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 studies. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Indicators of inappropriate tumour marker use through the mining of electronic health records.

PubMed

Gion, Massimo; Cardinali, Giulia; Trevisiol, Chiara; Zappa, Marco; Rainato, Giulia; Fabricio, Aline S C

2017-08-01

Although the issue of monitoring appropriateness of tumour markers (TMs) request in outpatients remains crucial, proper indicators are still demanding. The present study developed and explored indicators of inappropriate TM ordering in outpatients through the data mining of electronic health records (EHRs). Carcinoembryonic antigen (CEA), alfa-fetoprotein (AFP), carbohydrate antigen (CA)125, CA15.3, CA19.9, and prostate-specific antigen (PSA) ordered in outpatients during a year were examined by mining EHRs of a Local Health Authority in Italy. Evidence-based criteria were used to develop performance indicators. Demographic and clinical information associated with TM orders were examined. A total of 80 813 TMs were ordered in 52 536 outpatients (1.54 markers/patient). Indicators related to disease codes, gender, age, and TM repetitions were developed, and their application showed that (1) CA15.3 and CEA are prevalently requested in patients with cancer (79.2% and 65.6%) whereas the other TMs are largely requested also in patients without cancer; (2) requests of PSA in women and of CA125 or CA15.3 in men are negligible; (3) although requests in people older than 80 years are relevant (16.4% of total), the highest rate of request of all markers occurs in patients aged 40 to 79 years; (4) CA15.3 and CEA are mainly requested in cancer cases between 50 and 79 years and AFP, CA19.9, and CA125 in those between 60 and 69 years; (5) <50% of PSA orders are associated with cancer code for all age intervals; and (6) multiple repetitions of AFP, CA125, CA15.3, CA19.9, and CEA are prevalent in cancer patients or benign diseases to which TMs are appropriate, whereas PSA repetitions occur mainly in patients without cancer. The developed indicators resulted suitable to monitor TM overordering in outpatients through the mining of EHRs. The present study is a first approach towards the use of big-data mining for TM appropriateness evaluation purposes. © 2017 John Wiley & Sons, Ltd.

LSENS, The NASA Lewis Kinetics and Sensitivity Analysis Code

NASA Technical Reports Server (NTRS)

Radhakrishnan, K.

2000-01-01

A general chemical kinetics and sensitivity analysis code for complex, homogeneous, gas-phase reactions is described. The main features of the code, LSENS (the NASA Lewis kinetics and sensitivity analysis code), are its flexibility, efficiency and convenience in treating many different chemical reaction models. The models include: static system; steady, one-dimensional, inviscid flow; incident-shock initiated reaction in a shock tube; and a perfectly stirred reactor. In addition, equilibrium computations can be performed for several assigned states. An implicit numerical integration method (LSODE, the Livermore Solver for Ordinary Differential Equations), which works efficiently for the extremes of very fast and very slow reactions, is used to solve the "stiff" ordinary differential equation systems that arise in chemical kinetics. For static reactions, the code uses the decoupled direct method to calculate sensitivity coefficients of the dependent variables and their temporal derivatives with respect to the initial values of dependent variables and/or the rate coefficient parameters. Solution methods for the equilibrium and post-shock conditions and for perfectly stirred reactor problems are either adapted from or based on the procedures built into the NASA code CEA (Chemical Equilibrium and Applications).

CESAR: A Code for Nuclear Fuel and Waste Characterisation

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

Vidal, J.M.; Grouiller, J.P.; Launay, A.

2006-07-01

CESAR (Simplified Evolution Code Applied to Reprocessing) is a depletion code developed through a joint program between CEA and COGEMA. In the late 1980's, the first use of this code dealt with nuclear measurement at the Laboratories of the La Hague reprocessing plant. The use of CESAR was then extended to characterizations of all entrance materials and for characterisation, via tracer, of all produced waste. The code can distinguish more than 100 heavy nuclides, 200 fission products and 100 activation products, and it can characterise both the fuel and the structural material of the fuel. CESAR can also make depletionmore » calculations from 3 months to 1 million years of cooling time. Between 2003-2005, the 5. version of the code was developed. The modifications were related to the harmonisation of the code's nuclear data with the JEF2.2 nuclear data file. This paper describes the code and explains the extensive use of this code at the La Hague reprocessing plant and also for prospective studies. The second part focuses on the modifications of the latest version, and describes the application field and the qualification of the code. Many companies and the IAEA use CESAR today. CESAR offers a Graphical User Interface, which is very user-friendly. (authors)« less

Methodology, status and plans for development and assessment of Cathare code

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

Bestion, D.; Barre, F.; Faydide, B.

1997-07-01

This paper presents the methodology, status and plans for the development, assessment and uncertainty evaluation of the Cathare code. Cathare is a thermalhydraulic code developed by CEA (DRN), IPSN, EDF and FRAMATOME for PWR safety analysis. First, the status of the code development and assessment is presented. The general strategy used for the development and the assessment of the code is presented. Analytical experiments with separate effect tests, and component tests are used for the development and the validation of closure laws. Successive Revisions of constitutive laws are implemented in successive Versions of the code and assessed. System tests ormore » integral tests are used to validate the general consistency of the Revision. Each delivery of a code Version + Revision is fully assessed and documented. A methodology is being developed to determine the uncertainty on all constitutive laws of the code using calculations of many analytical tests and applying the Discrete Adjoint Sensitivity Method (DASM). At last, the plans for the future developments of the code are presented. They concern the optimization of the code performance through parallel computing - the code will be used for real time full scope plant simulators - the coupling with many other codes (neutronic codes, severe accident codes), the application of the code for containment thermalhydraulics. Also, physical improvements are required in the field of low pressure transients and in the modeling for the 3-D model.« less

Analysis of Phenix end-of-life natural convection test with the MARS-LMR code

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

Jeong, H. Y.; Ha, K. S.; Lee, K. L.

The end-of-life test of Phenix reactor performed by the CEA provided an opportunity to have reliable and valuable test data for the validation and verification of a SFR system analysis code. KAERI joined this international program for the analysis of Phenix end-of-life natural circulation test coordinated by the IAEA from 2008. The main objectives of this study were to evaluate the capability of existing SFR system analysis code MARS-LMR and to identify any limitation of the code. The analysis was performed in three stages: pre-test analysis, blind posttest analysis, and final post-test analysis. In the pre-test analysis, the design conditionsmore » provided by the CEA were used to obtain a prediction of the test. The blind post-test analysis was based on the test conditions measured during the tests but the test results were not provided from the CEA. The final post-test analysis was performed to predict the test results as accurate as possible by improving the previous modeling of the test. Based on the pre-test analysis and blind test analysis, the modeling for heat structures in the hot pool and cold pool, steel structures in the core, heat loss from roof and vessel, and the flow path at core outlet were reinforced in the final analysis. The results of the final post-test analysis could be characterized into three different phases. In the early phase, the MARS-LMR simulated the heat-up process correctly due to the enhanced heat structure modeling. In the mid phase before the opening of SG casing, the code reproduced the decrease of core outlet temperature successfully. Finally, in the later phase the increase of heat removal by the opening of the SG opening was well predicted with the MARS-LMR code. (authors)« less

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.

Modeling of laser induced air plasma and shock wave dynamics using 2D-hydrodynamic simulations

NASA Astrophysics Data System (ADS)

Paturi, Prem Kiran; S, Sai Shiva; Chelikani, Leela; Ikkurthi, Venkata Ramana; C. D., Sijoy; Chaturvedi, Shashank; Acrhem, University Of Hyderabad Team; Computational Analysis Division, Bhabha Atomic Research Centre, Visakhapatnam Team

2017-06-01

The laser induced air plasma dynamics and the SW evolution modeled using the two dimensional hydrodynamic code by considering two different EOS: ideal gas EOS with charge state effects taken into consideration and Chemical Equilibrium applications (CEA) EOS considering the chemical kinetics of different species will be presented. The inverse bremsstrahlung absorption process due to electron-ion and electron-neutrals is considered for the laser-air interaction process for both the models. The numerical results obtained with the two models were compared with that of the experimental observations over the time scales of 200 - 4000 ns at an input laser intensity of 2.3 ×1010 W/cm2. The comparison shows that the plasma and shock dynamics differ significantly for two EOS considered. With the ideas gas EOS the asymmetric expansion and the subsequent plasma dynamics have been well reproduced as observed in the experiments, whereas with the CEA model these processes were not reproduced due to the laser energy absorption occurring mostly at the focal volume. ACRHEM team thank DRDO, India for funding.

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

Reduced Equations for Calculating the Combustion Rates of Jet-A and Methane Fuel

NASA Technical Reports Server (NTRS)

Molnar, Melissa; Marek, C. John

2003-01-01

Simplified kinetic schemes for Jet-A and methane fuels were developed to be used in numerical combustion codes, such as the National Combustor Code (NCC) that is being developed at Glenn. These kinetic schemes presented here result in a correlation that gives the chemical kinetic time as a function of initial overall cell fuel/air ratio, pressure, and temperature. The correlations would then be used with the turbulent mixing times to determine the limiting properties and progress of the reaction. A similar correlation was also developed using data from NASA's Chemical Equilibrium Applications (CEA) code to determine the equilibrium concentration of carbon monoxide as a function of fuel air ratio, pressure, and temperature. The NASA Glenn GLSENS kinetics code calculates the reaction rates and rate constants for each species in a kinetic scheme for finite kinetic rates. These reaction rates and the values obtained from the equilibrium correlations were then used to calculate the necessary chemical kinetic times. Chemical kinetic time equations for fuel, carbon monoxide, and NOx were obtained for both Jet-A fuel and methane.

Design and Testing of a Liquid Nitrous Oxide and Ethanol Fueled Rocket Engine

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

Youngblood, Stewart

A small-scale, bi-propellant, liquid fueled rocket engine and supporting test infrastructure were designed and constructed at the Energetic Materials Research and Testing Center (EMRTC). This facility was used to evaluate liquid nitrous oxide and ethanol as potential rocket propellants. Thrust and pressure measurements along with high-speed digital imaging of the rocket exhaust plume were made. This experimental data was used for validation of a computational model developed of the rocket engine tested. The developed computational model was utilized to analyze rocket engine performance across a range of operating pressures, fuel-oxidizer mixture ratios, and outlet nozzle configurations. A comparative study ofmore » the modeling of a liquid rocket engine was performed using NASA CEA and Cantera, an opensource equilibrium code capable of being interfaced with MATLAB. One goal of this modeling was to demonstrate the ability of Cantera to accurately model the basic chemical equilibrium, thermodynamics, and transport properties for varied fuel and oxidizer operating conditions. Once validated for basic equilibrium, an expanded MATLAB code, referencing Cantera, was advanced beyond CEAs capabilities to predict rocket engine performance as a function of supplied propellant flow rate and rocket engine nozzle dimensions. Cantera was found to comparable favorably to CEA for making equilibrium calculations, supporting its use as an alternative to CEA. The developed rocket engine performs as predicted, demonstrating the developedMATLAB rocket engine model was successful in predicting real world rocket engine performance. Finally, nitrous oxide and ethanol were shown to perform well as rocket propellants, with specific impulses experimentally recorded in the range of 250 to 260 seconds.« less

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.

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

Thermal Analysis on Plume Heating of the Main Engine on the Crew Exploration Vehicle Service Module

NASA Technical Reports Server (NTRS)

Wang, Xiao-Yen J.; Yuko, James R.

2007-01-01

The crew exploration vehicle (CEV) service module (SM) main engine plume heating is analyzed using multiple numerical tools. The chemical equilibrium compositions and applications (CEA) code is used to compute the flow field inside the engine nozzle. The plume expansion into ambient atmosphere is simulated using an axisymmetric space-time conservation element and solution element (CE/SE) Euler code, a computational fluid dynamics (CFD) software. The thermal analysis including both convection and radiation heat transfers from the hot gas inside the engine nozzle and gas radiation from the plume is performed using Thermal Desktop. Three SM configurations, Lockheed Martin (LM) designed 604, 605, and 606 configurations, are considered. Design of multilayer insulation (MLI) for the stowed solar arrays, which is subject to plume heating from the main engine, among the passive thermal control system (PTCS), are proposed and validated.

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.

Meshless modelling of dynamic behaviour of glasses under intense shock loadings: Application to matter ejection during high velocity impacts on thin brittle targets

NASA Astrophysics Data System (ADS)

Michel, Y.; Chevalier, J.-M.; Durin, C.; Espinosa, C.; Malaise, F.; Barrau, J.-J.

2006-08-01

The purpose of this study is to present a new material model adapted to SPH modelling of dynamic behaviour of glasses under shock loadings. This model has the ability to reproduce fragmentation and densification of glasses under compression as well as brittle tensile failure. It has been implemented in Ls-Dyna software and coupled with a SPH code. By comparison with CEA-CESTA experimental data the model has been validated for fused silica and Pyrex glass for stress level up to 35GPa. For Laser MegaJoule applications, the present material model was applied to 3D high velocity impacts on thin brittle targets with good agreement with experimental data obtained using CESTA's double stage light gas gun in term of damages and matter ejection.

A physician-led initiative to improve clinical documentation results in improved health care documentation, case mix index, and increased contribution margin.

PubMed

Aiello, Francesco A; Judelson, Dejah R; Durgin, Jonathan M; Doucet, Danielle R; Simons, Jessica P; Durocher, Dawn M; Flahive, Julie M; Schanzer, Andres

2018-05-04

Clinical documentation is the key determinant of inpatient acuity of illness and payer reimbursement. Every inpatient hospitalization is placed into a diagnosis related group with a relative value based on documented procedures, conditions, comorbidities and complications. The Case Mix Index (CMI) is an average of these diagnosis related groups and directly impacts physician profiling, medical center profiling, reimbursement, and quality reporting. We hypothesize that a focused, physician-led initiative to improve clinical documentation of vascular surgery inpatients results in increased CMI and contribution margin. A physician-led coding initiative to educate physicians on the documentation of comorbidities and conditions was initiated with concurrent chart review sessions with coding specialists for 3 months, and then as needed, after the creation of a vascular surgery documentation guide. Clinical documentation and billing for all carotid endarterectomy (CEA) and open infrainguinal procedures (OIPs) performed between January 2013 and July 2016 were stratified into precoding and postcoding initiative groups. Age, duration of stay, direct costs, actual reimbursements, contribution margin (CM), CMI, rate of complication or comorbidity, major complication or comorbidity, severity of illness, and risk of mortality assigned to each discharge were abstracted. Data were compared over time by standardizing Centers for Medicare and Medicaid Services (CMS) values for each diagnosis related group and using a CMS base rate reimbursement. Among 458 CEA admissions, postcoding initiative CEA patients (n = 253) had a significantly higher CMI (1.36 vs 1.25; P = .03), CM ($7859 vs $6650; P = .048), and CMS base rate reimbursement ($8955 vs $8258; P = .03) than precoding initiative CEA patients (n = 205). The proportion of admissions with a documented major complication or comorbidity and complication or comorbidity was significantly higher after the coding initiative (43% vs 27%; P < .01). Among 504 OIPs, postcoding initiative patients (n = 227) had a significantly higher CMI (2.23 vs 2.05; P < .01), actual reimbursement ($23,203 vs $19,909; P < .01), CM ($12,165 vs $8840; P < .01), and CMS base rate reimbursement ($14,649 vs $13,496; P < .01) than precoding initiative patients (n = 277). The proportion of admissions with a documented major complication or comorbidity and complication or comorbidity was significantly higher after the coding initiative (61% vs 43%; P < .01). For both CEA and OIPs, there were no differences in age, duration of stay, total direct costs, or primary insurance status between the precoding and postcoding patient groups. Accurate and detailed clinical documentation is required for key stakeholders to characterize the acuity of inpatient admissions and ensure appropriate reimbursement; it is also a key component of risk-adjustment methods for assessing quality of care. A physician-led documentation initiative significantly increased CMI and CM. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

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 identify perioperative strokes and to a lesser degree, symptom status. PMID:23490294

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 and increased postoperative complications. Further efforts are warranted to contain costs in minorities undergoing carotid revascularization. Copyright © 2013 Elsevier Inc. All rights reserved.

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. PMID:26503065

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.

Human-Robot Cooperation with Commands Embedded in Actions

NASA Astrophysics Data System (ADS)

Kobayashi, Kazuki; Yamada, Seiji

In this paper, we first propose a novel interaction model, CEA (Commands Embedded in Actions). It can explain the way how some existing systems reduce the work-load of their user. We next extend the CEA and build ECEA (Extended CEA) model. The ECEA enables robots to achieve more complicated tasks. On this extension, we employ ACS (Action Coding System) which can describe segmented human acts and clarifies the relationship between user's actions and robot's actions in a task. The ACS utilizes the CEA's strong point which enables a user to send a command to a robot by his/her natural action for the task. The instance of the ECEA led by using the ACS is a temporal extension which has the user keep a final state of a previous his/her action. We apply the temporal extension of the ECEA for a sweeping task. The high-level task, a cooperative task between the user and the robot can be realized. The robot with simple reactive behavior can sweep the region of under an object when the user picks up the object. In addition, we measure user's cognitive loads on the ECEA and a traditional method, DCM (Direct Commanding Method) in the sweeping task, and compare between them. The results show that the ECEA has a lower cognitive load than the DCM significantly.

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.

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.

Recent Improvement of Measurement Instrumentation to Supervise Nuclear Operations and to Contribute Input Data to 3D Simulation Code - 13289

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

Mahe, Charly; Chabal, Caroline

2013-07-01

The CEA has developed many compact characterization tools to follow sensitive operations in a nuclear environment. Usually, these devices are made to carry out radiological inventories, to prepare nuclear interventions or to supervise some special operations. These in situ measurement techniques mainly take place at different stages of clean-up operations and decommissioning projects, but they are also in use to supervise sensitive operations when the nuclear plant is still operating. In addition to this, such tools are often associated with robots to access very highly radioactive areas, and thus can be used in accident situations. Last but not least, themore » radiological data collected can be entered in 3D calculation codes used to simulate the doses absorbed by workers in real time during operations in a nuclear environment. Faced with these ever-greater needs, nuclear measurement instrumentation always has to involve on-going improvement processes. Firstly, this paper will describe the latest developments and results obtained in both gamma and alpha imaging techniques. The gamma camera has been used by the CEA since the 1990's and several changes have made this device more sensitive, more compact and more competitive for nuclear plant operations. It is used to quickly identify hot spots, locating irradiating sources from 50 keV to 1500 keV. Several examples from a wide field of applications will be presented, together with the very latest developments. The alpha camera is a new camera used to see invisible alpha contamination on several kinds of surfaces. The latest results obtained allow real time supervision of a glove box cleaning operation (for {sup 241}Am contamination). The detection principle as well as the main trials and results obtained will be presented. Secondly, this paper will focus on in situ gamma spectrometry methods developed by the CEA with compact gamma spectrometry probes (CdZnTe, LaBr{sub 3}, NaI, etc.). The radiological data collected is used to quantify the activity of hot spots and can also then be entered in 3D models of nuclear plants to simulate intervention scenarios. Recent developments and results will be presented regarding this. Finally, thanks to a large amount of feedback, the interest of using complementary measurements will be discussed. In fact, the recent use of 3D simulation codes requires very accurate knowledge of nuclear plant radiological data. The use of coupled devices such as imaging devices, (gamma and alpha cameras), gamma spectrometry, dose rate mapping, collimated / un-collimated measurements and many other physical values gives an approach to the radiological knowledge of a process or plant with the lowest possible uncertainty. In line with this, the paper will conclude with the future developments and trials that could be assessed in that field of application. (authors)« less

Assessment and Mitigation of Radiation, EMP, Debris & Shrapnel Impacts at Megajoule-Class Laser Facilities

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

Eder, D C; Anderson, R W; Bailey, D S

2009-10-05

The generation of neutron/gamma radiation, electromagnetic pulses (EMP), debris and shrapnel at mega-Joule class laser facilities (NIF and LMJ) impacts experiments conducted at these facilities. The complex 3D numerical codes used to assess these impacts range from an established code that required minor modifications (MCNP - calculates neutron and gamma radiation levels in complex geometries), through a code that required significant modifications to treat new phenomena (EMSolve - calculates EMP from electrons escaping from laser targets), to a new code, ALE-AMR, that is being developed through a joint collaboration between LLNL, CEA, and UC (UCSD, UCLA, and LBL) for debrismore » and shrapnel modelling.« less

Characterization of the CALIBAN Critical Assembly Neutron Spectra using Several Adjustment Methods Based on Activation Foils Measurement

NASA Astrophysics Data System (ADS)

Casoli, Pierre; Grégoire, Gilles; Rousseau, Guillaume; Jacquet, Xavier; Authier, Nicolas

2016-02-01

CALIBAN is a metallic critical assembly managed by the Criticality, Neutron Science and Measurement Department located on the French CEA Center of Valduc. The reactor is extensively used for benchmark experiments dedicated to the evaluation of nuclear data, for electronic hardening or to study the effect of the neutrons on various materials. Therefore CALIBAN irradiation characteristics and especially its central cavity neutron spectrum have to be very accurately evaluated. In order to strengthen our knowledge of this spectrum, several adjustment methods based on activation foils measurements are being studied for a few years in the laboratory. Firstly two codes included in the UMG package have been tested and compared: MAXED and GRAVEL. More recently, the CALIBAN cavity spectrum has been studied using CALMAR, a new adjustment tool currently under development at the CEA Center of Cadarache. The article will discuss and compare the results and the quality of spectrum rebuilding obtained with the UMG codes and with the CALMAR software, from a set of activation measurements carried out in the CALIBAN irradiation cavity.

