saphir-titane (génération d'harmoniques UV/X dans des gaz). - Une avancée particulièrement intéressante a été récemment réalisée, notamment au LOA, par injection d'un laser X (plasma) par un faisceau X de bonne qualité (polarisation, divergence, temps, contraste...) issu de la génération d'harmoniques élevées par une chaîne saphir-titane femto. - On notera aussi les avancées réalisées dans le domaine des sources incohérentes de forte intensité dans le domaine des X par interaction optimisée de l'interaction laser de puissance-agrégats (GPS-Paris 6 et 7, CEA Saclay), ainsi que par techniques X-pinch à fils à foyer de 10 microns (LPTP-École Polytechnique). - La génération d'harmoniques d'ordres élevés à partir de chaînes laser amplifiées a continué à faire l

  16. Applications of CELSS technology to controlled environment agriculture

    NASA Technical Reports Server (NTRS)

    Bates, Maynard E.; Bubenheim, David L.

    1991-01-01

    Controlled environment agriculture (CEA) is defined as the use of environmental manipulation for the commercial production of organisms, whether plants or animals. While many of the technologies necessary for aquaculture systems in North America is nevertheless doubling approximately every five years. Economic, cultural, and environmental pressures all favor CEA over field production for many non-commodity agricultural crops. Many countries around the world are already dependent on CEA for much of their fresh food. Controlled ecological life support systems (CELSS), under development at ARC, KSC, and JSC expand the concept of CEA to the extent that all human requirements for food, oxygen, and water will be provided regenerated by processing of waste streams to supply plant inputs. The CELSS will likely contain plants, humans, possibly other animals, microorganisms and physically and chemical processors. In effect, NASA will create engineered ecosystems. In the process of developing the technology for CELSS, NASA will develop information and technology which will be applied to improving the efficiency, reliability, and cost effectiveness for CEA, improving its resources recycling capabilities, and lessening its environmental impact to negligible levels.

  17. A novel lable-free electrochemical immunosensor for carcinoembryonic antigen based on gold nanoparticles-thionine-reduced graphene oxide nanocomposite film modified glassy carbon electrode.

    PubMed

    Kong, Fen-Ying; Xu, Mao-Tian; Xu, Jing-Juan; Chen, Hong-Yuan

    2011-10-15

    In this paper, gold nanoparticle-thionine-reduced graphene oxide (GNP-THi-GR) nanocomposites were prepared to design a label-free immunosensor for the sensitive detection of carcinoembryonic antigen (CEA). The nanocomposites with good biocompatibility, excellent redox electrochemical activity and large surface area were coated onto the glassy carbon electrode (GCE) surface and then CEA antibody (anti-CEA) was immobilized on the electrode to construct the immunosensor. The morphologies and electrochemistry of the formed nanocomposites were investigated by using scanning electron microscopy (SEM), ultraviolet-visible (UV-vis) spectrometry, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). CV and differential pulse voltammetry (DPV) studies demonstrated that the formation of antibody-antigen complexes decreased the peak current of THi in the GNP-THi-GR nanocomposites. The decreased currents were proportional to the CEA concentration in the range of 10-500 pg/mL with a detection limit of 4 pg/mL. The proposed method was simple, fast and inexpensive for the determination of CEA at very low levels. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Internal carotid artery rupture caused by carotid shunt insertion

    PubMed Central

    Illuminati, Giulio; Caliò, Francesco G.; Pizzardi, Giulia; Vietri, Francesco

    2015-01-01

    Introduction Shunting is a well-accepted method of maintaining cerebral perfusion during carotid endarterectomy (CEA). Nonetheless, shunt insertion may lead to complications including arterial dissection, embolization, and thrombosis. We present a complication of shunt insertion consisting of arterial wall rupture, not reported previously. Presentation of case A 78-year-old woman underwent CEA combined with coronary artery bypass grafting (CABG). At the time of shunt insertion an arterial rupture at the distal tip of the shunt was detected and was repaired via a small saphenous vein patch. Eversion CEA and subsequent CABG completed the procedure whose postoperative course was uneventful. Discussion Shunting during combined CEA-CABG may be advisable to assure cerebral protection from possible hypoperfusion due to potential hemodynamic instability of patients with severe coronary artery disease. Awareness and prompt management of possible shunt-related complications, including the newly reported one, may contribute to limiting their harmful effect. Conclusion Arterial wall rupture is a possible, previously not reported, shunt-related complication to be aware of when performing CEA. PMID:26255001

  19. Internal carotid artery rupture caused by carotid shunt insertion.

    PubMed

    Illuminati, Giulio; Caliò, Francesco G; Pizzardi, Giulia; Vietri, Francesco

    2015-01-01

    Shunting is a well-accepted method of maintaining cerebral perfusion during carotid endarterectomy (CEA). Nonetheless, shunt insertion may lead to complications including arterial dissection, embolization, and thrombosis. We present a complication of shunt insertion consisting of arterial wall rupture, not reported previously. A 78-year-old woman underwent CEA combined with coronary artery bypass grafting (CABG). At the time of shunt insertion an arterial rupture at the distal tip of the shunt was detected and was repaired via a small saphenous vein patch. Eversion CEA and subsequent CABG completed the procedure whose postoperative course was uneventful. Shunting during combined CEA-CABG may be advisable to assure cerebral protection from possible hypoperfusion due to potential hemodynamic instability of patients with severe coronary artery disease. Awareness and prompt management of possible shunt-related complications, including the newly reported one, may contribute to limiting their harmful effect. Arterial wall rupture is a possible, previously not reported, shunt-related complication to be aware of when performing CEA. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Isolation of aquatic yeasts with the ability to neutralize acidic media, from an extremely acidic river near Japan's Kusatsu-Shirane Volcano.

    PubMed

    Mitsuya, Daisuke; Hayashi, Takuya; Wang, Yu; Tanaka, Mami; Okai, Masahiko; Ishida, Masami; Urano, Naoto

    2017-07-01

    The Yukawa River is an extremely acidic river whose waters on the east foot of the Kusatu-Shirane Volcano (in Gunma Prefecture, Japan) contain sulfate ions. Here we isolated many acid-tolerant yeasts from the Yukawa River, and some of them neutralized an acidic R2A medium containing casamino acid. Candida fluviatilis strain CeA16 had the strongest acid tolerance and neutralizing activity against the acidic medium. To clarify these phenomena, we performed neutralization tests with strain CeA16 using casamino acid, a mixture of amino acids, and 17 single amino acid solutions adjusted to pH 3.0, respectively. Strain CeA16 neutralized not only acidic casamino acid and the mixture of amino acids but also some of the acidic single amino acid solutions. Seven amino acids were strongly decomposed by strain CeA16 and simultaneously released ammonium ions. These results suggest strain CeA16 is a potential yeast as a new tool to neutralize acidic environments. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Serum biochemical markers in lung cancer.

    PubMed Central

    Burt, R. W.; Ratcliffe, J. G.; Stack, B. H.; Cuthbert, J.; Kennedy, R. S.; Corker, C. S.; Franchimont, P.; Spilg, W. G.; Stimson, W. H.

    1978-01-01

    The prevalence of elevated serum levels of 5 potential tumour-associated antigens was determined in patients with lung cancer sampled at the time of initial presentation, using age- and sex-matched patients with benign lung disease as controls. Elevated levels (greater than upper 95th centile of controls) were found as follows: carcinoembryonic antigen (CEA), 17%; pregnancy-associated alpha-macroglobulin (PAM), 16%; casein 14%; human chorionic gonadotrophin (HCG) 6%; alpha-foetoprotein (AFP), 1.5%. The prevalence of elevated CEA levels (but not other markers) was higher in patients with evidence of extra-thoracic tumour spread (23%) mainly due to anaplastic tumours and adenocarcinomas. A degree of concordance of elevated marker levels occurred with CEA, HCG, casein and AFP, but there was a striking discordance of elevated CEA and PAM levels. Simultaneous assays of CEA and PAM will detect the majority of patients with elevations of any of the markers studied, and are likely to be the most useful biochemical markers in following the response of lung tumours to therapy. PMID:77672

  2. Hexapeptide fragment of carcinoembryonic antigen which acts as an agonist of heterogeneous ribonucleoprotein M.

    PubMed

    Palermo, Nicholas Y; Thomas, Peter; Murphy, Richard F; Lovas, Sándor

    2012-04-01

    Colorectal cancers with metastatic potential secrete the glycoprotein carcinoembryonic antigen (CEA). CEA has been implicated in colorectal cancer metastasis by inducing Kupffer cells to produce inflammatory cytokines which, in turn, make the hepatic micro-environment ideal for tumor cell implantation. CEA binds to the heterogeneous ribonucleoprotein M (hnRNP M) which acts as a cell surface receptor in Kupffer cells. The amino acid sequence in CEA, which binds the hnRNP M receptor, is Tyr-Pro-Glu-Leu-Pro-Lys. In this study, the structure of Ac-Tyr-Pro-Glu-Leu-Pro-Lys-NH₂ (YPELPK) was investigated using electronic circular dichroism, vibrational circular dichroism, and molecular dynamics simulations. The binding of the peptide to hnRNP M was also investigated using molecular docking calculations. The biological activity of YPELPK was studied using differentiated human THP-1 cells, which express hnRNP M on their surface and secrete IL-6 when stimulated by CEA. YPELPK forms a stable polyproline-II helix and stimulates IL-6 production of THP-1 cells at micromolar concentrations. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

  3. Importance of the Postoperative Carcinoembryonic Antigen Level during Follow-Up after Curative Resection in Patients with Liver Metastatic Colorectal Carcinoma.

    PubMed

    Hashimoto, Takuzo; Itabashi, Michio; Ogawa, Shinpei; Hirosawa, Tomoichiro; Bamba, Yoshiko; Kaji, Sanae; Ubukata, Mamiko; Shimizu, Satoru; Sugihara, Kenichi; Kameoka, Shingo

    2014-06-01

    To validate the conventional Japanese grading of liver metastasis for no residual tumor resection in Stage IV colorectal cancer (CRC) with liver metastasis and to identify risk factors for postoperative recurrence. The subjects of this study were 1792 Stage IV CRC patients with liver metastasis. In 1792 cases, including unresectable cases, there was a significantly different prognosis by grade (P < 0.0001). In 421 R0 cases, there was no significant difference between Grade A and Grade B (P = 0.8527). In 381 cases without extra-hepatic metastasis, the prognosis was not significantly different among three grades. On multivariate analysis, carcinoembryonic antigen within 3 months from R0 operation (3M-CEA) was an independent risk factor regardless of extrahepatic metastasis. There was a significantly different prognosis (P < 0.0001) among Grade A', defined as a normal 3M-CEA level, Grade B', defined as Grade A or B and an abnormal 3M-CEA level, and Grade C', defined as Grade C and an abnormal 3M-CEA level. The postoperative CEA level is an important risk factor during follow-up after curative resection in patients with liver metastatic colorectal carcinoma. The combination of the 3M-CEA level and conventional grading of liver metastasis is useful for follow-up of R0 resection cases.

  4. Validation of Carotid Artery Revascularization Coding in Ontario Health Administrative Databases.

    PubMed

    Hussain, Mohamad A; Mamdani, Muhammad; Saposnik, Gustavo; Tu, Jack V; Turkel-Parrella, David; Spears, Julian; Al-Omran, Mohammed

    2016-04-02

    The positive predictive value (PPV) of carotid endarterectomy (CEA) and carotid artery stenting (CAS) procedure and post-operative complication coding were assessed in Ontario health administrative databases. Between 1 April 2002 and 31 March 2014, a random sample of 428 patients were identified using Canadian Classification of Health Intervention (CCI) procedure codes and Ontario Health Insurance Plan (OHIP) billing codes from administrative data. A blinded chart review was conducted at two high-volume vascular centers to assess the level of agreement between the administrative records and the corresponding patients' hospital charts. PPV was calculated with 95% confidence intervals (CIs) to estimate the validity of CEA and CAS coding, utilizing hospital charts as the gold standard. Sensitivity of CEA and CAS coding were also assessed by linking two independent databases of 540 CEA-treated patients (Ontario Stroke Registry) and 140 CAS-treated patients (single-center CAS database) to administrative records. PPV for CEA ranged from 99% to 100% and sensitivity ranged from 81.5% to 89.6% using CCI and OHIP codes. A CCI code with a PPV of 87% (95% CI, 78.8-92.9) and sensitivity of 92.9% (95% CI, 87.4-96.1) in identifying CAS was also identified. PPV for post-admission complication diagnosis coding was 71.4% (95% CI, 53.7-85.4) for stroke/transient ischemic attack, and 82.4% (95% CI, 56.6-96.2) for myocardial infarction. Our analysis demonstrated that the codes used in administrative databases accurately identify CEA and CAS-treated patients. Researchers can confidently use administrative data to conduct population-based studies of CEA and CAS.

  5. Looking up, down, and sideways: Reconceiving cumulative effects assessment as a mindset

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

    Sinclair, A. John, E-mail: jsincla@umanitoba.ca; Doelle, Meinhard, E-mail: mdoelle@dal.ca; Duinker, Peter N., E-mail: peter.duinker@dal.ca

    Despite all the effort that has gone into defining, researching and establishing best practices for cumulative effects assessment (CEA), understanding remains weak and practice wanting. At one extreme of implementation, CEA can be described as merely an irritant to the completion of a project-specific environmental assessment (EA). At the other extreme, the conceptual view is that all effects in EA should be deemed cumulative unless demonstrated otherwise. Our purpose here is to consider how we might reconceive CEA as a mindset that is at the heart of absolutely every assessment of valued ecosystem component (VEC) to ensure that we understandmore » the relative contributions of various stressors and can decide when cumulative effects may foreclose future activities due to impacts on VECs. Conceptually, we ground the CEA mindset in the context of three lenses that must all be functioning and working together for the mindset to be operative: a technical lens; a law and policy lens; and a participatory lens. Our arguments are based on a review of the CEA, strategic effects assessment (SEA) and regional effects assessment literatures, an examination and consideration of Canadian EA and SEA case practice, and our combined professional experiences. Through using the Bay of Fundy in Canada as a case example, we establish the concept of the CEA mindset and an approach for moving forward with implementation. - Highlights: • Conceptualization of cumulative effects assessment as a mindset. • Elaboration of technical, law and policy and participation lenses critical to CEA • Coordination and integration of cumulative effects for valued ecosystem components • Application in Bay of Fundy ecosystem and terrestrial watershed.« less

  6. Universal access to HIV treatment in developing countries: going beyond the misinterpretations of the 'cost-effectiveness' algorithm.

    PubMed

    Moatti, Jean Paul; Marlink, Richard; Luchini, Stephane; Kazatchkine, Michel

    2008-07-01

    Economic cost-effectiveness analysis (CEA) has been proposed as the appropriate tool to set priorities for resource allocation among available health interventions. Controversy remains about the way CEA should be used in the field of HIV/AIDS. This paper reviews the general literature in health economics and public economics about the use of CEA for priority setting in public health, in order better to inform current debates about resource allocation in the fight against HIV/AIDS. Theoretical and practical limitations of CEA do not raise major problems when it is applied to compare alternatives for treating the same medical condition or public health problem. Using CEA to set priorities among different health interventions by ranking them from the lowest to the highest values of their cost per life-year saved is appropriate only under the very restrictive and unrealistic assumptions that all interventions compared are discrete and finite alternatives that cannot vary in terms of size and scale. In order for CEA to inform resource allocation compared across programmes to fight the AIDS epidemic, a pragmatic interpretation of this economic approach, like that proposed by the Commission on Macroeconomics and Health, is better suited. Interventions, like a number of preventive strategies and first-line antiretroviral treatments for HIV, whose marginal costs per additional life-year saved are less than three times the gross domestic product per capita, should be considered cost-effective. Because of their empirical and theoretical limitations, results of CEA should only be one element in priority setting among interventions for HIV/AIDS, which should also be informed by explicit debates about societal and ethical preferences.

  7. Systematic review and quality assessment of cost-effectiveness analysis of pharmaceutical therapies for advanced colorectal cancer.

    PubMed

    Leung, Henry W C; Chan, Agnes L F; Leung, Matthew S H; Lu, Chin-Li

    2013-04-01

    To systematically review and assess the quality of cost-effectiveness analyses (CEAs) of pharmaceutical therapies for metastatic colorectal cancer (mCRC). The MEDLINE, EMBASE, Cochrane, and EconLit databases were searched for the Medical Subject Headings or text key words quality-adjusted, QALY, life-year gained (LYG), and cost-effectiveness (January 1, 1999-December 31, 2009). Original CEAs of mCRC pharmacotherapy published in English were included. CEAs that measured health effects in units other than quality-adjusted life years or LYG and letters to the editor, case reports, posters, and editorials were excluded. Each article was independently assessed by 2 trained reviewers according to a quality checklist created by the Panel on Cost-Effectiveness in Health and Medicine. Twenty-four CEA studies pertaining to pharmaceutical therapies for mCRC were identified. All studies showed a wide variation in methodologic approaches, which resulted in a different range of incremental cost-effectiveness ratios reported for each regimen. We found common methodologic flaws in a significant number of CEA studies, including lack of clear description for critique of data quality; lack of method for adjusting costs for inflation and methods for obtaining expert judgment; no results of model validation; wide differences in the types of perspective, time horizon, study design, cost categories, and effect outcomes; and no quality assessment of data (cost and effectiveness) for the interventions evaluation. This study has shown a wide variation in the methodology and quality of cost-effectiveness analysis for mCRC. Improving quality and harmonization of CEA for cancer treatment is needed. Further study is suggested to assess the quality of CEA methodology outside the mCRC disease state.

  8. Cancer mortality risk among biology research workers in France: first results of two retrospective cohorts studies.

    PubMed

    Guseva Canu, Irina; Rogel, Agnès; Samson, Eric; Benhamou, Simone; Laplanche, Agnès; Tirmarche, Margot

    2008-05-01

    To investigate all-cause and cancer mortality of biological research laboratories workers of the French Atomic Energy Commission (CEA) and the National Institute of Health and Medical Research (INSERM). Two cohorts, bioCEA (N = 3,509) and bioINSERM (N = 4,966) were followed from 1968 to 1994 and 1980 to 1993, respectively. The mortality of each cohort was compared with that of the French population by computation of the standardized mortality ratio (SMR) with their 90% confidence interval (90% CI). Trend and heterogeneity tests were computed in order to study SMRs variation by job characteristics. In the bioCEA cohort individual dosimetry data being available, a trend test was also computed according to ionizing radiation cumulative dose. The SMRs were significantly below one in both cohorts for all-cause mortality (bioCEA: SMR = 0.52 [0.46-0.59], bioINSERM: SMR = 0.56 [0.46-0.67]) and for all-cancer mortality (bioCEA: SMR = 0.66 [0.54-0.80], bioINSERM: SMR = 0.55 [0.39-0.75]). There were some specific cancer sites for which the SMR was higher than 1, but not significantly. In the bioCEA cohort a positive trend was observed between ionizing radiation cumulative doses and all-cause as well as all-cancer SMRs. This study on two French cohorts of biological research workers found a favorable mortality pattern. These findings are consistent with recent publications. The positive trend of cancer mortality according to ionizing radiation exposure among bioCEA cohort needs to be confirmed with more precise assessment of exposures and information on individual risk factors.

  9. Beware of Kinked Frontiers: A Systematic Review of the Choice of Comparator Strategies in Cost-Effectiveness Analyses of Human Papillomavirus Testing in Cervical Screening.

    PubMed

    O'Mahony, James F; Naber, Steffie K; Normand, Charles; Sharp, Linda; O'Leary, John J; de Kok, Inge M C M

    2015-12-01

    To systematically review the choice of comparator strategies in cost-effectiveness analyses (CEAs) of human papillomavirus testing in cervical screening. The PubMed, Web of Knowledge, and Scopus databases were searched to identify eligible model-based CEAs of cervical screening programs using human papillomavirus testing. The eligible CEAs were reviewed to investigate what screening strategies were chosen for analysis and how this choice might have influenced estimates of the incremental cost-effectiveness ratio (ICER). Selected examples from the reviewed studies are presented to illustrate how the omission of relevant comparators might influence estimates of screening cost-effectiveness. The search identified 30 eligible CEAs. The omission of relevant comparator strategies appears likely in 18 studies. The ICER estimates in these cases are probably lower than would be estimated had more comparators been included. Five of the 30 studies restricted relevant comparator strategies to sensitivity analyses or other subanalyses not part of the principal base-case analysis. Such exclusion of relevant strategies from the base-case analysis can result in cost-ineffective strategies being identified as cost-effective. Many of the CEAs reviewed appear to include insufficient comparator strategies. In particular, they omit strategies with relatively long screening intervals. Omitting relevant comparators matters particularly if it leads to the underestimation of ICERs for strategies around the cost-effectiveness threshold because these strategies are the most policy relevant from the CEA perspective. Consequently, such CEAs may not be providing the best possible policy guidance and lead to the mistaken adoption of cost-ineffective screening strategies. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  10. Ovarian Cancer, Stem Cells, and Bioreactors

    DTIC Science & Technology

    2009-10-01

    also indirectly assessed by measuring CEA and CA125 levels in the circulating medium. CEA and CA125, belonging to the CEA antigen family, are...with OVC#6 could not be detected. The low level of CA125 may be due to a dilution of the protein in the circulating medium as protein concentrations...lower than 8.7U/ml are below the assay sensitivity. Unfortunately, we have been unable to obtain the CA125 circulating level for either patient so

  11. When is critical care medicine cost-effective? A systematic review of the cost-effectiveness literature.

    PubMed

    Talmor, Daniel; Shapiro, Nathan; Greenberg, Dan; Stone, Patricia W; Neumann, Peter J

    2006-11-01

    Receiving care in an intensive care unit can greatly influence patients' survival and quality of life. Such treatments can, however, be extremely resource intensive. Therefore, it is increasingly important to understand the costs and consequences associated with interventions aimed at reducing mortality and morbidity of critically ill patients. Cost-effectiveness analyses (CEAs) have become increasingly common to aid decisions about the allocation of scarce healthcare resources. To identify published original CEAs presenting cost/quality-adjusted life year or cost/life-year ratios for treatments used in intensive care units, to summarize the results in an accessible format, and to identify areas in critical care medicine that merit further economic evaluation. We conducted a systematic search of the English-language literature for original CEAs of critical care interventions published from 1993 through 2003. We collected data on the target population, therapy or program, study results, analytic methods employed, and the cost-effectiveness ratios presented. We identified 19 CEAs published through 2003 with 48 cost-effectiveness ratios pertaining to treatment of severe sepsis, acute respiratory failure, and general critical care interventions. These ratios ranged from cost saving to 958,423 US dollars/quality-adjusted life year and from 1,150 to 575,054 US dollars/life year gained. Many studies reported favorable cost-effectiveness profiles (i.e., below 50,000 US dollars/life year or quality-adjusted life year). Specific interventions such as activated protein C for patients with severe sepsis have been shown to provide good value for money. However, overall there is a paucity of CEA literature on the management of the critically ill, and further high-quality CEA is needed. In particular, research should focus on costly interventions such as 24-hr intensivist availability, early goal-directed therapy, and renal replacement therapy. Recent guidelines for the conduct

  12. Diagnostic value of soluble B7-H4 and carcinoembryonic antigen in distinguishing malignant from benign pleural effusion.

    PubMed

    Jing, Xiaogang; Wei, Fei; Li, Jing; Dai, Lingling; Wang, Xi; Jia, Liuqun; Wang, Huan; An, Lin; Yang, Yuanjian; Zhang, Guojun; Cheng, Zhe

    2018-03-01

    To explore the diagnostic value of joint detection of soluble B7-H4 (sB7-H4) and carcinoembryonic antigen (CEA) in identifying malignant pleural effusion (MPE) from benign pleural effusion (BPE). A total of 97 patients with pleural effusion specimens were enrolled from The First Affiliated Hospital of Zhengzhou University between June 2014 and December 2015. All cases were categorized into malignant pleural effusion group (n = 55) and benign pleural effusion group (n = 42) according to etiologies. Enzyme-linked immunosorbent assay was applied to examine the levels of sB7-H4 in pleural effusion and meanwhile CEA concentrations were detected by electro-chemiluminescence immunoassays. Receiver operating characteristic (ROC) curve was established to assess the diagnostic value of sB7-H4 and CEA in pleural effusion. The correlation between sB7-H4 and CEA levels was analyzed by Pearson's product-moment. The concentrations of sB7-H4 and CEA in MPE exhibited obviously higher than those of BPE ([60.08 ± 35.04] vs. [27.26 ± 9.55] ng/ml, P = .000; [41.49 ± 37.16] vs. [2.41 ± 0.94] ng/ml, P = .000). The AUC area under ROC curve of sB7-H4 and CEA was 0.884 and 0.954, respectively. Two cutoff values by ROC curve analysis of sB7-H4 36.5 ng/ml and CEA 4.18 ng/ml were obtained, with a corresponding sensitivity (81.82%, 87.28%), specificity (90.48%, 95.24%), accuracy (85.57%, 90.72%), positive predictive value (PPV) (91.84%, 96.0%), negative predictive value (NPV) (79.17%, 85.11%), positive likelihood ratio (PLR) (8.614, 18.327), and negative likelihood ratio (NLR) (0.201, 0.134). When sB7-H4 and CEA were combined to detect pleural effusion, it obtained a higher sensitivity 90.91% and specificity 97.62%. Furthermore, correlation analysis result showed that the level of sB7-H4 was correlated with CEA level (r = .770, P = .000). sB7-H4 was a potentially valuable tumor marker in the differentiation between BPE and MPE. The combined detection of sB7-H4 and

  13. Study of pharmaceutical industrial problems

    NASA Technical Reports Server (NTRS)

    Pincus, J. H.

    1979-01-01

    The growth of a human colon carcinoma cell line (SK-CO-1) and its production of carcinoembryonic antigen (CEA) in monolayer culture and on single layers of glass beads in unit gravity were evaluated. The limitations of using a microsphere-cell growth system in unit gravity were identified and how these may be overcome in space was considered. The project had the following tasks: (1) growth of cultured human colon carcinoma cells on a monolayer and CEA production; (2) evaluation of CEA production and release by SK-CO-1 cells grown on glass beads; (3) evaluation of other microcarriers for growing SK-CO-1 cells and determination of the minimum amount of culture medium needed for cell growth; and (4) growth of SK-CO-1 cells on collagen monolayers and CEA production.

  14. Future costs in cost effectiveness analysis.

    PubMed

    Lee, Robert H

    2008-07-01

    This paper resolves several controversies in CEA. Generalizing [Garber, A.M., Phelps, C.E., 1997. Economic foundations of cost-effectiveness analysis. Journal of Health Economics 16 (1), 1-31], the paper shows accounting for unrelated future costs distorts decision making. After replicating [Meltzer, D., 1997. Accounting for future costs in medical cost-effectiveness analysis. Journal of Health Economics 16 (1), 33-64] quite different conclusion that unrelated future costs should be included in CEA, the paper shows that Meltzer's findings result from modeling the budget constraint as an annuity, which is problematic. The paper also shows that related costs should be included in CEA. This holds for a variety of models, including a health maximization model. CEA should treat costs in the manner recommended by Garber and Phelps.

  15. HD 50844: a new look at δ Scuti stars from CoRoT space photometry

    NASA Astrophysics Data System (ADS)

    Poretti, E.; Michel, E.; Garrido, R.; Lefèvre, L.; Mantegazza, L.; Rainer, M.; Rodríguez, E.; Uytterhoeven, K.; Amado, P. J.; Martín-Ruiz, S.; Moya, A.; Niemczura, E.; Suárez, J. C.; Zima, W.; Baglin, A.; Auvergne, M.; Baudin, F.; Catala, C.; Samadi, R.; Alvarez, M.; Mathias, P.; Paparò, M.; Pápics, P.; Plachy, E.

    2009-10-01

    , Belgium, Brazil, Germany, and Spain. This work is based on ground-based observations made with ESO telescopes at the La Silla Observatory under the ESO Large Programme LP178.D-0361 and on data collected at the Observatorio de Sierra Nevada (Spain), at the Observatorio Astronómico Nacional San Pedro Mártir (Mexico), and at the Piszkéstetö Mountain Station of Konkoly Observatory (Hungary). Table 2 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/506/85 Current address: Laboratoire AIM, CEA/DSM CNRS Université Paris Diderot, CEA, IRFU, SAp, centre de Saclay, 91191 Gif-sur-Yvette, France.

  16. Endarterectomy achieves lower stroke and death rates compared with stenting in patients with asymptomatic carotid stenosis.

    PubMed

    Kakkos, Stavros K; Kakisis, Ioannis; Tsolakis, Ioannis A; Geroulakos, George

    2017-08-01

    It is currently unclear if carotid artery stenting (CAS) is as safe as carotid endarterectomy (CEA) for patients with significant asymptomatic stenosis. The aim of our study was to perform a systematic review and meta-analysis of trials comparing CAS with CEA. On March 17, 2017, a search for randomized controlled trials was performed in MEDLINE and Scopus databases with no time limits. We performed meta-analyses with Peto odds ratios (ORs) and 95% confidence intervals (CIs). Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation method. The primary safety and efficacy outcome measures were stroke or death rate at 30 days and ipsilateral stroke at 1 year (including ipsilateral stroke and death rate at 30 days), respectively. Perioperative stroke, ipsilateral stroke, myocardial infarction (MI), and cranial nerve injury (CNI) were all secondary outcome measures. The systematic review of the literature identified nine randomized controlled trials reporting on 3709 patients allocated into CEA (n = 1479) or CAS (n = 2230). Stroke or death rate at 30 days was significantly higher for CAS (64/2176 [2.94%]) compared with CEA (27/1431 [1.89%]; OR, 1.57; 95% CI, 1.01-2.44; P = .044), with low level of heterogeneity beyond chance (I 2  = 0%). Also, stroke rate at 30 days was significantly higher for CAS (63/2176 [2.90%]) than for CEA (26/1431 [1.82%]; OR, 1.63; 95% CI, 1.04-2.54; P = .032; I 2  = 0%). MI at 30 days was nonsignificantly lower for CAS (12/1815 [0.66%]) compared with CEA (16/1070 [1.50%]; OR, 0.53; 95% CI, 0.24-1.14; P = .105; I 2  = 0%); however, CNI at 30 days was significantly lower for CAS (2/1794 [0.11%]) than for CEA (33/1061 [3.21%]; OR, 0.13; 95% CI, 0.07-0.26; P < .00001; I 2  = 0%). Regarding the long-term outcome of stroke or death rate at 30 days plus ipsilateral stroke during follow-up, this was significantly higher for CAS (79/2173 [3.64%]) than for CEA (35/1430 [2.45%]; OR, 1

  17. [Evaluation of the diagnosis value of carcinoembryonic antigen in malignant pleural effusion].

    PubMed

    Yu, Y X; Tong, Z H; Zhou, X X; Liang, L R; Wang, Z; Xu, L L; Wang, X J; Wu, Y B; Li, H J; Lu, Z

    2018-02-06

    Objective: To investigate the diagnostic value of serum and pleural fluid carcinoembryonic antigen (CEA) for malignant pleural effusion (MPE). Methods: The concentration of CEA in serum and pleural fluid of 286 patients with the diagnosis confirmed by pleural biopsy through medical thoracoscopy were retrospectively analyzed. MPE was confirmed in 171 cases which were divided into two groups (adenocarcinoma group with 121cases and non-adenocarcinoma group with 50 cases) and benign pleural effusion in 115 cases. The optimal cutoff for MPE and MPE caused by adenocarcinoma were determined by using the ROC curve. Results: The concentration of serum CEA 12.27(3.80, 58.45) μg/L was significantly higher in MPE caused by adenocarcinoma than that of non-adenocarcinoma 1.91(1.08, 4.55) μg/L and benign effusion 1.32(0.86, 2.27) μg/L (both P <0.001), but there was no statistically significant difference between benign and non-adenocarcinoma effusion ( P =0.728). The concentration of pleural fluid CEA 160.70(30.48, 1 000.00) μg/L was significantly higher in MPE caused by adenocarcinoma than that of non-adenocarcinoma 1.77(0.51, 11.39) μg/L and benign effusion 1.09(0.60, 1.68) μg/L (both P <0.001), and higher in non-adenocarcinoma effusion than that of benign effusion ( P <0.05). The cutoff value of serum and pleural fluid CEA for MPE was 3.10 and 5.83 μg/L, the sensitivity respectively was 67.3% and 74.3%, the specificity respectively was 87.8% and 98.3%, positive predictive value respectively was 89.2% and 98.5%, negative predictive value respectively was 64.3% and 72.0%. The cutoff value of serum and pleural fluid CEA for MPE caused by adenocarcinoma was 3.54 and 7.30 μg/L, the sensitivity respectively was 76.0% and 91.7%, the specificity respectively was 74.0% and 72.0%, positive predictive value respectively was 87.6% and 88.8%, negative predictive value respectively was 56.1% and 78.3%. Conclusions: The concentration of serum and pleural fluid CEA have diagnostic

  18. Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis.