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

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 should not be used to analyze CEA and CAS. NSQIP data do not adequately identify high-risk patients, but do accurately identify perioperative strokes and to a lesser degree, symptom status. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

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.

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…

Clinical study of cultured epithelial autografts in liquid suspension in severe burn patients.

PubMed

Yim, Haejun; Yang, Hyeong Tae; Cho, Yong Suk; Seo, Cheong Hoon; Lee, Boung Chul; Ko, Jang Hyu; Kwak, In Suk; Kim, Dohern; Hur, Jun; Kim, Jong Hyun; Chun, Wook

2011-09-01

We address the clinical application of the suspension type cultured epithelial autografts (CEAs), Keraheal™ (MCTT, Seoul, Korea), along with the effects, application method, merits and demerits thereof. From February 2007 to June 2010, 29 burn patients with extensive burns, participated in the suspension type of CEA clinical test. A widely meshed autograft (1:4-6 ratio) was applied to the wound bed and the suspension type CEA was sprayed with a Tissomat cell sprayer, followed by a Tissucol spray, a fibrin sealant. The patients' (men/women=26/3) median (interquartile ranges) age was 42 (30-49) years old, the burned TBSA was 55 (44-60) %, and the full thickness burn area was 40 (30-46.5) %. The area of Keraheal™ applied was 800 (400-1200) cm(2). The take rate was 96 (90.5-99) % and 100 (98.5-100) % at 2 and 4 weeks after treatment with Keraheal™, respectively. The Vancouver burn scar scale was 5 (4-6.5), 4 (3-6), and 3 (2-4) at 8, 12 and 24 weeks after the Keraheal™ application. Widely meshed autograft must be applied in massive burns but it's take rate is greatly reduced. The CEAs enhance the take rate of a wide meshed autograft in massive burns and allow for grafting wide meshed autograft together with acellular dermal matrix in some cases. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

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.

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.

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.

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.

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.

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

Thermodynamics of Gas Turbine Cycles with Analytic Derivatives in OpenMDAO

NASA Technical Reports Server (NTRS)

Gray, Justin; Chin, Jeffrey; Hearn, Tristan; Hendricks, Eric; Lavelle, Thomas; Martins, Joaquim R. R. A.

2016-01-01

A new equilibrium thermodynamics analysis tool was built based on the CEA method using the OpenMDAO framework. The new tool provides forward and adjoint analytic derivatives for use with gradient based optimization algorithms. The new tool was validated against the original CEA code to ensure an accurate analysis and the analytic derivatives were validated against finite-difference approximations. Performance comparisons between analytic and finite difference methods showed a significant speed advantage for the analytic methods. To further test the new analysis tool, a sample optimization was performed to find the optimal air-fuel equivalence ratio, , maximizing combustion temperature for a range of different pressures. Collectively, the results demonstrate the viability of the new tool to serve as the thermodynamic backbone for future work on a full propulsion modeling tool.

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.

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 cataplexy is substantially increased by selective activation of GABAergic neurons in the central nucleus of the amygdala (CeA). We also demonstrate that inhibition of these neurons reduces reward-promoted cataplexy. These results build upon prior work to establish the CeA as a crucial element in the neural mechanisms of cataplexy. These results demonstrate the importance of the CeA in regulating responses to rewarding stimuli, shedding light on the broader neurobiology of emotions and motor control. PMID:28235898

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.

TRIPOLI-4® - MCNP5 ITER A-lite neutronic model benchmarking

NASA Astrophysics Data System (ADS)

Jaboulay, J.-C.; Cayla, P.-Y.; Fausser, C.; Lee, Y.-K.; Trama, J.-C.; Li-Puma, A.

2014-06-01

The aim of this paper is to present the capability of TRIPOLI-4®, the CEA Monte Carlo code, to model a large-scale fusion reactor with complex neutron source and geometry. In the past, numerous benchmarks were conducted for TRIPOLI-4® assessment on fusion applications. Experiments (KANT, OKTAVIAN, FNG) analysis and numerical benchmarks (between TRIPOLI-4® and MCNP5) on the HCLL DEMO2007 and ITER models were carried out successively. In this previous ITER benchmark, nevertheless, only the neutron wall loading was analyzed, its main purpose was to present MCAM (the FDS Team CAD import tool) extension for TRIPOLI-4®. Starting from this work a more extended benchmark has been performed about the estimation of neutron flux, nuclear heating in the shielding blankets and tritium production rate in the European TBMs (HCLL and HCPB) and it is presented in this paper. The methodology to build the TRIPOLI-4® A-lite model is based on MCAM and the MCNP A-lite model (version 4.1). Simplified TBMs (from KIT) have been integrated in the equatorial-port. Comparisons of neutron wall loading, flux, nuclear heating and tritium production rate show a good agreement between the two codes. Discrepancies are mainly included in the Monte Carlo codes statistical error.

Modeling of local steam condensation on walls in presence of non-condensable gases. Application to a loca calculation in reactor containment using the multidimensional geyser/tonus code

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

Benet, L.V.; Caroli, C.; Cornet, P.

1995-09-01

This paper reports part of a study of possible severe pressurized water reactor (PWR) accidents. The need for containment modeling, and in particular for a hydrogen risk study, was reinforced in France after 1990, with the requirement that severe accidents must be taken into account in the design of future plants. This new need of assessing the transient local hydrogen concentration led to the development, in the Mechanical Engineering and Technology Department of the French Atomic Energy Commission (CEA/DMT), of the multidimensional code GEYSER/TONUS for containment analysis. A detailed example of the use of this code is presented. The mixturemore » consisted of noncondensable gases (air or air plus hydrogen) and water vapor and liquid water. This is described by a compressible homogeneous two-phase flow model and wall condensation is based on the Chilton-Colburn formula and the analogy between heat and mass transfer. Results are given for a transient two-dimensional axially-symmetric computation for the first hour of a simplified accident sequence. In this there was an initial injection of a large amount of water vapor followed by a smaller amount and by hydrogen injection.« less

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.

NASA Glenn Coefficients for Calculating Thermodynamic Properties of Individual Species

NASA Technical Reports Server (NTRS)

McBride, Bonnie J.; Zehe, Michael J.; Gordon, Sanford

2002-01-01

This report documents the library of thermodynamic data used with the NASA Glenn computer program CEA (Chemical Equilibrium with Applications). This library, containing data for over 2000 solid, liquid, and gaseous chemical species for temperatures ranging from 200 to 20,000 K, is available for use with other computer codes as well. The data are expressed as least-squares coefficients to a seven-term functional form for C((sup o)(sub p)) (T) / R with integration constants for H (sup o) (T) / RT and S(sup o) (T) / R. The NASA Glenn computer program PAC (Properties and Coefficients) was used to calculate thermodynamic functions and to generate the least-squares coefficients. PAC input was taken from a variety of sources. A complete listing of the database is given along with a summary of thermodynamic properties at 0 and 298.15 K.

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

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.

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

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.

Preliminary Analysis of the BASALA-H Experimental Programme

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

Blaise, Patrick; Fougeras, Philippe; Philibert, Herve

2002-07-01

This paper is focused on the preliminary analysis of results obtained on the first cores of the first phase of the BASALA (Boiling water reactor Advanced core physics Study Aimed at mox fuel Lattice) programme, aimed at studying the neutronic parameters in ABWR core in hot conditions, currently under investigation in the French EOLE critical facility, within the framework of a cooperation between NUPEC, CEA and Cogema. The first 'on-line' analysis of the results has been made, using a new preliminary design and safety scheme based on the French APOLLO-2 code in its 2.4 qualified version and associated CEA-93 V4more » (JEF-2.2) Library, that will enable the Experimental Physics Division (SPEx) to perform future core designs. It describes the scheme adopted and the results obtained in various cases, going to the critical size determination to the reactivity worth of the perturbed configurations (voided, over-moderated, and poisoned with Gd{sub 2}O{sub 3}-UO{sub 2} pins). A preliminary study on the experimental results on the MISTRAL-4 is resumed, and the comparison of APOLLO-2 versus MCNP-4C calculations on these cores is made. The results obtained show very good agreements between the two codes, and versus the experiment. This work opens the way to the future full analysis of the experimental results of the qualifying teams with completely validated schemes, based on the new 2.5 version of the APOLLO-2 code. (authors)« less

Comparison of deterministic and stochastic approaches for isotopic concentration and decay heat uncertainty quantification on elementary fission pulse

NASA Astrophysics Data System (ADS)

Lahaye, S.; Huynh, T. D.; Tsilanizara, A.

2016-03-01

Uncertainty quantification of interest outputs in nuclear fuel cycle is an important issue for nuclear safety, from nuclear facilities to long term deposits. Most of those outputs are functions of the isotopic vector density which is estimated by fuel cycle codes, such as DARWIN/PEPIN2, MENDEL, ORIGEN or FISPACT. CEA code systems DARWIN/PEPIN2 and MENDEL propagate by two different methods the uncertainty from nuclear data inputs to isotopic concentrations and decay heat. This paper shows comparisons between those two codes on a Uranium-235 thermal fission pulse. Effects of nuclear data evaluation's choice (ENDF/B-VII.1, JEFF-3.1.1 and JENDL-2011) is inspected in this paper. All results show good agreement between both codes and methods, ensuring the reliability of both approaches for a given evaluation.

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.

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.

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, FR) Co-chair: Georgios KATALAGARIANAKIS (EC, BE) Mélanie AUFFAN (CEREGE, FR) Jorge BOCZKOWSKI (INSERM, FR) Jean-Yves BOTTERO (CEREGE, FR) Jacques BOUILLARD (INERIS, FR) Derk BROUWER (TNO, NL) Marie CARRIERE (CEA, FR) Claude EMOND (U. MONTREAL, CA) Cassandra ENGEMAN (UCSB, USA) Eric GAFFET (CNRS, FR) François GENSDARMES (IRSN, FR) Alexei GRINBAUM (CEA, FR) Antje GROBE (U.STUTTGART, DE) Peter HOET (KUL, BE) Eric QUEMENEUR (CEA, FR) Olivier LE BIHAN (INERIS, FR) Robert MUIR (NANEUM, UK) Tinh NGUYEN (NIST, USA) Bernd NOWACK (EMPA, CH) Günter OBERDÖRSTER (U. ROCHESTER, USA) David PUI (U. MINNESOTA, USA) Michael RIEDIKER (IST, CH) Yves SAMSON (CEA, FR) Ken TAKEDA (U. TOKYO, JP) Olivier WITSCHGER (INRS, FR) The PDF contains a list of sponsor logos, the conference programme and planning documents.

On use of ZPR research reactors and associated instrumentation and measurement methods for reactor physics studies

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

Chauvin, J.P.; Blaise, P.; Lyoussi, A.

2015-07-01

The French atomic and alternative energies -CEA- is strongly involved in research and development programs concerning the use of nuclear energy as a clean and reliable source of energy and consequently is working on the present and future generation of reactors on various topics such as ageing plant management, optimization of the plutonium stockpile, waste management and innovative systems exploration. Core physics studies are an essential part of this comprehensive R and D effort. In particular, the Zero Power Reactor (ZPR) of CEA: EOLE, MINERVE and MASURCA play an important role in the validation of neutron (as well photon) physicsmore » calculation tools (codes and nuclear data). The experimental programs defined in the CEA's ZPR facilities aim at improving the calculation routes by reducing the uncertainties of the experimental databases. They also provide accurate data on innovative systems in terms of new materials (moderating and decoupling materials) and new concepts (ADS, ABWR, new MTR (e.g. JHR), GENIV) involving new fuels, absorbers and coolant materials. Conducting such interesting experimental R and D programs is based on determining and measuring main parameters of phenomena of interest to qualify calculation tools and nuclear data 'libraries'. Determining these parameters relies on the use of numerous and different experimental techniques using specific and appropriate instrumentation and detection tools. Main ZPR experimental programs at CEA, their objectives and challenges will be presented and discussed. Future development and perspectives regarding ZPR reactors and associated programs will be also presented. (authors)« less

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

TOPLHA and ALOHA: comparison between Lower Hybrid wave coupling codes

NASA Astrophysics Data System (ADS)

Meneghini, Orso; Hillairet, J.; Goniche, M.; Bilato, R.; Voyer, D.; Parker, R.

2008-11-01

TOPLHA and ALOHA are wave coupling simulation tools for LH antennas. Both codes are able to account for realistic 3D antenna geometries and use a 1D plasma model. In the framework of a collaboration between MIT and CEA laboratories, the two codes have been extensively compared. In TOPLHA the EM problem is self consistently formulated by means of a set of multiple coupled integral equations having as domain the triangles of the meshed antenna surface. TOPLHA currently uses the FELHS code for modeling the plasma response. ALOHA instead uses a mode matching approach and its own plasma model. Comparisons have been done for several plasma scenarios on different antenna designs: an array of independent waveguides, a multi-junction antenna and a passive/active multi-junction antenna. When simulating the same geometry and plasma conditions the two codes compare remarkably well both for the reflection coefficients and for the launched spectra. The different approach of the two codes to solve the same problem strengthens the confidence in the final results.

GABAergic Neurons of the Central Amygdala Promote Cataplexy.

PubMed

Mahoney, Carrie E; Agostinelli, Lindsay J; Brooks, Jessica N K; Lowell, Bradford B; Scammell, Thomas E

2017-04-12

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 cataplexy is substantially increased by selective activation of GABAergic neurons in the central nucleus of the amygdala (CeA). We also demonstrate that inhibition of these neurons reduces reward-promoted cataplexy. These results build upon prior work to establish the CeA as a crucial element in the neural mechanisms of cataplexy. These results demonstrate the importance of the CeA in regulating responses to rewarding stimuli, shedding light on the broader neurobiology of emotions and motor control. Copyright © 2017 the authors 0270-6474/17/373995-12$15.00/0.

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.

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.

Work plan for improving the DARWIN2.3 depleted material balance calculation of nuclides of interest for the fuel cycle

NASA Astrophysics Data System (ADS)

Rizzo, Axel; Vaglio-Gaudard, Claire; Martin, Julie-Fiona; Noguère, Gilles; Eschbach, Romain

2017-09-01

DARWIN2.3 is the reference package used for fuel cycle applications in France. It solves the Boltzmann and Bateman equations in a coupling way, with the European JEFF-3.1.1 nuclear data library, to compute the fuel cycle values of interest. It includes both deterministic transport codes APOLLO2 (for light water reactors) and ERANOS2 (for fast reactors), and the DARWIN/PEPIN2 depletion code, each of them being developed by CEA/DEN with the support of its industrial partners. The DARWIN2.3 package has been experimentally validated for pressurized and boiling water reactors, as well as for sodium fast reactors; this experimental validation relies on the analysis of post-irradiation experiments (PIE). The DARWIN2.3 experimental validation work points out some isotopes for which the depleted concentration calculation can be improved. Some other nuclides have no available experimental validation, and their concentration calculation uncertainty is provided by the propagation of a priori nuclear data uncertainties. This paper describes the work plan of studies initiated this year to improve the accuracy of the DARWIN2.3 depleted material balance calculation concerning some nuclides of interest for the fuel cycle.

[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.

Emphasis on High Power Lithium Ion Technology for Pulse-Load Operations: Terrestrial Developments Potential Benefits to Space Application

NASA Astrophysics Data System (ADS)

Fusalba, Florence; Chami, Marianne; Rey, Marlene; Moreau, Gilles; Reynier, Yvan; Azais, Philippe

2014-08-01

Currently Li-ion batteries are preferred to supply space missions owing to their large energy density. However, these batteries are designed for standard missions without high-power pulsed payloads, therefore for low C-rates profiles, and do not answer the needs of high- power space applications. More enhanced power sources compatible with extended thermal environment are therefore needed for some space applications like next generation launchers or radar satellites. It is believed that synergy between terrestrial and space sectors could foster the avoidance of multiple financing for the development of similar technologies and systems, as well as dual-use of facilities, providing some real applications for synergy. CEA experienced terrestrial requirements for Hybrid Electric Vehicle applications, start & stop, e-buses and other larger vehicles. In this frame, materials especially designed for high power needs, new cells conception and recently hybrid supercapacitors developments at CEA are discussed as potential solutions for space high power feature.

Microscopic predictions of fission yields based on the time dependent GCM formalism

NASA Astrophysics Data System (ADS)

Regnier, D.; Dubray, N.; Schunck, N.; Verrière, M.

2016-03-01

Accurate knowledge of fission fragment yields is an essential ingredient of numerous applications ranging from the formation of elements in the r-process to fuel cycle optimization in nuclear energy. The need for a predictive theory applicable where no data is available, together with the variety of potential applications, is an incentive to develop a fully microscopic approach to fission dynamics. One of the most promising theoretical frameworks is the time-dependent generator coordinate method (TDGCM) applied under the Gaussian overlap approximation (GOA). Previous studies reported promising results by numerically solving the TDGCM+GOA equation with a finite difference technique. However, the computational cost of this method makes it difficult to properly control numerical errors. In addition, it prevents one from performing calculations with more than two collective variables. To overcome these limitations, we developed the new code FELIX-1.0 that solves the TDGCM+GOA equation based on the Galerkin finite element method. In this article, we briefly illustrate the capabilities of the solver FELIX-1.0, in particular its validation for n+239Pu low energy induced fission. This work is the result of a collaboration between CEA,DAM,DIF and LLNL on nuclear fission theory.

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.

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.

Recent enhancements of the PMCC infrasound signal detector

NASA Astrophysics Data System (ADS)

Brachet, N.; Mialle, P.; Matoza, R. S.; Le Pichon, A.; Cansi, Y.; Ceranna, L.

2010-12-01

The Progressive Multi-Channel Correlation (PMCC) is an antenna technique that is commonly being used by the scientific community for detecting coherent signals recorded on infrasound arrays. The PMCC detector, originally developed by CEA/DASE (Cansi, 1995), was installed in 2004 in the operational environment of the International Data Centre (IDC) of the Comprehensive nuclear Test Ban Treaty Organization (CTBTO) in Vienna. During the last 5 years, several changes have been made by the IDC to enhance the PMCC source code and parameter configuration, and the detector has exhibited good performance in terms of detection sensitivity and robustness. Recent studies performed at the CEA/DASE have shown that the IDC version (DFX/Geotool-PMCC) and the DASE version (WinPMCC) of PMCC software benefit from the implementation of the adaptive processing window duration and a log-spaced frequency bands. This tested configuration enables better detection and characterization of all received signals in their wave-front parameter space (e.g., frequency-azimuth space, frequency-trace-velocity space). A new release of the WinPMCC software - running under Windows or Linux operating systems - including a fully configurable filtering and detection parameters is now available upon request. We present the results of a statistical analysis on 10 years of infrasound data recorded at the IMS stations IS26, Germany and IS22, New Caledonia. A comparison is made between the automatic detections produced by the IDC, and the reprocessed detections using the optimized filtering and detection configuration parameters. Work is also underway at the CEA/DASE to determine more rigorously the azimuth and speed uncertainties. The current algorithm estimates the uncertainties based on statistical analysis of the distribution of PMCC detection pixels in the azimuth-speed space. The new code that is being considered performs the calculation of infrasound measurement errors as a function of physical parameters, i.e. dependant on the array geometry and the wave properties.

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.

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 poor prognosis. Routine measurement of postoperative, rather than preoperative, CEA is warranted. Patients with elevated postoperative CEA are at increased risk for recurrence, especially within the first 12 months after surgery.

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

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.

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

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

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).

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 system and their integration in the safety system of nuclear reactors. It also gives a solid background for the follow up and the development of the neutron detection systems. Another field of activity of the INSTN is the development of new teaching tools using software applications. We describe hereafter two applications that have recently been developed by the institute, O.S.I.R.I.S and DOSIMEX. The INSTN and the company OREKA have developed an innovative teaching tool named O.S.I.R.I.S. The tool is built on a virtual 3D environment in which users operate in a totally free way. The action is located in a pressurised water reactor in the environment of a steam generator building. The users are students or professionals who want to learn and train on concrete situations on how to protect the workers against radiation. Through the use of this serious game, users must: establish a predictive dose evaluation, implement the principles of radiation protection, perform the dose result of the operation, analyse the gap between the predictive collective dose and the collective dose achieved, and decide about the lessons to provide feedback. Taking into account the increasing constraints related to radiation protection, it is essential to use computer codes to evaluate the dose rates generated by sources of ionizing radiation. Many powerful codes exist but are often relatively complex to implement and are dedicated to experts. In addition, these codes are often 'black boxes' that does not allow the user to understand the underlying physics. The objective of DOSIMEX codes developed by the INSTN is to give, by the means of a VBA code with a simple interface, the ability to easily conduct a wide range of radiological exposure situations: calculation of gamma, beta, neutron equivalent dose rate, calculation of internal contamination and atmospheric transfer.« less

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

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.

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

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.

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

Labor Resource Audit and Analysis: A Tool for Management Planning and Control

DTIC Science & Technology

1989-06-01

RM(onn17 COSA~ CODES B 5OBJECT TERMS (Continge pn rev@rj !~cea and f, entfa y.block R V FIELD GROUP SUB-GROUP re-; P anning; labor; ugLr og; a e...David 1 hplr., chairman Department of Admi srtv Sine KnealeT-Mg;fi Dea ofInformation and-ln sine ii ABSTRACT This study was conducted in an effort to...Audit ---------------------------------- 84 viii ACKNOWLEDGMENTS A wide variety of authorities in their field have contributed material to this study. I

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.

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.

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.

[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.

Electrochemical immunoassay for carcinoembryonic antigen based on signal amplification strategy of nanotubular mesoporous PdCu alloy.

PubMed

Cai, Yanyan; Li, He; Li, Yuyang; Zhao, Yanfang; Ma, Hongmin; Zhu, Baocun; Xu, Caixia; Wei, Qin; Wu, Dan; Du, Bin

2012-01-01

Interests in using nanoporous metals for biosensing applications have been increasing. Herein, nanotubular mesoporous PdCu (NM-PdCu) alloy is used to fabricate a novel label-free electrochemical immunosensor for cancer biomarker carcinoembryonic antigen (CEA). It operates through physisorption of anti-CEA on NM-PdCu and the mixture of sulfonated graphene sheets (HSO(3)-GS) and thionine (TH) functionalized glassy carbon electrode interface as the detection platform. In this study, chitosan (CS)-PdCu is bound very strongly to carcinoembryonic antibody (anti-CEA), because of the good electron conductivity, high surface area, and good biocompatibility. CS-PdCu is immobilized on electrodes by electrostatic interactions between the negatively charged sulfo group of HSO(3)-GS and the abundant positively charged amino groups of chitosan. TH acts as the redox probe. Under the optimized conditions, the electrochemical immunosensor exhibits a wide working range from 0.01 to 12 ng/mL with a low detection limit of 4.86 pg/mL. The accuracy, reproducibility, and stability of the immunosensor are acceptable. The assay is evaluated for real serum samples, receiving satisfactory results. The nanoporous metal materials-based immunoassay provides a promising approach in clinical application and thus represents a versatile detection method. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

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

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.

Enhancing the sensitivity of mid-IR quantum cascade laser-based cavity-enhanced absorption spectroscopy using RF current perturbation.

PubMed

Manfred, Katherine M; Kirkbride, James M R; Ciaffoni, Luca; Peverall, Robert; Ritchie, Grant A D

2014-12-15

The sensitivity of mid-IR quantum cascade laser (QCL) off-axis cavity-enhanced absorption spectroscopy (CEAS), often limited by cavity mode structure and diffraction losses, was enhanced by applying a broadband RF noise to the laser current. A pump-probe measurement demonstrated that the addition of bandwidth-limited white noise effectively increased the laser linewidth, thereby reducing mode structure associated with CEAS. The broadband noise source offers a more sensitive, more robust alternative to applying single-frequency noise to the laser. Analysis of CEAS measurements of a CO(2) absorption feature at 1890  cm(-1) averaged over 100 ms yielded a minimum detectable absorption of 5.5×10(-3)  Hz(-1/2) in the presence of broadband RF perturbation, nearly a tenfold improvement over the unperturbed regime. The short acquisition time makes this technique suitable for breath applications requiring breath-by-breath gas concentration information.

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, 146-432 cm/s) after eCEA that were subsequently examined by axial imaging, the mean percentage stenosis was 8% ± 11% by NASCET, 11% ± 5% by ECST, and 20% ± 9% by CSA criteria. For eight pCEA arteries with PSV >125 cm/s (median velocity, 148 cm/s; interquartile range, 139-242 cm/s), the corresponding NASCET, ECST, and CSA stenoses were 8% ± 35%, 26% ± 32%, and 25% ± 33%, respectively. NASCET internal carotid diameter reduction of at least 50% was noted by axial imaging after two of the eight pCEAs, and the PSV exceeded 200 cm/s in each case. The presence of hemodynamically significant carotid artery restenosis may be overestimated by standard duplex criteria after eCEA and perhaps after pCEA. Insufficient information currently exists to determine what PSV does correspond to hemodynamically significant restenosis. Published by Elsevier Inc.

Development of Yield and Tensile Strength Design Curves for Alloy 617

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

Nancy Lybeck; T. -L. Sham

2013-10-01

The U.S. Department of Energy Very High Temperature Reactor Program is acquiring data in preparation for developing an Alloy 617 Code Case for inclusion in the nuclear section of the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel (B&PV) Code. A draft code case was previously developed, but effort was suspended before acceptance by ASME. As part of the draft code case effort, a database was compiled of yield and tensile strength data from tests performed in air. Yield strength and tensile strength at temperature are used to set time independent allowable stress for construction materials in B&PVmore » Code, Section III, Subsection NH. The yield and tensile strength data used for the draft code case has been augmented with additional data generated by Idaho National Laboratory and Oak Ridge National Laboratory in the U.S. and CEA in France. The standard ASME Section II procedure for generating yield and tensile strength at temperature is presented, along with alternate methods that accommodate the change in temperature trends seen at high temperatures, resulting in a more consistent design margin over the temperature range of interest.« less

Verification of the predictive capabilities of the 4C code cryogenic circuit model

NASA Astrophysics Data System (ADS)

Zanino, R.; Bonifetto, R.; Hoa, C.; Richard, L. Savoldi

2014-01-01

The 4C code was developed to model thermal-hydraulics in superconducting magnet systems and related cryogenic circuits. It consists of three coupled modules: a quasi-3D thermal-hydraulic model of the winding; a quasi-3D model of heat conduction in the magnet structures; an object-oriented a-causal model of the cryogenic circuit. In the last couple of years the code and its different modules have undergone a series of validation exercises against experimental data, including also data coming from the supercritical He loop HELIOS at CEA Grenoble. However, all this analysis work was done each time after the experiments had been performed. In this paper a first demonstration is given of the predictive capabilities of the 4C code cryogenic circuit module. To do that, a set of ad-hoc experimental scenarios have been designed, including different heating and control strategies. Simulations with the cryogenic circuit module of 4C have then been performed before the experiment. The comparison presented here between the code predictions and the results of the HELIOS measurements gives the first proof of the excellent predictive capability of the 4C code cryogenic circuit module.

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-guided biopsies), whilst low p-CEA may support a follow-up. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Pile noise experiment in MINERVE reactor to estimate kinetic parameters using various data processing methods

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

Geslot, Benoit; Gruel, Adrien; Pepino, Alexandra

2015-07-01

MINERVE is a two-zone pool type zero power reactor operated by CEA (Cadarache, France). Kinetic parameters of the core (prompt neutron decay constant, delayed neutron fraction, generation time) have been recently measured using various pile noise experimental techniques, namely Feynman-α, Rossi-α and Cohn-α. Results are discussed and compared to each other's. The measurement campaign has been conducted in the framework of a tri-partite collaboration between CEA, SCK.CEN and PSI. Results presented in this paper were obtained thanks to a time-stamping acquisition system developed by CEA. PSI performed simultaneous measurements which are presented in a companion paper. Signals come from twomore » high efficiency fission chambers located in the graphite reflector next to the core driver zone. Experiments were conducted at critical state with a reactor power of 0.2 W. The core integral fission rate is obtained from a calibrated miniature fission chamber located at the center of the core. Other results obtained in two sub-critical configurations will be presented elsewhere. Best estimate delayed neutron fraction comes from the Cohn-α method: 747 ± 15 pcm (1σ). In this case, the prompt decay constant is 79 ± 0.5 s{sup -1} and the generation time is 94.5 ± 0.7 μs. Other methods give consistent results within the confidence intervals. Experimental results are compared to calculated values obtained from a full 3D core modeling with the CEA-developed Monte Carlo code TRIPOLI4.9 associated with its continuous energy JEFF3.1.1-based library. A very good agreement is observed for the calculated delayed neutron fraction (748.7 ± 0.4 pcm at 1σ), that is a difference of -0.3% with the experiment. On the contrary, a 10% discrepancy is observed for the calculated generation time (104.4 ± 0.1 μs at 1σ). (authors)« less

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 available that show much better agreement with the measured values.« less

The Missing Stakeholder Group: Why Patients Should be Involved in Health Economic Modelling.

PubMed

van Voorn, George A K; Vemer, Pepijn; Hamerlijnck, Dominique; Ramos, Isaac Corro; Teunissen, Geertruida J; Al, Maiwenn; Feenstra, Talitha L

2016-04-01

Evaluations of healthcare interventions, e.g. new drugs or other new treatment strategies, commonly include a cost-effectiveness analysis (CEA) that is based on the application of health economic (HE) models. As end users, patients are important stakeholders regarding the outcomes of CEAs, yet their knowledge of HE model development and application, or their involvement therein, is absent. This paper considers possible benefits and risks of patient involvement in HE model development and application for modellers and patients. An exploratory review of the literature has been performed on stakeholder-involved modelling in various disciplines. In addition, Dutch patient experts have been interviewed about their experience in, and opinion about, the application of HE models. Patients have little to no knowledge of HE models and are seldom involved in HE model development and application. Benefits of becoming involved would include a greater understanding and possible acceptance by patients of HE model application, improved model validation, and a more direct infusion of patient expertise. Risks would include patient bias and increased costs of modelling. Patient involvement in HE modelling seems to carry several benefits as well as risks. We claim that the benefits may outweigh the risks and that patients should become involved.

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.

An evolution of technologies and applications of gamma imagers in the nuclear cycle industry

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

Khalil, R. A.; Carrel, F.; Menaa, N.

The tracking of radiation contamination and distribution has become a high priority in the nuclear cycle industry in order to respect the ALARA principle which is a main challenge during decontamination and dismantling activities. To support this need, AREVA/CANBERRA and CEA LIST have been actively carrying out research and development on a gamma-radiation imager. In this paper we will present the new generation of gamma camera, called GAMPIX. This system is based on the Timepix chip, hybridized with a CdTe substrate. A coded mask could be used in order to increase the sensitivity of the camera. Moreover, due to themore » USB connection with a standard computer, this gamma camera is immediately operational and user-friendly. The final system is a very compact gamma camera (global weight is less than 1 kg without any shielding) which could be used as a hand-held device for radioprotection purposes. In this article, we present the main characteristics of this new generation of gamma camera and we expose experimental results obtained during in situ measurements. Even though we present preliminary results the final product is under industrialization phase to address various applications specifications. (authors)« less

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.

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.

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.

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.

Surgical dissection of the internal carotid artery under flow control by proximal vessel clamping reduces embolic infarcts during carotid endarterectomy.

PubMed

Yoshida, Kazumichi; Kurosaki, Yoshitaka; Funaki, Takeshi; Kikuchi, Takayuki; Ishii, Akira; Takahashi, Jun C; Takagi, Yasushi; Yamagata, Sen; Miyamoto, Susumu

2014-01-01

To evaluate the efficacy of flow control of the internal carotid artery (ICA) by the clamping of the common carotid artery, external carotid artery, and superior thyroid artery during surgical ICA dissection to reduce ischemic complications after carotid endarterectomy (CEA). Sixty-seven patients (59 men; age, 70.5 ± 6.2 years) who underwent CEA by the same surgeon were retrospectively studied. Both conventional CEA (n = 29) and flow-control CEA (n = 38) were performed with the patient under general anesthesia and with the use of somatosensory-evoked potential and near-infrared spectroscopy monitoring as a guide for selective shunting. The number of new postoperative infarcts was assessed with preoperative and postoperative diffusion-weighted images (DWIs) obtained within 3 days of surgery. In addition to surgical technique, the effects of the following factors on new infarcts also were examined: age, side of ICA stenosis, high-grade stenosis, symptoms, and application of shunting. New postoperative DWI lesions were observed in 7 of 67 patients (10.4%), and none of them was symptomatic. With respect to operative technique, the incidence rate of DWI spots was significantly lower in the flow-control group (2.6%) than in the conventional group (20.7%), odds ratio: 0.069; 95% confidence interval: 0.006-0.779; P = 0.031). On multiple logistic regression analysis, age, side of ICA stenosis, high-grade stenosis, symptoms, and the use of internal shunting did not have significant effects on new postoperative DWI lesions, whereas technique did have an effect. The proximal flow-control technique for CEA helps avoid embolic complications during surgical ICA dissection. Copyright © 2014 Elsevier Inc. All rights reserved.

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-R therapeutic modalities that may significantly diminish the metastatic potential of CEA overexpressing colorectal tumors.

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.

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

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

Clinically Relevant Reduction in Persistent Facial Erythema of Rosacea on the First Day of Treatment With Oxymetazoline Cream 1.0.

PubMed

Tanghetti, Emil A; Dover, Jeffrey S; Goldberg, David J; Dhawan, Sunil S; Luo, Lei; Berk, David R; Ahluwalia, Gurpreet; Alvandi, Nancy

2018-06-01

Persistent facial erythema is a clinically challenging feature of rosacea. To evaluate persistent erythema reduction on the first day of treatment from pooled data from two pivotal trials of topical oxymetazoline cream 1.0% (oxymetazoline) in persistent facial erythema of rosacea. In two identically designed, phase 3, multicenter trials, adults with moderate to severe persistent facial erythema of rosacea (Clinician Erythema Assessment [CEA] grade ≥3 and Subject Self-Assessment [SSA] grade ≥3) were randomized 1:1 to once-daily topical oxymetazoline or vehicle; the primary efficacy endpoint was ≥2-grade composite CEA and SSA improvement from baseline on day 29. This post hoc analysis evaluated the proportion of patients achieving ≥1-grade composite and individual CEA and SSA improvement at 1, 3, 6, 9, and 12 hours postdose on day 1 (N=885). Significantly more patients achieved ≥1-grade composite and individual CEA and SSA improvement with the first application of oxymetazoline than with vehicle (P less than 0.001) at all postdose time points, beginning with hour 1. Day 1 safety assessments were similar between treatments. Short-term, post hoc analysis. A ≥1-grade improvement in persistent erythema achieved after the first dose of once-daily topical oxymetazoline demonstrated clinically meaningful improvement from the beginning of therapy. J Drugs Dermatol. 2018;17(6):621-626.

[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.

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.

Novel electrochemical redox-active species: one-step synthesis of polyaniline derivative-Au/Pd and its application for multiplexed immunoassay

NASA Astrophysics Data System (ADS)

Wang, Liyuan; Feng, Feng; Ma, Zhanfang

2015-11-01

Electrochemical redox-active species play crucial role in electrochemically multiplexed immunoassays. A one-pot method for synthesizing four kinds of new electrochemical redox-active species was reported using HAuCl4 and Na2PdCl4 as dual oxidating agents and aniline derivatives as monomers. The synthesized polyaniline derivative-Au/Pd composites, namely poly(N-methyl-o-benzenediamine)-Au/Pd, poly(N-phenyl-o-phenylenediamine)-Au/Pd, poly(N-phenyl-p-phenylenediamine)-Au/Pd and poly(3,3’,5,5’-tetramethylbenzidine)-Au/Pd, exhibited electrochemical redox activity at -0.65 V, -0.3 V, 0.12 V, and 0.5 V, respectively. Meanwhile, these composites showed high H2O2 electrocatalytic activity because of the presence of Au/Pd. The as-prepared composites were used as electrochemical immunoprobes in simultaneous detection of four tumor biomarkers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199), carbohydrate antigen 72-4 (CA724), and alpha fetoprotein (AFP)). This immunoassay shed light on potential applications in simultaneous gastric cancer (related biomarkers: CEA, CA199, CA724) and liver cancer diagnosis (related biomarkers: CEA, CA199, AFP). The present strategy to the synthesize redox species could be easily extended to other polymers such as polypyrrole derivatives and polythiophene derivatives. This would be of great significance in the electrochemical detection of more analytes.

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

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

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.

[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.

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

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

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

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.

[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.