    PubMed

    Holubar, Marisa; Stavroulakis, Maria Christina; Maldonado, Yvonne; Ioannidis, John P A; Contopoulos-Ioannidis, Despina

    2017-01-01

    Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited. We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries. We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the adoption of the target

  19. Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis

    PubMed Central

    Maldonado, Yvonne; Ioannidis, John P. A.; Contopoulos-Ioannidis, Despina

    2017-01-01

    Background Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited. Methods We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries. Results We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the

  20. A Systematic Review and Methodological Evaluation of Published Cost-Effectiveness Analyses of Aromatase Inhibitors versus Tamoxifen in Early Stage Breast Cancer

    PubMed Central

    John-Baptiste, Ava A.; Wu, Wei; Rochon, Paula; Anderson, Geoffrey M.; Bell, Chaim M.

    2013-01-01

    Background A key priority in developing policies for providing affordable cancer care is measuring the value for money of new therapies using cost-effectiveness analyses (CEAs). For CEA to be useful it should focus on relevant outcomes and include thorough investigation of uncertainty. Randomized controlled trials (RCTs) of five years of aromatase inhibitors (AI) versus five years of tamoxifen in the treatment of post-menopausal women with early stage breast cancer, show benefit of AI in terms of disease free survival (DFS) but not overall survival (OS) and indicate higher risk of fracture with AI. Policy-relevant CEA of AI versus tamoxifen should focus on OS and include analysis of uncertainty over key assumptions. Methods We conducted a systematic review of published CEAs comparing an AI to tamoxifen. We searched Ovid MEDLINE, EMBASE, PsychINFO, and the Cochrane Database of Systematic Reviews without language restrictions. We selected CEAs with outcomes expressed as cost per life year or cost per quality adjusted life year (QALY). We assessed quality using the Neumann checklist. Using structured forms two abstractors collected descriptive information, sources of data, baseline assumptions on effectiveness and adverse events, and recorded approaches to assessing parameter uncertainty, methodological uncertainty, and structural uncertainty. Results We identified 1,622 citations and 18 studies met inclusion criteria. All CE estimates assumed a survival benefit for aromatase inhibitors. Twelve studies performed sensitivity analysis on the risk of adverse events and 7 assumed no additional mortality risk with any adverse event. Sub-group analysis was limited; 6 studies examined older women, 2 examined women with low recurrence risk, and 1 examined women with multiple comorbidities. Conclusion Published CEAs comparing AIs to tamoxifen assumed an OS benefit though none has been shown in RCTs, leading to an overestimate of the cost-effectiveness of AIs. Results of these

  1. A systematic review and methodological evaluation of published cost-effectiveness analyses of aromatase inhibitors versus tamoxifen in early stage breast cancer.

    PubMed

    John-Baptiste, Ava A; Wu, Wei; Rochon, Paula; Anderson, Geoffrey M; Bell, Chaim M

    2013-01-01

    A key priority in developing policies for providing affordable cancer care is measuring the value for money of new therapies using cost-effectiveness analyses (CEAs). For CEA to be useful it should focus on relevant outcomes and include thorough investigation of uncertainty. Randomized controlled trials (RCTs) of five years of aromatase inhibitors (AI) versus five years of tamoxifen in the treatment of post-menopausal women with early stage breast cancer, show benefit of AI in terms of disease free survival (DFS) but not overall survival (OS) and indicate higher risk of fracture with AI. Policy-relevant CEA of AI versus tamoxifen should focus on OS and include analysis of uncertainty over key assumptions. We conducted a systematic review of published CEAs comparing an AI to tamoxifen. We searched Ovid MEDLINE, EMBASE, PsychINFO, and the Cochrane Database of Systematic Reviews without language restrictions. We selected CEAs with outcomes expressed as cost per life year or cost per quality adjusted life year (QALY). We assessed quality using the Neumann checklist. Using structured forms two abstractors collected descriptive information, sources of data, baseline assumptions on effectiveness and adverse events, and recorded approaches to assessing parameter uncertainty, methodological uncertainty, and structural uncertainty. We identified 1,622 citations and 18 studies met inclusion criteria. All CE estimates assumed a survival benefit for aromatase inhibitors. Twelve studies performed sensitivity analysis on the risk of adverse events and 7 assumed no additional mortality risk with any adverse event. Sub-group analysis was limited; 6 studies examined older women, 2 examined women with low recurrence risk, and 1 examined women with multiple comorbidities. Published CEAs comparing AIs to tamoxifen assumed an OS benefit though none has been shown in RCTs, leading to an overestimate of the cost-effectiveness of AIs. Results of these CEA analyses may be suboptimal for

  2. Using Real-World Data in Health Technology Assessment (HTA) Practice: A Comparative Study of Five HTA Agencies.

    PubMed

    Makady, Amr; van Veelen, Ard; Jonsson, Páll; Moseley, Owen; D'Andon, Anne; de Boer, Anthonius; Hillege, Hans; Klungel, Olaf; Goettsch, Wim

    2018-03-01

    Reimbursement decisions are conventionally based on evidence from randomised controlled trials (RCTs), which often have high internal validity but low external validity. Real-world data (RWD) may provide complimentary evidence for relative effectiveness assessments (REAs) and cost-effectiveness assessments (CEAs). This study examines whether RWD is incorporated in health technology assessment (HTA) of melanoma drugs by European HTA agencies, as well as differences in RWD use between agencies and across time. HTA reports published between 1 January 2011 and 31 December 2016 were retrieved from websites of agencies representing five jurisdictions: England [National Institute for Health and Care Excellence (NICE)], Scotland [Scottish Medicines Consortium (SMC)], France [Haute Autorité de santé (HAS)], Germany [Institute for Quality and Efficacy in Healthcare (IQWiG)] and The Netherlands [Zorginstituut Nederland (ZIN)]. A standardized data extraction form was used to extract information on RWD inclusion for both REAs and CEAs. Overall, 52 reports were retrieved, all of which contained REAs; CEAs were present in 25 of the reports. RWD was included in 28 of the 52 REAs (54%), mainly to estimate melanoma prevalence, and in 22 of the 25 (88%) CEAs, mainly to extrapolate long-term effectiveness and/or identify drug-related costs. Differences emerged between agencies regarding RWD use in REAs; the ZIN and IQWiG cited RWD for evidence on prevalence, whereas the NICE, SMC and HAS additionally cited RWD use for drug effectiveness. No visible trend for RWD use in REAs and CEAs over time was observed. In general, RWD inclusion was higher in CEAs than REAs, and was mostly used to estimate melanoma prevalence in REAs or to predict long-term effectiveness in CEAs. Differences emerged between agencies' use of RWD; however, no visible trends for RWD use over time were observed.

  3. Imaging with indium111-labeled anticarcinoembryonic antigen monoclonal antibody ZCE-025 of recurrent colorectal or carcinoembryonic antigen-producing cancer in patients with rising serum carcinoembryonic antigen levels and occult metastases

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

    Patt, Y.Z.; Lamki, L.M.; Shanken, J.

    1990-07-01

    We tested whether nuclear imaging with indium111 (111In)-labeled murine monoclonal (MoAb) anticarcinoembryonic antigen (anti-CEA) ZCE-025 antibody could detect recurrent disease in patients with a rising serum CEA level but negative findings for computed tomographic (CT) scans of the abdomen and pelvis, chest radiograph, and colonoscopy or barium enema. Twenty patients with a history of completely resected CEA-producing adenocarcinoma and a rising serum CEA level were given an intravenous infusion of 2 mg of 111In-labeled ZCE-025 mixed with 38 mg of unlabeled ZCE-025. Planar and single-photon emission CT (SPECT) scans were acquired at 72 and 144 hours, and in 19 ofmore » the 20 patients these were positive. Of those 19, 13 underwent exploratory surgery, and cancer was found in 10, and two had a diagnostic biopsy, which confirmed cancer. Three patients who had negative laparotomies and all four patients who did not undergo surgery or biopsy were followed radiologically. In all seven, cancer was subsequently detected at the sites suggested by the ZCE-025 scan. Thus, tumor was confirmed in all 19 patients with positive scans. Five of 13 patients who were explored benefited from the study and the exploratory laparotomy, as disease was entirely resected in four or was subjected to definitive radiation therapy to the pelvis in the fifth. In two additional patients who were not explored, MoAb imaging resulted in definitive therapy to regionally confined recurrent disease. 111In-labeled anti-CEA MoAb ZCE-025 scanning in patients with rising CEA successfully imaged metastatic colorectal cancer that eluded detection by other methods and affected the care given to some. These results suggest an important role for 111In-labeled ZCE-025 scanning among patients with rising CEA and otherwise occult metastatic cancer.« less

  4. Does the academic performance of psychiatrists influence success in the NHS Clinical Excellence Award Scheme?

    PubMed Central

    Mitchell, Alex J; Crowfoot, Daniel; Leaver, James; Hughes, Samantha

    2011-01-01

    Objectives Given the uncertainty about factors that influence receipt of Clinical Excellence Awards (CEA) and recent availability of advanced research metrics, we examined the factors that predict CEA success using a convenience sample of English psychiatrists. Design Observational study examining region, subspecialty, H-index, M-index, number of publications, years since registration and years in specialty. Setting ACCEA Nominal Roll, cross-referenced with data from the GMC's list of registered medical practitioners and Thompson's Web of Science database. Participants A total of 494 psychiatrists including 245 with national levels awards and a random sample with local level awards. Main outcome measures Receipt of local or national CEA awards in 2008 and 2009. Results Of those with national awards, 126 had university contracts and 119 NHS contracts. Across all staff, years since qualification in medicine and H-index were the dominant influences. For local awards we found that years worked in the specialty was the main predictor of a CEA award with a smaller contribution from H-index. For national awards to university staff (academics) years on the medical register and publication rate were significant predictors. For national awards to NHS staff (non-academics) H-index and total cites were predictive, but these were themselves related to age. Conclusions Progression in CEAs among psychiatrists is strongly influenced by age (years spent in specialty and years on the medical register) with an additional contribution from research productivity. Currently, research impact is crudely assessed in the CEA process. We suggest that CEA committees formally assess the impact of NHS-related research using standardized research metrics which are openly available. We also suggest that supporting organizations and local trusts adhere to the rules mandated by the ACCEA. PMID:21541089

  5. Does preoperative measurement of cerebral blood flow with acetazolamide challenge in addition to preoperative measurement of cerebral blood flow at the resting state increase the predictive accuracy of development of cerebral hyperperfusion after carotid endarterectomy? Results from 500 cases with brain perfusion single-photon emission computed tomography study.

    PubMed

    Oshida, Sotaro; Ogasawara, Kuniaki; Saura, Hiroaki; Yoshida, Koji; Fujiwara, Shunro; Kojima, Daigo; Kobayashi, Masakazu; Yoshida, Kenji; Kubo, Yoshitaka; Ogawa, Akira

    2015-01-01

    The purpose of the present study was to determine whether preoperative measurement of cerebral blood flow (CBF) with acetazolamide in addition to preoperative measurement of CBF at the resting state increases the predictive accuracy of development of cerebral hyperperfusion after carotid endarterectomy (CEA). CBF at the resting state and cerebrovascular reactivity (CVR) to acetazolamide were quantitatively assessed using N-isopropyl-p-[(123)I]-iodoamphetamine (IMP)-autoradiography method with single-photon emission computed tomography (SPECT) before CEA in 500 patients with ipsilateral internal carotid artery stenosis (≥ 70%). CBF measurement using (123)I-IMP SPECT was also performed immediately and 3 days after CEA. A region of interest (ROI) was automatically placed in the middle cerebral artery territory in the affected cerebral hemisphere using a three-dimensional stereotactic ROI template. Preoperative decreases in CBF at the resting state [95% confidence intervals (CIs), 0.855 to 0.967; P = 0.0023] and preoperative decreases in CVR to acetazolamide (95% CIs, 0.844 to 0.912; P < 0.0001) were significant independent predictors of post-CEA hyperperfusion. The area under the receiver operating characteristic curve for prediction of the development of post-CEA hyperperfusion was significantly greater for CVR to acetazolamide than for CBF at the resting state (difference between areas, 0.173; P < 0.0001). Sensitivity, specificity, and positive- and negative-predictive values for the prediction of the development of post-CEA hyperperfusion were significantly greater for CVR to acetazolamide than for CBF at the resting state (P < 0.05, respectively). The present study demonstrated that preoperative measurement of CBF with acetazolamide in addition to preoperative measurement of CBF at the resting state increases the predictive accuracy of the development of post-CEA hyperperfusion.

  6. Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala

    PubMed Central

    Varodayan, Florence P.; Soni, Neeraj; Bajo, Michal; Luu, George; Madamba, Samuel G.; Schweitzer, Paul; Parsons, Loren H.; Roberto, Marisa

    2015-01-01

    The endogenous cannabinoids (eCBs) influence the acute response to ethanol and the development of tolerance, dependence and relapse. Chronic alcohol exposure alters eCB levels and type 1 cannabinoid receptor (CB1) expression and function in brain regions associated with addiction. CB1 inhibits GABA release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naïve rats, CB1 agonist WIN 55,212-2 (WIN) decreased the frequency of spontaneous and miniature GABAA receptor-mediated inhibitory postsynaptic currents (s/mIPSCs). This effect was prevented by CB1 antagonism, but not type 2 cannabinoid receptor (CB2) antagonism. After 2–3 weeks of intermittent ethanol exposure, these WIN inhibitory effects were attenuated, suggesting ethanol-induced impairments in CB1 function. The CB1 antagonist AM251 revealed a tonic eCB/CB1 control of GABAergic transmission in the alcohol-naïve CeA that was occluded by calcium chelation in the postsynaptic cell. Chronic ethanol exposure abolished this tonic CB1 influence on mIPSC, but not sIPSC, frequency. Finally, acute ethanol increased CeA GABA release in both naïve and ethanol exposed rats. Although CB1 activation prevented this effect, the AM251- and ethanol-induced GABA release were additive, ruling out a direct participation of CB1 signaling in the ethanol effect. Collectively, these observations demonstrate an important CB1 influence on CeA GABAergic transmission and indicate that the CeA is particularly sensitive to alcohol-induced disruptions of CB1 signaling. PMID:25940135

  7. Meta‐analysis of the procedural risks of carotid endarterectomy and carotid artery stenting over time

    PubMed Central

    Lokuge, K.; de Waard, D. D.; Halliday, A.; Gray, A.; Bulbulia, R.

    2017-01-01

    Background Stroke/death rates within 30 days of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in RCTs inform current clinical guidelines. However, the risks may have changed in recent years with wider use of effective stroke prevention therapies, especially statins, improved patient selection and growing operator expertise. The aim of this study was to investigate whether the procedural stroke/death risks from CEA and CAS have changed over time. Methods MEDLINE and Embase were searched systematically from inception to May 2016 for observational cohort studies of CEA and CAS. Studies included reported on more than 1000 patients, with 30‐day outcomes after the procedure according to patients' symptom status (recent stroke or transient ischaemic attack). Restricted maximum likelihood random‐effects and meta‐regressions methods were used to synthesize procedural stroke/death rates of CEA and CAS according to year of study recruitment completion. Results Fifty‐one studies, including 223 313 patients undergoing CEA and 72 961 undergoing CAS, were reviewed. Procedural stroke/death risks of CEA decreased over time in symptomatic and asymptomatic patients. Risks were substantially lower in studies completing recruitment in 2005 or later, both in symptomatic (5·11 per cent before 2005 versus 2·68 per cent from 2005 onwards; P = 0·002) and asymptomatic (3·17 versus 1·50 per cent; P < 0·001) patients. Procedural stroke/death rates of CAS did not change significantly over time (4·77 per cent among symptomatic and 2·59 per cent among asymptomatic patients). There was substantial heterogeneity in event rates and recruitment periods were long. Conclusions Risks of procedural stroke/death following CEA appear to have decreased substantially. There was no evidence of a change in stroke/death rates following CAS. PMID:29205297

  8. Can delivery systems use cost-effectiveness analysis to reduce healthcare costs and improve value?

    PubMed

    Savitz, Lucy A; Savitz, Samuel T

    2016-01-01

    Understanding costs and ensuring that we demonstrate value in healthcare is a foundational presumption as we transform the way we deliver and pay for healthcare in the U.S. With a focus on population health and payment reforms underway, there is increased pressure to examine cost-effectiveness in healthcare delivery. Cost-effectiveness analysis (CEA) is a type of economic analysis comparing the costs and effects (i.e. health outcomes) of two or more treatment options. The result is expressed as a ratio where the denominator is the gain in health from a measure (e.g. years of life or quality-adjusted years of life) and the numerator is the incremental cost associated with that health gain. For higher cost interventions, the lower the ratio of costs to effects, the higher the value. While CEA is not new, the approach continues to be refined with enhanced statistical techniques and standardized methods. This article describes the CEA approach and also contrasts it to optional approaches, in order for readers to fully appreciate caveats and concerns. CEA as an economic evaluation tool can be easily misused owing to inappropriate assumptions, over reliance, and misapplication. Twelve issues to be considered in using CEA results to drive healthcare delivery decision-making are summarized. Appropriately recognizing both the strengths and the limitations of CEA is necessary for informed resource allocation in achieving the maximum value for healthcare services provided.

  9. The predictive value of preoperative carcinoembryonic antigen level in the prognosis of colon cancer.

    PubMed

    Kirat, Hasan T; Ozturk, Ersin; Lavery, Ian C; Kiran, Ravi P

    2012-10-01

    We evaluated factors associated with an increased preoperative carcinoembryonic antigen (CEA) level for colon cancer patients undergoing elective curative surgery and assessed whether this was associated with prognosis when accounting for other potential confounders. Prospectively accrued data of patients with stage I, II, and III colon cancer undergoing surgery (1980-2008) were retrieved retrospectively. Patients with a preoperative CEA level greater than 5 ng/mL (group B) were compared with those with a CEA level of 5 ng/mL or less (group A). There were 651 patients (379 men) with a median age of 67 years (range, 21-94 y) and a median follow-up period of 5.9 years. Groups A (n = 451) and B (n = 200) had similar ages and tumor locations. Group B had larger tumors; more patients with T3 and N1/N2; and more patients with stage II/III tumors, and hence greater use of chemotherapy (P = .04). On multivariate analysis, patient age, tumor stage, and differentiation were associated with oncologic outcomes. A CEA level greater than 5 ng/mL was not associated independently with recurrence, recurrence-free survival (P = .47), or overall survival (P = .3). An increased preoperative CEA level is a marker for a more advanced tumor stage. For adequately staged patients, a high preoperative CEA level is not associated independently with oncologic outcomes. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Glucose oxidase-initiated cascade catalysis for sensitive impedimetric aptasensor based on metal-organic frameworks functionalized with Pt nanoparticles and hemin/G-quadruplex as mimicking peroxidases.

    PubMed

    Zhou, Xingxing; Guo, Shijing; Gao, Jiaxi; Zhao, Jianmin; Xue, Shuyan; Xu, Wenju

    2017-12-15

    Based on cascade catalysis amplification driven by glucose oxidase (GOx), a sensitive electrochemical impedimetric aptasensor for protein (carcinoembryonic antigen, CEA as tested model) was proposed by using Cu-based metal-organic frameworks functionalized with Pt nanoparticles, aptamer, hemin and GOx (Pt@CuMOFs-hGq-GOx). CEA aptamer loaded onto Pt@CuMOFs was bound with hemin to form hemin@G-quadruplex (hGq) with mimicking peroxidase activity. Through sandwich-type reaction of target CEA and CEA aptamers (Apt1 and Apt2), the obtained Pt@CuMOFs-hGq-GOx as signal transduction probes (STPs) was captured to the modified electrode interface. When 3,3-diaminobenzidine (DAB) and glucose were introduced, the cascade reaction was initiated by GOx to catalyze the oxidation of glucose, in situ generating H 2 O 2 . Simultaneously, the decomposition of the generated H 2 O 2 was greatly promoted by Pt@CuMOFs and hGq as synergistic peroxide catalysts, accompanying with the significant oxidation process of DAB and the formation of nonconductive insoluble precipitates (IPs). As a result, the electron transfer in the resultant sensing interface was effectively hindered and the electrochemical impedimetric signal (EIS) was efficiently amplified. Thus, the high sensitivity of the proposed CEA aptasensor was successfully improved with 0.023pgmL -1 , which may be promising and potential in assaying certain clinical disease related to CEA. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Intrinsic functional connectivity of the central nucleus of the amygdala and bed nucleus of the stria terminalis.

    PubMed

    Gorka, Adam X; Torrisi, Salvatore; Shackman, Alexander J; Grillon, Christian; Ernst, Monique

    2018-03-01

    The central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST), two nuclei within the central extended amygdala, function as critical relays within the distributed neural networks that coordinate sensory, emotional, and cognitive responses to threat. These structures have overlapping anatomical projections to downstream targets that initiate defensive responses. Despite these commonalities, researchers have also proposed a functional dissociation between the CeA and BNST, with the CeA promoting responses to discrete stimuli and the BNST promoting responses to diffuse threat. Intrinsic functional connectivity (iFC) provides a means to investigate the functional architecture of the brain, unbiased by task demands. Using ultra-high field neuroimaging (7-Tesla fMRI), which provides increased spatial resolution, this study compared the iFC networks of the CeA and BNST in 27 healthy individuals. Both structures were coupled with areas of the medial prefrontal cortex, hippocampus, thalamus, and periaqueductal gray matter. Compared to the BNST, the bilateral CeA was more strongly coupled with the insula and regions that support sensory processing, including thalamus and fusiform gyrus. In contrast, the bilateral BNST was more strongly coupled with regions involved in cognitive and motivational processes, including the dorsal paracingulate gyrus, posterior cingulate cortex, and striatum. Collectively, these findings suggest that responses to sensory stimulation are preferentially coordinated by the CeA and cognitive and motivational responses are preferentially coordinated by the BNST. Published by Elsevier Inc.

  12. Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons

    PubMed Central

    Roberto, Marisa; Madamba, Samuel G.; Moore, Scott D.; Tallent, Melanie K.; Siggins, George R.

    2003-01-01

    We examined the interaction of ethanol with the γ-aminobutyric acid (GABA)ergic system in neurons of slices of the rat central amygdala nucleus (CeA), a brain region thought to be critical for the reinforcing effects of ethanol. Brief superfusion of 11–66 mM ethanol significantly increased GABA type A (GABAA) receptor-mediated inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) in most CeA neurons, with a low apparent EC50 of 20 mM. Acute superfusion of 44 mM ethanol increased the amplitude of evoked GABAA IPSPs and IPSCs in 70% of CeA neurons. The ethanol enhancement of IPSPs and IPSCs occurred to a similar extent in the presence of the GABA type B (GABAB) receptor antagonist CGP 55845A, suggesting that this receptor is not involved in the ethanol effect on CeA neurons. Ethanol superfusion also decreased paired-pulse facilitation of evoked GABAA IPSPs and IPSCs and always increased the frequency and sometimes the amplitude of spontaneous miniature GABAA IPSCs as well as responses to local GABA application, indicating both presynaptic and postsynaptic sites of action for ethanol. Thus, the CeA is the first brain region to reveal, without conditional treatments such as GABAB antagonists, consistent, low-dose ethanol enhancement of GABAergic transmission at both pre- and postsynaptic sites. These findings add further support to the contention that the ethanol–GABA interaction in CeA plays an important role in the reinforcing effects of ethanol. PMID:12566570

  13. Cost-effectiveness Analysis with Influence Diagrams.

    PubMed

    Arias, M; Díez, F J

    2015-01-01

    Cost-effectiveness analysis (CEA) is used increasingly in medicine to determine whether the health benefit of an intervention is worth the economic cost. Decision trees, the standard decision modeling technique for non-temporal domains, can only perform CEA for very small problems. To develop a method for CEA in problems involving several dozen variables. We explain how to build influence diagrams (IDs) that explicitly represent cost and effectiveness. We propose an algorithm for evaluating cost-effectiveness IDs directly, i.e., without expanding an equivalent decision tree. The evaluation of an ID returns a set of intervals for the willingness to pay - separated by cost-effectiveness thresholds - and, for each interval, the cost, the effectiveness, and the optimal intervention. The algorithm that evaluates the ID directly is in general much more efficient than the brute-force method, which is in turn more efficient than the expansion of an equivalent decision tree. Using OpenMarkov, an open-source software tool that implements this algorithm, we have been able to perform CEAs on several IDs whose equivalent decision trees contain millions of branches. IDs can perform CEA on large problems that cannot be analyzed with decision trees.

  14. Collie Eye Anomaly in Switzerland.

    PubMed

    Walser-Reinhardt, L; Hässig, M; Spiess, B

    2009-12-01

    In this retrospective study, the results of 3'527 eye examinations in 6 different breeds affected with Collie Eye Anomaly (CEA) over a period of 8 years (1999 - 2007) are described. CEA was divided into three main ophthalmoscopic features, a) choroidal hypoplasia (CRH), b) CRH and coloboma and c) coloboma alone. Of the 101 Smooth Collies 8.9 % showed signs of CRH, whereas 36.9 % of Rough Collies were affected with CRH, 2.8 % with CRH and coloboma and 0.38 % with coloboma alone. Choroidal hypoplasia was present in 13.1 %, CRH and coloboma in 1.8 % and coloboma alone in 0.2 % of the Shetland Sheepdogs. Only one Australian Shepherd dog had CRH, while 0.7 % of the Border Collies were affected with CRH. None of the Nova Scotia Duck Tolling Retrievers were affected with CEA. There were no statistically significant differences in the occurrence of CEA between males and females, nor was there any relation between coat colors. Significant differences could be shown between dogs younger or older than 8 weeks at first examination. CEA was more often diagnosed in dogs younger than 8 weeks within the Rough Collie and Shetland Sheepdog.

  15. The impact of childhood emotional abuse and experiential avoidance on maladaptive problem solving and intimate partner violence.

    PubMed

    Bell, Kathryn M; Higgins, Lorrin

    2015-04-16

    The purpose of the current study was to examine the joint influences of experiential avoidance and social problem solving on the link between childhood emotional abuse (CEA) and intimate partner violence (IPV). Experiential avoidance following CEA may interfere with a person's ability to effectively problem solve in social situations, increasing risk for conflict and interpersonal violence. As part of a larger study, 232 women recruited from the community completed measures assessing childhood emotional, physical, and sexual abuse, experiential avoidance, maladaptive social problem solving, and IPV perpetration and victimization. Final trimmed models indicated that CEA was indirectly associated with IPV victimization and perpetration via experiential avoidance and Negative Problem Orientation (NPO) and Impulsivity/Carelessness Style (ICS) social problem solving strategies. Though CEA was related to an Avoidance Style (AS) social problem solving strategy, this strategy was not significantly associated with IPV victimization or perpetration. Experiential avoidance had both a direct and indirect effect, via NPO and ICS social problem solving, on IPV victimization and perpetration. Findings suggest that CEA may lead some women to avoid unwanted internal experiences, which may adversely impact their ability to effectively problem solve in social situations and increase IPV risk.

  16. Elucidating the relation between childhood emotional abuse and depressive symptoms in adulthood: The mediating role of maladaptive interpersonal processes

    PubMed Central

    Massing-Schaffer, Maya; Liu, Richard T.; Kraines, Morganne A.; Choi, Jimmy Y.; Alloy, Lauren B.

    2015-01-01

    Objective The purpose of this study is to assess the potential unique and relative mediating effects of three interpersonal risk factors (i.e., excessive reassurance-seeking [ERS], negative feedback seeking [NFS], and rejection sensitivity [RS]) in the relationship between childhood emotional abuse (CEA) and depressive symptoms. Method One hundred eighty-five undergraduates were followed over a four-month interval. Participants completed assessments of childhood abuse history, ERS, NFS, and RS, and depressive symptoms at baseline, as well as depressive symptoms at four-month followup. Results Findings from single-mediator analyses indicated that RS and NFS, but not ERS, mediated the relationship between CEA and prospective depressive symptoms, after accounting for childhood sexual and physical abuse, as well as baseline depressive symptoms. In our multi-mediator model, only RS remained a significant mediator of the relationship between CEA and prospective depressive symptoms. Conclusions The current study provides preliminary evidence that negative behavioral styles may function as a mechanism linking prior experiences of CEA to subsequent depressive symptoms. Clinical implications of these findings suggest that targeting maladaptive behavioral tendencies, particularly RS, may be an effective adjunct in behavioral modification treatments of CEA victims at risk for depression. PMID:26246650

  17. Efficacy and Safety of 3 Different Anesthesia Techniques Used in Total Hip Arthroplasty

    PubMed Central

    Liang, Chengwei; Wei, Jionglin; Cai, Xiaoxi; Lin, Weilong; Fan, Yongqian; Yang, Fengjian

    2017-01-01

    Background This study compared the efficacy and safety of 3 different anesthesia techniques used in total hip arthroplasty (THA). Material/Methods We allocated 198 patients preparing to undertake THA into 3 groups: general anesthesia group (GA group, n=66), caudal epidural anesthesia group (CEA group, n=66), and spinal-epidural anesthesia group (SEA group, n=66). We compared postoperative adverse effects occurring in patients of the 3 anesthesia groups. The Visual Analog Scale (VAS) score, Minimum Mental State Examination (MMSE) score, and β-amyloid (Aβ) expression were calculated to determine the effects of different anesthesia on the postoperative pain and cognitive dysfunction of patients. Results The CEA and SEA groups had lower rates of perioperative adverse effects than in the GA group. Patients in the GA group required significantly higher administration of analgesics after the surgery than those in CEA and SEA groups. Higher Aβ expression levels and VAS scores, as well as lower MMSE scores, were also seen in the GA group compared with the other 2 groups. Conclusions CEA and SEA were more effective than GA in THA, and CEA seemed to be a better anesthesia technique than SEA. PMID:28767640

  18. The Impact of Childhood Emotional Abuse and Experiential Avoidance on Maladaptive Problem Solving and Intimate Partner Violence

    PubMed Central

    Bell, Kathryn M.; Higgins, Lorrin

    2015-01-01

    The purpose of the current study was to examine the joint influences of experiential avoidance and social problem solving on the link between childhood emotional abuse (CEA) and intimate partner violence (IPV). Experiential avoidance following CEA may interfere with a person’s ability to effectively problem solve in social situations, increasing risk for conflict and interpersonal violence. As part of a larger study, 232 women recruited from the community completed measures assessing childhood emotional, physical, and sexual abuse, experiential avoidance, maladaptive social problem solving, and IPV perpetration and victimization. Final trimmed models indicated that CEA was indirectly associated with IPV victimization and perpetration via experiential avoidance and Negative Problem Orientation (NPO) and Impulsivity/Carelessness Style (ICS) social problem solving strategies. Though CEA was related to an Avoidance Style (AS) social problem solving strategy, this strategy was not significantly associated with IPV victimization or perpetration. Experiential avoidance had both a direct and indirect effect, via NPO and ICS social problem solving, on IPV victimization and perpetration. Findings suggest that CEA may lead some women to avoid unwanted internal experiences, which may adversely impact their ability to effectively problem solve in social situations and increase IPV risk. PMID:25893570

  19. A high-sensitivity electrochemical aptasensor of carcinoembryonic antigen based on graphene quantum dots-ionic liquid-nafion nanomatrix and DNAzyme-assisted signal amplification strategy.

    PubMed

    Huang, Jing-Yi; Zhao, Lang; Lei, Wan; Wen, Wei; Wang, Yi-Jia; Bao, Ting; Xiong, Hua-Yu; Zhang, Xiu-Hua; Wang, Sheng-Fu

    2018-01-15

    In this work, we have developed an electrochemical aptasensor for high-sensitivity determination of carcinoembryonic antigen (CEA) based on lead ion (Pb 2+ )-dependent DNAzyme-assisted signal amplification and graphene quantum dot-ionic liquid-nafion (GQDs-IL-NF) composite film. We designed hairpin DNA containing CEA-specific aptamers and DNAzyme chains. In the presence of CEA, hairpin DNA recognized the target and performed a DNAzyme-assisted signal amplification reaction to yield a large number of single-stranded DNA. The GQDs-IL-NF composite film was immobilized on the glassy carbon electrode for the interaction with single-stranded DNA through noncovalent π-π stacking interaction. Therefore, the methylene blue-labeled substrate DNA (MB-substrate) was fixed on the electrode and exhibited an initial electrochemical signal. Under optimal conditions, the response current change was proportional to the concentration of CEA, demonstrating a wide linear range from 0.5fgmL -1 to 0.5ngmL -1 , with a low detection limit of 0.34fgmL -1 . Furthermore, the proposed aptasensor was successfully applied in determining CEA in serum samples, showing its superior prospects in clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Computer Program for Calculation of Complex Chemical Equilibrium Compositions and Applications II. Users Manual and Program Description. 2; Users Manual and Program Description

    NASA Technical Reports Server (NTRS)

    McBride, Bonnie J.; Gordon, Sanford

    1996-01-01

    This users manual is the second part of a two-part report describing the NASA Lewis CEA (Chemical Equilibrium with Applications) program. The program obtains chemical equilibrium compositions of complex mixtures with applications to several types of problems. The topics presented in this manual are: (1) details for preparing input data sets; (2) a description of output tables for various types of problems; (3) the overall modular organization of the program with information on how to make modifications; (4) a description of the function of each subroutine; (5) error messages and their significance; and (6) a number of examples that illustrate various types of problems handled by CEA and that cover many of the options available in both input and output. Seven appendixes give information on the thermodynamic and thermal transport data used in CEA; some information on common variables used in or generated by the equilibrium module; and output tables for 14 example problems. The CEA program was written in ANSI standard FORTRAN 77. CEA should work on any system with sufficient storage. There are about 6300 lines in the source code, which uses about 225 kilobytes of memory. The compiled program takes about 975 kilobytes.

  1. Ultrasonographic character of carotid plaque and postprocedural brain embolisms in carotid artery stenting and carotid endarterectomy.

    PubMed

    Mitsuoka, Hiroshi; Shintani, Tsunehiro; Furuya, Hidekazu; Nakao, Yoshinaga; Higashi, Shigeki

    2011-01-01

    To investigate ultrasonographic character of carotid plaques, and incidences of brain embolism in carotid angioplasty and stenting (CAS) and carotid endarterectomy (CEA). CEA (22/25 symptomatic lesions) and CAS (17/20 symptomatic lesions) between 2007 and 2010. Embolic protection devices (15 occlusion and 5 filtering devices) were used during CAS. Carotid plaques were classified into three categories (I: calcificated, II: intermediately echogenic, III: echolucent). Magnetic resonance imaging (MRI) was used to investigate brain emboli. Ultrasonographic character of the plaques in CEA cases (I: 4%, II: 88%, III: 8%) was different from the one in CAS cases (I: 10%, II: 90%, III: 0%). The incidence of brain embolism in the CAS cases was 52.6% while 0% in the CEA cases (p = 0.00037). CAS had high incidences of brain embolism in any plaques (I: 100%, II: 43.8%). In the most recent 9 procedures of CAS using occlusion devices, averaged number of embolic lesion was 1.0 (0 post operative day; 0 POD). The number increased as 1.4 (1 POD) and 2.0 (7 POD). CEA should be currently the first choice for most patients with a high-grade and symptomatic carotid artery stenosis.

  2. Laser megajoule 1.06-μm mirror production with very high laser damage threshold

    NASA Astrophysics Data System (ADS)

    Pinot, B.; Leplan, Herve; Houbre, Francois; Lavastre, Eric; Poncetta, Jean-Christophe; Chabassier, Genevieve

    2002-03-01

    As part of the LMJ (Laser Megajoule) program, CEA is building the LIL laser with full size optics and LMJ requirements. SAGEM has been selected as the supplier of large optical components and coatings with very high laser- induced damage threshold. Including spare parts, about 100 mirrors 610*430 mm2 with LIDT-3ns>25 J/cm2 have to be produced. Using a 5 m3 vacuum chamber and the 100 J/cm2 mirror coating process developed at CEA-LETI, with Hafnium and SiO2 materials, we are now typically in a serial production phase. To date, about thirty mirrors have been delivered. This paper focuses on the acceptance tests performed after coating, at SAGEM then CEA: LIDT measurement and Raster-Scan on samples; reflectance mapping on CEA automatic photometer; reflected wavefront deformation with \

  3. 77 FR 41110 - Exemptive Order Regarding Compliance With Certain Swap Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-12

    ... delay compliance with certain entity-level requirements of the CEA (and Commission regulations promulgated thereunder), subject to specified conditions. Additionally, with respect to transaction-level.... major swap participants may delay compliance with certain entity-level requirements of the CEA (and...

  4. Hispanic ethnicity is associated with increased costs after carotid endarterectomy and carotid stenting in the United States.

    PubMed

    Propper, Brandon; Black, James H; Schneider, Eric B; Lum, Ying Wei; Malas, Mahmoud B; Arnold, Margaret W; Abularrage, Christopher J

    2013-09-01

    We have previously demonstrated an adverse impact of black race and Hispanic ethnicity on the outcomes of carotid endarterectomy (CEA) and carotid artery stenting (CAS). The current study was undertaken to examine the influence of race and ethnicity on the cost of CEA and CAS. The Nationwide Inpatient Sample (2005-2009) was queried using ICD-9 codes for CEA and CAS in patients with carotid artery stenosis. The primary outcome was total hospital charges. Multivariate analysis was performed using a generalized linear model adjusting for age, sex, race, comorbidities (Charlson index), high-risk status, procedure type, symptomatic status, year, insurance type, and surgeon and hospital operative volumes and characteristics. Hispanic and black patients were more likely to have a symptomatic presentation, and were more likely to undergo either CEA or CAS by low-volume surgeons at low-volume hospitals (P < 0.05, all). They were also less likely to have private insurance or Medicare (P < 0.001). Overall, CEA was less expensive than CAS over the 4-y study period ($29,502 ± $104 versus $46,713 ± $409, P < 0.001). Total hospital charges after CEA were increased in both blacks ($39,562 ± $843) and Hispanics ($45,325 ± $735) compared with whites on univariate analysis ($28,403 ± $101, P < 0.001). After CAS, total hospital charges were similarly increased in both blacks ($51,770 ± $2085) and Hispanics ($63,637 ± $2766) compared with whites on univariate analysis ($45,550 ± $412, P < 0.001). On multivariable analysis, however, only Hispanic ethnicity remained independently associated with increased charges after both CEA (exponentiated coefficient 1.18; 95% CI [1.15-1.20]; P < 0.001) and CAS (exponentiated coefficient 1.17; 95% CI [1.09-1.24]; P < 0.001). Hispanic ethnicity was independently associated with increased hospital charges after both CEA and CAS. The increased charges seen in black patients were explained, in part, by decreased surgeon operative volume

  5. The risk of carotid artery stenting compared with carotid endarterectomy is greatest in patients treated within 7 days of symptoms.

    PubMed

    Rantner, Barbara; Goebel, Georg; Bonati, Leo H; Ringleb, Peter A; Mas, Jean-Louis; Fraedrich, Gustav

    2013-03-01

    Among patients with symptomatic carotid artery stenosis, carotid artery stenting (CAS) is associated with a higher risk of periprocedural stroke or death than carotid endarterectomy (CEA). Uncertainty remains whether the balance of risk changes with time since the most recent ischemic event. We investigated the association of time between the qualifying ischemic event and treatment (0-7 days, 8-14 days, and >14 days) with the risk of stroke or death within 30 days after CAS or CEA in a pooled analysis of data from individual patients randomized in the Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial, and the International Carotid Stenting Study (ICSS). Data were analyzed with a fixed-effect binomial regression model adjusted for source trial. Information on time of qualifying event was available for 2839 patients. In the first 30 days after intervention, any stroke or death occurred significantly more often in the CAS group (110/1434 [7.7%]) compared with the CEA group (54/1405 [3.8%]; crude risk ratio, 2.0; 95% confidence interval, 1.5-2.7). Patients undergoing CEA within the first 7 days of the qualifying event had the lowest periprocedural stroke or death rate (3/106 [2.8%]). Patients treated with CAS in the same period had a 9.4% risk of periprocedural stroke or death (13/138; risk ratio CAS vs CEA: 3.4; 95% confidence interval, 1.01-11.8; adjusted for age, sex, and type of qualifying event). Patients treated between 8 and 14 days showed a periprocedural stroke or death rate of 3.4% (7/208) and 8.1% (19/234), respectively, for CEA and CAS. The latest treatment group had 4% complications in the CEA group (44/1091) and 7.3% in the CAS group (78/1062). The increase in risk of CAS compared with CEA appears to be greatest in patients treated within 7 days of symptoms. Early surgery might remain most effective in stroke prevention in patients

  6. Advances in greenhouse automation and controlled environment agriculture: A transition to plant factories and urban farming

    USDA-ARS?s Scientific Manuscript database

    Greenhouse cultivation has evolved from simple covered rows of open-fields crops to highly sophisticated controlled environment agriculture (CEA) facilities that projected the image of plant factories for urban farming. The advances and improvements in CEA have promoted the scientific solutions for ...

  7. COMMITTEES: Committees

    NASA Astrophysics Data System (ADS)

    2010-01-01

    TAUP STEERING COMMITTEE F T Avignone, University of South Carolina B C Barish, CALTECH E Bellotti, University of Milano, INFN J Bernabeu, University of Valencia A Bottino (Chair), University of Torino, INFN N Fornengo, University of Torino, INFN T Kajita, ICRR University of Tokyo C W Kim, Johns Hopkins University, KIAS V Matveev, INR Moscow J Morales, University of Zaragoza G Raffelt, MPI Munchen D Sinclair, University of Carleton M Spiro, IN2P3 TAUP 2009 INTERNATIONAL ADVISORY COMMITTEE J J Aubert, CNRS Marseille M Baldo-Ceolin, University of Padova, INFN G Bellini, University of Milano, INFN L Bergstrom, University of Stockholm R Bernabei, University of Roma Tor Vergata, INFN A Bettini, University of Padova, INFN, LSC S Bilenky, JINR Dubna D O Caldwell, UCSB J Cronin, University of Chicago A Dar, Technion Haifa G Domogatsky, INR Moscow J Ellis, CERN E Fernandez, IFAE Barcelona E Fiorini, University of Milano, INFN T Gaisser, University of Delaware G Gelmini, UCLA G Gerbier, CEA Saclay A Giazotto, INFN Pisa F Halzen, University of Wisconsin W Haxton, University of Washington T Kirsten MPI Heidelberg L Maiani, University of Roma La Sapienza, INFN A McDonald, Queen's University K Nakamura, KEK R Petronzio, INFN, University of Roma Tor Vergata L Resvanis, University of Athens F Ronga INFN, LNF C Rubbia INFN, LNGS A Smirnov, ICTP Trieste C Spiering, DESY N Spooner, University of Sheffield A Suzuki, KEK S Ting MIT, CERN M S Turner, FNAL, University of Chicago J W F Valle, IFIC Valencia D Vignaud, APC Paris G Zatsepin, INR Moscow TAUP 2009 ORGANIZING COMMITTEE R Aloisio, LNGS R Antolini, LNGS F Arneodo, LNGS Z Berezhiani, University of L'Aquila, INFN V Berezinsky, LNGS R Cerulli, LNGS E Coccia [Chair], LNGS/INFN, U of Roma Tor Vergata N D'Ambrosio, LNGS N Fornengo, University of Torino, INFN M Laubenstein, LNGS O Palamara, LNGS L Pandola [Scientific Secretary], LNGS

  8. Gemini Spectroscopy of Supernovae from the Supernova Legacy Survey: Improving High-Redshift Supernova Selection and Classification

    NASA Astrophysics Data System (ADS)

    Howell, D. A.; Sullivan, M.; Perrett, K.; Bronder, T. J.; Hook, I. M.; Astier, P.; Aubourg, E.; Balam, D.; Basa, S.; Carlberg, R. G.; Fabbro, S.; Fouchez, D.; Guy, J.; Lafoux, H.; Neill, J. D.; Pain, R.; Palanque-Delabrouille, N.; Pritchet, C. J.; Regnault, N.; Rich, J.; Taillet, R.; Knop, R.; McMahon, R. G.; Perlmutter, S.; Walton, N. A.

    2005-12-01

    We present new techniques for improving the efficiency of supernova (SN) classification at high redshift using 64 candidates observed at Gemini North and South during the first year of the Supernova Legacy Survey (SNLS). The SNLS is an ongoing 5 year project with the goal of measuring the equation of state of dark energy by discovering and following over 700 high-redshift SNe Ia using data from the Canada-France-Hawaii Telescope Legacy Survey. We achieve an improvement in the SN Ia spectroscopic confirmation rate: at Gemini 71% of candidates are now confirmed as SNe Ia, compared to 54% using the methods of previous surveys. This is despite the comparatively high redshift of this sample, in which the median SN Ia redshift is z=0.81 (0.155<=z<=1.01). These improvements were realized because we use the unprecedented color coverage and light curve sampling of the SNLS to predict whether a candidate is a SN Ia and to estimate its redshift, before obtaining a spectrum, using a new technique called the ``SN photo-z.'' In addition, we have improved techniques for galaxy subtraction and SN template χ2 fitting, allowing us to identify candidates even when they are only 15% as bright as the host galaxy. The largest impediment to SN identification is found to be host galaxy contamination of the spectrum-when the SN was at least as bright as the underlying host galaxy the target was identified more than 90% of the time. However, even SNe in bright host galaxies can be easily identified in good seeing conditions. When the image quality was better than 0.55", the candidate was identified 88% of the time. Over the 5 year course of the survey, using the selection techniques presented here, we will be able to add ~170 more confirmed SNe Ia than would be possible using previous methods. APC, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05, France. DSM/DAPNIA, CEA/Saclay, 91191 Gif-sur-Yvette Cedex, France.

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

    Very, F.; Rosenkrantz, E.; Combette, P.

    The development of advanced instrumentation for in-pile experiments in Material Testing Reactor constitutes a main goal for the improvement of the nuclear fuel behavior knowledge. An acoustic method for fission gas release detection was tested with success during a first experiment called REMORA 3 in 2010 and 2011, and the results were used to differentiate helium and fission gas release kinetics under transient operating conditions. This experiment was lead at OSIRIS reactor (CEA Saclay, France). The maximal temperature on the sensor during the irradiation was about 150 deg. C. In this paper we present a thick film transducer produce bymore » screen printing process. The screen printing of piezoelectric offers a wide range of possible applications for the development of acoustic sensors and piezoelectric structure for measurements in high temperature environment. We firstly produced a Lead Zirconate Titanate (PZT) based paste composed of Pz27 powder from Ferroperm, CF7575 glass, and organic solvent ESL 400. Likewise a Bismuth Titanate based paste synthesized in our laboratory was produced. With these inks we produced thick film up to 130 μm by screen printing process. Material properties characterizations of these thick-film resonators are essential for device design and applications. The piezoelectric coefficients d33 and pyro-electric P(T) coefficient are investigated. The highest P(T) and d33 are respectively 80 μC.m{sup -2}.K{sup -1} and 130 μC.N{sup -1} for the PZT transducer -which validates the fabrication process-. In view of the development of this transducer oriented for high temperature and irradiation environment, we investigated the electrical properties of the transducers for different ranges of frequencies and temperature - from 20 Hz up to 40 MHz between 30 and 400 deg. C. We highlight the evolution of the impedance response and piezoelectric parameters of screen printed piezoelectric structures on alumina. Shortly an irradiation will be

  10. Development work for a superconducting linear collider

    NASA Technical Reports Server (NTRS)

    Matheisen, Axel

    1995-01-01

    For future linear e(+)e(-) colliders in the TeV range several alternatives are under discussion. The TESLA approach is based on the advantages of superconductivity. High Q values of the accelerator structures give high efficiency for converting RF power into beam power. A low resonance frequency for the RF structures can be chosen to obtain a large number of electrons (positrons) per bunch. For a given luminosity the beam dimensions can be chosen conservatively which leads to relaxed beam emittance and tolerances at the final focus. Each individual superconducting accelerator component (resonator cavity) of this linear collider has to deliver an energy gain of 25 MeV/m to the beam. Today s.c. resonators are in use at CEBAF/USA, at DESY/Germany, Darmstadt/Germany KEK/Japan and CERN/Geneva. They show acceleration gradients between 5 MV/m and 10 MV/m. Encouraging experiments at CEA Saclay and Cornell University showed acceleration gradients of 20 MV/m and 25 MV/m in single and multicell structures. In an activity centered at DESY in Hamburg/Germany the TESLA collaboration is constructing a 500 MeV superconducting accelerator test facility (TTF) to demonstrate that a linear collider based on this technique can be built in a cost effective manner and that the necessary acceleration gradients of more than 15 MeV/m can be reached reproducibly. The test facility built at DESY covers an area of 3.000 m2 and is divided into 3 major activity areas: (1) The testlinac, where the performance ofthe modular components with an electron beam passing the 40 m long acceleration section can be demonstrated. (2) The test area, where all individual resonators are tested before installation into a module. (3) The preparation and assembly area, where assembly of cavities and modules take place. We report here on the design work to reach a reduction of costs compared to actual existing superconducting accelerator structures and on the facility set up to reach high acceleration gradients in

  11. Preparation and characterization of a novel skin substitute.

    PubMed

    Castagnoli, Carlotta; Fumagalli, Mara; Alotto, Daniela; Cambieri, Irene; Casarin, Stefania; Ostorero, Alessia; Casimiri, Raffaella; Germano, Patrizia; Pezzuto, Carla; Stella, Maurizio

    2010-01-01

    Autologous epidermal cell cultures (CEA) represent a possibility to treat extensive burn lesions, since they allow a significative surface expansion which cannot be achieved with other surgical techniques based on autologous grafting. Moreover currently available CEA preparations are difficult to handle and their take rate is unpredictable. This study aimed at producing and evaluating a new cutaneous biosubstitute made up of alloplastic acellular glycerolized dermis (AAGD) and CEA to overcome these difficulties. A procedure that maintained an intact basement membrane was developed, so as to promote adhesion and growth of CEA on AAGD. Keratinocytes were seeded onto AAGD and cultured up to 21 days. Viability tests and immunohistochemical analysis with specific markers were carried out at 7, 14, and 21 days, to evaluate keratinocyte adhesion, growth, and maturation. Our results support the hypothesis that this newly formed skin substitute could allow its permanent engraftment in clinical application.

  12. Utility of the Lone Star Retractor System in Microsurgical Carotid Endarterectomy.

    PubMed

    Toyota, Shingo; Kumagai, Tetsuya; Goto, Tetsu; Mori, Kanji; Taki, Takuyu

    2017-05-01

    The retractor system is an important device in carotid endarterectomy (CEA). We applied the Lone Star (LS) Retractor System, which is a self-retaining retractor originally designed for improved visualization in many other surgical fields, in microsurgical CEA. The LS disposal retractor (14.1 cm × 14.1 cm) and LS elastic stays (5-mm sharp hook) were used as a retractor system in 38 consecutive CEAs. Using the LS retractor system, a shallow operative field could be obtained by lifting up the connective tissue surrounding the deep structures hooked by the LS elastic stays. The LS elastic stays were quick and easy to handle in the microsurgical operative field. There were no complications using the LS retractor system. The application of the LS retractor system in microsurgical CEA is feasible. An additional merit is that it is single use. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Carcinoembryonic antigen induces signal transduction in Kupffer cells.

    PubMed

    Gangopadhyay, A; Lazure, D A; Thomas, P

    1997-09-16

    Carcinoembryonic antigen (CEA), an intercellular adhesion molecule and a mediator of hepatic metastasis, is processed by an 80 kDa receptor on murine and human Kupffer cells in the liver. Activation of rat Kupffer cells in vitro by CEA via the 80 kDa receptor produced cytokines IL-1alpha and TNF-alpha which involved tyrosine phosphorylation. The peak response of TNF-alpha was 5.6 times greater than the corresponding IL-1alpha response and was associated with enhanced tyrosine phosphorylation of 108 and 125 kDa proteins. Lipopolysaccharide (LPS) treatment, on the other hand, phosphorylated two major proteins with MW of 93 and 119 kDa associated with the loss of phosphorylation from a 125 kDa protein. Results demonstrate that CEA-induced IL-1alpha and TNF-alpha production involves tyrosine phosphorylation and the signaling in CEA treated cells is different than that seen with LPS stimulation.

  14. Reliability of plain radiographic parameters for developmental dysplasia of the hip in children.

    PubMed

    Upasani, Vidyadhar V; Bomar, James D; Parikh, Gaurav; Hosalkar, Harish

    2012-07-01

    Few studies have evaluated the reliability and reproducibility of the femoral neck-shaft angle (NSA), center-edge angle (CEA), and acetabular index (AI) in young children with developmental dysplasia of the hip (DDH). We wanted to determine whether these parameters could be used reliably by practitioners. Fifty radiographs from 21 children with DDH were reviewed. Analysis was performed by three observers, at two time periods. The intra- and inter-observer reliability for each measure was assessed. At time period one, we noted a "high" level of agreement between observers when measuring the NSA, a "low" level when measuring the CEA, and a "moderate" level when measuring the AI. At time period two, we noted a "very high" level of agreement between observers when measuring the NSA and a "high" level when measuring the CEA and AI. When comparing the measurements of observer 1 at the two different time periods, we noted nearly "very high" agreement when measuring the NSA, a "moderate" agreement when measuring the CEA, and a "high" agreement for the AI. In comparing the measurements of observer 2, we noted "very high" agreement for the NSA and "high" agreement for the CEA and AI. In comparing the measurements for observer 3, we noted nearly "very high" agreement for the NSA, nearly "high" agreement for the CEA, and "high" agreement for the AI. It is difficult to reliably measure three-dimensional pelvic morphology on a frontal plane radiograph, especially when important pelvic landmarks have yet to ossify.

  15. Two-color immunostaining of liver fine needle aspiration biopsies with CD34 and carcinoembryonic antigen. Potential utilization in the diagnosis of primary hepatocellular carcinoma vs. metastatic tumor.

    PubMed

    Yoder, Michael; Zimmerman, Robert L; Bibbo, Marluce

    2004-04-01

    To examine immunohistochemical staining of cell block material with antibodies against vascular marker CD34 and polyclonal carcinoembryonic antigen (pCEA) for their clinical utility as part of a 2-color staining protocol in fine needle aspiration (FNA) biopsy of liver masses to distinguish metastases from primary hepatocellular carcinoma (HCC). The authors obtained cell block material from 96 liver FNAs and performed simultaneous (i.e., "dual-color") immunohistochemical staining utilizing antibodies against vascular marker CD34 and pCEA. Cases were blinded and evaluated by the authors for staining pattern and intensity. A consensus was obtained, the results were unblinded, and the diagnoses were correlated. After staining, 89 cases had sufficient tissue for evaluation. Of the 19 HCC cases, 16 (84%) showed peripheral staining with CD34, and 13 (68%) showed a canalicular or mixed canalicular-cytoplasmic staining pattern for pCEA. Thirteen cases (68%) showed staining for both antigens. All HCC exhibited immunostaining for at least 1 antibody in an appropriate staining pattern. Of the 67 cases of metastatic malignancy, 5 (7%) showed a predominantly transgressing pattern of CD34 staining, 43 (64%) showed a predominantly cytoplasmic or mixed cytoplasmic-canalicular pattern of pCEA staining, and 2 cases (3%) showed staining for both antigens in a transgressing CD34 pattern and cytoplasmic pCEA pattern. None of the 3 normal liver tissue blocks showed staining with either antigen. Two-color immunohistochemical staining of liver cell block material obtained by FNA with antibodies to CD34 and pCEA can be helpful in differentiating metastatic tumors vs. primary HCC.

  16. The Endocannabinoid System Tonically Regulates Inhibitory Transmission and Depresses the Effect of Ethanol in Central Amygdala

    PubMed Central

    Roberto, Marisa; Cruz, Maureen; Bajo, Michal; Siggins, George R; Parsons, Loren H; Schweitzer, Paul

    2010-01-01

    The central amygdala (CeA) has a major role in alcohol dependence and reinforcement, and behavioral and neurochemical evidence suggests a role for the endocannabinoid (eCB) system in ethanol binging and dependence. We used a slice preparation to investigate the physiological role of cannabinoids and their interaction with ethanol on inhibitory synaptic transmission in CeA. Superfusion of the cannabinoid receptor (CB1) agonist WIN55212-2 (WIN2) onto CeA neurons decreased evoked GABAA receptor-mediated inhibitory postsynaptic potentials (IPSPs) in a concentration-dependent manner, an effect prevented by the CB1 antagonists Rimonabant (SR141716, SR1) and AM251. SR1 or AM251 applied alone augmented IPSPs, revealing a tonic eCB activity that decreased inhibitory transmission in CeA. Paired-pulse analysis suggested a presynaptic CB1 mechanism. Intracellular BAPTA abolished the ability of AM251 to augment IPSPs, demonstrating the eCB-driven nature and postsynaptic origin of the tonic CB1-dependent control of GABA release. Superfusion of ethanol increased IPSPs and addition of WIN2 reversed the ethanol effect. Similarly, previous superfusion of WIN2 prevented subsequent ethanol effects on GABAergic transmission. The ethanol-induced augmentation of IPSPs was additive to CB1 blockade, ruling out a participation of CB1 in the action of acute ethanol. Our study points to an important role of CB1 in CeA in which the eCBs tonically regulate neuronal activity, and suggests a potent mechanism for modulating CeA tone during challenge with ethanol. PMID:20463657

  17. Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics.

    PubMed

    Jin, Zhe; Bhandage, Amol K; Bazov, Igor; Kononenko, Olga; Bakalkin, Georgy; Korpi, Esa R; Birnir, Bryndis

    2014-01-01

    The central amygdala (CeA) has a role for mediating fear and anxiety responses. It is also involved in emotional imbalance caused by alcohol abuse and dependence and in regulating relapse to alcohol abuse. Growing evidences suggest that excitatory glutamatergic and inhibitory γ-aminobutyric acid-ergic (GABAergic) transmissions in the CeA are affected by chronic alcohol exposure. Human post-mortem CeA samples from male alcoholics (n = 9) and matched controls (n = 9) were assayed for the expression level of ionotropic glutamate and GABA-A receptors subunit mRNAs using quantitative real-time reverse transcription-PCR (RT-qPCR). Our data revealed that out of the 16 ionotropic glutamate receptor subunits, mRNAs encoding two AMPA [2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid] receptor subunits GluA1 and GluA4; one kainate receptor subunit GluK2; one NMDA (N-methyl-D-aspartate) receptor subunit GluN2D and one delta receptor subunit GluD2 were significantly decreased in the CeA of alcoholics. In contrast, of the 19 GABA-A receptor subunits, only the mRNA encoding the α2 subunit was significantly down-regulated in the CeA of the alcoholics as compared with control subjects. Our findings imply that the down-regulation of specific ionotropic glutamate and GABA-A receptor subunits in the CeA of alcoholics may represent one of the molecular substrates underlying the new balance between excitatory and inhibitory neurotransmission in alcohol dependence.

  18. Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics

    PubMed Central

    Jin, Zhe; Bhandage, Amol K.; Bazov, Igor; Kononenko, Olga; Bakalkin, Georgy; Korpi, Esa R.; Birnir, Bryndis

    2014-01-01

    The central amygdala (CeA) has a role for mediating fear and anxiety responses. It is also involved in emotional imbalance caused by alcohol abuse and dependence and in regulating relapse to alcohol abuse. Growing evidences suggest that excitatory glutamatergic and inhibitory γ-aminobutyric acid-ergic (GABAergic) transmissions in the CeA are affected by chronic alcohol exposure. Human post-mortem CeA samples from male alcoholics (n = 9) and matched controls (n = 9) were assayed for the expression level of ionotropic glutamate and GABA-A receptors subunit mRNAs using quantitative real-time reverse transcription-PCR (RT-qPCR). Our data revealed that out of the 16 ionotropic glutamate receptor subunits, mRNAs encoding two AMPA [2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid] receptor subunits GluA1 and GluA4; one kainate receptor subunit GluK2; one NMDA (N-methyl-D-aspartate) receptor subunit GluN2D and one delta receptor subunit GluD2 were significantly decreased in the CeA of alcoholics. In contrast, of the 19 GABA-A receptor subunits, only the mRNA encoding the α2 subunit was significantly down-regulated in the CeA of the alcoholics as compared with control subjects. Our findings imply that the down-regulation of specific ionotropic glutamate and GABA-A receptor subunits in the CeA of alcoholics may represent one of the molecular substrates underlying the new balance between excitatory and inhibitory neurotransmission in alcohol dependence. PMID:25278838

  19. Immunohistochemistry of carcinoembryonic antigen: characterisation of cross-reactions with other glycoproteins.

    PubMed Central

    Isaacson, P; Judd, M A

    1977-01-01

    In the course of demonstrating carcinoembryonic antigen (CEA) in normal human small intestine cross-reactivity of specific antiserum against red blood cells, vascular endothelium, and Paneth cell granules was noted. Pretreatment of sections with periodic acid eliminated these cross-reactions without affecting the staining of CEA, indicating that the antigenic determinants shared between CEA and other glycoproteins are in the carbohydrate portion of the molecules. These findings emphasise the caution with which immunohistochemical results should be regarded even when they are apparently well controlled. Images Fig. 6 Fig. 7 Fig. 8 Fig. 3 Fig. 4 Fig. 5 Fig. 1 Fig. 2 PMID:73495

  20. Electrochemical immunosensor for simultaneous detection of multiplex cancer biomarkers based on graphene nanocomposites.

    PubMed

    Chen, Xia; Jia, Xinle; Han, Jingman; Ma, Jie; Ma, Zhanfang

    2013-12-15

    In this work, a sandwich-format electrochemical immunosensor for simultaneous determination of carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) was fabricated using biofunctional carboxyl graphene nanosheets (CGS) as immunosensing probes, which were fabricated by means of immobilization of toluidine blue (TB) and labeled anti-CEA (Ab2,1), Prussian blue (PB) and anti-AFP (Ab2,2) successively on CGS. The capture anti-CEA (Ab1,1) and anti-AFP (Ab1,2) were immobilized onto the chitosan-Au nanoparticles (CHIT-AuNPs) modified electrode through 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxy succinimide (EDC/NHS). Experimental results revealed that this sandwich-type immunoassay enabled simultaneous detection of CEA and AFP with linear range of 0.5-60 ng mL(-1) for both analytes. The detection limit was 0.1 ng mL(-1) for CEA and 0.05 ng mL(-1) for AFP (S/N=3). The assay results of serum samples with the proposed method were in a good agreement with the reference values from the standard ELISA method. And the negligible cross-reactivity between the two analytes allows it to possess potential promise in clinical diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. AuNPs/CNOs/SWCNTs/chitosan-nanocomposite modified electrochemical sensor for the label-free detection of carcinoembryonic antigen.