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 and after the procedure, respectively. From 2003 to 2014, CEA procedures were performed more frequently in locoregional anesthesia (10.1% to 29.1%, P<0.001). The same trend was observed for the application of the eversion technique (37.0% to 41.6%, P<0.001), the neurophysiological monitoring (49.8% to 61.8%, P<0.001), and the intra-procedural assessment of the treated artery (44.5% to 69.7%, P<0.001). In contrast, shunting was used less frequently (48.1% to 43.0%, P<0.001). Averagely 95.7% of all endovascular procedures were performed using stent-angioplasty. In 54.2% a protection device was used. Nitinol and bare metal stents were used in 74.1% and 21.4% of cases, respectively. The in-hospital rate of any stroke or death decreased from 2.0% to 1.1% in asymptomatic patients treated with CEA without a contralateral stenosis ≥75% or occlusion, P<0.001). In patients treated with CAS this rate did not increase (1.7% to 1.8%, p=0.909). The corresponding rates in CEA and CAS patients with severe contralateral stenosis or occlusion varied between 1.9%-3.1% and 2.2%-2.6%, respectively. In symptomatic patients (group B) with a stenosis of 50 percent or more, the rate of any stroke or death decreased significantly after CEA from 4.2% to 2.4% (P<0.001) and remained stable after CAS (3.9% to 3.5%, P=0.577). This report on 327,452 carotid procedures analysed one of the largest quality registries on CEA and CAS worldwide. Data indicate that treated patients became older and sicker, whereas in contrast, the in-hospital rates of stroke or death are decreasing over time.

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.

Comprehensive Environmental Assessment: A Meta-Assessment Approach

PubMed Central

2012-01-01

With growing calls for changes in the field of risk assessment, improved systematic approaches for addressing environmental issues with greater transparency and stakeholder engagement are needed to ensure sustainable trade-offs. Here we describe the comprehensive environmental assessment (CEA) approach as a holistic way to manage complex information and to structure input from diverse stakeholder perspectives to support environmental decision-making for the near- and long-term. We further note how CEA builds upon and incorporates other available tools and approaches, describe its current application at the U.S. Environmental Protection Agency, and point out how it could be extended in evaluating a major issue such as the sustainability of biofuels. PMID:22889372

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.

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

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

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.

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 patient outcomes and societal costs. For future ophthalmic treatments, CEAs need to be improved and only published when they are of sufficient quality and validity. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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 and acceptable midterm mortality, the observed outcomes do not support use of contralateral carotid artery occlusion as a selection criterion for CAS over CEA in the absence of other indications. Copyright © 2012 Society for Vascular Surgery. All rights reserved.

Cost-effectiveness analyses and their role in improving healthcare strategies.

PubMed

Rodriguez, Maria I; Caughey, Aaron B

2013-12-01

In this era of healthcare reform, attention is focused on increasing the quality of care and access to services, while simultaneously reducing the cost. Economic evaluations can play an important role in translating research to evidence-based practice and policy. Cost-effectiveness analysis (CEA) and its utility for clinical and policy decision making among U.S. obstetricians and gynecologists is reviewed. Three case examples demonstrating the value of this methodology in decision making are considered. A discussion of the methodologic principles of CEA, the advantages, and the limitations of the methodology are presented. CEA can play an important role in evidence-based decision making, with value for clinicians and policy makers alike. These studies are of particular interest in the field of obstetrics and gynecology, in which uncertainty from epidemiologic or clinical trials exists, or multiple perspectives need to be considered (maternal, neonatal, and societal). As with all research, it is essential that economic evaluations are conducted according to established methodologic standards. Interpretation and application of results should occur with a clear understanding of both the value and the limitations of economic evaluations.

High resolution measurements of the {sup 241}Am(n,2n) reaction cross section

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

Sage, C.; European Commission, Joint Research Centre, Institute for Reference Materials and Measurements, Retieseweg 111, B-2440 Geel; Commissariat a L'Energie Atomique Cadarache, DEN/CAD/DER/SPRC/LEPh, F-13108 St Paul-lez-Durance

Measurements of the {sup 241}Am(n,2n) reaction cross section have been performed at the Joint Research Centre (JRC) Geel in the frame of a collaboration between the European Commission (EC) JRC and French laboratories from CNRS and the Commissariat a L'Energie Atomique (CEA) Cadarache. Raw material coming from the Atalante facility of CEA Marcoule has been transformed by JRC Karlsruhe into suitable {sup 241}AmO{sub 2} samples embedded in Al{sub 2}O{sub 3} matrices specifically designed for these measurements. The irradiations were carried out at the 7-MV Van de Graaff accelerator. The {sup 241}Am(n,2n) reaction cross section was determined relative to the {supmore » 27}Al(n,alpha){sup 24}Na standard cross section. The measurements were performed in four sessions, using quasi-mono-energetic neutrons with energies ranging from 8 to 21 MeV produced via the {sup 2}H(d,n){sup 3}He and the {sup 3}H(d,n){sup 4}He reactions. The induced activity was measured by standard gamma-ray spectrometry using a high-purity germanium detector. Below 15 MeV, the present results are in agreement with data obtained earlier. Above 15 MeV, these measurements allowed the experimental investigation of the {sup 241}Am(n,2n) reaction cross section for the first time. The present data are in good agreement with predictions obtained with the talys code that uses an optical and fission model developed at CEA.« less

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

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

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

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.

[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.

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 nucleus of amygdala (CeA) optogenetic stimulation with one option for earning intravenous cocaine makes that option almost the exclusive focus of intense pursuit and consumption. CeA stimulation also elevated the effort cost rats were willing to pay for cocaine and made associated cues become intensely attractive. However, we also show that CeA laser had no reinforcing properties at all when given alone for the same rats. Therefore, CeA laser pairing makes its associated cocaine option and cues become powerfully attractive in a nearly addictive fashion. Copyright © 2017 the authors 0270-6474/17/378330-19$15.00/0.

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 nucleus of amygdala (CeA) optogenetic stimulation with one option for earning intravenous cocaine makes that option almost the exclusive focus of intense pursuit and consumption. CeA stimulation also elevated the effort cost rats were willing to pay for cocaine and made associated cues become intensely attractive. However, we also show that CeA laser had no reinforcing properties at all when given alone for the same rats. Therefore, CeA laser pairing makes its associated cocaine option and cues become powerfully attractive in a nearly addictive fashion. PMID:28751460

15 CFR 950.7 - Center for Environmental Assessment Services (CEAS).

Code of Federal Regulations, 2010 CFR

2010-01-01

..., validated multidisciplinary data sets for international and national study (such undertakings as the recent... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE ENVIRONMENTAL DATA AND INFORMATION § 950.7 Center for... data analyses, applications, assessments, and interpretations to meet their particular requirements...

15 CFR 950.7 - Center for Environmental Assessment Services (CEAS).

Code of Federal Regulations, 2012 CFR

2012-01-01

..., validated multidisciplinary data sets for international and national study (such undertakings as the recent... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE ENVIRONMENTAL DATA AND INFORMATION § 950.7 Center for... data analyses, applications, assessments, and interpretations to meet their particular requirements...

15 CFR 950.7 - Center for Environmental Assessment Services (CEAS).

Code of Federal Regulations, 2011 CFR

2011-01-01

..., validated multidisciplinary data sets for international and national study (such undertakings as the recent... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE ENVIRONMENTAL DATA AND INFORMATION § 950.7 Center for... data analyses, applications, assessments, and interpretations to meet their particular requirements...

15 CFR 950.7 - Center for Environmental Assessment Services (CEAS).

Code of Federal Regulations, 2014 CFR

2014-01-01

..., validated multidisciplinary data sets for international and national study (such undertakings as the recent... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE ENVIRONMENTAL DATA AND INFORMATION § 950.7 Center for... data analyses, applications, assessments, and interpretations to meet their particular requirements...

15 CFR 950.7 - Center for Environmental Assessment Services (CEAS).

Code of Federal Regulations, 2013 CFR

2013-01-01

..., validated multidisciplinary data sets for international and national study (such undertakings as the recent... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE ENVIRONMENTAL DATA AND INFORMATION § 950.7 Center for... data analyses, applications, assessments, and interpretations to meet their particular requirements...

Experimental validation of the DARWIN2.3 package for fuel cycle applications

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

San-Felice, L.; Eschbach, R.; Bourdot, P.

2012-07-01

The DARWIN package, developed by the CEA and its French partners (AREVA and EDF) provides the required parameters for fuel cycle applications: fuel inventory, decay heat, activity, neutron, {gamma}, {alpha}, {beta} sources and spectrum, radiotoxicity. This paper presents the DARWIN2.3 experimental validation for fuel inventory and decay heat calculations on Pressurized Water Reactor (PWR). In order to validate this code system for spent fuel inventory a large program has been undertaken, based on spent fuel chemical assays. This paper deals with the experimental validation of DARWIN2.3 for the Pressurized Water Reactor (PWR) Uranium Oxide (UOX) and Mixed Oxide (MOX) fuelmore » inventory calculation, focused on the isotopes involved in Burn-Up Credit (BUC) applications and decay heat computations. The calculation - experiment (C/E-1) discrepancies are calculated with the latest European evaluation file JEFF-3.1.1 associated with the SHEM energy mesh. An overview of the tendencies is obtained on a complete range of burn-up from 10 to 85 GWd/t (10 to 60 GWcVt for MOX fuel). The experimental validation of the DARWIN2.3 package for decay heat calculation is performed using calorimetric measurements carried out at the Swedish Interim Spent Fuel Storage Facility for Pressurized Water Reactor (PWR) assemblies, covering a large burn-up (20 to 50 GWd/t) and cooling time range (10 to 30 years). (authors)« less

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 thresholds. There was no evidence of a sustained decline in procedural risk after CAS. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

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.

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.

Transparent stakeholder engagement in practice: Lessons learned from applying comprehensive environmental assessment to research planning for nanomaterials.

PubMed

Powers, Christina; Hendren, Christine; Wang, Amy; Davis, J Michael

2014-10-01

As efforts to develop new applications of engineered nanoscale materials (ENMs) continue to grow, so too has interest in the environmental, health, and safety (EHS) implications of these materials. However, thorough evaluation and interpretation of such implications could require substantial resources (e.g., estimated as >$120 million per year in federal funding 2013-2017). A structured, strategic approach for transparently planning research would support improved linkages between ENM research and risk assessments, and thereby enhance the utility of financial and other resources for EHS studies of ENMs. For this reason, we applied Comprehensive Environmental Assessment (CEA) as an approach to provide transparent input into research planning for 2 types of ENMs: nanoscale titanium dioxide and nanoscale silver. For each of these CEA applications, we employed a collective judgment method known as Nominal Group Technique (NGT) in 2 workshops sponsored by the US Environmental Protection Agency (USEPA). The objective of this paper is to present the outcomes of these CEA applications in the context of how our methodology can inform future efforts to identify collective goals in science (e.g., research priorities) through structured decision support approaches. Outcomes include clear lists of research priorities for each ENM developed through transparently engaging stakeholders having diverse technical and sector perspectives. In addition, we identified several procedural aspects that could be refined, including emphasizing breakout group interactions, identifying broad information priorities before more detailed research questions, and using rating rather than ranking prioritization methods. Beyond the research directions identified for specific ENMs, lessons learned about engaging stakeholders in research planning are expected to inform future research planning efforts for ENMs and other emerging materials across the scientific community. © 2014 SETAC.

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.

ThermoBuild: Online Method Made Available for Accessing NASA Glenn Thermodynamic Data

NASA Technical Reports Server (NTRS)

McBride, Bonnie; Zehe, Michael J.

2004-01-01

The new Web site program "ThermoBuild" allows users to easily access and use the NASA Glenn Thermodynamic Database of over 2000 solid, liquid, and gaseous species. A convenient periodic table allows users to "build" the molecules of interest and designate the temperature range over which thermodynamic functions are to be displayed. ThermoBuild also allows users to build custom databases for use with NASA's Chemical Equilibrium with Applications (CEA) program or other programs that require the NASA format for thermodynamic properties. The NASA Glenn Research Center has long been a leader in the compilation and dissemination of up-to-date thermodynamic data, primarily for use with the NASA CEA program, but increasingly for use with other computer programs.

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.

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

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

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.

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

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.

Covariance generation and uncertainty propagation for thermal and fast neutron induced fission yields

NASA Astrophysics Data System (ADS)

Terranova, Nicholas; Serot, Olivier; Archier, Pascal; De Saint Jean, Cyrille; Sumini, Marco

2017-09-01

Fission product yields (FY) are fundamental nuclear data for several applications, including decay heat, shielding, dosimetry, burn-up calculations. To be safe and sustainable, modern and future nuclear systems require accurate knowledge on reactor parameters, with reduced margins of uncertainty. Present nuclear data libraries for FY do not provide consistent and complete uncertainty information which are limited, in many cases, to only variances. In the present work we propose a methodology to evaluate covariance matrices for thermal and fast neutron induced fission yields. The semi-empirical models adopted to evaluate the JEFF-3.1.1 FY library have been used in the Generalized Least Square Method available in CONRAD (COde for Nuclear Reaction Analysis and Data assimilation) to generate covariance matrices for several fissioning systems such as the thermal fission of U235, Pu239 and Pu241 and the fast fission of U238, Pu239 and Pu240. The impact of such covariances on nuclear applications has been estimated using deterministic and Monte Carlo uncertainty propagation techniques. We studied the effects on decay heat and reactivity loss uncertainty estimation for simplified test case geometries, such as PWR and SFR pin-cells. The impact on existing nuclear reactors, such as the Jules Horowitz Reactor under construction at CEA-Cadarache, has also been considered.

The Self-Powered Detector Simulation `MATiSSe' Toolbox applied to SPNDs for severe accident monitoring in PWRs

NASA Astrophysics Data System (ADS)

Barbot, Loïc; Villard, Jean-François; Fourrez, Stéphane; Pichon, Laurent; Makil, Hamid

2018-01-01

In the framework of the French National Research Agency program on nuclear safety and radioprotection, the `DIstributed Sensing for COrium Monitoring and Safety' project aims at developing innovative instrumentation for corium monitoring in case of severe accident in a Pressurized Water nuclear Reactor. Among others, a new under-vessel instrumentation based on Self-Powered Neutron Detectors is developed using a numerical simulation toolbox, named `MATiSSe'. The CEA Instrumentation Sensors and Dosimetry Lab developed MATiSSe since 2010 for Self-Powered Neutron Detectors material selection and geometry design, as well as for their respective partial neutron and gamma sensitivity calculations. MATiSSe is based on a comprehensive model of neutron and gamma interactions which take place in Selfpowered neutron detector components using the MCNP6 Monte Carlo code. As member of the project consortium, the THERMOCOAX SAS Company is currently manufacturing some instrumented pole prototypes to be tested in 2017. The full severe accident monitoring equipment, including the standalone low current acquisition system, will be tested during a joined CEA-THERMOCOAX experimental campaign in some realistic irradiation conditions, in the Slovenian TRIGA Mark II research reactor.

New measurement system for on line in core high-energy neutron flux monitoring in materials testing reactor conditions.

PubMed

Geslot, B; Vermeeren, L; Filliatre, P; Lopez, A Legrand; Barbot, L; Jammes, C; Bréaud, S; Oriol, L; Villard, J-F

2011-03-01

Flux monitoring is of great interest for experimental studies in material testing reactors. Nowadays, only the thermal neutron flux can be monitored on line, e.g., using fission chambers or self-powered neutron detectors. In the framework of the Joint Instrumentation Laboratory between SCK-CEN and CEA, we have developed a fast neutron detector system (FNDS) capable of measuring on line the local high-energy neutron flux in fission reactor core and reflector locations. FNDS is based on fission chambers measurements in Campbelling mode. The system consists of two detectors, one detector being mainly sensitive to fast neutrons and the other one to thermal neutrons. On line data processing uses the CEA depletion code DARWIN in order to disentangle fast and thermal neutrons components, taking into account the isotopic evolution of the fissile deposit. The first results of FNDS experimental test in the BR2 reactor are presented in this paper. Several fission chambers have been irradiated up to a fluence of about 7 × 10(20) n∕cm(2). A good agreement (less than 10% discrepancy) was observed between FNDS fast flux estimation and reference flux measurement.

New measurement system for on line in core high-energy neutron flux monitoring in materials testing reactor conditions

NASA Astrophysics Data System (ADS)

Geslot, B.; Vermeeren, L.; Filliatre, P.; Lopez, A. Legrand; Barbot, L.; Jammes, C.; Bréaud, S.; Oriol, L.; Villard, J.-F.

2011-03-01

Flux monitoring is of great interest for experimental studies in material testing reactors. Nowadays, only the thermal neutron flux can be monitored on line, e.g., using fission chambers or self-powered neutron detectors. In the framework of the Joint Instrumentation Laboratory between SCK-CEN and CEA, we have developed a fast neutron detector system (FNDS) capable of measuring on line the local high-energy neutron flux in fission reactor core and reflector locations. FNDS is based on fission chambers measurements in Campbelling mode. The system consists of two detectors, one detector being mainly sensitive to fast neutrons and the other one to thermal neutrons. On line data processing uses the CEA depletion code DARWIN in order to disentangle fast and thermal neutrons components, taking into account the isotopic evolution of the fissile deposit. The first results of FNDS experimental test in the BR2 reactor are presented in this paper. Several fission chambers have been irradiated up to a fluence of about 7 × 1020 n/cm2. A good agreement (less than 10% discrepancy) was observed between FNDS fast flux estimation and reference flux measurement.

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 MC.

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.

Safety Criticality Standards Using the French CRISTAL Code Package: Application to the AREVA NP UO{sub 2} Fuel Fabrication Plant

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

Doucet, M.; Durant Terrasson, L.; Mouton, J.

2006-07-01

Criticality safety evaluations implement requirements to proof of sufficient sub critical margins outside of the reactor environment for example in fuel fabrication plants. Basic criticality data (i.e., criticality standards) are used in the determination of sub critical margins for all processes involving plutonium or enriched uranium. There are several criticality international standards, e.g., ARH-600, which is one the US nuclear industry relies on. The French Nuclear Safety Authority (DGSNR and its advising body IRSN) has requested AREVA NP to review the criticality standards used for the evaluation of its Low Enriched Uranium fuel fabrication plants with CRISTAL V0, the recentlymore » updated French criticality evaluation package. Criticality safety is a concern for every phase of the fabrication process including UF{sub 6} cylinder storage, UF{sub 6}-UO{sub 2} conversion, powder storage, pelletizing, rod loading, assembly fabrication, and assembly transportation. Until 2003, the accepted criticality standards were based on the French CEA work performed in the late seventies with the APOLLO1 cell/assembly computer code. APOLLO1 is a spectral code, used for evaluating the basic characteristics of fuel assemblies for reactor physics applications, which has been enhanced to perform criticality safety calculations. Throughout the years, CRISTAL, starting with APOLLO1 and MORET 3 (a 3D Monte Carlo code), has been improved to account for the growth of its qualification database and for increasing user requirements. Today, CRISTAL V0 is an up-to-date computational tool incorporating a modern basic microscopic cross section set based on JEF2.2 and the comprehensive APOLLO2 and MORET 4 codes. APOLLO2 is well suited for criticality standards calculations as it includes a sophisticated self shielding approach, a P{sub ij} flux determination, and a 1D transport (S{sub n}) process. CRISTAL V0 is the result of more than five years of development work focusing on theoretical approaches and the implementation of user-friendly graphical interfaces. Due to its comprehensive physical simulation and thanks to its broad qualification database with more than a thousand benchmark/calculation comparisons, CRISTAL V0 provides outstanding and reliable accuracy for criticality evaluations for configurations covering the entire fuel cycle (i.e. from enrichment, pellet/assembly fabrication, transportation, to fuel reprocessing). After a brief description of the calculation scheme and the physics algorithms used in this code package, results for the various fissile media encountered in a UO{sub 2} fuel fabrication plant will be detailed and discussed. (authors)« less

Individualized prediction of perineural invasion in colorectal cancer: development and validation of a radiomics prediction model.