    PubMed

    Rizwan, Mohammad; Elma, Syazwani; Lim, Syazana Abdullah; Ahmed, Minhaz Uddin

    2018-06-01

    In this work, a nanocomposite of gold nanoparticles (AuNPs), carbon nano-onions (CNOs), single-walled carbon nanotubes (SWCNTs) and chitosan (CS) (AuNPs/CNOs/SWCNTs/CS) was prepared for the development of highly sensitive electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA), clinical tumor marker. Firstly, layer-by-layer fabrication of the CEA-immunosensors was studied using cyclic voltammetry (CV) and square wave voltammetry (SWV). By combining the advantages of large surface area and electronic properties of AuNPs, CNOs, SWCNTs, and film forming properties of CS, AuNPs/CNOs/SWCNTs/CS-nanocomposite-modified glassy carbon electrode showed a 200% increase in effective surface area and electronic conductivity. The calibration plot gave a negative linear relationship between log[concentration] of CEA and electrical current with a correlation coefficient of 0.9875. The CEA-immunosensor demonstrated a wide linear detection range of 100 fg mL -1 to 400 ng mL -1 with a low detection limit of 100 fg mL -1 . In addition to high sensitivity, reproducibility and large stability, CEA-immunosensor provided an excellent selectivity and resistant-to-interference in the presence of other antigens in serum and hence a potential to be used with real samples. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Simultaneous Detection of α-Fetoprotein and Carcinoembryonic Antigen Based on Si Nanowire Field-Effect Transistors.

    PubMed

    Zhu, Kuiyu; Zhang, Ye; Li, Zengyao; Zhou, Fan; Feng, Kang; Dou, Huiqiang; Wang, Tong

    2015-08-05

    Primary hepatic carcinoma (PHC) is one of the most common malignancies worldwide, resulting in death within six to 20 months. The survival rate can be improved by effective treatments when diagnosed at an early stage. The α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) have been identified as markers that are expressed at higher levels in PHC patients. In this study, we employed silicon nanowire field-effect transistors (SiNW-FETs) with polydimethylsiloxane (PDMS) microfluidic channels to simultaneously detect AFP and CEA in desalted human serum. Dual-channel PDMS was first utilized for the selective modification of AFP and CEA antibodies on SiNWs, while single-channel PDMS offers faster and more sensitive detection of AFP and CEA in serum. During the SiNW modification process, 0.1% BSA was utilized to minimize nonspecific protein binding from serum. The linear dynamic ranges for the AFP and CEA detection were measured to be 500 fg/mL to 50 ng/mL and 50 fg/mL to 10 ng/mL, respectively. Our work demonstrates the promising potential of fabricated SiNW-FETs as a direct detection kit for multiple tumor markers in serum; therefore, it provides a chance for early stage diagnose and, hence, more effective treatments for PHC patients.

  3. Comparison of Neurocognitive Outcomes after Carotid Endarterectomy and Carotid Artery Stenting.

    PubMed

    Kim, Jerry J; Schwartz, Samuel; Wen, Johnny; deVirgilio, Christian; Lobue, Abeline; Walot, Irwin; Koopmann, Matthew; Donayre, Carlos; White, Rodney A

    2015-10-01

    Cognitive and emotional outcomes after carotid endarterectomy (CEA) and carotid artery stenting with embolic protection device (CAS + EPD) are not clear. Patients were entered prospectively into a United States Food and Drug Administration-approved single-center physician-sponsored investigational device exemption between 2004 and 2010 and received either CEA or CAS + EPD. Patients underwent cognitive testing preprocedure and at 6, 12, and 60 months postprocedure. Cognitive domains assessed included attention, memory, executive, motor function, visual spatial functioning, language, and processing speed. Beck Depression and anxiety scales were also compared. There were a total of 38 patients that met conventional indications for carotid surgery (symptomatic with ≥50% stenosis or asymptomatic with ≥70% stenosis)-12 patients underwent CEA, whereas 26 patients underwent CAS + EPD. Both CEA and CAS + EPD patients showed postprocedure improvement in memory and executive function. No differences were seen at follow-up in regards to emotional dysfunction (depression and anxiety), attention, visual spatial functioning, language, motor function, and processing speed. Only two patients underwent neuropsychiatric testing at 60 months-these CAS + EPD patients showed sustained improvement in memory, visual spatial, and executive functions. In conclusion, cognitive and emotional outcomes were similar between CEA and CAS + EPD patients.

  4. Neuropeptide Y Opposes Alcohol Effects on GABA Release in Amygdala and Blocks the Transition to Alcohol Dependence

    PubMed Central

    Gilpin, Nicholas W.; Misra, Kaushik; Herman, Melissa A.; Cruz, Maureen T.; Koob, George F.; Roberto, Marisa

    2011-01-01

    Background During the transition to alcohol and drug addiction, neuromodulator systems in the extended amygdala are recruited to mediate aspects of withdrawal and relapse via convergence on inhibitory GABA neurons in central amygdala (CeA). Methods This study investigated the role of neuropeptide Y (NPY) in excessive alcohol drinking by making rats dependent on alcohol via alcohol vapor inhalation. This study also utilized intracellular and whole-cell recording techniques to determine the effects of NPY on GABAergic inhibitory transmission in CeA, synaptic mechanisms involved in these NPY effects, and NPY interactions with alcohol in the CeA of alcohol-naïve and alcohol-dependent rats. Results Chronic NPY treatment blocked excessive operant alcohol-reinforced responding associated with alcohol dependence, as well as gradual increases in alcohol responding by intermittently tested non-dependent controls. NPY decreased baseline GABAergic transmission and reversed alcohol-induced enhancement of inhibitory transmission in CeA by suppressing GABA release via actions at presynaptic Y2 receptors. Conclusions These results highlight NPY modulation of GABAergic signaling in central amygdala as a promising pharmacotheraputic target for the treatment of alcoholism. GABA neurons in the CeA likely constitute a major point of convergence for neuromodulator systems recruited during the transition to alcohol dependence. PMID:21459365

  5. Genomic Islands in Pathogenic Filamentous Fungus Aspergillus fumigatus

    USDA-ARS?s Scientific Manuscript database

    We present the genome sequences of a new clinical isolate, CEA10, of an important human pathogen, Aspergillus fumigatus, and two closely related, but rarely pathogenic species, Neosartorya fischeri NRRL181 and Aspergillus clavatus NRRL1. Comparative genomic analysis of CEA10 with the recently sequen...

  6. Preparation of Fe(3)O(4)@C@CNC multifunctional magnetic core/shell nanoparticles and their application in a signal-type flow-injection photoluminescence immunosensor.

    PubMed

    Chu, Chengchao; Li, Meng; Li, Long; Ge, Shenguang; Ge, Lei; Yu, Jinghua; Yan, Mei; Song, Xianrang

    2013-11-01

    We describe here the preparation of carbon-coated Fe3O4 magnetic nanoparticles that were further fabricated into multifunctional core/shell nanoparticles (Fe3O4@C@CNCs) through a layer-by-layer self-assembly process of carbon nanocrystals (CNCs). The nanoparticles were applied in a photoluminescence (PL) immunosensor to detect the carcinoembryonic antigen (CEA), and CEA primary antibody was immobilized onto the surface of the nanoparticles. In addition, CEA secondary antibody and glucose oxidase were covalently bonded to silica nanoparticles. After stepwise immunoreactions, the immunoreagent was injected into the PL cell using a flow-injection PL system. When glucose was injected, hydrogen peroxide was obtained because of glucose oxidase catalysis and quenched the PL of the Fe3O4@C@CNC nanoparticles. The here proposed PL immunosensor allowed us to determine CEA concentrations in the 0.005–50 ng·mL-1 concentration range, with a detection limit of 1.8 pg·mL-1.

  7. Evidence for Management of Carotid Artery Stenosis

    PubMed Central

    YOSHIDA, Kazumichi; MIYAMOTO, Susumu

    2015-01-01

    In this review, we presented the evidence concerning carotid artery stenosis treatment in symptomatic stenosis and asymptomatic stenosis separately, and discussed the future challenges. The validity of carotid endarterectomy (CEA) to treat moderate or greater degree of symptomatic carotid artery stenosis appears to be established. Due to the additional option of carotid artery stenting (CAS), it is necessary to comprehensively determine whether CEA or CAS is more appropriate for each individual patient. Moreover, since there are rapid advancements in devices for CAS and improvements in treatment outcomes, continual learning of the latest treatment method is essential. For asymptomatic stenosis, due to improvements in the outcomes with best medical treatment (BMT), it is essential to re-evaluate the use of invasive CEA/CAS. Continual verification of the latest randomized clinical trial that compares CEA, CAS, and BMT, and establishment of a diagnostic method that can accurately extract the group of patients who have the highest future risk of developing ischemia, are desired. PMID:25739437

  8. Assessment of children's emotional adjustment: construction and validation of a new instrument.

    PubMed

    Thorlacius, Ö; Gudmundsson, E

    2015-09-01

    The present study describes the Children's Emotional Adjustment Scale (CEAS), a 47-item parent-reported scale designed to capture children's emotional functioning on four continuous dimensions. A large community sample of mothers of children (n = 606) aged 6-13 years was used to examine the psychometric properties of the CEAS. Exploratory and confirmatory factor analysis supported the hypothesized four-factor structure of the instrument: (1) temper control; (2) anxiety control; (3) mood repair; and (4) social assertiveness. Cronbach's alphas for the factors were consistently above 0.90, and convergent validity of the factors was satisfactory with maternal ratings of child psychopathology. Children rated by their mothers as having emotional problems in the clinical range on the Strengths and Difficulties Questionnaire had significantly lower scores on the CEAS scales. The CEAS is a psychometrically sound instrument, covering healthy emotional adjustment as well as maladjustment. The scale might prove to be valuable in the assessment and screening of behaviours underlying child psychopathology. © 2014 John Wiley & Sons Ltd.

  9. Experience-dependent modification of a central amygdala fear circuit

    PubMed Central

    Li, Haohong; Penzo, Mario A.; Taniguchi, Hiroki; Kopec, Charles D.; Huang, Z. Josh; Li, Bo

    2013-01-01

    The amygdala is essential for fear learning and expression. The central amygdala (CeA), once viewed as a passive relay between the amygdala complex and downstream fear effectors, has emerged as an active participant in fear conditioning. However, how CeA contributes to the learning and expression of fear is unclear. Here we show in mice that fear conditioning induces robust plasticity of excitatory synapses onto inhibitory neurons in the lateral subdivision of CeA (CeL). This experience-dependent plasticity is cell-specific, bidirectional, and expressed presynaptically by inputs from the lateral amygdala. In particular, preventing synaptic potentiation onto somatostatin-positive neurons impairs fear memory formation. Furthermore, activation of these neurons is necessary for fear memory recall and sufficient to drive fear responses. Our findings support a model in which the fear conditioning-induced synaptic modifications in CeL favor the activation of somatostatin-positive neurons, which inhibit CeL output thereby disinhibiting the medial subdivision of CeA and releasing fear expression. PMID:23354330

  10. Magneto-controlled bioelectronics for the antigen-antibody interaction based on magnetic-core/gold-shell nanoparticles functionalized biomimetic interface.

    PubMed

    Tang, Dianping; Yuan, Ruo; Chai, Yaqin

    2008-02-01

    A new protein assay system for the antigen-antibody interaction was developed by immobilization of carcinoembryonic antibody (anti-CEA) onto magnetic-core/gold-shell nanoparticles-functionalized biomimetic interface on multiporous polythionine modified magnetic carbon paste electrodes (MCPE). Differential pulse voltammetric (DPV) technique was employed to investigate the antigen-antibody interaction in pH 6.8 acetate acid buffer solution after incubation with various CEA samples for 50 min at room temperature. The peak currents decreased with increased CEA concentration, and were proportional to the CEA concentration in the range of 1.5-60 ng/ml with a detection limit of 0.3 ng/ml at a signal-to-noise ratio of 3. Moreover, the selectivity, reproducibility and stability of the proposed immunoassay system were acceptable. Compared with the conventional immunoassays, the developed immunoassay system was simple and rapid without multiple labeling and separation steps. Importantly, the proposed methodology would be valuable for diagnosis and monitoring of carcinoma and its metastasis.

  11. Adenovirus tumor targeting and hepatic untargeting by a coxsackie/adenovirus receptor ectodomain anti-carcinoembryonic antigen bispecific adapter.

    PubMed

    Li, Hua-Jung; Everts, Maaike; Pereboeva, Larisa; Komarova, Svetlana; Idan, Anat; Curiel, David T; Herschman, Harvey R

    2007-06-01

    Adenovirus vectors have a number of advantages for gene therapy. However, because of their lack of tumor tropism and their preference for liver infection following systemic administration, they cannot be used for systemic attack on metastatic disease. Many epithelial tumors (e.g., colon, lung, and breast) express carcinoembryonic antigen (CEA). To block the natural hepatic tropism of adenovirus and to "retarget" the virus to CEA-expressing tumors, we used a bispecific adapter protein (sCAR-MFE), which fuses the ectodomain of the coxsackie/adenovirus receptor (sCAR) with a single-chain anti-CEA antibody (MFE-23). sCAR-MFE untargets adenovirus-directed luciferase transgene expression in the liver by >90% following systemic vector administration. Moreover, sCAR-MFE can "retarget" adenovirus to CEA-positive epithelial tumor cells in cell culture, in s.c. tumor grafts, and in hepatic tumor grafts. The sCAR-MFE bispecific adapter should, therefore, be a powerful agent to retarget adenovirus vectors to epithelial tumor metastases.

  12. Doxorubicin-anti-carcinoembryonic antigen immunoconjugate activity in vitro.

    PubMed

    Richardson, V J; Ford, C H; Tsaltas, G; Gallant, M E

    1989-04-01

    An in vitro model consisting of a series of 11 human cancer cell lines with varying density of expression of membrane carcinoembryonic antigen (CEA) has been used to evaluate conjugates of doxorubicin (Adriamycin) covalently linked by a carbodiimide method to goat polyclonal antibodies and mouse monoclonal antibodies to CEA. Conjugates were produced which retained both antigen binding and drug cytotoxicity. IC50 values were determined for free drug, free drug mixed with unconjugated antibodies and for the immunoconjugates. Cell lines that were very sensitive to free drug (IC50 less than 100 ng/ml) were also found to be highly sensitive to conjugated drug and similarly cell lines resistant to drug (IC50 greater than 1,000 ng/ml) were also resistant to conjugated drug. Although there was no correlation between CEA expression and conjugates efficacy, competitive inhibition studies using autologous antibody to block conjugate binding to cells indicated immunoconjugates specificity for the CEA target.

  13. Impact of Provider Characteristics on Outcomes of Carotid Endarterectomy for Asymptomatic Carotid Stenosis in New York State.

    PubMed

    Meltzer, Andrew J; Agrusa, Christopher; Connolly, Peter H; Schneider, Darren B; Sedrakyan, Art

    2017-11-01

    The purpose of this study is to explore the impact of surgeon characteristics (including annual volume, specialty, and years in practice) on outcomes of carotid endarterectomy (CEA) for asymptomatic carotid atherosclerosis in New York State. The New York Statewide Planning and Cooperation System database was utilized to identify patients undergoing CEA from 2004 to 2011. Provider characteristics were determined by linkage to the New York Office of Professions and National Provider Identification databases. Provider-level factors were characterized by defining 5 quintiles of equal size for each factor. Hierarchical logistic regression models were created to evaluate the impact of provider characteristics on outcome. In total, 36,495 patients underwent CEA for asymptomatic disease performed by vascular (75.7%), general (16.1%), cardiac (6%), and neuro (2.1%) surgeons. Outcomes of interest included in-hospital mortality (0.26%), stroke (0.45%), and the composite end point of mortality, stroke, or cardiac complication (2.2%). Unadjusted outcomes improved with increasing surgeon annual CEA volume. Mid-career surgeons had lower mortality and stroke rates than early or late-career surgeons. Odds of mortality were increased when surgery was performed by the lowest volume providers (quintile 1; 0-11 CEA/year) (odds ratio [OR] 2.62, 95% confidence interval [CI] 1.3-5.28) or a nonspecialty trained (general) surgeon (OR 1.64, 95% 1.01-2.67). After adjustment for all patient-level factors, provider volume remained an independent predictor of outcome, with significantly increased odds of mortality for volume quintile 1 (OR 2.57, 95% CI 1.27-5.23) and quintile 2 (12-22 CEA/year) (0.30%; OR 2.07, 95% CI 1-4.27) surgeons. Adverse events after CEA for asymptomatic disease are comparatively rare. However, surgeon characteristics impact outcome, with the best results offered by high-volume, mid-career, specialty-trained surgeons. Efforts to define the optimal treatment of asymptomatic

  14. A phase I clinical study of immunotherapy for advanced colorectal cancers using carcinoembryonic antigen-pulsed dendritic cells mixed with tetanus toxoid and subsequent IL-2 treatment.

    PubMed

    Liu, Ko-Jiunn; Chao, Tsu-Yi; Chang, Jang-Yang; Cheng, Ann-Lii; Ch'ang, Hui-Ju; Kao, Woei-Yau; Wu, Yu-Chen; Yu, Wei-Lan; Chung, Tsai-Rong; Whang-Peng, Jacqueline

    2016-08-24

    To better evaluate and improve the efficacy of dendritic cell (DC)-based cancer immunotherapy, we conducted a clinical study of patients with advanced colorectal cancer using carcinoembryonic antigen (CEA)-pulsed DCs mixed with tetanus toxoid and subsequent interleukin-2 treatment. The tetanus toxoid in the vaccine preparation serves as an adjuvant and provides a non-tumor specific immune response to enhance vaccine efficacy. The aims of this study were to (1) evaluate the toxicity of this treatment, (2) observe the clinical responses of vaccinated patients, and (3) investigate the immune responses of patients against CEA before and after treatment. Twelve patients were recruited and treated in this phase I clinical study. These patients all had metastatic colorectal cancer and failed standard chemotherapy. We first subcutaneously immunized patients with metastatic colorectal cancer with 1 × 10(6) CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 10(6) CEA-pulsed DCs alone. Low-dose interleukin-2 was administered subcutaneously following the final DC vaccination to boost the growth of T cells. Patients were evaluated for adverse event and clinical status. Blood samples collected before, during, and after treatment were analyzed for T cell proliferation responses against CEA. No severe treatment-related side effects or toxicity was observed in patients who received the regular 4 DC vaccine injections. Two patients had stable disease and 10 patients showed disease progression. A statistically significant increase in proliferation against CEA by T cells collected after vaccination was observed in 2 of 9 patients. The results of this study indicate that it is feasible and safe to treat colorectal cancer patients using this protocol. An increase in the anti-CEA immune response and a clinical benefit was observed in a small fraction of patients. This treatment protocol should be further evaluated in

  15. 1NON-INVASIVE RADIOIODINE IMAGING FOR ACCURATE QUANTITATION OF NIS REPORTER GENE EXPRESSION IN TRANSPLANTED HEARTS

    PubMed Central

    Ricci, Davide; Mennander, Ari A; Pham, Linh D; Rao, Vinay P; Miyagi, Naoto; Byrne, Guerard W; Russell, Stephen J; McGregor, Christopher GA

    2008-01-01

    Objectives We studied the concordance of transgene expression in the transplanted heart using bicistronic adenoviral vector coding for a transgene of interest (human carcinoembryonic antigen: hCEA - beta human chorionic gonadotropin: βhCG) and for a marker imaging transgene (human sodium iodide symporter: hNIS). Methods Inbred Lewis rats were used for syngeneic heterotopic cardiac transplantation. Donor rat hearts were perfused ex vivo for 30 minutes prior to transplantation with University of Wisconsin (UW) solution (n=3), with 109 pfu/ml of adenovirus expressing hNIS (Ad-NIS; n=6), hNIS-hCEA (Ad-NIS-CEA; n=6) and hNIS-βhCG (Ad-NIS-CG; n=6). On post-operative day (POD) 5, 10, 15 all animals underwent micro-SPECT/CT imaging of the donor hearts after tail vein injection of 1000 μCi 123I and blood sample collection for hCEA and βhCG quantification. Results Significantly higher image intensity was noted in the hearts perfused with Ad-NIS (1.1±0.2; 0.9±0.07), Ad-NIS-CEA (1.2±0.3; 0.9±0.1) and Ad-NIS-CG (1.1±0.1; 0.9±0.1) compared to UW group (0.44±0.03; 0.47±0.06) on POD 5 and 10 (p<0.05). Serum levels of hCEA and βhCG increased in animals showing high cardiac 123I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and βhCG (R2=0.99 and R2=0.96 respectively). Conclusions These data demonstrate that hNIS is an excellent reporter gene for the transplanted heart. The expression level of hNIS can be accurately and non-invasively monitored by serial radioisotopic single photon emission computed tomography (SPECT) imaging. High concordance has been demonstrated between imaging and soluble marker peptides at the maximum transgene expression on POD 5. PMID:17980613

  16. Orexin-1 receptor antagonist in central nucleus of the amygdala attenuates the acquisition of flavor-taste preference in rats.

    PubMed

    Risco, Severiano; Mediavilla, Cristina

    2014-11-01

    Previous studies demonstrated that the intracerebroventricular administration of SB-334867-A, a selective antagonist of orexin OX1R receptors, blocks the acquisition of saccharin-induced conditioned flavor preference (CFP) but not LiCl-induced taste aversion learning (TAL). Orexinergic fibers from the lateral hypothalamus end in the central nucleus of the amygdala (CeA), which expresses orexin OX1R receptors. Taste and sensory inputs also are present in CeA, which may contribute to the development of taste learning. This study analyzed the effect of two doses (1.5 and 6μg/0.5μl) of SB-334867-A administered into the CeA on flavor-taste preference induced by saccharin and on TAL induced by a single administration of LiCl (0.15M, 20ml/kg, i.p.). Outcomes indicate that inactivation of orexinergic receptors in the CeA attenuates flavor-taste preference in a two-bottle test (saccharin vs. water). Intra-amygdalar SB-334867-A does not affect gustatory processing or the preference for the sweet taste of saccharin given that SB-334867-A- and DMSO-treated groups (control animals) increased the intake of the saccharin-associated flavor across training acquisition sessions. Furthermore, SB-334867-A in the CeA does not block TAL acquisition ruling out the possibility that functional inactivation of OX1R receptors interferes with taste processing. Orexin receptors in the CeA appear to intervene in the association of a flavor with orosensory stimuli, e.g., a sweet and pleasant taste, but could be unnecessary when the association is established with visceral stimuli, e.g., lithium chloride. These data suggest that orexinergic projections to the CeA may contribute to the reinforcing signals facilitating the acquisition of taste learning and the change in hedonic evaluation of the taste, which would have important implications for the OX1R-targeted pharmacological treatment of eating disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Accuracy of administrative data versus clinical data to evaluate carotid endarterectomy and carotid stenting

    PubMed Central

    Bensley, Rodney P; Yoshida, Shunsuke; Lo, Ruby C; Fokkema, Margriet; Hamdan, Allen D; Wyers, Mark C; Chaikof, Elliot L; Schermerhorn, Marc L

    2013-01-01

    Objectives Administrative data have been used to compare carotid endarterectomy (CEA) and carotid artery stenting (CAS). However, there are limitations in defining symptom status, CMS high-risk status, as well as complications. Therefore, we did a direct comparison between administrative data and physician chart review as well as between data collected for the National Surgical Quality Improvement Program (NSQIP) and physician chart review for CEA and CAS. Methods We performed an outcomes analysis on all CEA and CAS procedures from 2005–2011. We obtained ICD-9 diagnosis codes from hospital discharge records regarding symptom status, high-risk status, and perioperative stroke. We also obtained data on all CEA patients submitted to NSQIP over the same time period. A physician then performed a chart review of the same patients to determine symptom status, high-risk status, and perioperative strokes and the results were compared. Results We identified 1342 patients who underwent CEA or CAS between 2005–2011 and 392 patients who underwent CEA that were submitted to NSQIP. Administrative data identified fewer symptomatic patients (17.0% vs. 34.0%), fewer physiologic high-risk patients (9.3% vs. 23.0%), fewer anatomic high-risk patients (0% vs. 15.2%), and a similar proportion of perioperative strokes (1.9% vs. 2.0%). However, administrative data identified 8 false positive and 9 false negative perioperative strokes. NSQIP data identified more symptomatic patients compared to chart review (44.1% vs. 30.3%), fewer physiologic high-risk patients (13.0% vs. 18.6%), fewer anatomic high-risk patients (0% vs. 6.6%), and a similar proportion of perioperative strokes (1.5% vs. 1.8%, only 1 false negative stroke and no false positives). Conclusions Administrative data are unreliable for determining symptom status, high-risk status, and perioperative stroke and should not be used to analyze CEA and CAS. NSQIP data do not adequately identify high-risk patients, but do accurately

  18. Role of the oxytocin system in amygdala subregions in the regulation of social interest in male and female rats.

    PubMed

    Dumais, Kelly M; Alonso, Andrea G; Bredewold, Remco; Veenema, Alexa H

    2016-08-25

    We previously found that oxytocin (OT) receptor (OTR) binding density in the medial amygdala (MeA) correlated positively with social interest (i.e., the motivation to investigate a conspecific) in male rats, while OTR binding density in the central amygdala (CeA) correlated negatively with social interest in female rats. Here, we determined the causal involvement of OTR in the MeA and CeA in the sex-specific regulation of social interest in adult rats by injecting an OTR antagonist (5ng/0.5μl/side) or OT (100pg/0.5μl/side) before the social interest test (4-min same-sex juvenile exposure). OTR blockade in the CeA decreased social interest in males but not females, while all other treatments had no behavioral effect. To further explore the sex-specific involvement of the OT system in the CeA in social interest, we used in vivo microdialysis to determine possible sex differences in endogenous OT release in the CeA during social interest. Interestingly, males and females showed similar levels of extracellular OT release at baseline and during social interest, suggesting that factors other than local OT release mediate the sex-specific role of CeA-OTR in social interest. Moreover, we found a positive correlation between CeA-OT release and social investigation time in females. This was further reflected by reduced CeA-OT release during social interest in females that expressed low compared to high social interest. We discuss the possibility that this reduction in OT release may be a consequence, rather than a cause, of exposure to a social stimulus. Overall, our findings show for the first time that extracellular OT release in the CeA is similar between males and females and that OTR in the CeA plays a causal role in the regulation of social interest toward juvenile conspecifics in males. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Mercury Information Clearinghouse

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

    Chad A. Wocken; Michael J. Holmes; Dennis L. Laudal

    2006-03-31

    The Canadian Electricity Association (CEA) identified a need and contracted the Energy & Environmental Research Center (EERC) to create and maintain an information clearinghouse on global research and development activities related to mercury emissions from coal-fired electric utilities. With the support of CEA, the Center for Air Toxic Metals{reg_sign} (CATM{reg_sign}) Affiliates, and the U.S. Department of Energy (DOE), the EERC developed comprehensive quarterly information updates that provide a detailed assessment of developments in the various areas of mercury monitoring, control, policy, and research. A total of eight topical reports were completed and are summarized and updated in this final CEAmore » quarterly report. The original quarterly reports can be viewed at the CEA Web site (www.ceamercuryprogram.ca). In addition to a comprehensive update of previous mercury-related topics, a review of results from the CEA Mercury Program is provided. Members of Canada's coal-fired electricity generation sector (ATCO Power, EPCOR, Manitoba Hydro, New Brunswick Power, Nova Scotia Power Inc., Ontario Power Generation, SaskPower, and TransAlta) and CEA, have compiled an extensive database of information from stack-, coal-, and ash-sampling activities. Data from this effort are also available at the CEA Web site and have provided critical information for establishing and reviewing a mercury standard for Canada that is protective of environment and public health and is cost-effective. Specific goals outlined for the CEA mercury program included the following: (1) Improve emission inventories and develop management options through an intensive 2-year coal-, ash-, and stack-sampling program; (2) Promote effective stack testing through the development of guidance material and the support of on-site training on the Ontario Hydro method for employees, government representatives, and contractors on an as-needed basis; (3) Strengthen laboratory analytical capabilities through

  20. Role of the oxytocin system in amygdala subregions in the regulation of social interest in male and female rats

    PubMed Central

    Dumais, Kelly M.; Alonso, Andrea G.; Bredewold, Remco; Veenema, Alexa H.

    2016-01-01

    We previously found that oxytocin (OT) receptor (OTR) binding density in the medial amygdala (MeA) correlated positively with social interest (i.e., the motivation to investigate a conspecific) in male rats, while OTR binding density in the central amygdala (CeA) correlated negatively with social interest in female rats. Here, we determined the causal involvement of OTR in the MeA and CeA in the sex-specific regulation of social interest in adult rats by injecting an OTR antagonist (5 ng/0.5 µl/side) or OT (100 pg/0.5 µl/side) before the social interest test (4-min same-sex juvenile exposure). OTR blockade in the CeA decreased social interest in males but not females, while all other treatments had no behavioral effect. To further explore the sex-specific involvement of the OT system in the CeA in social interest, we used in vivo microdialysis to determine possible sex differences in endogenous OT release in the CeA during social interest. Interestingly, males and females showed similar levels of extracellular OT release at baseline and during social interest, suggesting that factors other than local OT release mediate the sex-specific role of CeA-OTR in social interest. Moreover, we found a positive correlation between CeA-OT release and social investigation time in females. This was further reflected by reduced CeA-OT release during social interest in females that expressed low compared to high social interest. We discuss the possibility that this reduction in OT release may be a consequence, rather than a cause, of exposure to a social stimulus. Overall, our findings show for the first time that extracellular OT release in the CeA is similar between males and females and that OTR in the CeA plays a causal role in the regulation of social interest towards juvenile conspecifics in males. PMID:27235738

  1. 76 FR 56103 - Retail Foreign Exchange Transactions; Conforming Changes to Existing Regulations in Response to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-12

    ... off-exchange foreign currency transactions with members of the retail public (i.e., retail forex... various provisions of the CEA as amended by the Dodd-Frank Act with respect to retail forex transactions... counterparty to a retail forex transaction under CEA Section 2(c)(2)(B) (``permitted counterparty''), which...

  2. Development and Validation of Children's Environmental Affect (Attitude, Sensitivity and Willingness to Take Action) Scale

    ERIC Educational Resources Information Center

    Erdogan, Mehmet; Marcinkowski, Thomas

    2015-01-01

    This study focuses on the design, development, validation, and psychometric properties of the Children's Environmental Affect Scale (CEAS). The following steps were taken in developing the CEAS. A substantial review of literature on environmental affect and EL helped the researchers identify several scales and questionnaires that, in turn, help…

  3. 75 FR 38478 - Orders Finding That the Mid-C Financial Peak Daily Contract and Mid-C Financial Off-Peak Daily...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-02

    ... exempt commercial market (``ECM'') under sections 2(h)(3)-(5) of the Commodity Exchange Act (``CEA'' or... (``Reauthorization Act'') \\4\\ significantly broadened the CFTC's regulatory authority with respect to ECMs by creating, in section 2(h)(7) of the CEA, a new regulatory category--ECMs on which significant price...

  4. 75 FR 42411 - Orders Finding That the SP-15 Financial Day-Ahead LMP Peak Daily Contract; SP-15 Financial Day...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-21

    ...''), an exempt commercial market (``ECM'') under sections 2(h)(3)-(5) of the Commodity Exchange Act (``CEA... (``Reauthorization Act'') \\5\\ significantly broadened the CFTC's regulatory authority with respect to ECMs by creating, in section 2(h)(7) of the CEA, a new regulatory category--ECMs on which significant price...

  5. Corrections to the one-photon approximation in the 0+-->2+ transition of 12C

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

    Paul Gueye; Madeleine Bernheim; J. F. Danel

    2001-04-18

    Contribution of higher order effects to the one-photon exchange approximation were studied in the first excited state of 12C by comparing inclusive inelastic scattering cross sections of electrons and positrons obtained at the Saclay Linear Accelerator. The data were compared to a distorted wave Born approximation (DWBA)calculation. The results indicate an effect less than 2% within 2sigma, compatible with what was observed in recent elastic scattering measurements.

  6. Anti-quorum sensing activity of flavonoid-rich fraction from Centella asiatica L. against Pseudomonas aeruginosa PAO1.