PubMed

Huang, Yanqi; He, Lan; Dong, Di; Yang, Caiyun; Liang, Cuishan; Chen, Xin; Ma, Zelan; Huang, Xiaomei; Yao, Su; Liang, Changhong; Tian, Jie; Liu, Zaiyi

2018-02-01

To develop and validate a radiomics prediction model for individualized prediction of perineural invasion (PNI) in colorectal cancer (CRC). After computed tomography (CT) radiomics features extraction, a radiomics signature was constructed in derivation cohort (346 CRC patients). A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen (CEA) level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation (separate from the cohort used to build the model) was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram. The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell's concordance index (c-index): 0.817; 95% confidence interval (95% CI): 0.811-0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination (c-index: 0.803; 95% CI: 0.794-0.812). Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment.

17 CFR Appendix to Part 48 - Form FBOT

Code of Federal Regulations, 2013 CFR

2013-04-01

... Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION REGISTRATION OF FOREIGN BOARDS OF... BOARD OF TRADE APPLICATION FOR REGISTRATION (IN ORDER TO PERMIT DIRECT ACCESS TO MEMBERS AND OTHER... foreign board of trade applying for registration pursuant to CEA section 4(b) and part 48 of the...

17 CFR Appendix to Part 48 - Form FBOT

Code of Federal Regulations, 2012 CFR

2012-04-01

... Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION REGISTRATION OF FOREIGN BOARDS OF... BOARD OF TRADE APPLICATION FOR REGISTRATION (IN ORDER TO PERMIT DIRECT ACCESS TO MEMBERS AND OTHER... foreign board of trade applying for registration pursuant to CEA section 4(b) and part 48 of the...

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

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.

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

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.

Comparing the cost-per-QALYs gained and cost-per-DALYs averted literatures.

PubMed

Neumann, Peter J; Anderson, Jordan E; Panzer, Ari D; Pope, Elle F; D'Cruz, Brittany N; Kim, David D; Cohen, Joshua T

2018-01-18

Background : We examined the similarities and differences between studies using two common metrics used in cost-effectiveness analyses (CEAs): cost per quality-adjusted life years (QALYs) gained and cost per disability-adjusted life year (DALY) averted. Methods : We used the Tufts Medical Center CEA Registry, which contains English-language cost-per-QALY gained studies, and  Global Cost-Effectiveness Analysis (GHCEA) Registry, which contains cost-per-DALY averted studies. We examined study characteristics including intervention type, sponsor, country, and primary disease, and also analysed the number of CEAs versus disease burden estimates for major diseases and conditions across three geographic regions. Results : We identified 6,438 cost-per-QALY and 543 cost-per-DALY studies published through 2016 and observed rapid growth in publication rates for both literatures. Cost-per-QALY studies were most likely to examine pharmaceuticals and interventions in high-income countries. Cost-per-DALY studies predominantly focused on infectious disease interventions and interventions in low and lower-middle income countries. We found discrepancies in the number of published CEAs for certain diseases and conditions in certain regions, suggesting "under-studied" areas (e.g., cardiovascular disease in Southeast Asia, East Asia, and Oceania and "overstudied" areas (e.g., HIV in Sub Saharan Africa) relative to disease burden in those regions. Conclusions : The number of cost-per QALY and cost-per-DALY analyses has grown rapidly with applications to diverse interventions and diseases.  Discrepancies between the number of published studies and disease burden suggest funding opportunities for future cost-effectiveness research.

Ghrelin Increases GABAergic Transmission and Interacts with Ethanol Actions in the Rat Central Nucleus of the Amygdala

PubMed Central

Cruz, Maureen T; Herman, Melissa A; Cote, Dawn M; Ryabinin, Andrey E; Roberto, Marisa

2013-01-01

The neural circuitry that processes natural rewards converges with that engaged by addictive drugs. Because of this common neurocircuitry, drugs of abuse have been able to engage the hedonic mechanisms normally associated with the processing of natural rewards. Ghrelin is an orexigenic peptide that stimulates food intake by activating GHS-R1A receptors in the hypothalamus. However, ghrelin also activates GHS-R1A receptors on extrahypothalamic targets that mediate alcohol reward. The central nucleus of the amygdala (CeA) has a critical role in regulating ethanol consumption and the response to ethanol withdrawal. We previously demonstrated that rat CeA GABAergic transmission is enhanced by acute and chronic ethanol treatment. Here, we used quantitative RT-PCR (qRT-PCR) to detect Ghsr mRNA in the CeA and performed electrophysiological recordings to measure ghrelin effects on GABA transmission in this brain region. Furthermore, we examined whether acute or chronic ethanol treatment would alter these electrophysiological effects. Our qRT-PCR studies show the presence of Ghsr mRNA in the CeA. In naive animals, superfusion of ghrelin increased the amplitude of evoked inhibitory postsynaptic potentials (IPSPs) and the frequency of miniature inhibitory postsynaptic currents (mIPSCs). Coapplication of ethanol further increased the ghrelin-induced enhancement of IPSP amplitude, but to a lesser extent than ethanol alone. When applied alone, ethanol significantly increased IPSP amplitude, but this effect was attenuated by the application of ghrelin. In neurons from chronic ethanol-treated (CET) animals, the magnitude of ghrelin-induced increases in IPSP amplitude was not significantly different from that in naive animals, but the ethanol-induced increase in amplitude was abolished. Superfusion of the GHS-R1A antagonists 𝒟-Lys3-GHRP-6 and JMV 3002 decreased evoked IPSP and mIPSC frequency, revealing tonic ghrelin activity in the CeA. 𝒟-Lys3-GHRP-6 and JMV 3002 also blocked ghrelin-induced increases in GABAergic responses. Furthermore, 𝒟-Lys3-GHRP-6 did not affect ethanol-induced increases in IPSP amplitude. These studies implicate a potential role for the ghrelin system in regulating GABAergic transmission and a complex interaction with ethanol at CeA GABAergic synapses. PMID:22968812

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.

[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.

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.

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.

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.

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

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.

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.

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.

Observations and Thermochemical Calculations for Hot-Jupiter Atmospheres

NASA Astrophysics Data System (ADS)

Blecic, Jasmina; Harrington, Joseph; Bowman, M. Oliver; Cubillos, Patricio; Stemm, Madison

2015-01-01

I present Spitzer eclipse observations for WASP-14b and WASP-43b, an open source tool for thermochemical equilibrium calculations, and components of an open source tool for atmospheric parameter retrieval from spectroscopic data. WASP-14b is a planet that receives high irradiation from its host star, yet, although theory does not predict it, the planet hosts a thermal inversion. The WASP-43b eclipses have signal-to-noise ratios of ~25, one of the largest among exoplanets. To assess these planets' atmospheric composition and thermal structure, we developed an open-source Bayesian Atmospheric Radiative Transfer (BART) code. My dissertation tasks included developing a Thermochemical Equilibrium Abundances (TEA) code, implementing the eclipse geometry calculation in BART's radiative transfer module, and generating parameterized pressure and temperature profiles so the radiative-transfer module can be driven by the statistical module.To initialize the radiative-transfer calculation in BART, TEA calculates the equilibrium abundances of gaseous molecular species at a given temperature and pressure. It uses the Gibbs-free-energy minimization method with an iterative Lagrangian optimization scheme. Given elemental abundances, TEA calculates molecular abundances for a particular temperature and pressure or a list of temperature-pressure pairs. The code is tested against the original method developed by White at al. (1958), the analytic method developed by Burrows and Sharp (1999), and the Newton-Raphson method implemented in the open-source Chemical Equilibrium with Applications (CEA) code. TEA, written in Python, is modular, documented, and available to the community via the open-source development site GitHub.com.Support for this work was provided by NASA Headquarters under the NASA Earth and Space Science Fellowship Program, grant NNX12AL83H, by NASA through an award issued by JPL/Caltech, and through the Science Mission Directorate's Planetary Atmospheres Program, grant NNX12AI69G.

Fast high-energy X-ray imaging for Severe Accidents experiments on the future PLINIUS-2 platform

NASA Astrophysics Data System (ADS)

Berge, L.; Estre, N.; Tisseur, D.; Payan, E.; Eck, D.; Bouyer, V.; Cassiaut-Louis, N.; Journeau, C.; Tellier, R. Le; Pluyette, E.

2018-01-01

The future PLINIUS-2 platform of CEA Cadarache will be dedicated to the study of corium interactions in severe nuclear accidents, and will host innovative large-scale experiments. The Nuclear Measurement Laboratory of CEA Cadarache is in charge of real-time high-energy X-ray imaging set-ups, for the study of the corium-water and corium-sodium interaction, and of the corium stratification process. Imaging such large and high-density objects requires a 15 MeV linear electron accelerator coupled to a tungsten target creating a high-energy Bremsstrahlung X-ray flux, with corresponding dose rate about 100 Gy/min at 1 m. The signal is detected by phosphor screens coupled to high-framerate scientific CMOS cameras. The imaging set-up is established using an experimentally-validated home-made simulation software (MODHERATO). The code computes quantitative radiographic signals from the description of the source, object geometry and composition, detector, and geometrical configuration (magnification factor, etc.). It accounts for several noise sources (photonic and electronic noises, swank and readout noise), and for image blur due to the source spot-size and to the detector unsharpness. In a view to PLINIUS-2, the simulation has been improved to account for the scattered flux, which is expected to be significant. The paper presents the scattered flux calculation using the MCNP transport code, and its integration into the MODHERATO simulation. Then the validation of the improved simulation is presented, through confrontation to real measurement images taken on a small-scale equivalent set-up on the PLINIUS platform. Excellent agreement is achieved. This improved simulation is therefore being used to design the PLINIUS-2 imaging set-ups (source, detectors, cameras, etc.).

75 FR 66829 - Determination of Foreign Exchange Swaps and Forwards

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-29

... Commodity Exchange Act (``CEA''), as amended by Title VII of the Dodd-Frank Wall Street Reform and Consumer... the application of the factors that the Secretary must consider in making a determination regarding... Treasury must consider the following factors: \\7\\ Notwithstanding any such determination by the Secretary...

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.

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.

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.

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.

Ability of thermochemical calculation to treat organic peroxides

NASA Astrophysics Data System (ADS)

Osmont, Antoine; Baudin, Gérard; Genetier, Marc

2017-06-01

Since 3 years, the CEA Gramat is developing a new thermochemical code, called SIAME, funded by DGA to help French defense industry at conceiving new explosives compositions. It enables the calculation of CJ detonation and deflagration points and combustion of explosives. The accuracy of the code has been checked on several compositions containing PETN, RDX, HMX, TNT, NTO. The error on the velocity of detonation is 3%. To enlarge the domain of validity of the code, organic peroxides have been considered. It is known that thermochemical simulation is in failure regarding compounds as simple as hydrogen peroxide. The computed velocity of detonation is 5720 m/s when shock planar impact gives 6150 m/s. The same discrepancy is found for TATP, with a calculated value at 5870 m/s when 5290 has been measured. Detonation velocity of TATP has been measured at two different densities. These velocities agree with other published values. A closer look at the enthalpy of formation of TATP has revealed that it comes from an article of 1932. Ab initio computations have given a totally different value, leading to better agreement with experiment.

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 in patients undergoing carotid revascularization. Conclusions In our regional vascular surgical practices, the overall outcomes of CAS and CEA are similar for asymptomatic patients. However, symptomatic patients treated with CAS are at a higher risk for stroke or death. (J Vasc Surg 2012;56:990-6.) PMID:22579135

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 carotid artery stenosis is from 0% to 100%. Similarly, at the center level, institutions range in the percentage of CEA procedures performed for a <80% asymptomatic carotid artery stenosis from 0% to 100%. Despite CEA being an extremely common procedure, there is widespread variation in the three primary determinants-preoperative imaging, carotid duplex ultrasound criteria, and threshold for surgery-of whether CEA is performed for asymptomatic carotid stenosis. Standardizing the approach to care for asymptomatic carotid artery stenosis will mitigate the significant downstream effects of this variation on health care costs. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

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...

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.

[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.

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

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.

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.

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

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%.

Good research practices for measuring drug costs in cost-effectiveness analyses: a societal perspective: the ISPOR Drug Cost Task Force report--Part II.

PubMed

Garrison, Louis P; Mansley, Edward C; Abbott, Thomas A; Bresnahan, Brian W; Hay, Joel W; Smeeding, James

2010-01-01

Major guidelines regarding the application of cost-effectiveness analysis (CEA) have recommended the common and widespread use of the "societal perspective" for purposes of consistency and comparability. The objective of this Task Force subgroup report (one of six reports from the International Society for Pharmacoeconomics and Outcomes Research [ISPOR] Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis [Drug Cost Task Force (DCTF)]) was to review the definition of this perspective, assess its specific application in measuring drug costs, identify any limitations in theory or practice, and make recommendations regarding potential improvements. Key articles, books, and reports in the methodological literature were reviewed, summarized, and integrated into a draft review and report. This draft report was posted for review and comment by ISPOR membership. Numerous comments and suggestions were received, and the report was revised in response to them. The societal perspective can be defined by three conditions: 1) the inclusion of time costs, 2) the use of opportunity costs, and 3) the use of community preferences. In practice, very few, if any, published CEAs have met all of these conditions, though many claim to have taken a societal perspective. Branded drug costs have typically used actual acquisition cost rather than the much lower social opportunity costs that would reflect only short-run manufacturing and distribution costs. This practice is understandable, pragmatic, and useful to current decision-makers. Nevertheless, this use of CEA focuses on static rather than dynamic efficacy and overlooks the related incentives for innovation. Our key recommendation is that current CEA practice acknowledge and embrace this limitation by adopting a new standard for the reference case as one of a "limited societal" or "health systems" perspective, using acquisition drug prices while including indirect costs and community preferences. The field of pharmacoeconomics also needs to acknowledge the limitations of this perspective when it comes to important questions of research and development costs, and incentives for innovation.

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.

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.

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

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.

French Atomic Energy Commission Decommissioning Programme and Feedback Experience - 12230

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

Guiberteau, Ph.; Nokhamzon, J.G.

Since the French Atomic and Alternatives Energy Commission (CEA) was founded in 1945 to carry out research programmes on use of nuclear, and its application France has set up and run various types of installations: research or prototypes reactors, process study or examination laboratories, pilot installations, accelerators, nuclear power plants and processing facilities. Some of these are currently being dismantled or must be dismantled soon so that the DEN, the Nuclear Energy Division, can construct new equipment and thus have available a range of R and D facilities in line with the issues of the nuclear industry of the future.more » Since the 1960's and 1970's in all its centres, the CEA has acquired experience and know-how through dismantling various nuclear facilities. The dismantling techniques are nowadays operational, even if sometimes certain specific developments are necessary to reduce the cost of operations. Thanks to availability of techniques and guarantees of dismantling programme financing now from two dedicated funds, close to euro 15,000 M for the next thirty years, for current or projected dismantling operations, the CEA's Nuclear Energy Division has been able to develop, when necessary, its immediate dismantling strategy. Currently, nearly thirty facilities are being dismantled by the CEA's Nuclear Energy Division operational units with industrial partners. Thus the next decade will see completion of the dismantling and radioactive clean-up of the Grenoble site and of the facilities on the Fontenay-aux-Roses site. By 2016, the dismantling of the UP1 plant at Marcoule, the largest dismantling work in France, will be well advanced, with all the process equipment dismantled. After an overview of the French regulatory framework, the paper will describe the DD and R (Decontamination Decommissioning and Remediation) strategy, programme and feedback experience inside the CEA's Nuclear Energy Division. A special feature of dismantling operations at the CEA comes from the diversity of facilities to be dismantled, which are predominantly research facilities and therefore have no series advantage. There is tremendous operating feedback, however. For more than twenty years in all its centres, the CEA has acquired experience and know-how through dismantling research reactors or critical models and laboratories or plants. The dismantling techniques are nowadays operational, even if sometimes certain specific developments are necessary to reduce the cost of operations. Thanks to availability of techniques and guarantees of dismantling programme financing from two dedicated funds, close to euro 15,000 Millions for the next thirty years, for current or projected dismantling operations, the Nuclear Energy Division has been able to develop, when necessary, its immediate dismantling strategy. Currently, nearly thirty facilities are being dismantled by the CEA's Nuclear Energy Division operational units with industrial partners. Thus the next decade will see completion of the dismantling and radioactive clean-up of the Grenoble site and of the facilities on the Fontenay-aux-Roses site. By 2020, the dismantling of the UP1 plant at Marcoule, one of the largest dismantling works in the world, will be well advanced, with all the process equipment dismantled. (authors)« less

Simplified Two-Time Step Method for Calculating Combustion and Emission Rates of Jet-A and Methane Fuel With and Without Water Injection

NASA Technical Reports Server (NTRS)

Molnar, Melissa; Marek, C. John

2005-01-01

A simplified kinetic scheme for Jet-A, and methane fuels with water injection was developed to be used in numerical combustion codes, such as the National Combustor Code (NCC) or even simple FORTRAN codes. The two time step method is either an initial time averaged value (step one) or an instantaneous value (step two). The switch is based on the water concentration in moles/cc of 1x10(exp -20). The results presented here results in a correlation that gives the chemical kinetic time as two separate functions. This two time step method is used as opposed to a one step time averaged method previously developed to determine the chemical kinetic time with increased accuracy. The first time averaged step is used at the initial times for smaller water concentrations. This gives the average chemical kinetic time as a function of initial overall fuel air ratio, initial water to fuel mass ratio, temperature, and pressure. The second instantaneous step, to be used with higher water concentrations, gives the chemical kinetic time as a function of instantaneous fuel and water mole concentration, pressure and temperature (T4). The simple correlations would then be compared to the turbulent mixing times to determine the limiting rates of the reaction. The NASA Glenn GLSENS kinetics code calculates the reaction rates and rate constants for each species in a kinetic scheme for finite kinetic rates. These reaction rates are used to calculate the necessary chemical kinetic times. Chemical kinetic time equations for fuel, carbon monoxide and NOx are obtained for Jet-A fuel and methane with and without water injection to water mass loadings of 2/1 water to fuel. A similar correlation was also developed using data from NASA's Chemical Equilibrium Applications (CEA) code to determine the equilibrium concentrations of carbon monoxide and nitrogen oxide as functions of overall equivalence ratio, water to fuel mass ratio, pressure and temperature (T3). The temperature of the gas entering the turbine (T4) was also correlated as a function of the initial combustor temperature (T3), equivalence ratio, water to fuel mass ratio, and pressure.

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

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.

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.

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

Development of Fast NbN RSFQ Logic Gates in Sigma-Delta Converters for Space Telecommunications

DTIC Science & Technology

2005-07-13

spatiales des circuits logiques supraconducteurs ” Internal Technical Reports, Alcatel Space & CEA, 2003. [3] P. Bunyk, K. Likharev and D. Zinoviev...films minces et de junctions Josephson en nitrures supraconducteurs (TiN et NbN), application à la logique RSFQ, PhD Thesis, Université J. Fourier

17 CFR Appendix to Part 48 - Form FBOT

Code of Federal Regulations, 2014 CFR

2014-04-01

... BOARDS OF TRADE Pt. 48, App. Appendix to Part 48—Form FBOT COMMODITY FUTURES TRADING COMMISSION FORM FBOT FOREIGN BOARD OF TRADE APPLICATION FOR REGISTRATION (IN ORDER TO PERMIT DIRECT ACCESS TO MEMBERS AND OTHER... foreign board of trade applying for registration pursuant to CEA section 4(b) and part 48 of the...