    PubMed

    Vasavi, H S; Arun, A B; Rekha, P D

    2016-02-01

    Inhibition of quorum sensing (QS), a cell-density dependent regulation of gene expression in bacteria by autoinducers is an attractive strategy for the development of antipathogenic agents. In this study, the anti-QS activity of the ethanolic extract of the traditional herb Centella asiatica was investigated by the biosensor bioassay using Chromobacterium violaceum CV026. The effect of ethyl acetate fraction (CEA) from the bioassay-guided fractionation of ethanol extract on QS-regulated violacein production in C. violaceum ATCC12472 and pyocyanin production, proteolytic and elastolytic activities, swarming motility, and biofilm formation in Pseudomonas aeruginosa PAO1 were evaluated. Possible mechanism of QS-inhibitory action on autoinducer activity was determined by measuring the acyl homoserine lactone using C. violaceum ATCC31532. Anti-QS compounds in the CEA fraction were identified using thin layer chromatography biosensor overlay assay. Ethanol extract of C. asiatica showed QS inhibition in C. violaceum CV026. Bioassay-guided fractionation of ethanol extract revealed that CEA was four times more active than the ethanol extract. CEA, at 400 μg/mL, completely inhibited violacein production in C. violaceum ATCC12472 without significantly affecting growth. CEA also showed inhibition of QS-regulated phenotypes, namely, pyocyanin production, elastolytic and proteolytic activities, swarming motility, and biofilm formation in P. aeruginosa PAO1 in a concentration-dependent manner. Thin layer chromatography of CEA with biosensor overlay showed anti-QS spot with an Rf value that corresponded with that of standard kaempferol. The anti-QS nature of C. asiatica herb can be further exploited for the formulation of drugs targeting bacterial infections where pathogenicity is mediated through QS. Copyright © 2014. Published by Elsevier B.V.

  7. Cost-effectiveness analysis: role and implications.

    PubMed

    Marsden, G; Wonderling, D

    2013-03-01

    Cost-effectiveness analysis (CEA) is often misperceived to be a cost-cutting exercise. The intention of CEA is not to identify and implement cheap technologies, but rather those which offer maximum health gain, subject to available funds. Such analysis is crucial for decision making in health care, as tight budget constraints mean spending in one area of healthcare displaces spending elsewhere. Therefore in order to achieve the greatest health gain for the overall population, treatments must be selected which provide the greatest health gain within the available funds. The relevance of CEA in health care systems is explained, using varicose vein treatment in the UK NHS as an example. Treatment for varicose veins is often not commissioned to at a local level, most likely because it is misperceived to be a cosmetic problem. However, this view does not take into account the impact of quality of life. CEA balances costs against a quantitative measure of health related quality of life, and could therefore be used to determine whether it is cost-effective to provide varicose vein treatment. The current literature on the cost-effectiveness of varicose vein treatment is reviewed, and an overview of cost-effectiveness principles is provided. Concepts such as economic modelling, incremental cost-effectiveness ratios (ICERs), net monetary benefit (NMB) and sensitivity analysis are explained, using examples relevant to varicose veins where appropriate. This article explains how, far from cutting costs and sacrificing patient health, CEA provides a useful tool to maximise the health of the population in the face of ever tightening budget constraints. CEA could be used to compare the cost-effectiveness of the various treatment options for varicose veins, and efficiencies realised.

  8. Proper exercise decreases plasma carcinoembryonic antigen levels with the improvement of body condition in elderly women.

    PubMed

    Ko, Il-Gyu; Park, Eung-Mi; Choi, Hye-Jung; Yoo, Jaehyun; Lee, Jong-Kyun; Jee, Yong-Seok

    2014-05-01

    Aging increases the risk of chronic diseases including cancers. Physical exercise has the beneficial effects for the elderly susceptible to the development of cancers, through maintaining a healthy body condition and improving the immune system. However, excessive or insufficient exercise might increase the risk for cancer. In the present study, we investigated what exercise frequency improves cancer-related biomarkers, such as carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), red blood cell (RBC), and white blood cell (WBC), and the body composition of elderly women. Fifty-four females, aged 70 to 77 years, were divided into 4 groups: control, 1-day exercise (1E), 2-3-day exercise (2-3E), and 5-day exercise (5E) groups. The control group did not participate in any physical activity, while the subjects in the exercise groups underwent the exercise program for 12 weeks. As results, CEA was significantly decreased in the exercise groups, with the lowest values in 2-3E group. In contrast, AFP, RBC and WBC were not significantly changed. CEA is an oncofetal glycoprotein that is overexpressed in adenocarcinomas. Although the function of CEA has not been fully understood, CEA has been suggested to be involved in the release of pro-inflammatory cytokines via stimulating monocytes and macrophages. Moreover, body weight and body mass index were improved in the exercise groups, with the lowest levels in 5E group. Thus, we suggest that exercise for 2-3 days per week decreases the expression of CEA and improves body condition, without loading fatigue or stress, which may contribute to preventing cancer in the elderly women.

  9. A novel rapid genotyping technique for Collie eye anomaly: SYBR Green-based real-time polymerase chain reaction method applicable to blood and saliva specimens on Flinders Technology Associates filter paper.

    PubMed

    Chang, Hye-Sook; Mizukami, Keijiro; Yabuki, Akira; Hossain, Mohammad A; Rahman, Mohammad M; Uddin, Mohammad M; Arai, Toshiro; Yamato, Osamu

    2010-09-01

    Collie eye anomaly (CEA) is a canine inherited ocular disease that shows a wide variety of manifestations and severity of clinical lesions. Recently, a CEA-associated mutation was reported, and a DNA test that uses conventional polymerase chain reaction (PCR) has now become available. The objective of the current study was to develop a novel rapid genotyping technique by using SYBR Green-based real-time PCR for future large-scale surveys as a key part in the strategy to eradicate CEA by selective breeding. First, a SYBR Green-based real-time PCR assay for genotyping of CEA was developed and evaluated by using purified DNA samples from normal, carrier, and affected Border Collies in which genotypes had previously been determined by conventional PCR. This real-time PCR assay demonstrated appropriate amplifications in all genotypes, and the results were consistent with those of conventional PCR. Second, the availability of Flinders Technology Associates filter paper (FTA card) as DNA templates for the real-time PCR assay was evaluated by using blood and saliva specimens to determine suitability for CEA screening. DNA-containing solution prepared from a disc of blood- or saliva-spotted FTA cards was available directly as templates for the real-time PCR assay when the volume of solution was 2.5% of the PCR mixture. In conclusion, SYBR Green-based real-time PCR combined with FTA cards is a rapid genotyping technique for CEA that can markedly shorten the overall time required for genotyping as well as simplify the sample preparation. Therefore, this newly developed technique suits large-scale screening in breeding populations of Collie-related breeds.

  10. Surface expression of heterogeneous nuclear RNA binding protein M4 on Kupffer cell relates to its function as a carcinoembryonic antigen receptor.

    PubMed

    Bajenova, Olga; Stolper, Eugenia; Gapon, Svetlana; Sundina, Natalia; Zimmer, Regis; Thomas, Peter

    2003-11-15

    Elevated concentrations of carcinoembryonic antigen (CEA) in the blood are associated with the development of hepatic metastases from colorectal cancers. Clearance of circulating CEA occurs through endocytosis by liver macrophages, Kupffer cells. Previously we identified heterogeneous nuclear ribonucleoproteins M4 (hnRNP M4) as a receptor (CEAR) for CEA. HnRNP M4 has two isoform proteins (p80, p76), the full-length hnRNP M4 (CEARL) and a truncated form (CEARS) with a deletion of 39 amino acids between RNA binding domains 1 and 2, generated by alternative splicing. The present study was undertaken to clarify any isoform-specific differences in terms of their function as CEA receptor and localization. We develop anti-CEAR isoform-specific antibodies and show that both CEAR splicing isoforms are expressed on the surface of Kupffer cells and can function as CEA receptor. Alternatively, in P388D1 macrophages CEARS protein has nuclear and CEARL has cytoplasmic localization. In MIP101 colon cancer and HeLa cells the CEARS protein is localized to the nucleus and CEARL to the cytoplasm. These findings imply that different functions are assigned to CEAR isoforms depending on the cell type. The search of 39 amino acids deleted region against the Prosite data base revealed the presence of N-myristylation signal PGGPGMITIP that may be involved in protein targeting to the plasma membrane. Overall, this report demonstrates that the cellular distribution, level of expression, and relative amount of CEARL and CEARS isoforms determine specificity for CEA binding and the expression of alternative spliced forms of CEAR is regulated in a tissue-specific manner.

  11. Which Cue to ‘Want?’ Central Amygdala Opioid Activation Enhances and Focuses Incentive Salience on a Prepotent Reward Cue

    PubMed Central

    Mahler, Stephen V.; Berridge, Kent C.

    2009-01-01

    The central nucleus of the amygdala (CeA) helps translate learning into motivation, and here we show that opioid stimulation of CeA magnifies and focuses learned incentive salience onto a specific reward cue (Pavlovian conditioned stimulus, or CS). This motivation enhancement makes that cue more attractive, noticeable, and liable to elicit appetitive and consummatory behaviors. To reveal the focusing of incentive salience, we exploited individual differences in an autoshaping paradigm in which a rat prefers to approach, nibble and sniff one of two reward-associated stimuli (its prepotent stimulus). The individually-prepotent cue is either a predictive CS+ that signals reward (8sec metal lever insertion), or instead the metal cup that delivers sucrose pellets (the reward source). Results indicated that CeA opioid activation by microinjection of the μ agonist DAMGO (0.1μg) selectively and reversibly enhanced the attractiveness of whichever reward CS was that rat's prepotent cue. CeA DAMGO microinjections made rats more vigorously approach their particular prepotent CS, and to energetically sniff and nibble it in a nearly frenzied consummatory fashion. Only the prepotent cue was enhanced as an incentive target, and alternative cues were not enhanced. Conversely, inactivation of CeA by muscimol microinjection (0.25μg) suppressed approach, nibbles and sniffs of the prepotent CS. Confirming modulation of incentive salience, unconditioned food intake was similarly increased by DAMGO microinjection and decreased by muscimol in CeA. We conclude that opioid neurotransmission in central amygdala helps determine which environmental stimuli become most ‘wanted,’ and how ‘wanted’ they become. This may powerfully guide reward-seeking behavior. PMID:19458221

  12. A clinical rule (sex, contralateral occlusion, age, and restenosis) to select patients for stenting versus carotid endarterectomy: systematic review of observational studies with validation in randomized trials.

    PubMed

    Touzé, Emmanuel; Trinquart, Ludovic; Felgueiras, Rui; Rerkasem, Kittipan; Bonati, Leo H; Meliksetyan, Gayané; Ringleb, Peter A; Mas, Jean-Louis; Brown, Martin M; Rothwell, Peter M

    2013-12-01

    Compared with carotid endarterectomy (CEA), carotid angioplasty and stenting (CAS) is associated with a higher risk of procedural stroke or death especially in patients with symptomatic stenosis. However, after the perioperative period, risk is similar with both treatments, suggesting that CAS could be an acceptable option in selected patients. We performed systematic reviews of observational studies of procedural risks of CEA or CAS and extracted data on 9 predefined risk factors (age, contralateral carotid occlusion, coronary artery disease, diabetes mellitus, sex, hypertension, peripheral artery disease, and type and side of stenosis). We calculated pooled relative risks of procedural stroke or death. Factors with differential effects on risk of CAS versus CEA were identified by interaction tests and used to derive a rule. The rule was tested using individual patient data from randomized trials of CAS versus CEA from the Carotid Stenting Trialists' Collaboration (CSTC). We identified 170 studies. The effects of sex, contralateral occlusion, age, and restenosis (SCAR) on the procedural risk of stroke or death differed. Patients with contralateral occlusion or restenosis and women<75 years were at relatively low risk for CAS (SCAR negative), with all others being high risk (SCAR positive). Among the 3049 patients in the CSTC validation, 694 (23%) patients were SCAR negative. The pooled RR of procedural stroke and death with CAS versus CEA was 0.93 (0.49-1.77; P=0.83) in SCAR-negative and 2.41 (1.68-3.45; P<0.0001) in SCAR-positive patients (P [interaction]=0.05). The SCAR rule is potentially useful to identify patients in whom CAS has a similar risk of perioperative stroke or death to CEA.

  13. Study of Laminar Flame 2-D Scalar Values at Various Fuel to Air Ratios Using an Imaging Fourier-Transform Spectrometer and 2-D CFD Analysis

    DTIC Science & Technology

    2013-03-01

    NASA- Glenn’s Chemical Equilibrium with Applications (CEA) program. UNICORN CFD predictions were in excellent agreement with CEA calculations at...49 Appendix A – UNICORN CFD Inputs and Instruction .....................................................50 Appendix B – NASA-Glenn...17 Figure 7: Schematic of UNICORN CFD card setup. ........................................................ 18 Figure 8: Averaged flame

  14. 75 FR 24626 - Order Finding That the TETCO-M3 Financial Basis Contract Traded on the IntercontinentalExchange...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... (``ECM'') under sections 2(h)(3)-(5) of the Commodity Exchange Act (``CEA'' or the ``Act''), performs a...\\ significantly broadened the CFTC's regulatory authority with respect to ECMs by creating, in section 2(h)(7) of the CEA, a new regulatory category--ECMs on which significant price discovery contracts (``SPDCs...

  15. 75 FR 24641 - Order Finding That the HSC1

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... commercial market (``ECM'') under sections 2(h)(3)--(5) of the Commodity Exchange Act (``CEA'' or the ``Act... (``Reauthorization Act'') \\4\\ significantly broadened the CFTC's regulatory authority with respect to ECMs by creating, in section 2(h)(7) of the CEA, a new regulatory category--ECMs on which significant price...

  16. 75 FR 24612 - Order Finding That the Zone 6-NY Financial Basis Contract Traded on the IntercontinentalExchange...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... (``ECM'') under sections 2(h)(3)-(5) of the Commodity Exchange Act (``CEA'' or the ``Act''), performs a... (``Reauthorization Act'') \\2\\ significantly broadened the CFTC's regulatory authority with respect to ECMs by creating, in section 2(h)(7) of the CEA, a new regulatory category--ECMs on which significant price...

  17. 75 FR 23679 - Order Finding That the ICE Malin Financial Basis Contract Traded on the IntercontinentalExchange...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-04

    ... commercial market (``ECM'') under sections 2(h)(3)-(5) of the Commodity Exchange Act (``CEA'' or the ``Act...\\ significantly broadened the CFTC's regulatory authority with respect to ECMs by creating, in section 2(h)(7) of the CEA, a new regulatory category--ECMs on which significant price discovery contracts (``SPDCs...

  18. 75 FR 24592 - Order Finding that the TETCO-M3 Financial Basis Contract Traded on the IntercontinentalExchange...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... (``ECM'') under sections 2(h)(3)-(5) of the Commodity Exchange Act (``CEA'' or the ``Act''), performs a... (``Reauthorization Act'') \\2\\ significantly broadened the CFTC's regulatory authority with respect to ECMs by creating, in section 2(h)(7) of the CEA, a new regulatory category--ECMs on which significant price...

  19. 75 FR 24586 - Order Finding That the San Juan Financial Basis Contract Traded on the IntercontinentalExchange...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... (``ECM'') under sections 2(h)(3)-(5) of the Commodity Exchange Act (``CEA'' or the ``Act''), performs a...\\ significantly broadened the CFTC's regulatory authority with respect to ECMs by creating, in section 2(h)(7) of the CEA, a new regulatory category--ECMs on which significant price discovery contracts (``SPDCs...

  20. 75 FR 23686 - Order Finding That the Carbon Financial Instrument Contract Offered for Trading on the Chicago...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-04

    ... commercial market (``ECM'') under Section 2(h)(3)-(5) of the Commodity Exchange Act (``CEA'' or the ``Act... (``Reauthorization Act'') \\2\\ significantly broadened the CFTC's regulatory authority with respect to ECMs by creating, in section 2(h)(7) of the CEA, a new regulatory category--ECMs on which significant price...

  1. 75 FR 23718 - Orders Finding That the Henry Financial Basis Contract, Henry Financial Index Contract and Henry...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-04

    ... exempt commercial market (``ECM'') under sections 2(h)(3)-(5) of the Commodity Exchange Act (``CEA'' or... with respect to ECMs by creating, in section 2(h)(7) of the CEA, a new regulatory category--ECMs on which significant price discovery contracts (``SPDCs'') are traded--and treating ECMs in that category...

  2. 75 FR 38469 - Orders Finding That the Mid-C Financial Peak Contract and Mid-C Financial Off-Peak Contract...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-02

    ... market (``ECM'') under sections 2(h)(3)-(5) of the Commodity Exchange Act (``CEA'' or the ``Act... CFTC's regulatory authority with respect to ECMs by creating, in section 2(h)(7) of the CEA, a new regulatory category--ECMs on which significant price discovery contracts (``SPDCs'') are traded--and treating...

  3. Innovation That Sticks Case Study Report: Ottawa Catholic School Board. Leading and Learning for Innovation, A Framework for District-Wide Change

    ERIC Educational Resources Information Center

    Canadian Education Association, 2016

    2016-01-01

    A Canadian Education Association (CEA) Selection Jury chose the Ottawa Catholic School Board (OCSB) out of 35 School District applicants from across Canada to participate in the 2015 "Innovation that Sticks" Case Study Program. From September to December 2015--through an Appreciative Inquiry interview process--the CEA researched how the…

  4. Patient characteristics and outcomes of carotid endarterectomy and carotid artery stenting: analysis of the German mandatory national quality assurance registry - 2003 to 2014.

    PubMed

    Kallmayer, M A; Tsantilas, P; Knappich, C; Haller, B; Storck, M; Stadlbauer, T; Kühnl, A; Zimmermann, A; Eckstein, H H

    2015-12-01

    In Germany, every surgical or endovascular procedure on the extracranial carotid artery is documented in a mandatory quality assurance registry. The purpose of this study is to describe the patient characteristics, the indications for treatment, and the short-term outcomes as well as to analyse the corresponding trends from 2003 to 2014. Data on demographics, peri-procedural measures, and outcomes were extracted from the annual quality reports published by the Federal Agency for Quality Assurance and the Institute for Applied Quality Improvement and Research in Health Care. Data were available from 2003 to 2014 for carotid endarterectomy (CEA) and from 2012 to 2014 for carotid artery stenting (CAS). The primary outcome event of this study is any stroke or death until discharge from hospital. Temporal trends of categorical variables were statistically analysed using the Cochran-Armitage test for trend. Between 2003 and 2014, 309,405 CEAs and 18,047 CAS procedures were documented in the database; 68.1% of all patients were male. The mean age of patients treated with CEA increased from 68.9 years in 2003 to 70.9 years in 2014. The proportion of patients with ASA stages III to V increased from 65% to 71% in CEA, whereas it decreased from 44% to 41% in CAS patients. 53.1% of all CEAs were performed for asymptomatic patients (group A), 34.4% for symptomatic patients treated electively (group B), and 11.2% a in a collective group including other indications for CEA or CAS (such as recurrent stenosis, carotid aneurysms, emergency treatment due to stroke-in-evolution). The corresponding data for CAS are 49.3%, 26.1% and 26.3% respectively. In group B, the interval between the neurological index event and CEA decreased from 28 to 8 days (P<0.001). In patients treated with CAS, this interval was 9 days in 2012 (no further data available). On average, 67.1% and 48.2% of surgically treated patients as well as 77.8% and 69.8% of CAS patients were neurologically assessed before

  5. Elevated Squamous Cell Carcinoma Antigen, Cytokeratin 19 Fragment, and Carcinoembryonic Antigen Levels in Diabetic Nephropathy

    PubMed Central

    Chen, Jianzhong; Zhang, Bin; Chen, Qingguang; Qiu, Yan; Luo, Qian; Gen, Yanna; Meng, Jiali

    2017-01-01

    Objective We aimed to explore whether squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (Cyfra21-1), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) are elevated in diabetic nephropathy (DN) and the association between urinary albumin-to-creatinine ratio (UACR) and tumor markers in diabetic patients. Methods Nondialysis patients with diabetes (n = 261) and 90 healthy controls were enrolled. DN was defined as an UACR ≥ 30 mg/g in the absence of a urinary tract infection or other renal abnormalities. Results Patients with DN had significantly higher serum SCC, Cyfra21-1, and CEA levels than those with normoalbuminuria and healthy controls. The rates of positive SCC, Cyfra21-1, and CEA significantly increased with increasing urinary albumin excretion (all P for trend < 0.001). In contrast, NSE was not affected by DN. SCC, Cyfra21-1, and CEA were significantly and positively correlated with UACR. In logistic regression, after multivariable adjustment, increased UACR was associated with increased odds ratio of elevated tumor marker levels (all P for trend < 0.05). Conclusions Serum levels of SCC, Cyfra21-1, and CEA are markedly increased with increasing urinary albumin excretion, which affects the specificity for diagnosis for lung cancer. Appropriate interpretation of tumor markers in diabetic patients is mandatory to avoid unnecessary and even hazardous biopsies. PMID:28744310

  6. Incorporating external evidence in trial-based cost-effectiveness analyses: the use of resampling methods

    PubMed Central

    2014-01-01

    Background Cost-effectiveness analyses (CEAs) that use patient-specific data from a randomized controlled trial (RCT) are popular, yet such CEAs are criticized because they neglect to incorporate evidence external to the trial. A popular method for quantifying uncertainty in a RCT-based CEA is the bootstrap. The objective of the present study was to further expand the bootstrap method of RCT-based CEA for the incorporation of external evidence. Methods We utilize the Bayesian interpretation of the bootstrap and derive the distribution for the cost and effectiveness outcomes after observing the current RCT data and the external evidence. We propose simple modifications of the bootstrap for sampling from such posterior distributions. Results In a proof-of-concept case study, we use data from a clinical trial and incorporate external evidence on the effect size of treatments to illustrate the method in action. Compared to the parametric models of evidence synthesis, the proposed approach requires fewer distributional assumptions, does not require explicit modeling of the relation between external evidence and outcomes of interest, and is generally easier to implement. A drawback of this approach is potential computational inefficiency compared to the parametric Bayesian methods. Conclusions The bootstrap method of RCT-based CEA can be extended to incorporate external evidence, while preserving its appealing features such as no requirement for parametric modeling of cost and effectiveness outcomes. PMID:24888356

  7. Incorporating external evidence in trial-based cost-effectiveness analyses: the use of resampling methods.

    PubMed

    Sadatsafavi, Mohsen; Marra, Carlo; Aaron, Shawn; Bryan, Stirling

    2014-06-03

    Cost-effectiveness analyses (CEAs) that use patient-specific data from a randomized controlled trial (RCT) are popular, yet such CEAs are criticized because they neglect to incorporate evidence external to the trial. A popular method for quantifying uncertainty in a RCT-based CEA is the bootstrap. The objective of the present study was to further expand the bootstrap method of RCT-based CEA for the incorporation of external evidence. We utilize the Bayesian interpretation of the bootstrap and derive the distribution for the cost and effectiveness outcomes after observing the current RCT data and the external evidence. We propose simple modifications of the bootstrap for sampling from such posterior distributions. In a proof-of-concept case study, we use data from a clinical trial and incorporate external evidence on the effect size of treatments to illustrate the method in action. Compared to the parametric models of evidence synthesis, the proposed approach requires fewer distributional assumptions, does not require explicit modeling of the relation between external evidence and outcomes of interest, and is generally easier to implement. A drawback of this approach is potential computational inefficiency compared to the parametric Bayesian methods. The bootstrap method of RCT-based CEA can be extended to incorporate external evidence, while preserving its appealing features such as no requirement for parametric modeling of cost and effectiveness outcomes.

  8. Magnetic immunoassay coupled with inductively coupled plasma mass spectrometry for simultaneous quantification of alpha-fetoprotein and carcinoembryonic antigen in human serum

    NASA Astrophysics Data System (ADS)

    Zhang, Xing; Chen, Beibei; He, Man; Zhang, Yiwen; Xiao, Guangyang; Hu, Bin

    2015-04-01

    The absolute quantification of glycoproteins in complex biological samples is a challenge and of great significance. Herein, 4-mercaptophenylboronic acid functionalized magnetic beads were prepared to selectively capture glycoproteins, while antibody conjugated gold and silver nanoparticles were synthesized as element tags to label two different glycoproteins. Based on that, a new approach of magnetic immunoassay-inductively coupled plasma mass spectrometry (ICP-MS) was established for simultaneous quantitative analysis of glycoproteins. Taking biomarkers of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as two model glycoproteins, experimental parameters involved in the immunoassay procedure were carefully optimized and analytical performance of the proposed method was evaluated. The limits of detection (LODs) for AFP and CEA were 0.086 μg L- 1 and 0.054 μg L- 1 with the relative standard deviations (RSDs, n = 7, c = 5 μg L- 1) of 6.5% and 6.2% for AFP and CEA, respectively. Linear range for both AFP and CEA was 0.2-50 μg L- 1. To validate the applicability of the proposed method, human serum samples were analyzed, and the obtained results were in good agreement with that obtained by the clinical chemiluminescence immunoassay. The developed method exhibited good selectivity and sensitivity for the simultaneous determination of AFP and CEA, and extended the applicability of metal nanoparticle tags based on ICP-MS methodology in multiple glycoprotein quantifications.

  9. Association of Very Low-Volume Practice With Vascular Surgery Outcomes in New York.

    PubMed

    Mao, Jialin; Goodney, Philip; Cronenwett, Jack; Sedrakyan, Art

    2017-08-01

    Little research has focused on very low-volume surgery, especially in the context of decreasing vascular surgery volume with the adoption of endovascular procedures. To investigate the existence and outcomes of open abdominal aortic aneurysm repair (OAR) and carotid endarterectomy (CEA) performed by very low-volume surgeons in New York. This cohort study examined inpatient data of patients undergoing elective OAR or CEA from 2000 to 2014 from all New York hospitals. Surgeons who performed 1 or less designated procedure per year on average were considered very low volume, as opposed to higher-volume surgeons. Temporal trends of the existence of very low-volume practice were evaluated. Hierarchical logistic regression was used to compare in-hospital outcomes and health care resource use between patients treated by very low-volume surgeons and higher-volume surgeons for both OAR and CEA, adjusting for patient, surgeon, and hospital characteristics. There were 8781 OAR procedures and 68 896 CEA procedures included in the study. The mean (SD) patient age was 71.7 (8.4) years for OAR and 71.5 (9.1) years for CEA. A total of 614 surgeons performed OAR and 1071 performed CEA in New York during the study period. Of these, 318 (51.8%) and 512 (47.8%), respectively, were very low-volume surgeons. Very low-volume surgeons were less likely to be vascular surgeons. The number and proportion of very low-volume surgeons decreased over years. Compared with patients treated by higher-volume surgeons, those treated by very low-volume surgeons were more likely to have higher in-hospital mortality (odds ratio [OR], 2.09; 95% CI, 1.41-3.08) following OAR and higher risks of postoperative myocardial infarction (OR, 1.83; 95% CI, 1.03-3.26) and stroke (OR, 1.78; 95% CI, 1.21-2.62) following CEA. Patients treated by very low-volume surgeons also had greater health care resource use following both surgeries, including prolonged length of stay (OR, 1.37; 95% CI, 1.11-1.70) following OAR as

  10. 75 FR 42390 - Orders Finding That the PJM WH Real Time Peak Contract and PJM WH Real Time Off-Peak Contract...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-21

    ... commercial market (``ECM'') under sections 2(h)(3)-(5) of the Commodity Exchange Act (``CEA'' or the ``Act... with respect to ECMs by creating, in section 2(h)(7) of the CEA, a new regulatory category--ECMs on which significant price discovery contracts (``SPDCs'') are traded--and treating ECMs in that category...

  11. Planning with Open Eyes and Open Hearts: An Alternative to Excessive Positivism

    ERIC Educational Resources Information Center

    O'Brien, John

    2007-01-01

    In this article, the author offers his critique on Holburn and Cea's notion on "excessive positivism" that person-centered planners are overconcerned with scientific verification and logical proof. The author believes that Holburn and Cea's notion blurs the important messages they have for person-centered planners by leading toward a debate about…

  12. Good research practices for measuring drug costs in cost effectiveness analyses: issues and recommendations: the ISPOR Drug Cost Task Force report--Part I.

    PubMed

    Hay, Joel W; Smeeding, Jim; Carroll, Norman V; Drummond, Michael; Garrison, Louis P; Mansley, Edward C; Mullins, C Daniel; Mycka, Jack M; Seal, Brian; Shi, Lizheng

    2010-01-01

    The assignment of prices or costs to pharmaceuticals can be crucial to results and conclusions that are derived from pharmacoeconomic cost effectiveness analyses (CEAs). Although numerous pharmacoeconomic practice guidelines are available in the literature and have been promulgated in many countries, these guidelines are either vague or silent about how drug costs should be established or measured. This is particularly problematic in pharmacoeconomic studies performed from the "societal" perspective, because typically the measured cost of a brand name pharmaceutical is not a true economic cost but also includes transfer payments from some members of society (patients and third party payers) to other members of society (pharmaceutical manufacturer stockholders) in large part as a reward for biomedical innovation. Moreover, there are numerous and complex institutional factors that influence how drug costs should be measured from other CEA perspectives, both internationally and within the domestic US context. The objective of this report is to provide guidance and recommendations on how drug costs should be measured for CEAs performed from a number of key analytic perspectives. ISPOR Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis (Drug Cost Task Force [DCTF]) was appointed with the advice and consent of the ISPOR Board of Directors. Members were experienced developers or users of CEA models, worked in academia, industry, and as advisors to governments, and came from several countries. Because how drug costs should be measured for CEAs depend on the perspectives, five Task Force subgroups were created to develop drug cost standards from the societal, managed care, US government, industry, and international perspective. The ISPOR Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis (DCTF) subgroups met to develop core assumptions and an outline before preparing six draft reports. They solicited

  13. Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells

    PubMed Central

    Lee, Hsin-chung; Ling, Qing-Dong; Yu, Wan-Chun; Hung, Chunh-Ming; Kao, Ta-Chun; Huang, Yi-Wei; Higuchi, Akon

    2013-01-01

    Purpose We evaluated the higher levels of carcinoembryonic antigen (CEA) secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs). Methods The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction. Results Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the untreated LoVo cells. Conclusion Production of CEA by LoVo cells can be stimulated by the addition of anticancer drugs. The drug-resistant subpopulation of LoVo colon cancer cells could stimulate the production of CEA, but these cells did not act as CSCs in in vivo tumor generation experiments. PMID:23818760

  14. Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center

    PubMed Central

    Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

    2017-01-01

    In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21–1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung’s criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy. PMID:28968445

  15. Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center.

    PubMed

    Otoshi, Takehiro; Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

    2017-01-01

    In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung's criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy.

  16. Dual Antiplatelet Therapy Does Not Increase the Risk of Bleeding After Carotid Endarterectomy: Results of a Prospective Study.