77 FR 50998 - Proposal To Exempt Certain Transactions Involving Not-for-Profit Electric Utilities; Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-23

.... Responsible Economic or Financial Innovation and Fair Competition 2. Applicability of CEA Section 4(a) 3... ``promote responsible economic or financial innovation and fair competition'' by exempting any transaction...), provides in full that: In order to promote responsible economic or financial innovation and fair...

Potentiometric Sensors Based on Surface Molecular Imprinting: Detection of Cancer Biomarkers and Viruses

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

Wang, Y.; Zhang, Z; Jain, V

2010-01-01

The continuing discovery of cancer biomarkers necessitates improved methods for their detection. Molecular imprinting using artificial materials provides an alternative to the detection of a wide range of substances. We applied surface molecular imprinting using self-assembled monolayers to design sensing elements for the detection of cancer biomarkers and other proteins. These elements consist of a gold-coated silicon chip onto which hydroxyl-terminated alkanethiol molecules and template biomolecule are co-adsorbed, where the thiol molecules are chemically bound to the metal substrate and self-assembled into highly ordered monolayers, the biomolecules can be removed, creating the foot-print cavities in the monolayer matrix for thismore » kind of template molecules. Re-adsorption of the biomolecules to the sensing chip changes its potential, which can be measured potentiometrically. We applied this method to the detection of carcinoembryonic antigen (CEA) in both solutions of purified CEA and in the culture medium of a CEA-producing human colon cancer cell line. The CEA assay, validated also against a standard immunoassay, was both sensitive (detection range 2.5-250 ng/mL) and specific (no cross-reactivity with hemoglobin; no response by a non-imprinted sensor). Similar results were obtained for human amylase. In addition, we detected virions of poliovirus in a specific manner (no cross-reactivity to adenovirus, no response by a non-imprinted sensor). Our findings demonstrate the application of the principles of molecular imprinting to the development of a new method for the detection of protein cancer biomarkers and to protein-based macromolecular structures such as the capsid of a virion. This approach has the potential of generating a general assay methodology that could be highly sensitive, specific, simple and likely inexpensive.« less

Pretargeting of carcinoembryonic antigen-expressing cancers with a trivalent bispecific fusion protein produced in myeloma cells.

PubMed

Rossi, Edmund A; Chang, Chien-Hsing; Losman, Michele J; Sharkey, Robert M; Karacay, Habibe; McBride, William; Cardillo, Thomas M; Hansen, Hans J; Qu, Zhengxing; Horak, Ivan D; Goldenberg, David M

2005-10-01

To characterize a novel trivalent bispecific fusion protein and evaluate its potential utility for pretargeted delivery of radionuclides to tumors. hBS14, a recombinant fusion protein that binds bispecifically to carcinoembryonic antigen (CEA) and the hapten, histamine-succinyl-glycine (HSG), was produced by transgenic myeloma cells and purified to near homogeneity in a single step using a novel HSG-based affinity chromatography system. Biochemical characterization included size-exclusion high-performance liquid chromatography (SE-HPLC), SDS-PAGE, and isoelectric focusing. Functional characterization was provided by BIAcore and SE-HPLC. The efficacy of hBS14 for tumor pretargeting was evaluated in CEA-expressing GW-39 human colon tumor-bearing nude mice using a bivalent HSG hapten (IMP-241) labeled with (111)In. Biochemical analysis showed that single-step affinity chromatography provided highly purified material. SE-HPLC shows a single protein peak consistent with the predicted molecular size of hBS14. SDS-PAGE analysis shows only two polypeptide bands, which are consistent with the calculated molecular weights of the hBS14 polypeptides. BIAcore showed the bispecific binding properties and suggested that hBS14 possesses two functional CEA-binding sites. This was supported by SE-HPLC immunoreactivity experiments. All of the data suggest that the structure of hBS14 is an 80 kDa heterodimer with one HSG and two CEA binding sites. Pretargeting experiments in the mouse model showed high uptake of radiopeptide in the tumor, with favorable tumor-to-nontumor ratios as early as 3 hours postinjection. The results indicate that hBS14 is an attractive candidate for use in a variety of pretargeting applications, particularly tumor therapy with radionuclides and drugs.

Platinum porous nanoparticles hybrid with metal ions as probes for simultaneous detection of multiplex cancer biomarkers.

PubMed

Wang, Zifeng; Liu, Na; Ma, Zhanfang

2014-03-15

In this work, platinum porous nanoparticles (PtPNPs) absorbed metal ions as electrochemical signals were fabricated. Clean-surface PtPNPs were prepared by a surfactant-free method and decorated with amino groups via 2-aminoethanethiol. Amino capped PtPNPs complexation with Cd(2+) and Cu(2+) to form PtPNPs-Cd(2+) and PtPNPs-Cu(2+) hybrids, respectively. Anti-CEA and Anti-AFP separately labeled with PtPNPs-Cd(2+) and PtPNPs-Cu(2+) were used as distinguishable signal tags for capturing antigens. The metal ions were detected in a single run through differential pulse voltammetry (DPV) without acid dissolution, electric potentials and peak heights of which reflected the identity and concentrations of the corresponding antigen. Ionic liquid reduced graphene oxide (IL-rGO) modified glassy carbon electrode (GCE) was used as a substrate, which was rich in amino groups to immobilize antibodies by glutaraldehyde through cross-link between aldehyde groups and amino groups. Using the proposed probes and platform, a novel sandwich-type electrochemical immunosensor for simultaneous detecting carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) was successfully developed. This immunoassay possessed good linearity from 0.05 ng mL(-1) to 200 ng mL(-1) for both CEA and AFP. The detection limit of CEA was 0.002 ng mL(-1) and that of AFP was 0.05 ng mL(-1) (S/N=3). Furthermore, analysis of clinical serum samples using this immunosensor was well consistent with the data determined by the enzyme-linked immunosorbent assay (ELISA). It suggested that the proposed electrochemical immunoassay provided a potential application of clinical screening for early-stage cancers. © 2013 Published by Elsevier B.V.

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.

[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 and malignant pleural effusion. Although the diagnostic value of B7-H4 may not precede to CEA, the combined detection of B7-H4 and CEA can improve the diagnostic sensitivity and specificity of MPE.

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.

[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.

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

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

[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.

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

Tommasi, J.; Ruggieri, J. M.; Lebrat, J. F.

The latest release (2.1) of the ERANOS code system, using JEF-2.2, JEFF-3.1 and ENDF/B-VI r8 multigroup cross-section libraries is currently being validated on fast reactor critical experiments at CEA-Cadarache (France). This paper briefly presents the library effect studies and the detailed best-estimate validation studies performed up to now as part of the validation process. The library effect studies are performed over a wide range of experimental configurations, using simple model and method options. They yield global trends about the shift from JEF-2.2 to JEFF-3.1 cross-section libraries, that can be related to individual sensitivities and cross-section changes. The more detailed, best-estimate,more » calculations have been performed up to now over three experimental configurations carried out in the MASURCA critical facility at CEA-Cadarache: two cores with a softened spectrum due to large amounts of graphite (MAS1A' and MAS1B), and a core representative of sodium-cooled fast reactors (CIRANO ZONA2A). Calculated values have been compared to measurements, and discrepancies analyzed in detail using perturbation theory. Values calculated with JEFF-3.1 were found to be within 3 standard deviations of the measured values, and at least of the same quality as the JEF-2.2 based results. (authors)« less

Prompt gamma neutron activation analysis of toxic elements in radioactive waste packages.

PubMed

Ma, J-L; Carasco, C; Perot, B; Mauerhofer, E; Kettler, J; Havenith, A

2012-07-01

The French Alternative Energies and Atomic Energy Commission (CEA) and National Radioactive Waste Management Agency (ANDRA) are conducting an R&D program to improve the characterization of long-lived and medium activity (LL-MA) radioactive waste packages. In particular, the amount of toxic elements present in radioactive waste packages must be assessed before they can be accepted in repository facilities in order to avoid pollution of underground water reserves. To this aim, the Nuclear Measurement Laboratory of CEA-Cadarache has started to study the performances of Prompt Gamma Neutron Activation Analysis (PGNAA) for elements showing large capture cross sections such as mercury, cadmium, boron, and chromium. This paper reports a comparison between Monte Carlo calculations performed with the MCNPX computer code using the ENDF/B-VII.0 library and experimental gamma rays measured in the REGAIN PGNAA cell with small samples of nickel, lead, cadmium, arsenic, antimony, chromium, magnesium, zinc, boron, and lithium to verify the validity of a numerical model and gamma-ray production data. The measurement of a ∼20kg test sample of concrete containing toxic elements has also been performed, in collaboration with Forschungszentrum Jülich, to validate the model in view of future performance studies for dense and large LL-MA waste packages. Copyright © 2012 Elsevier Ltd. All rights reserved.

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 due to the delayed gamma rays. In this paper we describe experiments in each of the three reactors and how we estimate delayed gamma rays with MIC measurements. The results and perspectives are discussed. (authors)« less

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 patients aged 70-74 years and older. The difference in older patients was almost wholly attributable to increasing periprocedural stroke risk in patients treated with CAS. Age had little effect on CEA periprocedural risk or on postprocedural risk after either procedure. None. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

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.

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.

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.

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.

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.

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

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

Corticotropin-Releasing Factor Modulation of Forebrain GABAergic Transmission has a Pivotal Role in the Expression of Anabolic Steroid-Induced Anxiety in the Female Mouse

PubMed Central

Oberlander, Joseph G; Henderson, Leslie P

2012-01-01

Increased anxiety is commonly observed in individuals who illicitly administer anabolic androgenic steroids (AAS). Behavioral effects of steroid abuse have become an increasing concern in adults and adolescents of both sexes. The dorsolateral bed nucleus of the stria terminalis (dlBnST) has a critical role in the expression of diffuse anxiety and is a key site of action for the anxiogenic neuromodulator, corticotropin releasing factor (CRF). Here we demonstrate that chronic, but not acute, exposure of female mice during adolescence to AAS augments anxiety-like behaviors; effects that were blocked by central infusion of the CRF receptor type 1 antagonist, antalarmin. AAS treatment selectively increased action potential (AP) firing in neurons of the central amygdala (CeA) that project to the dlBnST, increased the frequency of GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in dlBnST target neurons, and decreased both c-FOS immunoreactivity (IR) and AP frequency in these postsynaptic cells. Acute application of antalarmin abrogated the enhancement of GABAergic inhibition induced by chronic AAS exposure whereas application of CRF to brain slices of naïve mice mimicked the actions of this treatment. These results, in concert with previous data demonstrating that chronic AAS treatment results in enhanced levels of CRF mRNA in the CeA and increased CRF-IR in the dlBnST neuropil, are consistent with a mechanism in which the enhanced anxiety elicited by chronic AAS exposure involves augmented inhibitory activity of CeA afferents to the dlBnST and CRF-dependent enhancement of GABAergic inhibition in this brain region. PMID:22298120

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…

[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.

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.

[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.

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.

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

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.

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 well tolerated and capable of eliciting anti-CEA host immune responses in early clinical studies. The results suggest that the administration of a recombinant poxvirus-based vaccine is compatible with celecoxib, and this combined chemoimmuno-based approach might lead to an additive therapeutic antitumor benefit not only in patients diagnosed with familial adenomatous polyposis but, perhaps, in other preventive settings in which COX-2 overexpression is associated with progression from premalignancy to neoplasia.

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 before carotid surgery was 4 times less likely to have a cardiac ischaemic event after carotid surgery. No complications related to coronary angiography were observed and no cervical haematomas occurred in patients undergoing surgery under aspirin and clopidogrel in this study. Systematic preoperative coronary angiography, possibly followed by PCI, significantly reduces the incidence of postoperative myocardial events after CEA in patients without clinical evidence of CAD. Copyright (c) 2009 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

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 performed. Clinical relevance will be measured as relative risk reduction, absolute risk reduction and the number needed to treat. Reduction of the periprocedural complications of CEA using sonolysis as a widely available and cheap method may significantly increase the safety of CEA and extend the indication criteria for CEA. ClinicalTrials.gov, NCT02398734 . Registered on 20 March 2015.

Incorporating interaction networks into the determination of functionally related hit genes in genomic experiments with Markov random fields

PubMed Central

Robinson, Sean; Nevalainen, Jaakko; Pinna, Guillaume; Campalans, Anna; Radicella, J. Pablo; Guyon, Laurent

2017-01-01

Abstract Motivation: Incorporating gene interaction data into the identification of ‘hit’ genes in genomic experiments is a well-established approach leveraging the ‘guilt by association’ assumption to obtain a network based hit list of functionally related genes. We aim to develop a method to allow for multivariate gene scores and multiple hit labels in order to extend the analysis of genomic screening data within such an approach. Results: We propose a Markov random field-based method to achieve our aim and show that the particular advantages of our method compared with those currently used lead to new insights in previously analysed data as well as for our own motivating data. Our method additionally achieves the best performance in an independent simulation experiment. The real data applications we consider comprise of a survival analysis and differential expression experiment and a cell-based RNA interference functional screen. Availability and implementation: We provide all of the data and code related to the results in the paper. Contact: sean.j.robinson@utu.fi or laurent.guyon@cea.fr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28881978

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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 innovation, while supporting health-care systems to pursue dynamic allocative efficiency. However, the long-term sustainability of health-care systems must be assessed before this proposal is adopted by policy makers.

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 of this value, thereby incentivizing innovation, while supporting health-care systems to pursue dynamic allocative efficiency. However, the long-term sustainability of health-care systems must be assessed before this proposal is adopted by policy makers. PMID:27123192

Will mesh-covered stents help reduce stroke associated with carotid stent angioplasty?

PubMed

Richards, Carly N; Schneider, Peter A

2017-03-01

Carotid stent angioplasty (CAS) has been shown to protect patient from future stroke long-term efficacy similar to carotid endarterectomy (CEA). The risk of minor stroke in the perioperative period is higher than with CEA and not related to cerebral protection during the CAS procedure since a significant portion of the neurologic events occur between 1 and 30 days following stent deployment. This observation suggests mechanisms integral to the stent itself may be pertinent such as plaque embolization thru the stent struts may occur. It appears that this embolic risk can be reduced by use of specific carotid stent designs that include a mesh covering to minimize the open struts areas and thus embolization through the carotid stent. Improvements in stent design that eliminate post-procedural debris embolization will expand the application of CAS for severe internal carotid artery atherosclerotic stenosis. Copyright © 2017. Published by Elsevier Inc.

Growth Conditions To Reduce Oxalic Acid Content of Spinach

NASA Technical Reports Server (NTRS)

Johnson-Rutzke, Corinne

2003-01-01

A controlled-environment agricultural (CEA) technique to increase the nutritive value of spinach has been developed. This technique makes it possible to reduce the concentration of oxalic acid in spinach leaves. It is desirable to reduce the oxalic acid content because oxalic acid acts as an anti-nutritive calcium-binding component. More than 30 years ago, an enzyme (an oxidase) that breaks down oxalic acid into CO2 and H2O2 was discovered and found to be naturally present in spinach leaves. However, nitrate, which can also be present because of the use of common nitratebased fertilizers, inactivates the enzyme. In the CEA technique, one cuts off the supply of nitrate and keeps the spinach plants cool while providing sufficient oxygen. This technique provides the precise environment that enables the enzyme to naturally break down oxalate. The result of application of this technique is that the oxalate content is reduced by 2/3 in one week.

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.

A Monte Carlo Simulation of Prompt Gamma Emission from Fission Fragments

NASA Astrophysics Data System (ADS)

Regnier, D.; Litaize, O.; Serot, O.

2013-03-01

The prompt fission gamma spectra and multiplicities are investigated through the Monte Carlo code FIFRELIN which is developed at the Cadarache CEA research center. Knowing the fully accelerated fragment properties, their de-excitation is simulated through a cascade of neutron, gamma and/or electron emissions. This paper presents the recent developments in the FIFRELIN code and the results obtained on the spontaneous fission of 252Cf. Concerning the decay cascades simulation, a fully Hauser-Feshbach model is compared with a previous one using a Weisskopf spectrum for neutron emission. A particular attention is paid to the treatment of the neutron/gamma competition. Calculations lead using different level density and gamma strength function models show significant discrepancies of the slope of the gamma spectra at high energy. The underestimation of the prompt gamma spectra obtained regardless our de-excitation cascade modeling choice is discussed. This discrepancy is probably linked to an underestimation of the post-neutron fragments spin in our calculation.

Divergent Routing of Positive and Negative Information from the Amygdala during Memory Retrieval.

PubMed

Beyeler, Anna; Namburi, Praneeth; Glober, Gordon F; Simonnet, Clémence; Calhoon, Gwendolyn G; Conyers, Garrett F; Luck, Robert; Wildes, Craig P; Tye, Kay M

2016-04-20

Although the basolateral amygdala (BLA) is known to play a critical role in the formation of memories of both positive and negative valence, the coding and routing of valence-related information is poorly understood. Here, we recorded BLA neurons during the retrieval of associative memories and used optogenetic-mediated phototagging to identify populations of neurons that synapse in the nucleus accumbens (NAc), the central amygdala (CeA), or ventral hippocampus (vHPC). We found that despite heterogeneous neural responses within each population, the proportions of BLA-NAc neurons excited by reward predictive cues and of BLA-CeA neurons excited by aversion predictive cues were higher than within the entire BLA. Although the BLA-vHPC projection is known to drive behaviors of innate negative valence, these neurons did not preferentially code for learned negative valence. Together, these findings suggest that valence encoding in the BLA is at least partially mediated via divergent activity of anatomically defined neural populations. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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

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.

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

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.

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.

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.

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.

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

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.

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

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.

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.

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).

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.

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 assist future studies using the CEA and Severin classification in the radiographic assessment of DDH treatment outcomes.

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 of CEAs in critical care may increase the number and improve the quality of future CEAs.

Proximity hybridization-regulated chemiluminescence resonance energy transfer for homogeneous immunoassay.

PubMed

Liu, Mengmeng; Wu, Jie; Yang, Kaili; Zong, Chen; Lei, Jianping; Ju, Huangxian

2016-07-01

Chemiluminescence resonance energy transfer (CRET) and the proximity ligation assay have been widely used in design of sensors for the bioanalysis. Here, a wash-free and homogeneous strategy was proposed to detect carcino-embryonic antigen (CEA) based on proximity hybridization-regulated CRET. The Cy5 demonstrated strong chemiluminescence (CL) via the oxidation of TCPO in the presence of H2O2 and energy transfer between excited TCPO and Cy5. Graphene oxide (GO) as an excellent quencher was used to produce the "Signal off" mode that little CL emission was observed through CRET between GO and the Cy5-labelled DNA3. Once CEA was introduced, the target-induced proximity hybridization occurred to form a proximate complex, which inhibited the CRET by preventing GO from absorbing Cy5-labelled DNA3. Furthermore, taking advantage of nicking endonuclease Nt.BbvCI for in situ recycling, the signal could be further amplified for highly sensitive CL detection. Our results showed that this strategy enabled a specific response to CEA with a detection range of 5 orders of magnitude, along with a detection limit of 3.2pg mL(-1). Apart from its easy operation, high sensitivity and acceptable accuracy, the proposed method needed only 0.3μL of sample, indicating its great opportunity for commercial application. Copyright © 2016 Elsevier B.V. All rights reserved.

How have systematic priority setting approaches influenced policy making? A synthesis of the current literature.

PubMed

Kapiriri, Lydia; Razavi, Donya

2017-09-01

There is a growing body of literature on systematic approaches to healthcare priority setting from various countries and different levels of decision making. This paper synthesizes the current literature in order to assess the extent to which program budgeting and marginal analysis (PBMA), burden of disease & cost-effectiveness analysis (BOD/CEA), multi-criteria decision analysis (MCDA), and accountability for reasonableness (A4R), are reported to have been institutionalized and influenced policy making and practice. We searched for English language publications on health care priority setting approaches (2000-2017). Our sources of literature included PubMed and Ovid databases (including Embase, Global Health, Medline, PsycINFO, EconLit). Of the four approaches PBMA and A4R were commonly applied in high income countries while BOD/CEA was exclusively applied in low income countries. PBMA and BOD/CEA were most commonly reported to have influenced policy making. The explanations for limited adoption of an approach were related to its complexity, poor policy maker understanding and resource requirements. While systematic approaches have the potential to improve healthcare priority setting; most have not been adopted in routine policy making. The identified barriers call for sustained knowledge exchange between researchers and policy-makers and development of practical guidelines to ensure that these frameworks are more accessible, applicable and sustainable in informing policy making. Copyright © 2017 Elsevier B.V. All rights reserved.

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 CEA could improve the diagnostic sensitivity and specificity for MPE. © 2017 John Wiley & Sons Ltd.

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 food derived from genetically engineered plants, http://www.icmr.nic.in/guide/Guidelines%20for%20Genetically%20Engineered%20Plants.pdf , 2008). Bioinformatics analysis, pepsin digestibility, thermal stability assay, immuno-screening and allergenicity assessment in BALB/c mice model demonstrated that the expressed CEA protein from transgenic B. juncea does not incite any allergenic response. The present study establishes CEA as an efficient insecticidal and non-allergenic protein to be utilized for controlling mustard aphid and similar hemipteran insects through the development of genetically modified plants.

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 stroke or death at 90 days. This study suggests that previous or simultaneous CEA in patients with unilateral severe asymptomatic carotid stenosis undergoing CABG could prevent stroke better than delayed CEA, without increasing the overall surgical risk. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

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. However, heavy hookah smoking substantially raises CEA levels. Low-nitrosamines smokeless tobacco of the SNUS Swedish type could be envisaged as an alternative to smoking for this category of users and also, in a broad harm reduction perspective, to the prevalent low-quality moist snuff called naswar.

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.

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.

[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 significance to MPE, especially MPE caused by adenocarcinoma. The diagnostic value of pleural fluid CEA is superior to serum CEA.

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 critical neurobiological mechanism that is required for alcohol dependence, suggesting that targeting dependence neuronal ensembles may lead to a better understanding of the etiology of alcohol use disorders, with implications for diagnosis, prevention, and treatment. Copyright © 2016 the authors 0270-6474/16/369446-08$15.00/0.

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, however, no significant difference for combined 30-day risk of death/stroke/myocardial infarction. Outcomes of hybrid or simultaneous CAS/CABG procedures show comparable results, albeit from rather small cohorts. While current evidence leans towards simultaneous CEA/CABG, the emergence of hybrid operating theatres in various institutions may allow larger cohorts with subsequent significant data on simultaneous CAS/CABG. A randomized controlled trial comparing both approaches would be crucial in informing future updates of existing guidelines. PMID:24368551

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

Thermal conductivity is a key property that must be known for proper design, testing, and deployment of new fuels and structural materials in nuclear reactors. Thermal conductivity is highly dependent on the physical structure, chemical composition, and the state of the material. Typically, thermal conductivity changes that occur during irradiation are currently measured out-of-pile using a 'cook and look' approach. But repeatedly removing samples from a test reactor to make measurements is expensive, has the potential to disturb phenomena of interest, and only provides understanding of the sample's end state when each measurement is made. There are also limited thermo-physicalmore » property data available for advanced fuels; and such data are needed for simulation codes, the development of next generation reactors, and advanced fuels for existing nuclear plants. Being able to quickly characterize fuel thermal conductivity during irradiation can improve the fidelity of data, reduce costs of post-irradiation examinations, increase understanding of how fuels behave under irradiation, and confirm or improve existing thermal conductivity measurement techniques. This paper discusses efforts to develop and evaluate an innovative in-pile thermal conductivity sensor based on the transient hot wire thermal conductivity method (THWM), using a single needle probe (NP) containing a line heat source and thermocouple embedded in the fuel. The sensor that has been designed and manufactured by the Idaho National Laboratory (INL) includes a unique combination of materials, geometry, and fabrication techniques that make the hot wire method suitable for in-pile applications. In particular, efforts were made to minimize the influence of the sensor and maximize fuel hot-wire heating. The probe has a thermocouple-like construction with high temperature resistant materials that remain ductile while resisting transmutation and materials interactions. THWM-NP prototypes were fabricated 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

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.

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.

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

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.

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

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.

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

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

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.

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.

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.

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.

Detection of special nuclear materials with the associate particle technique

NASA Astrophysics Data System (ADS)

Carasco, Cédric; Deyglun, Clément; Pérot, Bertrand; Eléon, Cyrille; Normand, Stéphane; Sannié, Guillaume; Boudergui, Karim; Corre, Gwenolé; Konzdrasovs, Vladimir; Pras, Philippe

2013-04-01

In the frame of the French trans-governmental R&D program against chemical, biological, radiological, nuclear and explosives (CBRN-E) threats, CEA is studying the detection of Special Nuclear Materials (SNM) by neutron interrogation with fast neutrons produced by an associated particle sealed tube neutron generator. The deuterium-tritium fusion reaction produces an alpha particle and a 14 MeV neutron almost back to back, allowing tagging neutron emission both in time and direction with an alpha particle position-sensitive sensor embedded in the generator. Fission prompt neutrons and gamma rays induced by tagged neutrons which are tagged by an alpha particle are detected in coincidence with plastic scintillators. This paper presents numerical simulations performed with the MCNP-PoliMi Monte Carlo computer code and with post processing software developed with the ROOT data analysis package. False coincidences due to neutron and photon scattering between adjacent detectors (cross talk) are filtered out to increase the selectivity between nuclear and benign materials. Accidental coincidences, which are not correlated to an alpha particle, are also taken into account in the numerical model, as well as counting statistics, and the time-energy resolution of the data acquisition system. Such realistic calculations show that relevant quantities of SNM (few kg) can be distinguished from cargo and shielding materials in 10 min acquisitions. First laboratory tests of the system under development in CEA laboratories are also presented.

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

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.

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.

Development and potential applications of microarrays based on fluorescent nanocrystal-encoded beads for multiplexed cancer diagnostics

NASA Astrophysics Data System (ADS)

Brazhnik, Kristina; Grinevich, Regina; Efimov, Anton E.; Nabiev, Igor; Sukhanova, Alyona

2014-05-01

Advanced multiplexed assays have recently become an indispensable tool for clinical diagnostics. These techniques provide simultaneous quantitative determination of multiple biomolecules in a single sample quickly and accurately. The development of multiplex suspension arrays is currently of particular interest for clinical applications. Optical encoding of microparticles is the most available and easy-to-use technique. This technology uses fluorophores incorporated into microbeads to obtain individual optical codes. Fluorophore-encoded beads can be rapidly analyzed using classical flow cytometry or microfluidic techniques. We have developed a new generation of highly sensitive and specific diagnostic systems for detection of cancer antigens in human serum samples based on microbeads encoded with fluorescent quantum dots (QDs). The designed suspension microarray system was validated for quantitative detection of (1) free and total prostate specific antigen (PSA) in the serum of patients with prostate cancer and (2) carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3) in the serum of patients with breast cancer. The serum samples from healthy donors were used as a control. The antigen detection is based on the formation of an immune complex of a specific capture antibody (Ab), a target antigen (Ag), and a detector Ab on the surface of the encoded particles. The capture Ab is bound to the polymer shell of microbeads via an adapter molecule, for example, protein A. Protein A binds a monoclonal Ab in a highly oriented manner due to specific interaction with the Fc-region of the Ab molecule. Each antigen can be recognized and detected due to a specific microbead population carrying the unique fluorescent code. 100 and 231 serum samples from patients with different stages of prostate cancer and breast cancer, respectively, and those from healthy donors were examined using the designed suspension system. The data were validated by comparing with the results of the "gold standard" enzyme-linked immunosorbent assay (ELISA). They have shown that our approach is a good alternative to the diagnostics of cancer markers using conventional assays, especially in early diagnostic applications.

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.

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.

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.

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.

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.

The internal jugular vein maintains its regional anatomy and patency after carotid endarterectomy: a prospective study.

PubMed

Khatri, V P; Wagner-Sevy, S; Espinosa, M H; Fisher, J B

2001-02-01

To validate the authors' published surface landmarks for gaining percutaneous access to the internal jugular vein (IJV), and to determine whether these surface landmarks were altered after neck surgery. Carotid puncture and pneumothorax continue to be the most frequent mechanical complications of percutaneous IJV venipuncture, particularly when the anterior or posterior approaches are used. The authors' modified technique of IJV venipuncture was associated with a 0.6% complication rate; notably, there were no instances of carotid artery puncture. Determining the accuracy of this method using duplex ultrasound would enhance the technique's applicability and safety. The authors also hypothesized that previous neck surgery would alter the regional anatomy in relation to these surface landmarks for IJV venipuncture. The authors prospectively evaluated 417 IJVs in 209 consecutive patients undergoing carotid duplex imaging before and after carotid endarterectomy (CEA). Patients who had undergone CEA were enrolled to investigate the effect of neck surgery on IJV anatomy. The opposite, nonoperated side of the neck served as a control for each patient. The position of the IJV in relation to the surface landmarks, the mobility of the IJV on neck rotation, and the size, patency, and relation of the IJV to the carotid artery were evaluated. Overall accuracy of the surface landmarks for locating the IJV percutaneously was 99% for the control group and 95% for the CEA group. With neck rotation, the IJV was located in a more lateral position in relation to the landmarks that would significantly reduce its accessibility. After neck rotation, it was also noted that the carotid artery moved behind the jugular vein in 85% of the patients in both groups. The mean size of the vein and its patency were similar in both groups. Duplex imaging validated the accuracy of the surface landmarks for IJV cannulation and documented the adverse effects of neck rotation. IJV anatomy is not altered after CEA.

The Internal Jugular Vein Maintains its Regional Anatomy and Patency After Carotid Endarterectomy: A Prospective Study

PubMed Central

Khatri, Vijay P.; Wagner-Sevy, Sam; Espinosa, Manuel H.; Fisher, Jay B.

2001-01-01

Objective To validate the authors’ published surface landmarks for gaining percutaneous access to the internal jugular vein (IJV), and to determine whether these surface landmarks were altered after neck surgery. Summary Background Data Carotid puncture and pneumothorax continue to be the most frequent mechanical complications of percutaneous IJV venipuncture, particularly when the anterior or posterior approaches are used. The authors’ modified technique of IJV venipuncture was associated with a 0.6% complication rate; notably, there were no instances of carotid artery puncture. Determining the accuracy of this method using duplex ultrasound would enhance the technique’s applicability and safety. The authors also hypothesized that previous neck surgery would alter the regional anatomy in relation to these surface landmarks for IJV venipuncture. Methods The authors prospectively evaluated 417 IJVs in 209 consecutive patients undergoing carotid duplex imaging before and after carotid endarterectomy (CEA). Patients who had undergone CEA were enrolled to investigate the effect of neck surgery on IJV anatomy. The opposite, nonoperated side of the neck served as a control for each patient. The position of the IJV in relation to the surface landmarks, the mobility of the IJV on neck rotation, and the size, patency, and relation of the IJV to the carotid artery were evaluated. Results Overall accuracy of the surface landmarks for locating the IJV percutaneously was 99% for the control group and 95% for the CEA group. With neck rotation, the IJV was located in a more lateral position in relation to the landmarks that would significantly reduce its accessibility. After neck rotation, it was also noted that the carotid artery moved behind the jugular vein in 85% of the patients in both groups. The mean size of the vein and its patency were similar in both groups. Conclusions Duplex imaging validated the accuracy of the surface landmarks for IJV cannulation and documented the adverse effects of neck rotation. IJV anatomy is not altered after CEA. PMID:11176136

The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic

PubMed Central

Gabitzsch, Elizabeth S.; Tsang, Kwong Yok; Palena, Claudia; David, Justin M.; Fantini, Massimo; Kwilas, Anna; Rice, Adrian E.; Latchman, Yvette; Hodge, James W.; Gulley, James L.; Madan, Ravi A.; Heery, Christopher R.; Balint, Joseph P.

2015-01-01

Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4+ and CD8+ T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no “antigenic competition” in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies. PMID:26374823

Qualification process of CR system and quantification of digital image quality

NASA Astrophysics Data System (ADS)

Garnier, P.; Hun, L.; Klein, J.; Lemerle, C.

2013-01-01

CEA Valduc uses several X-Ray generators to carry out many inspections: void search, welding expertise, gap measurements, etc. Most of these inspections are carried out on silver based plates. For several years, the CEA/Valduc has decided to qualify new devices such as digital plates or CCD/flat panel plates. On one hand, the choice of this technological orientation is to forecast the assumed and eventual disappearance of silver based plates; on the other hand, it is also to keep our skills mastering up-to-date. The main improvement brought by numerical plates is the continuous progress of the measurement accuracy, especially with image data processing. It is now common to measure defects thickness or depth position within a part. In such applications, data image processing is used to obtain complementary information compared to scanned silver based plates. This scanning procedure is harmful for measurements which imply a data corruption of the resolution, the adding of numerical noise and is time expensive. Digital plates enable to suppress the scanning procedure and to increase resolution. It is nonetheless difficult to define, for digital images, single criteria for the image quality. A procedure has to be defined in order to estimate quality of the digital data itself; the impact of the scanning device and the configuration parameters are also to be taken into account. This presentation deals with the qualification process developed by CEA/Valduc for digital plates (DUR-NDT) based on the study of quantitative criteria chosen to define a direct numerical image quality that could be compared with scanned silver based pictures and the classical optical density. The versatility of the X-Ray parameters is also discussed (X-ray tension, intensity, time exposure). The aim is to be able to transfer the year long experience of CEA/Valduc with silver-based plates inspection to these new digital plates supports. This is an industrial stake.

LED-CE-DOAS measurements of NO2: intercomparison with CaRDS

NASA Astrophysics Data System (ADS)

Thalman, R. M.; Washenfelder, R.; Brown, S. S.; Volkamer, R.

2009-04-01

The combination of cavity enhanced absorption spectroscopy (CEAS) with Light Emitting Diode (LED) light sources lends itself to the application of the well established Differential Optical Absorption Spectroscopy (DOAS) technique (LED-CE-DOAS). In contrast to other broad band CEAS (BB-CEAS) techniques, CE-DOAS relies only on the measurement of relative intensity changes, i.e., does not require knowledge of the light intensity in the absence of trace gases (I0). With CE-DOAS there is no necessity for sampling lines to supply air samples into a cavity, or filters to remove aerosols from the airstream, as measurements are possible in a cavity that can be open to the atmosphere. A novel LED-CE-DOAS instrument was built at CU Boulder for the sensitive and selective detection of nitrogen dioxide (NO2), glyoxal (CHOCHO), iodine oxide (IO), water, and oxygen dimers (O4). CU Boulder's LED-CE-DOAS instrument was collocated to NOAA's NO2 Cavity Ring Down (CaRDS) instrument to test different CE-DOAS data retrieval algorithms for NO2 and O4. Both instruments were collocated to sample known NO2 concentrations from the same gas manifold, and to sample atmospheric air in a parking lot. This contribution focuses on the instrument components, challenges and means to retrieve quantitative concentrations of NO2 by LED-CE-DOAS, i.e., the distortion of NO2 and O4 absorption features due to different effective path lengths induced by (1) changes in the mirror reflectivity with wavelength, and (2) changes in light extinction across the absorption bands due to differential trace gas absorption features. We demonstrate that simultaneous measurements of O4 and NO2 enable to characterize the effective pathlength in the absence and presence of NO2 and perform absolute measurements based only on relative intensity measurements. To our knowledge these are the first CEAS measurements that rely solely on relative intensity measurements.

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.

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.

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 low compared to cigarette smokers. However, heavy hookah smoking substantially raises CEA levels. Low-nitrosamines smokeless tobacco of the SNUS Swedish type could be envisaged as an alternative to smoking for this category of users and also, in a broad harm reduction perspective, to the prevalent low-quality moist snuff called naswar. PMID:18501010

Nanoporous Gold as a Solid Support for Protein Immobilization for the Development of Immunoassays, and for Biomolecular Interaction Studies

NASA Astrophysics Data System (ADS)

Pandey, Binod Prasad

Nanoporous gold (NPG) is a versatile material of high surface area to volume ratio that can be readily modified with self-assembled monolayers of alkanethiols to which biomolecules can be linked. NPG presents new opportunities for the development of immunoassays, and for the development of carbohydrate based assays. This thesis explores the use of NPG as a support for self-assembled monolayers, their linkage to antibody-enzyme conjugates for immunoassay development, and for the study and application of carbohydrate-protein interactions. Direct kinetic electrochemical immunoassays were developed on NPG for prostate specific antigen (PSA) and carcinoembryonic antigen (CEA). The decrease in enzymatic conversion of p-aminophenylphosphate to p-aminophenol, by alkaline phosphatase conjugated to an antibody, due to steric hindrance caused by the presence of antigen on antibody, was observed as a drop in peak current in square-wave voltammetry. Detection limit of these assays was 0.075 ng mL -1 and 0.015 ng mL-1 for PSA and CEA, respectively. Similarly, the linear range of determination of these biomarkers extended up to 30 ng mL-1 and 10 ng mL-1 for PSA and CEA, respectively. Minimal interference was observed using newborn calf serum as a substitute for the human serum matrix. A rapid and sensitive enzyme linked lectinsorbant assay was also developed for the study of glycoprotein-lectin interactions on the NPG surface. Self-assembled monolayers of alkanethiols on NPG were characterized by cyclic voltammetry and electrochemical impedance spectroscopy. Similarly, the applicability of this surface for the formation of carbohydrate monolayers and its application for lectin carbohydrate interactions was also studied. Pure and mixed SAMs of 8-mercaptooctyl β-D-mannopyranoside (αMan-C8-SH) and α-D-Gal-(1→4)-β-D-Gal-(1α)-D-Glc-1-O-mercaptooctane (Gb3-C8-SH) with alkanethiols having varying tail groups were prepared. Binding affinity and binding kinetics of concanavalin A to mannoside and soybean agglutinin to galactose in these SAMs were found to be different on NPG than on flat polycrystalline gold, and was also sensitive to the chemical composition of the modified surfaces.

New Reduced Two-Time Step Method for Calculating Combustion and Emission Rates of Jet-A and Methane Fuel With and Without Water Injection

NASA Technical Reports Server (NTRS)

Molnar, Melissa; Marek, C. John

2004-01-01

A simplified kinetic scheme for Jet-A, and methane fuels with water injection was developed to be used in numerical combustion codes, such as the National Combustor Code (NCC) or even simple FORTRAN codes that are being developed at Glenn. The two time step method is either an initial time averaged value (step one) or an instantaneous value (step two). The switch is based on the water concentration in moles/cc of 1x10(exp -20). The results presented here results in a correlation that gives the chemical kinetic time as two separate functions. This two step method is used as opposed to a one step time averaged method previously developed to determine the chemical kinetic time with increased accuracy. The first time averaged step is used at the initial times for smaller water concentrations. This gives the average chemical kinetic time as a function of initial overall fuel air ratio, initial water to fuel mass ratio, temperature, and pressure. The second instantaneous step, to be used with higher water concentrations, gives the chemical kinetic time as a function of instantaneous fuel and water mole concentration, pressure and temperature (T4). The simple correlations would then be compared to the turbulent mixing times to determine the limiting properties of the reaction. The NASA Glenn GLSENS kinetics code calculates the reaction rates and rate constants for each species in a kinetic scheme for finite kinetic rates. These reaction rates were then used to calculate the necessary chemical kinetic times. Chemical kinetic time equations for fuel, carbon monoxide and NOx were obtained for Jet-A fuel and methane with and without water injection to water mass loadings of 2/1 water to fuel. A similar correlation was also developed using data from NASA's Chemical Equilibrium Applications (CEA) code to determine the equilibrium concentrations of carbon monoxide and nitrogen oxide as functions of overall equivalence ratio, water to fuel mass ratio, pressure and temperature (T3). The temperature of the gas entering the turbine (T4) was also correlated as a function of the initial combustor temperature (T3), equivalence ratio, water to fuel mass ratio, and pressure.