    PubMed

    Illuminati, Giulio; Schneider, Fabrice; Pizzardi, Giulia; Masci, Federica; Calio', Francesco G; Ricco, Jean-Baptiste

    2017-04-01

    The purpose of this study was to evaluate the risk of bleeding and other postoperative complications of carotid endarterectomy (CEA) in patients receiving dual antiplatelet therapy (DAPT). From January 2005 to December 2015, 188 consecutive patients undergoing CEA and receiving DAPT (aspirin 100 mg + clopidogrel 75 mg) were enrolled in a prospective study. All of them underwent coronary artery stenting with drug-eluting stents during the 6 months preceding CEA. In the entire series, DAPT was continued until the evening before CEA and resumed on the evening of the operation. All patients received intraoperative heparinization (5,000 IU before carotid clamping), which was reversed in 5 patients. In addition, all of them were given 2,000 units of enoxaparin every 12 hr after the operation, beginning 6 hr after completion of the operation, and until discharge. All the patients presented with carotid artery stenosis >70% (North American Symptomatic Carotid Endarterectomy Trial [NASCET] criteria), which was symptomatic in 42 patients (transient ischemic attack, n = 32; minor stroke, n = 10) and asymptomatic in 146. The CEA technique was standard, with prosthetic patch closure in 109 cases (58%) and eversion in 79 (42%). The primary endpoints of the study were occurrence of a postoperative cervical hematoma requiring surgical hemostasis and occurrence of cranial nerve injuries. The secondary endpoint was the combined rate of postoperative mortality, stroke, and myocardial ischemia. No postoperative cervical hematoma requiring surgical evacuation occurred in this series. One hypoglossal nerve palsy, regressive within 2 weeks, was observed. Postoperative mortality and neurologic and cardiac morbidity were nil. CEA under DAPT yields results comparable with those obtained in patients receiving a single antiplatelet treatment. No hemorrhagic complications were observed in this prospective series. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Activation of the Jasmonic Acid Pathway by Depletion of the Hydroperoxide Lyase OsHPL3 Reveals Crosstalk between the HPL and AOS Branches of the Oxylipin Pathway in Rice

    PubMed Central

    Tang, Jiuyou; Wang, Weihong; Zhang, Fengxia; Wang, Guodong; Chu, Jinfang; Yan, Cunyu; Wang, Taoqing; Chu, Chengcai; Li, Chuanyou

    2012-01-01

    The allene oxide synthase (AOS) and hydroperoxide lyase (HPL) branches of the oxylipin pathway, which underlie the production of jasmonates and aldehydes, respectively, function in plant responses to a range of stresses. Regulatory crosstalk has been proposed to exist between these two signaling branches; however, there is no direct evidence of this. Here, we identified and characterized a jasmonic acid (JA) overproduction mutant, cea62, by screening a rice T-DNA insertion mutant library for lineages that constitutively express the AOS gene. Map-based cloning was used to identify the underlying gene as hydroperoxide lyase OsHPL3. HPL3 expression and the enzyme activity of its product, (E)-2-hexenal, were depleted in the cea62 mutant, which resulted in the dramatic overproduction of JA, the activation of JA signaling, and the emergence of the lesion mimic phenotype. A time-course analysis of lesion formation and of the induction of defense responsive genes in the cea62 mutant revealed that the activation of JA biosynthesis and signaling in cea62 was regulated in a developmental manner, as was OsHPL3 activity in the wild-type plant. Microarray analysis showed that the JA-governed defense response was greatly activated in cea62 and this plant exhibited enhanced resistance to the T1 strain of the bacterial blight pathogen Xanthomonasoryzaepvoryzae (Xoo). The wounding response was attenuated in cea62 plants during the early stages of development, but partially recovered when JA levels were elevated during the later stages. In contrast, the wounding response was not altered during the different developmental stages of wild-type plants. These findings suggest that these two branches of the oxylipin pathway exhibit crosstalk with regards to biosynthesis and signaling and cooperate with each other to function in diverse stress responses. PMID:23209649

  18. Carotid Artery Stent Placement and Carotid Endarterectomy: A Challenge for Urgent Treatment after Stroke-Early and 12-Month Outcomes in a Comprehensive Stroke Center.

    PubMed

    Rocco, Alessandro; Sallustio, Fabrizio; Toschi, Nicola; Rizzato, Barbara; Legramante, Jacopo; Ippoliti, Arnaldo; Marchetti, Andrea Ascoli; Pampana, Enrico; Gandini, Roberto; Diomedi, Marina

    2018-06-20

    To compare feasibility, 12-month outcome, and periprocedural and postprocedural risks between carotid artery stent (CAS) placement and carotid endarterectomy (CEA) performed within 1 week after transient ischemic attack (TIA) or mild to severe stroke onset in a single comprehensive stroke center. Retrospective analysis of prospective data collected from 1,148 patients with ischemic stroke admitted to a single stroke unit between January 2013 and July 2015 was conducted. Among 130 consecutive patients with symptomatic carotid stenosis, 110 (10 with TIA, 100 with stroke) with a National Institutes of Health Stroke Scale (NIHSS) score < 20 and a prestroke modified Rankin Scale (mRS) score < 2 were eligible for CAS placement or CEA and treated according to the preference of the patient or a surrogate. Periprocedural (< 48 h) and postprocedural complications, functional outcome, stroke, and death rate up to 12 months were analyzed. Sixty-two patients were treated with CAS placement and 48 were treated with CEA. Several patients presented with moderate or major stroke (45.8% CEA, 64.5% CAS). NIHSS scores indicated slightly greater severity at onset in patients treated with a CAS vs CEA (6.6 ± 5.7 vs 4.2 ± 3.4; P = .08). Complication rates were similar between groups. mRS scores showed a significant improvement over time and a significant interaction with age in both groups. Similar incidences of death or stroke were shown on survival analysis. A subanalysis in patients with NIHSS scores ≥ 4 showed no differences in complication rate and outcome. CAS placement and CEA seem to offer early safe and feasible secondary stroke prevention treatments in experienced centers, even after major atherosclerotic stroke. Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.

  19. Epidural analgesia in patients with traumatic rib fractures: a systematic review of randomised controlled trials.

    PubMed

    Duch, P; Møller, M H

    2015-07-01

    Traumatic rib fractures are a common condition associated with considerable morbidity and mortality. Observational studies have suggested improved outcome in patients receiving continuous epidural analgesia (CEA). The aim of the present systematic review of randomised controlled trials (RCTs) was to assess the benefit and harm of CEA compared with other analgesic interventions in patients with traumatic rib fractures. We performed a systematic review with meta-analysis and trial sequential analysis (TSA). Eligible trials were RCTs comparing CEA with other analgesic interventions in patients with traumatic rib fractures. Cumulative relative risks (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were estimated, and risk of systematic and random errors was assessed. The predefined primary outcome measures were mortality, pneumonia and duration of mechanical ventilation. A total of six trials (n = 223) were included; all were judged as having a high risk of bias. In the conventional meta-analyses, there was no statistically significant difference in mortality (RR 2.18, 95% CI 0.21-22.42; P = 0.51; I(2)  = 0%), duration of mechanical ventilation (MD -7.53, 95% CI -16.32 to 1.26; P = 0.09; I(2)  = 91%) or pneumonia (RR 0.49, 95% CI 0.19-1.25; P = 0.13; I(2)  = 0%) between CEA and other analgesic interventions. Subgroup analyses and sensitivity analyses, including TSA confirmed the results. The quality and quantity of evidence for the use of CEA in patients with traumatic rib fractures is low, and there is no firm evidence for benefit or harm of CEA compared with other analgesic interventions. Well-powered RCTs with low risk of bias reporting clinically relevant patient-centred outcome measures are needed. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  20. Clinical and angiographic risk factors for stroke and death within 30 days after carotid endarterectomy and stent-protected angioplasty: a subanalysis of the SPACE study.

    PubMed

    Stingele, Robert; Berger, Jürgen; Alfke, Karsten; Eckstein, Hans-Henning; Fraedrich, Gustav; Allenberg, Jens; Hartmann, Marius; Ringleb, Peter A; Fiehler, Jens; Bruckmann, H; Hennerici, M; Jansen, O; Klein, G; Kunze, A; Marx, P; Niederkorn, K; Schmiedt, W; Solymosi, L; Zeumer, H; Hacke, W

    2008-03-01

    Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are used to prevent ischaemic stroke in patients with stenosis of the internal carotid artery. Better knowledge of risk factors could improve assignment of patients to these procedures and reduce overall risk. We aimed to assess the risk of stroke or death associated with CEA and CAS in patients with different risk factors. We analysed data from 1196 patients randomised to CAS or CEA in the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE) trial. The primary outcome event was death or ipsilateral stroke (ischaemic or haemorrhagic) with symptoms that lasted more than 24 h between randomisation and 30 days after therapy. Six predefined variables were assessed as potential risk factors for this outcome: age, sex, type of qualifying event, side of intervention, degree of stenosis, and presence of high-grade contralateral stenosis or occlusion. The SPACE trial is registered at Current Controlled Trials, with the international standard randomised controlled trial number ISRCTN57874028. Risk of ipsilateral stroke or death increased significantly with age in the CAS group (p=0.001) but not in the CEA group (p=0.534). Classification and regression tree analysis showed that the age that gave the greatest separation between high-risk and low-risk populations who had CAS was 68 years: the rate of primary outcome events was 2.7% (8/293) in patients who were 68 years old or younger and 10.8% (34/314) in older patients. Other variables did not differ between the CEA and CAS groups. Of the predefined covariates, only age was significantly associated with the risk of stroke and death. The lower risk after CAS versus CEA in patients up to 68 years of age was not detectable in older patients. This finding should be interpreted with caution because of the drawbacks of post-hoc analyses.

  1. Systematic Review of Guidelines for the Management of Asymptomatic and Symptomatic Carotid Stenosis.

    PubMed

    Abbott, Anne L; Paraskevas, Kosmas I; Kakkos, Stavros K; Golledge, Jonathan; Eckstein, Hans-Henning; Diaz-Sandoval, Larry J; Cao, Longxing; Fu, Qiang; Wijeratne, Tissa; Leung, Thomas W; Montero-Baker, Miguel; Lee, Byung-Chul; Pircher, Sabine; Bosch, Marije; Dennekamp, Martine; Ringleb, Peter

    2015-11-01

    We systematically compared and appraised contemporary guidelines on management of asymptomatic and symptomatic carotid artery stenosis. We systematically searched for guideline recommendations on carotid endarterectomy (CEA) or carotid angioplasty/stenting (CAS) published in any language between January 1, 2008, and January 28, 2015. Only the latest guideline per writing group was selected. Each guideline was analyzed independently by 2 to 6 authors to determine clinical scenarios covered, recommendations given, and scientific evidence used. Thirty-four eligible guidelines were identified from 23 different regions/countries in 6 languages. Of 28 guidelines with asymptomatic carotid artery stenosis procedural recommendations, 24 (86%) endorsed CEA (recommended it should or may be provided) for ≈50% to 99% average-surgical-risk asymptomatic carotid artery stenosis, 17 (61%) endorsed CAS, 8 (29%) opposed CAS, and 1 (4%) endorsed medical treatment alone. For asymptomatic carotid artery stenosis patients considered high-CEA-risk because of comorbidities, vascular anatomy, or undefined reasons, CAS was endorsed in 13 guidelines (46%). Thirty-one of 33 guidelines (94%) with symptomatic carotid artery stenosis procedural recommendations endorsed CEA for patients with ≈50% to 99% average-CEA-risk symptomatic carotid artery stenosis, 19 (58%) endorsed CAS and 9 (27%) opposed CAS. For high-CEA-risk symptomatic carotid artery stenosis because of comorbidities, vascular anatomy, or undefined reasons, CAS was endorsed in 27 guidelines (82%). Guideline procedural recommendations were based only on results of trials in which patients were randomized 12 to 34 years ago, rarely reflected medical treatment improvements and often understated potential CAS hazards. Qualifying terminology summarizing recommendations or evidence lacked standardization, impeding guideline interpretation, and comparison. This systematic review has identified many opportunities to modernize and

  2. Neuronal Correlates of Fear Conditioning in the Bed Nucleus of the Stria Terminalis

    ERIC Educational Resources Information Center

    Haufler, Darrell; Nagy, Frank Z.; Pare, Denis

    2013-01-01

    Lesion and inactivation studies indicate that the central amygdala (CeA) participates in the expression of cued and contextual fear, whereas the bed nucleus of the stria terminalis (BNST) is only involved in the latter. The basis for this functional dissociation is unclear because CeA and BNST form similar connections with the amygdala and…

  3. Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including early detection of cancers

    DOEpatents

    Martinez, Jennifer S [Santa Fe, NM; Swanson, Basil I [Los Alamos, NM; Shively, John E [Arcadia, CA; Li, Lin [Monrovia, CA

    2009-06-02

    An assay element is described including recognition ligands adapted for binding to carcinoembryonic antigen (CEA) bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of CEA is described including injecting a possible CEA-containing sample into a sensor cell including the assay element, maintaining the sample within the sensor cell for time sufficient for binding to occur between CEA present within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

  4. Bifunctional antibody-Renilla luciferase fusion protein for in vivo optical detection of tumors.

    PubMed

    Venisnik, Katy M; Olafsen, Tove; Loening, Andreas M; Iyer, Meera; Gambhir, Sanjiv S; Wu, Anna M

    2006-10-01

    An anti-carcinoembryonic antigen (CEA) antibody fragment, the anti-CEA diabody, was fused to the bioluminescence enzyme Renilla luciferase (RLuc) to generate a novel optical imaging probe. Native RLuc or one of two stabilized variants (RLucC124A, RLuc8) was used as the bioluminescent moiety. A bioluminescence ELISA showed that diabody-luciferase could simultaneously bind to CEA and emit light. In vivo optical imaging of tumor-bearing mice demonstrated specific targeting of diabody-RLuc8 to CEA-positive xenografts, with a tumor:background ratio of 6.0 +/- 0.8 at 6 h after intravenous injection, compared with antigen-negative tumors at 1.0 +/- 0.1 (P = 0.05). Targeting and distribution was also evaluated by microPET imaging using (124)I-diabody-RLuc8 and confirmed that the optical signal was due to antibody-mediated localization of luciferase. Renilla luciferase, fused to biospecific sequences such as engineered antibodies, can be administered systemically to provide a novel, sensitive method for optical imaging based on expression of cell surface receptors in living organisms.

  5. Induction of carcinoembryonic antigen expression in a three-dimensional culture system

    NASA Technical Reports Server (NTRS)

    Jessup, J. M.; Brown, D.; Fitzgerald, W.; Ford, R. D.; Nachman, A.; Goodwin, T. J.; Spaulding, G.

    1994-01-01

    MIP-101 is a poorly differentiated human colon carcinoma cell line established from ascites that produces minimal amounts of carcinoembryonic antigen (CEA), a 180 kDa glycoprotein tumor marker, and nonspecific cross-reacting antigen (NCA), a related protein that has 50 and 90 kDa isoforms, in vitro in monolayer culture. MIP-101 produces CEA when implanted into the peritoneum of nude mice but not when implanted into subcutaneous tissue. We tested whether MIP-101 cells may be induced to express CEA when cultured on microcarrier beads in three-dimensional cultures, either in static cultures as non-adherent aggregates or under dynamic conditions in a NASA-designed low shear stress bioreactor. MIP- 101 cells proliferated well under all three conditions and increased CEA and NCA production 3 - 4 fold when grown in three-dimensional cultures compared to MIP-101 cells growing logarithmically in monolayers. These results suggest that three-dimensional growth in vitro simulates tumor function in vivo and that three-dimensional growth by itself may enhance production of molecules that are associated with the metastatic process.

  6. A Central Amygdala CRF Circuit Facilitates Learning about Weak Threats.

    PubMed

    Sanford, Christina A; Soden, Marta E; Baird, Madison A; Miller, Samara M; Schulkin, Jay; Palmiter, Richard D; Clark, Michael; Zweifel, Larry S

    2017-01-04

    Fear is a graded central motive state ranging from mild to intense. As threat intensity increases, fear transitions from discriminative to generalized. The circuit mechanisms that process threats of different intensity are not well resolved. Here, we isolate a unique population of locally projecting neurons in the central nucleus of the amygdala (CeA) that produce the neuropeptide corticotropin-releasing factor (CRF). CRF-producing neurons and CRF in the CeA are required for discriminative fear, but both are dispensable for generalized fear at high US intensities. Consistent with a role in discriminative fear, CRF neurons undergo plasticity following threat conditioning and selectively respond to threat-predictive cues. We further show that excitability of genetically isolated CRF-receptive (CRFR1) neurons in the CeA is potently enhanced by CRF and that CRFR1 signaling in the CeA is critical for discriminative fear. These findings demonstrate a novel CRF gain-control circuit and show separable pathways for graded fear processing. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Cost and cost-effectiveness studies in urologic oncology using large administrative databases.

    PubMed

    Wang, Ye; Mossanen, Matthew; Chang, Steven L

    2018-04-01

    Urologic cancers are not only among the most common types of cancers, but also among the most expensive cancers to treat in the United States. This study aimed to review the use of CEAs and other cost analyses in urologic oncology using large databases to better understand the value of management strategies of these cancers. A literature review on CEAs and other cost analyses in urologic oncology using large databases. The options for and costs of diagnosing, treating, and following patients with urologic cancers can be expected to rise in the coming years. There are numerous opportunities in each urologic cancer to use CEAs to both lower costs and provide high-quality services. Improved cancer care must balance the integration of novelty with ensuring reasonable costs to patients and the health care system. With the increasing focus cost containment, appreciating the value of competing strategies in caring for our patients is pivotal. Leveraging methods such as CEAs and harnessing large databases may help evaluate the merit of established or emerging strategies. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Effects of selective excitotoxic lesions of the nucleus accumbens core, anterior cingulate cortex, and central nucleus of the amygdala on autoshaping performance in rats.

    PubMed

    Cardinal, Rudolf N; Parkinson, John A; Lachenal, Guillaume; Halkerston, Katherine M; Rudarakanchana, Nung; Hall, Jeremy; Morrison, Caroline H; Howes, Simon R; Robbins, Trevor W; Everitt, Barry J

    2002-08-01

    The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an unpaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS+ significantly less often than controls, failing to discriminate between the CS+ and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations.

  9. Carotid Stenting for Restenosis after Endarterectomy

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

    Counsell, Andrew, E-mail: mzysapc@doctors.org.uk; Ghosh, Jonathan, E-mail: jonathanghosh@mac.com; McCollum, Charles C. N., E-mail: charles.mccollum@manchester.ac.uk

    2011-06-15

    Introduction: Restenosis after carotid endarterectomy (CEA) has been described in 8-19% of patients, 14-23% of whom become symptomatic. This study analyzes our experience with carotid artery stenting (CAS) for post-CEA recurrent stenoses.MethodRetrospective database and case-note review. Results: Between January 2000 and September 2008, a total of 27 patients (15 symptomatic) with hemodynamically significant internal carotid artery post-CEA restenosis underwent CAS. Median stenosis of target vessels was 90% (range 75-95%). There was one periprocedural death (3.7%); no others occurred during the median 34-month follow-up (range 0.1-84 months). There was one late transient ischemic attack 12 months after CAS that was notmore » associated with in-stent restenosis. One 90% restenosis and one occlusion were detected during follow-up at 38 and 57 months after CAS. The remaining patients had no evidence of further restenosis and remained free from cerebrovascular symptoms. Conclusion: CAS offers a feasible option for the management of carefully selected patients with symptomatic and asymptomatic restenosis after CEA.« less

  10. Memory consolidation within the central amygdala is not necessary for modulation of cerebellar learning.

    PubMed

    Steinmetz, Adam B; Ng, Ka H; Freeman, John H

    2017-06-01

    Amygdala lesions impair, but do not prevent, acquisition of cerebellum-dependent eyeblink conditioning suggesting that the amygdala modulates cerebellar learning. Two-factor theories of eyeblink conditioning posit that a fast-developing memory within the amygdala facilitates slower-developing memory within the cerebellum. The current study tested this hypothesis by impairing memory consolidation within the amygdala with inhibition of protein synthesis, transcription, and NMDA receptors in rats. Rats given infusions of anisomycin or DRB into the central amygdala (CeA) immediately after each eyeblink conditioning session were severely impaired in contextual and cued fear conditioning, but were completely unimpaired in eyeblink conditioning. Rats given the NMDA antagonist ifenprodil into the CeA before each eyeblink conditioning session also showed impaired fear conditioning, but no deficit in eyeblink conditioning. The results indicate that memory formation within the CeA is not necessary for its modulation of cerebellar learning mechanisms. The CeA may modulate cerebellar learning and retention through an attentional mechanism that develops within the training sessions. © 2017 Steinmetz et al.; Published by Cold Spring Harbor Laboratory Press.

  11. Differential Involvement of Brain-Derived Neurotrophic Factor in Reconsolidation and Consolidation of Conditioned Taste Aversion Memory

    PubMed Central

    Wang, Yue; Zhang, Tian-Yi; Xin, Jian; Li, Ting; Yu, Hui; Li, Na; Chen, Zhe-Yu

    2012-01-01

    Consolidated memory can re-enter states of transient instability following reactivation, which is referred to as reconsolidation, and the exact molecular mechanisms underlying this process remain unexplored. Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptic plasticity and memory processes. We have recently observed that BDNF signaling in the central nuclei of the amygdala (CeA) and insular cortex (IC) was involved in the consolidation of conditioned taste aversion (CTA) memory. However, whether BDNF in the CeA or IC is required for memory reconsolidation is still unclear. In the present study, using a CTA memory paradigm, we observed increased BDNF expression in the IC but not in the CeA during CTA reconsolidation. We further determined that BDNF synthesis and signaling in the IC but not in the CeA was required for memory reconsolidation. The differential, spatial-specific roles of BDNF in memory consolidation and reconsolidation suggest that dissociative molecular mechanisms underlie reconsolidation and consolidation, which might provide novel targets for manipulating newly encoded and reactivated memories without causing universal amnesia. PMID:23185492

  12. Lessons from EVA-3S and SPACE

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

    Beckett, David; Gaines, Peter A.

    2008-01-15

    Carotid endarterectomy (CEA) was established as the gold standard for treatment of carotid occlusive disease by several landmark papers published in the 1990s. With the continued trend toward less invasive therapies, carotid artery stenting (CAS) has challenged CEA for treatment of significant carotid artery disease. Several trials have now compared CEA and CAS and a subsequent Cochrane review indicated that the 30-day complication rates were equivalent. Unfortunately, comparative long-term data are still lacking. Two new trials comparing CAS with CAE in patients with symptomatic internal carotid artery disease have recently been published, but to what extent have they usefully addedmore » to the available data?.« less

  13. A Community-Engaged Art Program for Older People: Fostering Social Inclusion

    ERIC Educational Resources Information Center

    Moody, Elaine; Phinney, Alison

    2012-01-01

    Social inclusion is an important factor in promoting optimum health and wellness for older adults. Community-engaged arts (CEA) have been promoted as a means to support social inclusion for this population, but little empirical evidence has been reported. The objective of this study was to explore the role of a CEA program in the social inclusion…

  14. Sustaining the Dream: A Response to Excessive Positivism in Person-Centered Planning

    ERIC Educational Resources Information Center

    Michaels, Craig A.

    2007-01-01

    This article presents the author's response to "Excessive Positivism in Person-Centered Planning," by Steve Holburn and Christine D. Cea. The author begins by complementing Holburn and Cea on their courage to voice concerns that perhaps may not appear to be politically correct or perhaps too bold to express in the context of a journal like…

  15. Educational Research: A Look Back

    ERIC Educational Resources Information Center

    Education Canada, 2010

    2010-01-01

    In September, 1958, The Canadian Education Association (CEA) hosted a panel discussion on the current status and emerging requirements of educational research in Canada. The panelists' comments are firmly rooted in the context of the 1950s. Half a century later, Penny Milton, CEO of CEA, takes a look at their comments and suggestions. This article…

  16. Education for Democracy: An Excerpt from the Archives

    ERIC Educational Resources Information Center

    Campbell, H. L.

    2009-01-01

    In this column, the author presents an excerpt from the President's Address to the 35th Annual Meeting of the Canadian Education Association (CEA), September 1958, Victoria. In his address, the CEA president talks about how the world pressures are building up in the form of demands for more and better education; and these demands are rising from…

  17. Increased resource utilization and overall morbidity are associated with general versus regional anesthesia for carotid endarterectomy in data collected by the Michigan Surgical Quality Collaborative.

    PubMed

    Hussain, Ahmad S; Mullard, Andrew; Oppat, William F; Nolan, Kevin D

    2017-09-01

    Advocates for performing carotid endarterectomy (CEA) under regional anesthesia (RA) cite reduction in hemodynamic instability and the ability for neurologic monitoring, but many still prefer general anesthesia (GA) as benefits of RA have not been clearly demonstrated, reliable RA may not be available in all centers, and a certain amount of movement by the patient during the procedure may not be uniformly tolerated. We evaluated the association of anesthesia type and perioperative morbidity and mortality as well as resource utilization in patients undergoing CEA using the Michigan Surgical Quality Collaborative (MSQC) database. Between 2012 and 2014, 4558 patients underwent CEA among the MSQC participating hospitals. Of these patients, 4008 underwent CEA under GA and 550 underwent CEA under RA. Data points were collected for each procedure, and a review of 30-day perioperative outcomes was conducted using the χ 2 test. Propensity score regression adjusted for case mix preoperative conditions as fixed effects, and a mixed model adjusted for site as a random effect. The two groups were similar in gender and incidence of hypertension, diabetes, congestive heart failure, and smoking history. The RA group tended to be of better functional status. After GA, there was a greater than twofold higher percentage of any morbidity (8.7% vs 4.2%). Further analysis demonstrated that patients undergoing GA had higher unadjusted rates for mortality (1.0% vs 0.0%), unplanned intubations (2.1% vs 0.6%), pneumonia (1.3% vs 0.0%), sepsis (0.8% vs 0.0%), and readmissions (9.2% vs 6.1%). Adjusting for case mix and random effect, there was statistically significantly higher overall morbidity (P = .0002), unplanned intubation (P = .0196), extended length of stay (P = .0007), emergency department visits (P = .0379), and readmissions (P = .0149) in the GA group. There was no statistically significant difference in incidence of myocardial infarction or cerebrovascular accident. Based on

  18. Accuracy of administrative data versus clinical data to evaluate carotid endarterectomy and carotid stenting.

    PubMed

    Bensley, Rodney P; Yoshida, Shunsuke; Lo, Ruby C; Fokkema, Margriet; Hamdan, Allen D; Wyers, Mark C; Chaikof, Elliot L; Schermerhorn, Marc L

    2013-08-01

    Administrative data have been used to compare carotid endarterectomy (CEA) and carotid artery stenting (CAS). However, there are limitations in defining symptom status, Centers for Medicare and Medicaid Services high-risk status, as well as complications. Therefore, we did a direct comparison between administrative data and physician chart review as well as between data collected for the National Surgical Quality Improvement Program (NSQIP) and physician chart review for CEA and CAS. We performed an outcomes analysis on all CEA and CAS procedures from 2005 to 2011. We obtained International Classification of Diseases, Ninth Revision diagnosis codes from hospital discharge records regarding symptom status, high-risk status, and perioperative stroke. We also obtained data on all CEA patients submitted to NSQIP over the same time period. One of the study authors (R.B.) then performed a chart review of the same patients to determine symptom status, high-risk status, and perioperative strokes and the results were compared. We identified 1342 patients who underwent CEA or CAS between 2005 and 2011 and 392 patients who underwent CEA that were submitted to NSQIP. Administrative data identified fewer symptomatic patients (17.0% vs 34.0%), physiologic high-risk patients (9.3% vs 23.0%), and anatomic high-risk patients (0% vs 15.2%). Although administrative data identified a similar proportion of perioperative strokes (1.9% vs 2.0%), this was due to the fact that these data identified eight false positive and nine false negative perioperative strokes. NSQIP data identified more symptomatic patients compared with chart review (44.1% vs 30.3%), fewer physiologic high-risk patients (13.0% vs 18.6%), fewer anatomic high-risk patients (0% vs 6.6%), and a similar proportion of perioperative strokes (1.5% vs 1.8%, only one false negative stroke and no false positives). Administrative data are unreliable for determining symptom status, high-risk status, and perioperative stroke and

  19. Long-term results of a randomized controlled trial analyzing the role of systematic pre-operative coronary angiography before elective carotid endarterectomy in patients with asymptomatic coronary artery disease.

    PubMed

    Illuminati, G; Schneider, F; Greco, C; Mangieri, E; Schiariti, M; Tanzilli, G; Barillà, F; Paravati, V; Pizzardi, G; Calio', F; Miraldi, F; Macrina, F; Totaro, M; Greco, E; Mazzesi, G; Tritapepe, L; Toscano, M; Vietri, F; Meyer, N; Ricco, J-B

    2015-04-01

    To evaluate the potential benefit of systematic preoperative coronary-artery angiography followed by selective coronary-artery revascularization on the incidence of myocardial infarction (MI) in patients undergoing carotid endarterectomy (CEA) without a previous history of coronary artery disease (CAD). We randomised 426 patients who were candidates for CEA, with no history of CAD, a normal electrocardiogram (ECG), and a normal cardiac ultrasound. In group A (n = 216) all patients underwent coronary angiography before CEA. In group B (n = 210) CEA was performed without coronary angiography. Patients were not blinded for relevant assessments during follow-up. Primary end-point was the occurrence of MI at 3.5 years. The secondary end-point was the overall survival rate. Median length of follow-up was 6.2 years. In group A, coronary angiography revealed significant coronary artery stenosis in 68 patients (31.5%). Among them, 66 underwent percutaneous Intervention (PCI) prior to CEA and 2 received combined CEA and coronary-artery bypass grafting (CABG). Postoperatively, no MI was observed in group A, whereas 6 MI occurred in group B, one of which was fatal (p = .01). During the study period, 3 MI occurred in group A (1.4%) and 33 were observed in group B (15.7%), 6 of which were fatal. The Cox model demonstrated a reduced risk of MI for patients in group A receiving coronary angiography (HR,.078; 95% CI, 0.024-0.256; p < .001). In addition, patients with diabetes and patients <70 years presented with an increased risk of MI. Survival analysis at 6 years by Kaplan-Meier estimates was 95.6 ± 3.2% in Group A and 89.7 ± 3.7% in group B (Log Rank = 6.54, p = .01). In asymptomatic coronary-artery patients, systematic coronary angiography prior to CEA followed by selective PCI or CABG significantly reduces the incidence of late MI and increases long-term survival. (ClinicalTrials.gov number, NCT02260453). Copyright © 2015 European Society for Vascular

  20. Analysis and comparison of the cost-effectiveness of statins according to the baseline low-density lipoprotein cholesterol level in Korea.

    PubMed

    Jeong, Y J; Kim, H; Baik, S J; Kim, T M; Yang, S J; Lee, S-H; Cho, J-H; Lee, H; Yim, H W; Choi, I Y; Yoon, K-H; Kim, H-S

    2017-06-01

    There are a few Korean studies on the economics of statins based on reduction in low-density lipoprotein cholesterol (LDL-C) data from other countries. This study aimed to analyse and compare the cost-effectiveness of statins according to the baseline LDL-C level in Korea. Between January 2009 and December 2015, the data of patients who were prescribed statins for the first time were extracted from electronic medical records. We performed a cost-effectiveness analysis (CEA) based on the LDL-C reduction rate (CEA-RR) and target achievement rate. Among high-intensity statins, the CEA-RR value of rosuvastatin (20 mg) was significantly lower than that of atorvastatin (40 mg) at all baseline LDL-C levels, except levels of 160-189 mg/dL. Additionally, at baseline LDL-C levels of 130-159 mg/dL, the CEA-RR value of rosuvastatin (20 mg) was three times lower than that of atorvastatin (40 mg) (9·1 ± 2·5 $/% vs. 31·7 ± 15·0 $/%, P < 0·001). Among moderate-to-low-intensity statins, rosuvastatin (5 mg) showed the lowest CEA-RR value (4·0 ± 0·6 $/%), and the value significantly increased for pitavastatin (2 mg) (8·0 ± 0·6 $/%), atorvastatin (10 mg) (9·5 ± 0·5 $/%), simvastatin (10·8 ± 1·1 $/%) and pravastatin (40 mg) (11·5 ± 0·9 $/%) in order (P < 0·0001). On changing from atorvastatin (10 mg) to atorvastatin (20 mg), the additional yearly cost was 16·0 and additional CEA-RR value was 2·74 $/%. On the other hand, on changing from atorvastatin (10 mg) to rosuvastatin (10 mg), the additional yearly cost was -16·3 and additional CEA-RR value was -1·8 $/%. We successfully compared the cost-effectiveness of statins according to the baseline LDL-C level in Korea. It is expected that our findings will help clinical decision-making with regard to statin prescription, and this will help reduce national medical expenditure. © 2017 John Wiley & Sons Ltd.

  1. Assessment of subchondral bone marrow lesions in knee osteoarthritis by MRI: a comparison of fluid sensitive and contrast enhanced sequences.

    PubMed

    Nielsen, Flemming K; Egund, Niels; Jørgensen, Anette; Peters, David A; Jurik, Anne Grethe

    2016-11-16

    Bone marrow lesions (BMLs) in knee osteoarthritis (OA) can be assessed using fluid sensitive and contrast enhanced sequences. The association between BMLs and symptoms has been investigated in several studies but only using fluid sensitive sequences. Our aims were to assess BMLs by contrast enhanced MRI sequences in comparison with a fluid sensitive STIR sequence using two different segmentation methods and to analyze the association between the MR findings and disability and pain. Twenty-two patients (mean age 61 years, range 41-79 years) with medial femoro-tibial knee OA obtained MRI and filled out a WOMAC questionnaire at baseline and follow-up (median interval of 334 days). STIR, dynamic contrast enhanced-MRI (DCE-MRI) and fat saturated T1 post-contrast (T1 CE FS) MRI sequences were obtained. All STIR and T1 CE FS sequences were assessed independently by two readers for STIR-BMLs and contrast enhancing areas of BMLs (CEA-BMLs) using manual segmentation and computer assisted segmentation, and the measurements were compared. DCE-MRIs were assessed for the relative distribution of voxels with an inflammatory enhancement pattern, N voxel , in the bone marrow. All findings were compared to WOMAC scores, including pain and overall symptoms, and changes from baseline to follow-up were analyzed. The average volume of CEA-BML was smaller than the STIR-BML volume by manual segmentation. The opposite was found for computer assisted segmentation where the average CEA-BML volume was larger than the STIR-BML volume. The contradictory finding by computer assisted segmentation was partly caused by a number of outliers with an apparent generally increased signal intensity in the anterior parts of the femoral condyle and tibial plateau causing an overestimation of the CEA-BML volume. Both CEA-BML, STIR-BML and N voxel were significantly correlated with symptoms and to a similar degree. A significant reduction in total WOMAC score was seen at follow-up, but no significant

  2. Natural killer cells activity in a metastatic colorectal cancer patient with complete and long lasting response to therapy.

    PubMed

    Ottaiano, Alessandro; Napolitano, Maria; Capozzi, Monica; Tafuto, Salvatore; Avallone, Antonio; Scala, Stefania

    2017-11-16

    Here we report a case of a 70-year-old man who received adjuvant chemotherapy with fluorouracile, folinic acid and oxaliplatin after a left hemicolectomy for a stage IIIb adenocarcinoma in May 2009. During follow-up he de-veloped abdominal lymphnodes metastases evidenced by positron emission tomography- computed tomography (PET-CT) scan and increase of carcinoembryonic antigen (CEA) level. Chemotherapy with capecitabine, oxaliplatin and bevacizumab was started in April 2012. Restaging showed a complete response and normalization of CEA. The patient received maintenance therapy with bevacizumab which was stopped in December 2013 for patient choice. In October 2014, a new increase in CEA was documented and PET-CT scan showed lung metastases. Analysis of RAS status revealed the absence of mutations, then the patient started a second-line chemotherapy with fluorouracile, folinic acid, irinotecan (folfiri) and panitumumab achieving, in January 2015, a complete response and normalization of CEA. Thereafter, folfiri was discontinued for toxicity; furthermore, upon the third occurrence of a grade 3 dermatologic toxicity, panitumumab was continued from June 2015 at 60% of the original dose and it was administered every three weeks. Until presentation of this case, the patient maintains a complete response, has no symptoms of disease and CEA is normal. Interestingly, this patient presented a high proportion of circulating natural killer (NK) cells (35.1%) with high cytotoxic activity against tumor cells. Study on the role of NK in patients with advanced colorectal cancer are ongoing.

  3. Knocking down amygdalar PTP1B in diet-induced obese rats improves insulin signaling/action, decreases adiposity and may alter anxiety behavior.

    PubMed

    Mendes, Natalia Ferreira; Castro, Gisele; Guadagnini, Dioze; Tobar, Natalia; Cognuck, Susana Quiros; Elias, Lucila Leico Kagohara; Boer, Patricia Aline; Prada, Patricia Oliveira

    2017-05-01

    Protein tyrosine phosphatase 1B (PTP1B) has been extensively implicated in the regulation of body weight, food intake, and energy expenditure. The role of PTP1B appears to be cell and brain region dependent. Herein, we demonstrated that chronic high-fat feeding enhanced PTP1B expression in the central nucleus of the amygdala (CeA) of rats compared to rats on chow. Knocking down PTP1B with oligonucleotide antisense (ASO) decreased its expression and was sufficient to improve the anorexigenic effect of insulin through IR/Akt signaling in the CeA. ASO treatment reduces body weight, fat mass, serum leptin levels, and food intake and also increases energy expenditure, without altering ambulatory activity. These changes were explained, at least in part, by the improvement of insulin sensitivity in the CeA, decreasing NPY and enhancing oxytocin expression. There was a slight decline in fasting blood glucose and serum insulin levels possibly due to leanness in rats treated with ASO. Surprisingly, the elevated plus maze test revealed an anxiolytic behavior after reduction of PTP1B in the CeA. Thus, the present study highlights the deleterious role that the amygdalar PTP1B has on energy homeostasis in obesity states. The reduction of PTP1B in the CeA may be a strategy for the treatment of obesity, insulin resistance and anxiety disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Esophagitis with eosinophil infiltration associated with congenital esophageal atresia and stenosis.

    PubMed

    Yamada, Yoshiyuki; Nishi, Akira; Kato, Masahiko; Toki, Fumiaki; Yamamoto, Hideki; Suzuki, Norio; Hirato, Junko; Hayashi, Yasuhide

    2013-01-01

    The esophagus is physiologically devoid of eosinophils, so their presence would suggest some underlying pathology. The prevalence of eosinophilic esophagitis (EoE) has steadily increased in Western countries. Previous studies have described EoE in association with congenital esophageal atresia (CEA), which is the most common congenital anomaly of the esophagus. However, the association remains unclear. We performed a retrospective histological analysis examining for eosinophil infiltration in the esophagus of patients with CEA following surgical repair or congenital esophageal stenosis (CES) who underwent esophageal biopsy or surgical resection in our hospital between 2005 and 2012. There were 6 patients with CEA following surgical repair or CES who had eosinophil-dominant infiltration in the esophagus. All had associated allergic disorders, including food allergies in 4. Moreover, all except for one fulfilled the histological criteria of EoE. Impairment of eosinophil infiltration and symptomatic improvement were observed in those treated with a proton pump inhibitor (PPI), either alone or in combination with steroids after esophageal dilatation. These findings suggest that CEA repair or CES in conjunction with allergic conditions and coexisting gastroesophageal reflux disease (GERD) may induce greater esophageal eosinophilic inflammation. In addition, esophageal dilatation followed by PPI treatment, alone or with steroids, may be a therapeutic strategy that can provide symptomatic relief by reducing eosinophilic inflammation in esophageal strictures or GERD associated with CEA or CES. Copyright © 2013 S. Karger AG, Basel.

  5. An institutional study of time delays for symptomatic carotid endarterectomy.

    PubMed

    Charbonneau, Philippe; Bonaventure, Paule Lessard; Drudi, Laura M; Beaudoin, Nathalie; Blair, Jean-François; Elkouri, Stéphane

    2016-12-01

    The aim of this study was to assess time delays between first cerebrovascular symptoms and carotid endarterectomy (CEA) at a single center and to systematically evaluate causes of these delays. Consecutive adult patients who underwent CEAs between January 2010 and September 2011 at a single university-affiliated center (Centre Hospitalier de l'Université Montréal-Hôtel-Dieu Hospital, Montreal) were identified from a clinical database and operative records. Covariates of interest were extracted from electronic medical records. Timing and nature of the first cerebrovascular symptoms were also documented. The first medical contact and pathway of referral were also assessed. When possible, the ABCD 2 score (age, blood pressure, clinical features, duration of symptoms, and diabetes) was calculated to calculate further risk of stroke. The nonparametric Wilcoxon test was used to assess differences in time intervals between two variables. The Kruskal-Wallis test was used to assess differences in time intervals in comparing more than two variables. A multivariate linear regression analysis was performed using covariates that were determined to be statistically significant in our sensitivity analyses. The cohort consisted of 111 patients with documented symptomatic carotid stenosis undergoing surgical intervention. Thirty-nine percent of all patients were operated on within 2 weeks from the first cerebrovascular symptoms. The median time between the occurrence of the first neurologic symptom and the CEA procedure was 25 (interquartile range [IQR], 11-85) days. The patient-dependent delay, defined as the median delay between the first neurologic symptom and the first medical contact, was 1 (IQR, 0-14) day. The medical-dependent delay was defined as the time interval between the first medical contact and CEA. This included the delay between the first medical contact and the request for surgery consultation (median, 3 [IQR, 1-10] days). The multivariate regression model

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

    Glascoe, Lee; Gowardhan, Akshay; Lennox, Kristin

    In the interest of promoting the international exchange of technical expertise, the US Department of Energy’s Office of Emergency Operations (NA-40) and the French Commissariat à l'Energie Atomique et aux énergies alternatives (CEA) requested that the National Atmospheric Release Advisory Center (NARAC) of Lawrence Livermore National Laboratory (LLNL) in Livermore, California host a joint table top exercise with experts in emergency management and atmospheric transport modeling. In this table top exercise, LLNL and CEA compared each other’s flow and dispersion models. The goal of the comparison is to facilitate the exchange of knowledge, capabilities, and practices, and to demonstrate themore » utility of modeling dispersal at different levels of computational fidelity. Two modeling approaches were examined, a regional scale modeling approach, appropriate for simple terrain and/or very large releases, and an urban scale modeling approach, appropriate for small releases in a city environment. This report is a summary of LLNL and CEA modeling efforts from this exercise. Two different types of LLNL and CEA models were employed in the analysis: urban-scale models (Aeolus CFD at LLNL/NARAC and Parallel- Micro-SWIFT-SPRAY, PMSS, at CEA) for analysis of a 5,000 Ci radiological release and Lagrangian Particle Dispersion Models (LODI at LLNL/NARAC and PSPRAY at CEA) for analysis of a much larger (500,000 Ci) regional radiological release. Two densely-populated urban locations were chosen: Chicago with its high-rise skyline and gridded street network and Paris with its more consistent, lower building height and complex unaligned street network. Each location was considered under early summer daytime and nighttime conditions. Different levels of fidelity were chosen for each scale: (1) lower fidelity mass-consistent diagnostic, intermediate fidelity Navier-Stokes RANS models, and higher fidelity Navier-Stokes LES for urban-scale analysis, and (2) lower-fidelity single

  7. Current usage and future directions for the bovine pericardial patch.

    PubMed

    Li, Xin; Guo, Yuanyuan; Ziegler, Kenneth R; Model, Lynn S; Eghbalieh, Sammy D D; Brenes, Robert A; Kim, Susun T; Shu, Chang; Dardik, Alan

    2011-05-01

    Bovine pericardium (BP) is widely used in surgery and is commonly used as a patch after arteriotomy in cardiovascular surgery. BP patches have several advantages compared with prosthetic patches, including superior biocompatability, easy handling, less suture line bleeding, and possibly reduced rates of infection. These advantages of BP have led to its common use during carotid endarterectomy (CEA). However, long-term clinical results reported after CEA have suggested several issues that may be related to the patch, including restenosis, pseudoaneurysm formation, infection, fibrosis, calcification, and thrombosis. These complications may diminish the long-term efficacy of CEA and suggest potential areas for improvement of surgical patches. Understanding the mechanisms by which BP heals after patch angioplasty may lead to next generation tissue-engineered patches. Published by Elsevier Inc.

  8. PREFACE: International Conference on Topics in Astroparticle and Underground Physics (TAUP 2011)

    NASA Astrophysics Data System (ADS)

    Oberauer, Lothar; Raffelt, Georg; Wagner, Robert

    2012-07-01

    'Tor Vergata' K DanzmannMax Planck Institute for Gravitational Physics S DodelsonFermilab G DomogatskyINR Moscow E FioriniUniversità di Milano Bicocca & INFN K FreeseUniversity of Michigan M FukugitaICRR Tokyo T GaisserUniversity of Delaware G GerbierCEA Saclay F HalzenUniversity of Wisconsin W HaxtonLNBL & UC Berkeley J HoughGlasgow University E KomatsuUniversity of Texas E KatsavounidisMassachusetts Institute of Technology M LindnerMax Planck Institute for Nuclear Physics K LeskoLBNL & UC Berkeley A McDonaldQueens University & SNO Laboratory H MurayamaIPMU Tokyo & UC Berkeley A OlintoUniversity of Chicago L ResvanisUniversity of Athens A RubbiaETH Zurich S SarkarUniversity of Oxford A SmirnovICTP Trieste N SmithSNO Laboratory C SpieringDESY Zeuthen N SpoonerUniversity of Sheffield Y SuzukiICRR Tokyo M TeshimaMax Planck Institute for Physics J W F ValleIFIC & University of Valencia L VotanoLNGS E WaxmanWeizmann Institute J WilkersonUniversity of North Carolina TAUP Steering Committee F T AvignoneUniversity of South Carolina B C BarishCaltech E BellottiUniversity of Milan Bicoccia & INFN J BernabeuUniversity of Valencia A BottinoUniversity of Turin & INFN (chair) N FornengoUniversity of Turin & INFN T KajitaICRR Tokyo C W KimJohns Hopkins University & KIAS V MatveevINR Moscow G RaffeltMax Planck Institute for Physics D SinclairUniversity of Carleton M SpiroCEA Saclay Parallel Session Conveners Dark Matter - Candidates and Searches J-C LanfranchiTechnische Universität München T Marrodán UndagoitiaUniversity of Zurich T BringmannUniversität Hamburg Cosmology J WellerLudwig-Maximilians-Universität München S HannestadUniversity of Aarhus Double Beta Decay, Neutrino Mass M HirschIFIC/CSIC - University of Valencia A GiulianiCNRS Orsay Neutrino Oscillations T LachenmaierUniversität Tübingen F SuekaneTohoku University Low-Energy Neutrinos (Geo, Solar, Supernova) A DigheTIFR Mumbai M ChenQueen's University M WurmUniversität Hamburg Gravitational Waves E Coccia

  9. Duplex ultrasound surveillance after carotid artery endarterectomy.

    PubMed

    Al Shakarchi, Julien; Lowry, Danielle; Nath, Jay; Khawaja, Aurangzaib Z; Inston, Nicholas; Tiwari, Alok

    2016-06-01

    After carotid endarterectomy (CEA), patients have been regularly followed up by duplex ultrasound imaging. However, the evidence for long-term follow-up is not clear, especially if the results from an early duplex scan are normal. This study assessed and systematically reviewed the evidence base for long-term surveillance after CEA and a normal early scan. Electronic databases were searched for studies assessing duplex surveillance after CEA in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome for this study was the incidence of restenosis after a normal early scan. The secondary outcome was the number of reinterventions after a normal early scan. The review included seven studies that reported 2317 procedures. Of those patients with a normal early scan, 2.8% (95% confidence interval, 0.7%-6%) developed a restenosis, and 0.4% (95% confidence interval, 0%-0.9%) underwent a reintervention for their restenosis during the follow-up period. This review confirms that routine postoperative duplex ultrasound surveillance after CEA is not necessary if the early duplex scan is normal. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  10. Endogenous central amygdala mu-opioid receptor signaling promotes sodium appetite in mice.

    PubMed

    Smith, Craig M; Walker, Lesley L; Leeboonngam, Tanawan; McKinley, Michael J; Denton, Derek A; Lawrence, Andrew J

    2016-11-29

    Due to the importance of dietary sodium and its paucity within many inland environments, terrestrial animals have evolved an instinctive sodium appetite that is commensurate with sodium deficiency. Despite a well-established role for central opioid signaling in sodium appetite, the endogenous influence of specific opioid receptor subtypes within distinct brain regions remains to be elucidated. Using selective pharmacological antagonists of opioid receptor subtypes, we reveal that endogenous mu-opioid receptor (MOR) signaling strongly drives sodium appetite in sodium-depleted mice, whereas a role for kappa (KOR) and delta (DOR) opioid receptor signaling was not detected, at least in sodium-depleted mice. Fos immunohistochemistry revealed discrete regions of the mouse brain displaying an increased number of activated neurons during sodium gratification: the rostral portion of the nucleus of the solitary tract (rNTS), the lateral parabrachial nucleus (LPB), and the central amygdala (CeA). The CeA was subsequently targeted with bilateral infusions of the MOR antagonist naloxonazine, which significantly reduced sodium appetite in mice. The CeA is therefore identified as a key node in the circuit that contributes to sodium appetite. Moreover, endogenous opioids, acting via MOR, within the CeA promote this form of appetitive behavior.

  11. [Significance of the TPS cytokeratin marker in the postoperative follow up of colorectal carcinoma patients].

    PubMed

    Rupert, K; Holubec, L; Nosek, J; Houdek, K; Topolcan, O; Treska, V

    2009-08-01

    Examination of tumour markers conducive to follow up of the patients with colorectal carcinoma. The tumour markers were examined in the population of patients with primarily established and histologically verified colorectal adenocarcinoma. The resection therapy resulted in the decrease in post-operative CEA levels. There were no changes in pre- and post-operative CA 19-9 levels; unlike with post-operative TPS levels having been significantly increased, probably due to reparation processes resulting from the surgery. It can be concluded that pre- and post-operative CEA levels are the most suitable markers to check the effect of surgery. With a 95%-specificity for the establishment of recidives, the highest sensitivity was reached with TPS (83%); the sensitivities of the classical tumour markers CEA and CA 19-9 were significantly lower (41% and 25%, respectively). The results should be interpreted with caution due to a small number of relapses regarding a short follow up and rather local-regional character of the recidives. However, TPS seems to be a promising marker for the follow up of the patients with colorectal carcinoma. Thus, an ideal combination seems to be that of CEA and TPS.

  12. Label-free cancer cell separation from human whole blood using inertial microfluidics at low shear stress.

    PubMed

    Lee, Myung Gwon; Shin, Joong Ho; Bae, Chae Yun; Choi, Sungyoung; Park, Je-Kyun

    2013-07-02

    We report a contraction-expansion array (CEA) microchannel device that performs label-free high-throughput separation of cancer cells from whole blood at low Reynolds number (Re). The CEA microfluidic device utilizes hydrodynamic field effect for cancer cell separation, two kinds of inertial effects: (1) inertial lift force and (2) Dean flow, which results in label-free size-based separation with high throughput. To avoid cell damages potentially caused by high shear stress in conventional inertial separation techniques, the CEA microfluidic device isolates the cells with low operational Re, maintaining high-throughput separation, using nondiluted whole blood samples (hematocrit ~45%). We characterized inertial particle migration and investigated the migration of blood cells and various cancer cells (MCF-7, SK-BR-3, and HCC70) in the CEA microchannel. The separation of cancer cells from whole blood was demonstrated with a cancer cell recovery rate of 99.1%, a blood cell rejection ratio of 88.9%, and a throughput of 1.1 × 10(8) cells/min. In addition, the blood cell rejection ratio was further improved to 97.3% by a two-step filtration process with two devices connected in series.

  13. Parameters of blood count and tumor markers in patients with borderline ovarian tumors: a retrospective analysis and relation to staging.

    PubMed

    Nomelini, Rosekeila Simões; da Silva, Taísa Morete; Tavares Murta, Beatriz Martins; Murta, Eddie Fernando Candido

    2012-01-01

    The aim of this paper was to evaluate the parameters of blood count and tumor markers in borderline ovarian tumors. We evaluated 21 patients who had confirmed histopathologic diagnosis of borderline ovarian tumor. We recorded age, parity, tumor type, stage of cancer, serum levels of tumor markers (CA-125, CA-15.3, CA-19.9, CEA, AFP), and the parameters of blood count, fasting glucose, disease-free survival and overall. The patients were divided into two groups, stage IA (n = 13) and stage IB-IIIC (n = 8). The unpaired t-test and Fisher's exact test were used, with P values of less than 0.05 being considered to indicate statistical significance. Levels of red blood cells, hematocrit, and hemoglobin were significantly higher in stage IA when compared with stage IB-IIIC (P < 0.05). The levels of tumor marker CEA had a tendency to be higher in the group stage IB-IIIC (0.08). Abnormal levels of CEA and CA-19.9 were found more frequently in stages IB-IIIC. Therefore, parameters of blood count, CEA, and CA-19.9 should be targeted for further research in identifying prognostic factors in borderline tumors.

  14. Layer-by-layer multienzyme assembly for highly sensitive electrochemical immunoassay based on tyramine signal amplification strategy.

    PubMed

    Zhou, Jun; Tang, Juan; Chen, Guonan; Tang, Dianping

    2014-04-15

    A new sandwich-type electrochemical immunosensor based on nanosilver-doped bovine serum albumin microspheres (Ag@BSA) with a high ratio of horseradish peroxidase (HRP) and detection antibody was developed for quantitative monitoring of biomarkers (carcinoembryonic antigen, CEA, used in this case) by coupling enzymatic biocatalytic precipitation with tyramine signal amplification strategy on capture antibody-modified glassy carbon electrode. Two immunosensing protocols (with and without tyramine signal amplification) were also investigated for the detection of CEA and improved analytical features were acquired with tyramine signal amplification strategy. With the labeling method, the performance and factors influencing the electrochemical immunoassay were studied and evaluated in detail. Under the optimal conditions, the electrochemical immunosensor exhibited a wide dynamic range of 0.005-80 ng mL(-1) toward CEA standards with a low detection limit of 5.0 pg mL(-1). Intra- and inter-assay coefficients of variation were below 11%. No significant differences at the 0.05 significance level were encountered in the analysis of 6 clinical serum specimens and 6 spiked new-born cattle serum samples between the electrochemical immunoassay and the commercialized electrochemiluminescent immunoassay method for the detection of CEA. © 2013 Published by Elsevier B.V.

  15. Graphene oxide-labeled sandwich-type impedimetric immunoassay with sensitive enhancement based on enzymatic 4-chloro-1-naphthol oxidation.

    PubMed

    Hou, Li; Cui, Yuling; Xu, Mingdi; Gao, Zhuangqiang; Huang, Jianxin; Tang, Dianping

    2013-09-15

    A new sandwich-type impedimetric immunosensor based on functionalized graphene oxide nanosheets with a high ratio of horseradish peroxidase (HRP) and detection antibody was developed for the detection of carcinoembryonic antigen (CEA) by coupling with enzymatic biocatalytic precipitation of 4-chloro-1-naphthol (4-CN) on the captured antibody-modified glassy carbon electrode. Two molecular tags (with and without the graphene oxide nanosheets) were investigated for the detection of CEA and improved analytical features were acquired with the graphene-based labeling. With the labeling method, the performance and factors influencing the properties of the impedimetric immunosensors were also studied and evaluated. Under the optimal conditions, the dynamic concentration range of the impedimetric immunosensors spanned from 1.0pgmL(-1) to 80ngmL(-1) CEA with a detection limit (LOD) of 0.64pgmL(-1). Intra- and inter-assay coefficients of variation were less than 7.5% and 11%, respectively. Additionally, the methodology was evaluated for CEA analysis of 10 clinical serum samples and 5 diluted serum samples, receiving in a good accordance with the results obtained by the impedimetric immunoassay and the commercialized electrochemiluminescent method. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Recommendations of the Panel on Cost-effectiveness in Health and Medicine.

    PubMed

    Weinstein, M C; Siegel, J E; Gold, M R; Kamlet, M S; Russell, L B

    1996-10-16

    To develop consensus-based recommendations for the conduct of cost-effectiveness analysis (CEA). This article, the second in a 3-part series, describes the basis for recommendations constituting the reference case analysis, the set of practices developed to guide CEAs that inform societal resource allocation decisions, and the content of these recommendations. The Panel on Cost-Effectiveness in Health and Medicine, a nonfederal panel with expertise in CEA, clinical medicine, ethics, and health outcomes measurement, was convened by the US Public Health Service (PHS). The panel reviewed the theoretical foundations of CEA, current practices, and alternative methods used in analyses. Recommendations were developed on the basis of theory where possible, but tempered by ethical and pragmatic considerations, as well as the needs of users. The panel developed recommendations through 2 1/2 years of discussions. Comments on preliminary drafts prepared by panel working groups were solicited from federal government methodologists, health agency officials, and academic methodologists. The panel's methodological recommendations address (1) components belonging in the numerator and denominator of a cost-effectiveness (C/E) ratio; (2) measuring resource use in the numerator of a C/E ratio; (3) valuing health consequences in the denominator of a C/E ratio; (4) estimating effectiveness of interventions; (5) incorporating time preference and discounting; and (6) handling uncertainty. Recommendations are subject to the ¿rule of reason,¿ balancing the burden engendered by a practice with its importance to a study. If researchers follow a standard set of methods in CEA, the quality and comparability of studies, and their ultimate utility, can be much improved.

  17. Structure and function of the amygdaloid NPY system: NPY Y2 receptors regulate excitatory and inhibitory synaptic transmission in the centromedial amygdala.

    PubMed

    Wood, J; Verma, D; Lach, G; Bonaventure, P; Herzog, H; Sperk, G; Tasan, R O

    2016-09-01

    The amygdala is essential for generating emotional-affective behaviors. It consists of several nuclei with highly selective, elaborate functions. In particular, the central extended amygdala, consisting of the central amygdala (CEA) and the bed nucleus of the stria terminalis (BNST) is an essential component actively controlling efferent connections to downstream effectors like hypothalamus and brain stem. Both, CEA and BNST contain high amounts of different neuropeptides that significantly contribute to synaptic transmission. Among these, neuropeptide Y (NPY) has emerged as an important anxiolytic and fear-reducing neuromodulator. Here, we characterized the expression, connectivity and electrophysiological function of NPY and Y2 receptors within the CEA. We identified several NPY-expressing neuronal populations, including somatostatin- and calretinin-expressing neurons. Furthermore, in the main intercalated nucleus, NPY is expressed primarily in dopamine D1 receptor-expressing neurons but also in interspersed somatostatin-expressing neurons. Interestingly, NPY neurons did not co-localize with the Y2 receptor. Retrograde tract tracing experiments revealed that NPY neurons reciprocally connect the CEA and BNST. Functionally, the Y2 receptor agonist PYY3-36, reduced both, inhibitory as well as excitatory synaptic transmission in the centromedial amygdala (CEm). However, we also provide evidence that lack of NPY or Y2 receptors results in increased GABA release specifically at inhibitory synapses in the CEm. Taken together, our findings suggest that NPY expressed by distinct populations of neurons can modulate afferent and efferent projections of the CEA via presynaptic Y2 receptors located at inhibitory and excitatory synapses.

  18. Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses

    PubMed Central

    Soares, Marta O.; Palmer, Stephen; Ades, Anthony E.; Harrison, David; Shankar-Hari, Manu; Rowan, Kathy M.

    2015-01-01

    Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk. PMID:25712447

  19. Relationships among measurements obtained by use of computed tomography and radiography and scores of cartilage microdamage in hip joints with moderate to severe joint laxity of adult dogs.

    PubMed

    Lopez, Mandi J; Lewis, Brooke P; Swaab, Megan E; Markel, Mark D

    2008-03-01

    To evaluate correlations among measurements on radiographic and computed tomography (CT) images with articular cartilage microdamage in lax hip joints of dogs. 12 adult mixed-breed hounds. Pelvic CT and radiography were performed. Hip joints were harvested following euthanasia. Orthopedic Foundation for Animals (OFA) and PennHIP radiograph reports were obtained. Norberg angle (NA) and radiographic percentage femoral head coverage (RPC) were determined. Center-edge angle (CEA), horizontal toit externe angle (HTEA), ventral acetabular sector angle (VASA), dorsal acetabular sector angle (DASA), horizontal acetabular sector angle (HASA), acetabular index (AI), and CT percentage femoral head coverage (CPC) were measured on 2-dimensional CT images. Femoral head-acetabular shelf percentage was measured on sagittal 3-dimensional CT (SCT) and transverse 3-dimensional CT (TCT) images. Light microscopy was used to score joint cartilage. Relationships of OFA confirmation and PennHIP osteoarthritis scores with radiography, CT, and cartilage variables and relationships of cartilage scores with radiography and CT measurements were evaluated with Spearman rank correlations. Pearson correlation was used for relationships of distraction index (DI) with radiography, CT, and cartilage variables. Significant relationships included PennHIP osteoarthritis score with cartilage score, CEA, HTEA, DASA, AI, CPC, and TCT; OFA confirmation score with cartilage score, NA, RPC, CEA, HTEA, DASA, AI, CPC, and TCT; cartilage score with NA, RPC, CEA, HTEA, DASA, HASA, AI, and TCT; and DI with cartilage score, CEA, HTEA, DASA, HASA, AI, and CPC. CT appeared to be a valuable imaging modality for predicting cartilage microdamage in canine hip joints.

  20. Activation of corticotropin-releasing factor receptors from the basolateral or central amygdala increases the tonic immobility response in guinea pigs: an innate fear behavior.

    PubMed

    Donatti, Alberto Ferreira; Leite-Panissi, Christie Ramos Andrade

    2011-11-20

    The tonic immobility (TI) behavior is an innate response associated with extreme threat situations such as a predator attack. Several studies have provided evidence suggesting an important role for corticotropin-releasing factor (CRF) in the regulation of the endocrine system, defensive behaviors and behavioral responses to stress. TI has been shown to be positively correlated with the basal plasma levels of corticosterone. CRF receptors and neurons that are immunoreactive to CRF are found in many cerebral regions, especially in the amygdaloid complex. Previous reports have demonstrated the involvement of the basolateral amygdaloid (BLA) and central amygdaloid (CeA) nuclei in the TI response. In this study, we evaluated the CRF system of the BLA and the CeA in the modulation of the TI response in guinea pigs. The activation of CRF receptors in the BLA and in the CeA promoted an increase in the TI response. In contrast, the inhibition of these receptors via alpha-helical-CRF(9-41) decreased the duration of the TI response. Moreover, neither the activation nor inhibition of CRF receptors in the BLA or the CeA altered spontaneous motor activity in the open-field test. These data suggest that the activation of the CRF receptors in the BLA or the CeA probably potentiates fear and anxiety, which may be one of the factors that promote an increase in the TI behavior. Therefore, these data support the role of the CRF system in the control of emotional responses, particularly in the modulation of innate fear. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. μ-Opioid Receptors Selectively Regulate Basal Inhibitory Transmission in the Central Amygdala: Lack of Ethanol Interactions

    PubMed Central

    Kang-Park, Maeng-Hee; Kieffer, Brigitte L.; Roberts, Amanda J.; Roberto, Marisa; Madamba, Samuel G.; Siggins, George Robert; Moore, Scott D.

    2009-01-01

    Endogenous opioid systems are implicated in the actions of ethanol. For example, μ-opioid receptor (MOR) knockout (KO) mice self-administer less alcohol than the genetically intact counterpart wild-type (WT) mice (Roberts et al., 2000). MOR KO mice also exhibit less anxiety-like behavior than WT mice (Filliol et al., 2000). To investigate the neurobiological mechanisms underlying these behaviors, we examined the effect of ethanol in brain slices from MOR KO and WT mice using sharp-electrode and whole-cell patch recording techniques. We focused our study in the central nucleus of the amygdala (CeA) because it is implicated in alcohol drinking behavior and stress behavior. We found that the amplitudes of evoked inhibitory postsynaptic currents (IPSCs) or inhibitory postsynaptic potentials (IPSPs) were significantly greater in MOR KO mice than WT mice. In addition, the baseline frequencies of spontaneous and miniature GABAA receptor-mediated inhibitory postsynaptic currents were significantly greater in CeA neurons from MOR KO than WT mice. However, ethanol enhancements of evoked IPSP and IPSC amplitudes and the frequency of miniature IPSCs were comparable between WT and MOR KO mice. Baseline spontaneous and miniature excitatory postsynaptic currents (EPSCs) and ethanol effects on EPSCs were not significantly different between MOR KO and WT mice. Based on knowledge of CeA circuitry and projections, we hypothesize that the role of MOR- and GABA receptor-mediated mechanisms in CeA underlying reinforcing effects of ethanol operate independently, possibly through pathway-specific responses within CeA. PMID:18854491

  2. Retinal ganglion cell complex and peripapillary retinal nerve fiber layer thicknesses following carotid endarterectomy.

    PubMed

    Guclu, Orkut; Guclu, Hande; Huseyin, Serhat; Korkmaz, Selcuk; Yuksel, Volkan; Canbaz, Suat; Pelitli Gurlu, Vuslat

    2018-06-23

    To examine changes in retinal ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (RNFL) thicknesses by optical coherence tomography (OCT) in contralateral and ipsilatateral eyes of carotid artery stenosis (CAS) patients before and after carotid endarterectomy (CEA). Forty-two consecutive patients diagnosed with CAS (70-99% stenosis rate) who underwent CEA were included in this prospective cross-sectional study. The indication for CEA was based on the Asymptomatic Carotid Atherosclerosis Study. Doppler ultrasonography and computed tomography angiography were performed to calculate CAS. All the subjects underwent an ophthalmological examination, including best corrected visual acuity (BCVA), intraocular pressure (IOP) measurements, biomicroscopy, fundoscopy, and OCT before and after the surgery. The mean preoperative intraocular pressure was 15.2 ± 2.1 mmHg in the ipsilateral eye and 15.8 ± 2.7 in the contralateral eye. The mean postoperative intraocular pressure in the ipsilateral and contralateral eye was 18.6 ± 3.0 and 19.3 ± 3.8, respectively. The intraocular pressure was significantly higher in postoperative eyes (p = 0.0001). There was a statistically significant decrease in peripapillary RNFL thickness in superior quadrants postoperatively in ipsilateral eyes. The retinal GCC layer thickness was not significantly different before and after CEA in ipsilateral and contralateral eyes. Carotid endarterectomy results in thinning of the superior peripapillary RNFL thickness. To the best of our knowledge, this is the first study to examine peripapillary RNFL and GCC thicknesses before and after CEA.

  3. Role of TLR4 in the Modulation of Central Amygdala GABA Transmission by CRF Following Restraint Stress.

    PubMed

    Varodayan, F P; Khom, S; Patel, R R; Steinman, M Q; Hedges, D M; Oleata, C S; Homanics, G E; Roberto, M; Bajo, M

    2018-01-04

    Stress induces neuroimmune responses via Toll-like receptor 4 (TLR4) activation. Here, we investigated the role of TLR4 in the effects of the stress peptide corticotropin-releasing factor (CRF) on GABAergic transmission in the central nucleus of the amygdala (CeA) following restraint stress. Tlr4 knock out (KO) and wild-type rats were exposed to no stress (naïve), a single restraint stress (1 h) or repeated restraint stress (1 h per day for 3 consecutive days). After 1 h recovery from the final stress session, whole-cell patch-clamp electrophysiology was used to investigate the effects of CRF (200 nM) on CeA GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). TLR4 does not regulate baseline GABAergic transmission in the CeA of naive and stress-treated animals. However, CRF significantly increased the mean sIPSC frequencies (indicating enhanced GABA release) across all genotypes and stress treatments, except for the Tlr4 KO rats that experienced repeated restraint stress. Overall, our results suggest a limited role for TLR4 in CRF's modulation of CeA GABAergic synapses in naïve and single stress rats, though TLR4-deficient rats that experienced repeated psychological stress exhibit a blunted CRF cellular response. TLR4 has a limited role in CRF's activation of the CeA under basal conditions, but interacts with the CRF system to regulate GABAergic synapse function in animals that experience repeated psychological stress. © The Author(s) 2018. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  4. Air Quality Cumulative Effects Assessment for U.S. Air Force Bases.

    DTIC Science & Technology

    1998-01-29

    forecasted activities. Consideration of multimedia effects and transmedia impacts is important, however, in CEA. Any quantification method developed...substantive areas, such as water quality, ecology, planing, archeology , and landscape architecture? 9. Are there public concerns due to the impact risks of...methods developed for CEA should consider multimedia effects and transmedia impacts. Portions of this research can be used, or modified, to address other

  5. 76 FR 54537 - Swap Data Repositories: Registration Standards, Duties and Core Principles

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-01

    ...The Commodity Futures Trading Commission (``CFTC'' or ``Commission'') is adopting its regulations to implement section 21 of the Commodity Exchange Act (``CEA'' or ``Act''), which establishes registration requirements, statutory duties, core principles and certain compliance obligations for registered swap data repositories (``SDRs''). Section 21 of the CEA was added by section 728 of the Dodd- Frank Wall Street Reform and Consumer Protection Act (``Dodd-Frank Act'').

  6. Changes in Gene Expression within the Extended Amygdala following Binge-Like Alcohol Drinking by Adolescent Alcohol-Preferring (P) Rats

    PubMed Central

    McBride, William J.; Kimpel, Mark W.; McClintick, Jeanette N.; Ding, Zheng-Ming; Edenberg, Howard J.; Liang, Tiebing; Rodd, Zachary A.; Bell, Richard L.

    2014-01-01

    The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by male adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions/day for 5 consecutive days/week for 3 weeks. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 – 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in biological processes involved with cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce changes in neuronal function. PMID:24355552

  7. Risk Factors For Stroke, Myocardial Infarction, or Death Following Carotid Endarterectomy: Results From the International Carotid Stenting Study.

    PubMed

    Doig, D; Turner, E L; Dobson, J; Featherstone, R L; de Borst, G J; Stansby, G; Beard, J D; Engelter, S T; Richards, T; Brown, M M

    2015-12-01

    Carotid endarterectomy (CEA) is standard treatment for symptomatic carotid artery stenosis but carries a risk of stroke, myocardial infarction (MI), or death. This study investigated risk factors for these procedural complications occurring within 30 days of endarterectomy in the International Carotid Stenting Study (ICSS). Patients with recently symptomatic carotid stenosis >50% were randomly allocated to endarterectomy or stenting. Analysis is reported of patients in ICSS assigned to endarterectomy and limited to those in whom CEA was initiated. The occurrence of stroke, MI, or death within 30 days of the procedure was reported by investigators and adjudicated. Demographic and technical risk factors for these complications were analysed sequentially in a binomial regression analysis and subsequently in a multivariable model. Eight-hundred and twenty-one patients were included in the analysis. The risk of stroke, MI, or death within 30 days of CEA was 4.0%. The risk was higher in female patients (risk ratio [RR] 1.98, 95% CI 1.02-3.87, p = .05) and with increasing baseline diastolic blood pressure (dBP) (RR 1.30 per +10 mmHg, 95% CI 1.02-1.66, p = .04). Mean baseline dBP, obtained at the time of randomization in the trial, was 78 mmHg (SD 13 mmHg). In a multivariable model, only dBP remained a significant predictor. The risk was not related to the type of surgical reconstruction, anaesthetic technique, or perioperative medication regimen. Patients undergoing CEA stayed a median of 4 days before discharge, and 21.2% of events occurred on or after the day of discharge. Increasing diastolic blood pressure was the only independent risk factor for stroke, MI, or death following CEA. Cautious attention to blood pressure control following symptoms attributable to carotid stenosis could reduce the risks associated with subsequent CEA. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Prognostic value of carcinoembryonic antigen level in patients with colorectal cancer liver metastasis treated with percutaneous microwave ablation under ultrasound guidance.

    PubMed

    Peng, Shaoyong; Huang, Pinzhu; Yu, Huichuan; Wen, Yanlin; Luo, Yanxin; Wang, Xiaolin; Zhou, Jiaming; Qin, Si; Li, Tuoyang; Chen, Yao; Liu, Guangjian; Huang, Meijin

    2018-03-01

    Thermal ablation is an alternative treatment for colorectal cancer liver metastasis (CRLM). However, prognostic factors in patients with CRLM who have undergone microwave ablation (MWA) have not been clearly defined. Therefore, this study aimed to analyze the risk factors associated with early recurrence in patients with CRLM treated with MWA.Herein, we retrospectively analyzed data for 140 patients with CRLM who underwent MWA from 2013 to 2015 in our institution. Patients were grouped by median pretreatment carcinoembryonic antigen (CEA) level into the high CEA level (>3.7 ng/mL) group and low CEA level (≤3.7 ng/mL) group. Variables that might affect overall survival were subjected to univariable and multivariable Cox regression analysis.Our results showed a median progression-free survival (PFS) and median liver progression-free survival (LPFS) of 9 and 11.5 months, respectively, for the 99 CRLM patients analyzed. Both the median PFS duration (7.5 vs. 12.0 months; hazard ratio [HR]: 1.852; 95% confidence interval [CI]: 1.131-3.034; P = .014) and LPFS duration (7.5 vs 14.0 months; HR: 2.117; 95% CI: 1.247-3.593; P = .005) were significantly shorter in the high CEA level group than in the low level group. In multivariable analysis, high CEA level, >3 tumors, and positive node status for the primary tumor were independent factors for PFS, with corrected HRs of 2.11 (95% CI: 1.257-3.555; P = .005), 2.450 (95% CI: 1.420-4.226; P = .001), and 2.265 (95% CI: 1.304-3.935; P = .004), respectively. However, age, tumor size, regional lymph node were not associated with LPFS.CEA level could be a valuable prognostic factor for early recurrence in patients with CRLM after MWA irrespective of the presence of early local recurrence in the liver or disease progression.

  9. Guidelines for the use of carotid endarterectomy: current recommendations from the Canadian Neurosurgical Society.

    PubMed

    Findlay, J M; Tucker, W S; Ferguson, G G; Holness, R O; Wallace, M C; Wong, J H

    1997-09-15

    To develop guidelines on the suitability of patients for carotid endarterectomy (CEA). For atherosclerotic carotid stenosis that has resulted in retinal or cerebral ischemia: antiplatelet drugs or CEA. For asymptomatic carotid stenosis: CEA or no surgery. Risk of stroke and death. Trials comparing CEA with nonsurgical management of carotid stenosis. Greatest weight was given to findings that were highly significant both statistically and clinically. Benefit: reduction in the risk of stroke. Major harms: iatrogenic stroke, cardiac complications and death secondary to surgical manipulations of the artery or the systemic stress of surgery. Costs were not considered. CEA is clearly recommended for patients with surgically accessible internal carotid artery (ICA) stenoses equal to or greater than 70% of the more distal, normal ICA lumen diameter, providing: (1) the stenosis is symptomatic, causing transient ischemic attacks or nondisabling stroke (including retinal infarction); (2) there is no worse distal, ipsilateral, carotid distribution arterial disease; (3) the patient is in stable medical condition; and (4) the rates of major surgical complications (stroke and death) among patients of the treating surgeon are less than 6%. Surgery is not recommended for asymptomatic stenoses of less than 60%. Symptomatic stenoses of less than 70% and asymptomatic stenoses of greater than 60% are uncertain indications. For these indications, consideration should be given to (1) patient presentation, age and medical condition; (2) plaque characteristics such as degree of narrowing, the presence of ulceration and any documented worsening of the plaque over time; (3) other cerebral arterial stenoses or occlusions, or cerebral infarcts identified through neuroimaging; and (4) surgical complication rates at the institution. CEA should not be considered for asymptomatic stenoses unless the combined stroke and death rate among patients of the surgeon is less than 3%. These guidelines

  10. Hybrid treatment of tandem, common carotid/innominate artery and ipsilateral carotid bifurcation stenoses by simultaneous, retrograde proximal stenting and eversion carotid endarterectomy: Preliminary results of a case series.

    PubMed

    Illuminati, Giulio; Pizzardi, Giulia; Pasqua, Rocco; Frezzotti, Francesca; Palumbo, Piergaspare; Macrina, Francesco; Calio', Francesco

    2018-04-01

    Tandem stenoses of the internal carotid artery (ICA) and proximal, ipsilateral common carotid artery (CCA) or innominate artery can be treated with a hybrid approach, combining conventional carotid endarterectomy (CEA) and retrograde stenting of the proximal stenosis, through surgical exposure of the carotid bifurcation. The purpose of this study was to evaluate the results of combining eversion CEA with retrograde CCA/innominate artery stenting. From January 2015 to July 2017, 7 patients, 6 men of a mean age of 72 years (range 59-83 years) underwent simultaneous, retrograde stenting of the proximal CCA/innominate artery and an eversion CEA of the ipsilateral ICA, through surgical exposure of the carotid bifurcation, for severe tandem stenoses. The proximal stenosis involved the left proximal CCA in 4 patients, the proximal innominate artery in 2 patients and the right CCA in one patient. The procedure was performed under general anesthesia in a conventional operating room equipped with a mobile C-arm. A covered, balloon expandable stent was deployed over the proximal stenosis via a 6-F sheath directly introduced into the proximal CCA through the obliquely transected carotid bulb. After removing the sheath, debris were flushed through the carotid bulb and eversion CEA completed the procedure. Study endpoints were: postoperative stroke/mortality rate, cardiac mortality and morbidity, peripheral nerve injury, cervical hematoma, overall late survival, freedom from ipsilateral stroke and patency of arterial reconstruction. No postoperative mortality or neurologic morbidity was observed in any patient. Cervical hematomas and peripheral nerve injuries were likewise absent. At a mean follow-up of 18 months, all the patients were alive, free from neurologic events of new onset and free from restenosis. Combined proximal stenting and eversion CEA for tandem lesions seems a valid treatment, with the advantages of eversion CEA over other techniques of carotid bifurcation

  11. Value of 18F-FDG PET/CT Combined With Tumor Markers in the Evaluation of Ascites.

    PubMed

    Han, Na; Sun, Xun; Qin, Chunxia; Hassan Bakari, Khamis; Wu, Zhijian; Zhang, Yongxue; Lan, Xiaoli

    2018-05-01

    The purpose of this study is to investigate the value of 18 F-FDG PET/CT combined with assessment of tumor markers in serum or ascites for the diagnosing and determining the prognosis of benign and malignant ascites. Patients with ascites of unknown cause who underwent evaluation with FDG PET/CT were included in this retrospective study. The maximum standardized uptake value (SUV max ) and levels of the tumor markers carbohydrate antigen-125 (CA-125) and carcinoembryonic antigen (CEA) in serum and ascites were recorded. The diagnostic values of FDG PET/CT, CEA and CA-125 levels in serum or ascites, and the combination of imaging plus tumor marker assessment were evaluated. Factors that were predictive of survival were also analyzed. A total of 177 patients were included. Malignant ascites was eventually diagnosed in 104 patients, and benign ascites was diagnosed in the remaining 73 patients. With the use of FDG PET/CT, 44 patients (42.3%) were found to have primary tumors. The sensitivity, specificity, and accuracy of FDG PET/CT were 92.3%, 83.6%, and 88.7%, respectively. CA-125 levels in serum and ascites showed much better sensitivity than did CEA levels, but they showed significantly lower specificity. If the combination of tumor markers and FDG PET/CT was analyzed, the sensitivity, specificity, and accuracy of tumor markers in serum were 96.6%, 78.1%, and 88.7%, and those of tumor markers in ascites were 97.7%, 80.0%, and 90.4%, respectively. Sex may be an important factor affecting survival time (hazard ratio, 0.471; p = 0.004), but age, CEA level, and FDG PET/CT findings could not predict survival. FDG PET/CT combined with assessment of tumor markers, especially CEA, increased the efficacy of diagnosis of ascites of unknown causes. Male sex conferred a poorer prognosis, whereas age, CEA level, and FDG uptake had no predictive significance in patients with malignant ascites.

  12. Prognostic value of carcinoembryonic antigen level in patients with colorectal cancer liver metastasis treated with percutaneous microwave ablation under ultrasound guidance

    PubMed Central

    Peng, Shaoyong; Huang, Pinzhu; Yu, Huichuan; Wen, Yanlin; Luo, Yanxin; Wang, Xiaolin; Zhou, Jiaming; Qin, Si; Li, Tuoyang; Chen, Yao; Liu, Guangjian; Huang, Meijin

    2018-01-01

    Abstract Thermal ablation is an alternative treatment for colorectal cancer liver metastasis (CRLM). However, prognostic factors in patients with CRLM who have undergone microwave ablation (MWA) have not been clearly defined. Therefore, this study aimed to analyze the risk factors associated with early recurrence in patients with CRLM treated with MWA. Herein, we retrospectively analyzed data for 140 patients with CRLM who underwent MWA from 2013 to 2015 in our institution. Patients were grouped by median pretreatment carcinoembryonic antigen (CEA) level into the high CEA level (>3.7 ng/mL) group and low CEA level (≤3.7 ng/mL) group. Variables that might affect overall survival were subjected to univariable and multivariable Cox regression analysis. Our results showed a median progression-free survival (PFS) and median liver progression-free survival (LPFS) of 9 and 11.5 months, respectively, for the 99 CRLM patients analyzed. Both the median PFS duration (7.5 vs. 12.0 months; hazard ratio [HR]: 1.852; 95% confidence interval [CI]: 1.131–3.034; P = .014) and LPFS duration (7.5 vs 14.0 months; HR: 2.117; 95% CI: 1.247–3.593; P = .005) were significantly shorter in the high CEA level group than in the low level group. In multivariable analysis, high CEA level, >3 tumors, and positive node status for the primary tumor were independent factors for PFS, with corrected HRs of 2.11 (95% CI: 1.257–3.555; P = .005), 2.450 (95% CI: 1.420–4.226; P = .001), and 2.265 (95% CI: 1.304–3.935; P = .004), respectively. However, age, tumor size, regional lymph node were not associated with LPFS. CEA level could be a valuable prognostic factor for early recurrence in patients with CRLM after MWA irrespective of the presence of early local recurrence in the liver or disease progression. PMID:29517661

  13. Protamine reduces bleeding complications associated with carotid endarterectomy without increasing the risk of stroke.

    PubMed

    Stone, David H; Nolan, Brian W; Schanzer, Andres; Goodney, Philip P; Cambria, Robert A; Likosky, Donald S; Walsh, Daniel B; Cronenwett, Jack L

    2010-03-01

    Controversy persists regarding the use of protamine during carotid endarterectomy (CEA) based on prior conflicting reports documenting both reduced bleeding as well as increased stroke risk. The purpose of this study was to determine the effect of protamine reversal of heparin anticoagulation on the outcome of CEA in a contemporary multistate registry. We reviewed a prospective regional registry of 4587 CEAs in 4311 patients performed by 66 surgeons from 11 centers in Northern New England from 2003-2008. Protamine use varied by surgeon (38% routine use, 44% rare use, 18% selective use). Endpoints were postoperative bleeding requiring reoperation as well as potential thrombotic complications, including stroke, death, and myocardial infarction (MI). Predictors of endpoints were determined by multivariate logistic regression after associated variables were identified by univariate analysis. Of the 4587 CEAs performed, 46% utilized protamine, while 54% did not. Fourteen patients (0.64%) in the protamine-treated group required reoperation for bleeding compared with 42 patients (1.66%) in the untreated cohort (P = .001). Protamine use did not affect the rate of MI (1.1% vs 0.91%, P = .51), stroke (0.78% vs 1.15%, P = .2), or death (0.23% vs 0.32%, P = .57) between treated and untreated patients, respectively. By multivariate analysis, protamine (odds ratio [OR] 0.32, 95% confidence interval [CI], 0.17-0.63; P = .001) and patch angioplasty (OR 0.46, 95% CI, 0.26-0.81; P = .007) were independently associated with diminished reoperation for bleeding. A single center was associated with a significantly higher rate of reoperation for bleeding (OR 6.47, 95% CI, 3.02-13.9; P < .001). Independent of protamine use, consequences of reoperation for bleeding were significant, with a four-fold increase in MI, a seven-fold increase in stroke, and a 30-fold increase in death. Protamine reduced serious bleeding requiring reoperation during CEA without increasing the risk of MI, stroke

  14. SPACE-2: A Missed Opportunity to Compare Carotid Endarterectomy, Carotid Stenting, and Best Medical Treatment in Patients with Asymptomatic Carotid Stenoses.

    PubMed

    Eckstein, H-H; Reiff, T; Ringleb, P; Jansen, O; Mansmann, U; Hacke, W

    2016-06-01

    Because of recent advances in best medical treatment (BMT), it is currently unclear whether any additional surgical or endovascular interventions confer additional benefit, in terms of preventing late ipsilateral carotid territory ischemic stroke in asymptomatic patients with significant carotid stenoses. The aim was to compare the stroke-preventive effects of BMT alone, with that of BMT in combination with carotid endarterectomy (CEA) or carotid artery stenting (CAS) in patients with high grade asymptomatic extracranial carotid artery stenosis. SPACE-2 was planned as a three-armed, randomized controlled trial (BMT alone vs. CEA plus BMT vs. CAS plus BMT, ISRCTN 78592017). However, because of slow patient recruitment, the three-arm study design was amended (July 2013) to become two parallel randomized studies (BMT alone vs. CEA plus BMT, and BMT alone vs. CAS plus BMT). The change in study design did not lead to any significant increase in patient recruitment, and trial recruitment ceased after recruiting 513 patients over a 5 year period (CEA vs. BMT (n = 203); CAS vs. BMT (n = 197), and BMT alone (n = 113)). The 30 day rate of death/stroke was 1.97% for patients undergoing CEA, and 2.54% for patients undergoing CAS. No strokes or deaths occurred in the first 30 days after randomization in patients randomized to BMT. There were several potential reasons for the low recruitment rates into SPACE-2, including the ability for referring doctors to refer their patients directly for CEA or CAS outwith the trial, an inability to convince patients (who had come "mentally prepared" that an intervention was necessary) to accept BMT, and other economic constraints. Because of slow recruitment rates, SPACE-2 had to be stopped after randomizing only 513 patients. The German Research Foundation will provide continued funding to enable follow up of all recruited patients, and it is also planned to include these data in any future meta-analysis prepared by the Carotid

  15. Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections.

    PubMed

    Alhadeff, Amber L; Holland, Ruby A; Nelson, Alexandra; Grill, Harvey J; De Jonghe, Bart C

    2015-08-05

    Cisplatin chemotherapy is used commonly to treat a variety of cancers despite severe side effects such as nausea, vomiting, and anorexia that compromise quality of life and limit treatment adherence. The neural mechanisms mediating these side effects remain elusive despite decades of clinical use. Recent data highlight the dorsal vagal complex (DVC), lateral parabrachial nucleus (lPBN), and central nucleus of the amygdala (CeA) as potential sites of action in mediating the side effects of cisplatin. Here, results from immunohistochemical studies in rats identified a population of cisplatin-activated DVC neurons that project to the lPBN and a population of cisplatin-activated lPBN calcitonin gene-related peptide (CGRP, a marker for glutamatergic neurons in the lPBN) neurons that project to the CeA, outlining a neuroanatomical circuit that is activated by cisplatin. CeA gene expressions of AMPA and NMDA glutamate receptor subunits were markedly increased after cisplatin treatment, suggesting that CeA glutamate receptor signaling plays a role in mediating cisplatin side effects. Consistent with gene expression results, behavioral/pharmacological data showed that CeA AMPA/kainate receptor blockade attenuates cisplatin-induced pica (a proxy for nausea/behavioral malaise in nonvomiting laboratory rodents) and that CeA NMDA receptor blockade attenuates cisplatin-induced anorexia and body weight loss in addition to pica, demonstrating that glutamate receptor signaling in the CeA is critical for the energy balance dysregulation caused by cisplatin treatment. Together, these data highlight a novel circuit and CGRP/glutamatergic mechanism through which cisplatin-induced malaise and energy balance dysregulation are mediated. To treat cancer effectively, patients must follow prescribed chemotherapy treatments without interruption, yet most cancer treatments produce side effects that devastate quality of life (e.g., nausea, vomiting, anorexia, weight loss). Although hundreds of

  16. Long-term comparative effectiveness of carotid stenting versus carotid endarterectomy in a large tertiary care vascular surgery practice.

    PubMed

    Garvin, Robert P; Ryer, Evan J; Berger, Andrea L; Elmore, James R

    2018-03-31

    Carotid interventional trials have strict inclusion and exclusion criteria that make translation of their results to the real-world population challenging. Furthermore, the specialty of the operating surgeon and the role of clinical decision-making are not well studied. This study compares the effectiveness of carotid endarterectomy (CEA) vs carotid artery stenting (CAS) in a real-world setting when the procedure is performed by fellowship-trained vascular surgeons. A retrospective study was conducted of all consecutive patients undergoing CEA and CAS performed by vascular surgeons in a large rural tertiary health care system from 2004 to 2014. Postoperative outcomes of stroke, acute myocardial infarction (AMI), and death were analyzed at 30 days and during the long term (median follow-up of 5.5 years for CEA and 4.8 years for CAS). Standard statistical analysis was performed. Differences in long-term outcomes were expressed as cumulative incidence functions for nondeath outcomes (stroke and AMI), which account for the high death rate in this population of vascular patients, and as Kaplan-Meier curves for death itself. From January 1, 2004, through December 31, 2014, there were 2331 carotid interventions performed (CEA, 1853; CAS, 478), all by fellowship-trained vascular surgeons. The average age of the patients was 71 years, and 63% were male, with more men in the CAS group (61.5% vs 67.8%; P = .011). Preoperatively, 30% of patients were symptomatic, and 77% of patients had high-grade stenosis in the 70% to 99% range. CEA patients were more likely to have preoperative hypertension (89.7% vs 86.2%; P = .029) and were less likely to have a history of cardiovascular disease (53.4% vs 59.4%; P = .018). There were no significant differences in 30-day outcomes between CEA and CAS (stroke, 1.1% vs 1.3% [P = .743]; AMI, 2.2% vs 1.7% [P = .474]; death, 0.7% vs 0.6% [P = .859]) or long-term outcomes (stroke, 6.8% vs 7.7% [P = .321]; AMI, 22.7% vs 21.0% [P = .886

  17. GABAergic Neurons of the Central Amygdala Promote Cataplexy

    PubMed Central

    Agostinelli, Lindsay J.; Lowell, Bradford B.

    2017-01-01

    Narcolepsy is characterized by chronic sleepiness and cataplexy—sudden muscle paralysis triggered by strong, positive emotions. This condition is caused by a lack of orexin (hypocretin) signaling, but little is known about the neural mechanisms that mediate cataplexy. The amygdala regulates responses to rewarding stimuli and contains neurons active during cataplexy. In addition, lesions of the amygdala reduce cataplexy. Because GABAergic neurons of the central nucleus of the amygdala (CeA) target brainstem regions known to regulate muscle tone, we hypothesized that these cells promote emotion-triggered cataplexy. We injected adeno-associated viral vectors coding for Cre-dependent DREADDs or a control vector into the CeA of orexin knock-out mice crossed with vGAT-Cre mice, resulting in selective expression of the excitatory hM3 receptor or the inhibitory hM4 receptor in GABAergic neurons of the CeA. We measured sleep/wake behavior and cataplexy after injection of saline or the hM3/hM4 ligand clozapine-N-oxide (CNO) under baseline conditions and under conditions that should elicit positive emotions. In mice expressing hM3, CNO approximately doubled the amount of cataplexy in the first 3 h after dosing under baseline conditions. Rewarding stimuli (chocolate or running wheels) also increased cataplexy, but CNO produced no further increase. In mice expressing hM4, CNO reduced cataplexy in the presence of chocolate or running wheels. These results demonstrate that GABAergic neurons of the CeA are sufficient and necessary for the production of cataplexy in mice, and they likely are a key part of the mechanism through which positive emotions trigger cataplexy. SIGNIFICANCE STATEMENT Cataplexy is one of the major symptoms of narcolepsy, but little is known about how strong, positive emotions trigger these episodes of muscle paralysis. Prior research shows that amygdala neurons are active during cataplexy and cataplexy is reduced by lesions of the amygdala. We found that

  18. Impact of repeated asenapine treatment on FosB/ΔFosB expression in neurons of the rat central nucleus of the amygdala: colocalization with corticoliberine (CRH) and effect of an unpredictable mild stress preconditioning.

    PubMed

    Majercikova, Z; Kiss, A

    2015-04-01

    FosB/ΔFosB expression in the central amygdalar nucleus (CeA) in response to repeated asenapine (ASE) treatment (an atypical antipsychotic used for the treatment of schizophrenia) was studied in normal rats and rats preconditioned with chronic unpredictable variable mild stress (CMS). The goal of this study was to reveal whether repeated ASE treatment for 14 days may: 1) induce FosB/ΔFosB expression in the amygdala, 2) activate CRH-synthesizing neurons in the CeA, and 3) interfere with 21 days lasting concomitant CMS preconditioning. Four groups of animals were studied: controls and ASE-, CMS-, and CMS+ASE-treated ones. CMS consisted of the restrain, social isolation, crowding, swimming, and cold and lasted 21 days. The ASE and CMS+ASE groups were from the 7th day of the experiment treated with ASE (0.3 mg/kg, subcutaneously - s.c.) twice a day, i.e. together for 14 days. Controls and CMS groups were treated with saline (300 µl/rat, s.c.) twice a day for 14 days. All the animals were sacrificed on the 22nd day, i.e. 16-18 hours after the last treatments. Single FosB/ΔFosB, FosB/ΔFosB colocalizations with CRH, and CRH immunolabeled perikarya were investigated in the CeA using a combined light and fluorescent immunohistochemistry. The distribution aspect of the black FosB/ΔFosB profiles was homogeneous over the whole CeA and no significant differences in the number of FosB/ΔFosB profiles between the individual groups of the rats really occurred. The level of colocalization pattern of FosB/ΔFosB in CRH perikarya was also very similar between the individual groups and in each case it reached approximately 10% of double-labeling. No differences were also seen in the number of CRH immunolabeled perikarya. The density of CRH nerve projections within the CeA was very alike in the individual groups of animals investigated. The study provides a new anatomical/functional finding about the lack of the stimulatory effect of the repeated ASE treatment on the expression of

  19. Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections

    PubMed Central

    Alhadeff, Amber L.; Holland, Ruby A.; Nelson, Alexandra; Grill, Harvey J.

    2015-01-01

    Cisplatin chemotherapy is used commonly to treat a variety of cancers despite severe side effects such as nausea, vomiting, and anorexia that compromise quality of life and limit treatment adherence. The neural mechanisms mediating these side effects remain elusive despite decades of clinical use. Recent data highlight the dorsal vagal complex (DVC), lateral parabrachial nucleus (lPBN), and central nucleus of the amygdala (CeA) as potential sites of action in mediating the side effects of cisplatin. Here, results from immunohistochemical studies in rats identified a population of cisplatin-activated DVC neurons that project to the lPBN and a population of cisplatin-activated lPBN calcitonin gene-related peptide (CGRP, a marker for glutamatergic neurons in the lPBN) neurons that project to the CeA, outlining a neuroanatomical circuit that is activated by cisplatin. CeA gene expressions of AMPA and NMDA glutamate receptor subunits were markedly increased after cisplatin treatment, suggesting that CeA glutamate receptor signaling plays a role in mediating cisplatin side effects. Consistent with gene expression results, behavioral/pharmacological data showed that CeA AMPA/kainate receptor blockade attenuates cisplatin-induced pica (a proxy for nausea/behavioral malaise in nonvomiting laboratory rodents) and that CeA NMDA receptor blockade attenuates cisplatin-induced anorexia and body weight loss in addition to pica, demonstrating that glutamate receptor signaling in the CeA is critical for the energy balance dysregulation caused by cisplatin treatment. Together, these data highlight a novel circuit and CGRP/glutamatergic mechanism through which cisplatin-induced malaise and energy balance dysregulation are mediated. SIGNIFICANCE STATEMENT To treat cancer effectively, patients must follow prescribed chemotherapy treatments without interruption, yet most cancer treatments produce side effects that devastate quality of life (e.g., nausea, vomiting, anorexia, weight loss

  20. Cost-effectiveness analysis: adding value to assessment of animal health welfare and production.

    PubMed

    Babo Martins, S; Rushton, J

    2014-12-01

    Cost-effectiveness analysis (CEA) has been extensively used in economic assessments in fields related to animal health, namely in human health where it provides a decision-making framework for choices about the allocation of healthcare resources. Conversely, in animal health, cost-benefit analysis has been the preferred tool for economic analysis. In this paper, the use of CEA in related areas and the role of this technique in assessments of animal health, welfare and production are reviewed. Cost-effectiveness analysis can add further value to these assessments, particularly in programmes targeting animal welfare or animal diseases with an impact on human health, where outcomes are best valued in natural effects rather than in monetary units. Importantly, CEA can be performed during programme implementation stages to assess alternative courses of action in real time.