Schlieren image velocimetry measurements in a rocket engine exhaust plume

NASA Astrophysics Data System (ADS)

Morales, Rudy; Peguero, Julio; Hargather, Michael

2017-11-01

Schlieren image velocimetry (SIV) measures velocity fields by tracking the motion of naturally-occurring turbulent flow features in a compressible flow. Here the technique is applied to measuring the exhaust velocity profile of a liquid rocket engine. The SIV measurements presented include discussion of visibility of structures, image pre-processing for structure visibility, and ability to process resulting images using commercial particle image velocimetry (PIV) codes. The small-scale liquid bipropellant rocket engine operates on nitrous oxide and ethanol as propellants. Predictions of the exhaust velocity are obtained through NASA CEA calculations and simple compressible flow relationships, which are compared against the measured SIV profiles. Analysis of shear layer turbulence along the exhaust plume edge is also presented.

In-Pile Sub-Miniature Fission Chambers Testing in BR2

NASA Astrophysics Data System (ADS)

Vermeeren, L.; Wéber, M.; Blandin, Ch.; Breaud, S.

2003-06-01

Three innovative sub-miniature fission chambers (SMFC), designed and manufactured at the Nuclear Measurement Systems Laboratory (LSMN) of CEA/Cadarache, were extensively tested in the BR2 research reactor at SCK•CEN, Mol. We present the experimental results for the (thermal) neutron sensitivity, the gamma-induced signal, the signal due to activation, the current picked up by the signal cable, the global current/voltage characteristics and the long term behaviour up to a thermal neutron fluence of 2.7·1021 n/cm2. We also compare the data with results from calculations with our FCD computer code. The onset of the saturation domain is well predicted by FCD; the neutron sensitivities can be accounted for perfectly after a refinement of the FCD model.

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, 1.51; 95% CI, 1.02-2.24; P = .04; I 2  = 0%). Quality of evidence for all stroke outcomes was graded moderate. Among patients with asymptomatic stenosis undergoing carotid intervention, there is moderate-quality evidence to suggest that CEA had significantly lower 30-day stroke and also stroke or death rates compared with CAS at the cost of higher CNI and nonsignificantly higher MI rates. The long-term efficacy of CEA in ipsilateral stroke prevention, taking into account perioperative stroke and death, was preserved during follow-up. There is an urgent need for high-quality research before a firm recommendation is made that CAS is inferior or not to CEA. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

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.

Multiplexed detection of tumor markers with multicolor quantum dots based on fluorescence polarization immunoassay.

PubMed

Tian, Jianniao; Zhou, Liujin; Zhao, Yanchun; Wang, Yuan; Peng, Yan; Zhao, Shulin

2012-04-15

A multicolor quantum dot (QD)-based nanosensor for multiplex detection of two tumor markers in a homogeneous format based on fluorescence polarization immunoassay was proposed. QDs520 and QDs620 were labeled alpha-fetoprotein(α-AFP) and carcinoembryonic antigen (CEA), respectively. After separated and purified by ultrafiltration, they were used in fluorescence polarization immunoassay for the simultaneous detection of human serum alpha-fetoprotein and carcinoembryonic antigen. Under the optimal conditions, the multi-analyte immunosensor had a wide linear range (from 0.5 ng mL(-1) to 500 ng mL(-1)) for both two tumor markers and good correlation (0.996 for α-AFP and 0.993 for CEA). The detection limits (LOD) were 0.36 ng mL(-1) for CEA and 0.28 ng mL(-1) for α-AFP (S/N=3). The carcinoembryonic antigen and fetoprotein in clinical serum samples were simultaneously detected. The results from 28 serum samples had a good agreement with enzyme-linked immunosorbent assay (ELISA). The relative standard deviation and the recovery suggested that the precision and the accuracy of this analytical method were satisfactory. This strategy with high sensitivity, good specificity, easy procedures and short analysis time shows great promise for clinical diagnoses and basic discovery. The application of QDs with longer fluorescence lifetime and small fluorescence polarization can be used for the determination of high molecular-weight substances which cannot be analyzed using dye fluorescence polarization immunoassay. Copyright © 2012 Elsevier B.V. All rights reserved.

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

Gold nanoparticle-based low limit of detection Love wave biosensor for carcinoembryonic antigens.

PubMed

Li, Shuangming; Wan, Ying; Su, Yan; Fan, Chunhai; Bhethanabotla, Venkat R

2017-09-15

In this work, a Love wave biosensing platform is described for detecting cancer-related biomarker carcinoembryonic antigen (CEA). An ST 90°-X quartz Love wave device with a layer of SiO 2 waveguide was combined with gold nanoparticles (Au NPs) to amplify the mass loading effect of the acoustic wave sensor to achieve a limit of detection of 37pg/mL. The strategy involves modifying the Au NPs with anti-CEA antibody conjugates to form nanoprobes in a sandwich immunoassay. The unamplified detection limit of the Love wave biosensor is 9.4ng/mL. This 2-3 order of magnitude reduction in the limit of detection brings the SAW platform into the range useful for clinical diagnosis. Measurement electronics and microfluidics are easily constructed for acoustic wave biosensors, such as the Love wave device described here, allowing for robust platforms for point of care applications for cancer biomarkers in general. Copyright © 2017 Elsevier B.V. All rights reserved.

Optical feedback cavity-enhanced absorption spectroscopy with a 3.24 μm interband cascade laser

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

Manfred, K. M.; Ritchie, G. A. D.; Lang, N.

2015-06-01

The development of interband cascade lasers (ICLs) has made the strong C-H transitions in the 3 μm spectral region increasingly accessible. We present the demonstration of a single mode distributed feedback ICL coupled to a V-shaped optical cavity in an optical feedback cavity-enhanced absorption spectroscopy (OF-CEAS) experiment. We achieved a minimum detectable absorption coefficient, α{sub min}, of (7.1±0.2)×10{sup −8} cm{sup −1} for a spectrum of CH{sub 4} at 3.24 μm with a two second acquisition time (100 scans averaged). This corresponds to a detection limit of 3 ppb CH{sub 4} at atmospheric pressure, which is comparable to previously reported OF-CEAS instruments with diodemore » lasers or quantum cascade lasers. The ability to frequency lock an ICL source in the important 3 μm region to an optical cavity holds great promise for future spectroscopic applications.« less

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 vaccination strategy depended on the inclusion of the herd protection effect. Inclusion of herd-protection effects in CEAs had a substantial impact in the estimated ICERs and made target-vaccination strategies more attractive options in almost half of the cases where ICERs were above the societal-willingness to pay threshold without herd-protection. More empirical epidemiologic data are needed to determine the size of herd-protection effects across diverse settings and also the size of negative vaccine effects, e.g. from serotype substitution.

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 adoption of the target vaccination strategy depended on the inclusion of the herd protection effect. Conclusions Inclusion of herd-protection effects in CEAs had a substantial impact in the estimated ICERs and made target-vaccination strategies more attractive options in almost half of the cases where ICERs were above the societal-willingness to pay threshold without herd-protection. More empirical epidemiologic data are needed to determine the size of herd-protection effects across diverse settings and also the size of negative vaccine effects, e.g. from serotype substitution. PMID:28249046

Multivariable optimization of liquid rocket engines using particle swarm algorithms

NASA Astrophysics Data System (ADS)

Jones, Daniel Ray

Liquid rocket engines are highly reliable, controllable, and efficient compared to other conventional forms of rocket propulsion. As such, they have seen wide use in the space industry and have become the standard propulsion system for launch vehicles, orbit insertion, and orbital maneuvering. Though these systems are well understood, historical optimization techniques are often inadequate due to the highly non-linear nature of the engine performance problem. In this thesis, a Particle Swarm Optimization (PSO) variant was applied to maximize the specific impulse of a finite-area combustion chamber (FAC) equilibrium flow rocket performance model by controlling the engine's oxidizer-to-fuel ratio and de Laval nozzle expansion and contraction ratios. In addition to the PSO-controlled parameters, engine performance was calculated based on propellant chemistry, combustion chamber pressure, and ambient pressure, which are provided as inputs to the program. The performance code was validated by comparison with NASA's Chemical Equilibrium with Applications (CEA) and the commercially available Rocket Propulsion Analysis (RPA) tool. Similarly, the PSO algorithm was validated by comparison with brute-force optimization, which calculates all possible solutions and subsequently determines which is the optimum. Particle Swarm Optimization was shown to be an effective optimizer capable of quick and reliable convergence for complex functions of multiple non-linear variables.

Liquid Engine Design: Effect of Chamber Dimensions on Specific Impulse

NASA Technical Reports Server (NTRS)

Hoggard, Lindsay; Leahy, Joe

2009-01-01

Which assumption of combustion chemistry - frozen or equilibrium - should be used in the prediction of liquid rocket engine performance calculations? Can a correlation be developed for this? A literature search using the LaSSe tool, an online repository of old rocket data and reports, was completed. Test results of NTO/Aerozine-50 and Lox/LH2 subscale and full-scale injector and combustion chamber test results were found and studied for this task. NASA code, Chemical Equilibrium with Applications (CEA) was used to predict engine performance using both chemistry assumptions, defined here. Frozen- composition remains frozen during expansion through the nozzle. Equilibrium- instantaneous chemical equilibrium during nozzle expansion. Chamber parameters were varied to understand what dimensions drive chamber C* and Isp. Contraction Ratio is the ratio of the nozzle throat area to the area of the chamber. L is the length of the chamber. Characteristic chamber length, L*, is the length that the chamber would be if it were a straight tube and had no converging nozzle. Goal: Develop a qualitative and quantitative correlation for performance parameters - Specific Impulse (Isp) and Characteristic Velocity (C*) - as a function of one or more chamber dimensions - Contraction Ratio (CR), Chamber Length (L ) and/or Characteristic Chamber Length (L*). Determine if chamber dimensions can be correlated to frozen or equilibrium chemistry.

Quantum Monte Carlo for large chemical systems: implementing efficient strategies for petascale platforms and beyond.

PubMed

Scemama, Anthony; Caffarel, Michel; Oseret, Emmanuel; Jalby, William

2013-04-30

Various strategies to implement efficiently quantum Monte Carlo (QMC) simulations for large chemical systems are presented. These include: (i) the introduction of an efficient algorithm to calculate the computationally expensive Slater matrices. This novel scheme is based on the use of the highly localized character of atomic Gaussian basis functions (not the molecular orbitals as usually done), (ii) the possibility of keeping the memory footprint minimal, (iii) the important enhancement of single-core performance when efficient optimization tools are used, and (iv) the definition of a universal, dynamic, fault-tolerant, and load-balanced framework adapted to all kinds of computational platforms (massively parallel machines, clusters, or distributed grids). These strategies have been implemented in the QMC=Chem code developed at Toulouse and illustrated with numerical applications on small peptides of increasing sizes (158, 434, 1056, and 1731 electrons). Using 10-80 k computing cores of the Curie machine (GENCI-TGCC-CEA, France), QMC=Chem has been shown to be capable of running at the petascale level, thus demonstrating that for this machine a large part of the peak performance can be achieved. Implementation of large-scale QMC simulations for future exascale platforms with a comparable level of efficiency is expected to be feasible. Copyright © 2013 Wiley Periodicals, Inc.

Validation of CESAR Thermal-hydraulic Module of ASTEC V1.2 Code on BETHSY Experiments

NASA Astrophysics Data System (ADS)

Tregoures, Nicolas; Bandini, Giacomino; Foucher, Laurent; Fleurot, Joëlle; Meloni, Paride

The ASTEC V1 system code is being jointly developed by the French Institut de Radioprotection et Sûreté Nucléaire (IRSN) and the German Gesellschaft für Anlagen und ReaktorSicherheit (GRS) to address severe accident sequences in a nuclear power plant. Thermal-hydraulics in primary and secondary system is addressed by the CESAR module. The aim of this paper is to present the validation of the CESAR module, from the ASTEC V1.2 version, on the basis of well instrumented and qualified integral experiments carried out in the BETHSY facility (CEA, France), which simulates a French 900 MWe PWR reactor. Three tests have been thoroughly investigated with CESAR: the loss of coolant 9.1b test (OECD ISP N° 27), the loss of feedwater 5.2e test, and the multiple steam generator tube rupture 4.3b test. In the present paper, the results of the code for the three analyzed tests are presented in comparison with the experimental data. The thermal-hydraulic behavior of the BETHSY facility during the transient phase is well reproduced by CESAR: the occurrence of major events and the time evolution of main thermal-hydraulic parameters of both primary and secondary circuits are well predicted.

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.

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.

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

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.

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.

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

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.

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.

Simplified Two-Time Step Method for Calculating Combustion Rates and Nitrogen Oxide Emissions for Hydrogen/Air and Hydorgen/Oxygen

NASA Technical Reports Server (NTRS)

Molnar, Melissa; Marek, C. John

2005-01-01

A simplified single rate expression for hydrogen combustion and nitrogen oxide production was developed. Detailed kinetics are predicted for the chemical kinetic times using the complete chemical mechanism over the entire operating space. These times are then correlated to the reactor conditions using an exponential fit. Simple first order reaction expressions are then used to find the conversion in the reactor. The method uses a two-time step kinetic scheme. The first time averaged step is used at the initial times with smaller water concentrations. This gives the average chemical kinetic time as a function of initial overall fuel air ratio, temperature, and pressure. The second instantaneous step is used at higher water concentrations (> 1 x 10(exp -20) moles/cc) in the mixture which gives the chemical kinetic time as a function of the instantaneous fuel and water mole concentrations, pressure and temperature (T4). The simple correlations are then compared to the turbulent mixing times to determine the limiting properties of the reaction. The NASA Glenn GLSENS kinetics code calculates the reaction rates and rate constants for each species in a kinetic scheme for finite kinetic rates. These reaction rates are used to calculate the necessary chemical kinetic times. This time is regressed over the complete initial conditions using the Excel regression routine. Chemical kinetic time equations for H2 and NOx are obtained for H2/air fuel and for the H2/O2. A similar correlation is also developed using data from NASA s Chemical Equilibrium Applications (CEA) code to determine the equilibrium temperature (T4) as a function of overall fuel/air ratio, pressure and initial temperature (T3). High values of the regression coefficient R2 are obtained.

Summary of Simplified Two Time Step Method for Calculating Combustion Rates and Nitrogen Oxide Emissions for Hydrogen/Air and Hydrogen/Oxygen

NASA Technical Reports Server (NTRS)

Marek, C. John; Molnar, Melissa

2005-01-01

A simplified single rate expression for hydrogen combustion and nitrogen oxide production was developed. Detailed kinetics are predicted for the chemical kinetic times using the complete chemical mechanism over the entire operating space. These times are then correlated to the reactor conditions using an exponential fit. Simple first order reaction expressions are then used to find the conversion in the reactor. The method uses a two time step kinetic scheme. The first time averaged step is used at the initial times with smaller water concentrations. This gives the average chemical kinetic time as a function of initial overall fuel air ratio, temperature, and pressure. The second instantaneous step is used at higher water concentrations (greater than l x 10(exp -20)) moles per cc) in the mixture which gives the chemical kinetic time as a function of the instantaneous fuel and water mole concentrations, pressure and temperature (T(sub 4)). The simple correlations are then compared to the turbulent mixing times to determine the limiting properties of the reaction. The NASA Glenn GLSENS kinetics code calculates the reaction rates and rate constants for each species in a kinetic scheme for finite kinetic rates. These reaction rates are used to calculate the necessary chemical kinetic times. This time is regressed over the complete initial conditions using the Excel regression routine. Chemical kinetic time equations for H2 and NOx are obtained for H2/Air fuel and for H2/O2. A similar correlation is also developed using data from NASA's Chemical Equilibrium Applications (CEA) code to determine the equilibrium temperature (T(sub 4)) as a function of overall fuel/air ratio, pressure and initial temperature (T(sub 3)). High values of the regression coefficient R squared are obtained.

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 CEA analyses may be suboptimal for guiding policy. PMID:23671612

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 guiding policy.

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.

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 visitors, their characteristics and their perception after their center visits. (authors)« less

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.

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

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 analysis and quality assurance programs; and (4) Create and maintain an information clearinghouse to ensure that all parties can keep informed on global mercury research and development activities.« less

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.

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

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

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 \

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.

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.

The Potential of Different Concepts of Fast Breeder Reactor for the French Fleet Renewal

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

Massara, Simone; Tetart, Philippe; Lecarpentier, David

2006-07-01

The performances of different concepts of Fast Breeder Reactor (Na-cooled, He-cooled and Pb-cooled FBR) for the current French fleet renewal are analyzed in the framework of a transition scenario to a 100% FBR fleet at the end of the 21. century. Firstly, the modeling of these three FBR types by means of a semi-analytical approach in TIRELIRE - STRATEGIE, the EDF fuel cycle simulation code, is presented, together with some validation elements against ERANOS, the French reference code system for neutronic FBR analysis (CEA). Afterwards, performances comparisons are made in terms of maximum deployable power, natural uranium consumption and wastemore » production. The results show that the FBR maximum deployable capacity, independently from the FBR technology, is highly sensitive to the fuel cycle options, like the spent nuclear fuel cooling time or the Minor Actinides management strategy. Thus, some of the key parameters defining the dynamic of FBR deployment are highlighted, to inform the orientation of R and D in the development and optimization of these systems. (authors)« less

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

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.

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

[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 confirmation in population studies.

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 with symptomatic carotid artery stenosis. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

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.

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

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.

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.

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.

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

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 well as higher charges (OR, 1.28; 95% CI, 1.01-1.62) and increased 30-day readmission (OR, 1.30; 95% CI 1.04-1.62) following CEA. The OAR and CEA procedures performed by very low-volume surgeons resulted in worse postoperative outcomes and greater lengths of stay. Although the percentage of very low-volume surgeons declined from 2000 to 2014, it remains concerning, given ready access to higher-volume surgeons. Future research is needed to understand the existence of this practice pattern in other surgical fields. Efforts to eliminate this practice pattern are warranted to ensure high-quality care for all patients.

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 45.6%, respectively, and the positive rate of CEA in triple-negative metastatic breast cancer is lower than in other subtypes (χ 2 =4.80, P=0.028). Therefore, serum CEA, CA19-9, CA125, CA15-3, and TPS can be used in the diagnosis of MBC, and different combinations of tumor markers have varying diagnostic value. Copyright © 2017 Elsevier B.V. All rights reserved.

SUMCOR: Cascade summing correction for volumetric sources applying MCNP6.

PubMed

Dias, M S; Semmler, R; Moreira, D S; de Menezes, M O; Barros, L F; Ribeiro, R V; Koskinas, M F

2018-04-01

The main features of code SUMCOR developed for cascade summing correction for volumetric sources are described. MCNP6 is used to track histories starting from individual points inside the volumetric source, for each set of cascade transitions from the radionuclide. Total and FEP efficiencies are calculated for all gamma-rays and X-rays involved in the cascade. Cascade summing correction is based on the matrix formalism developed by Semkow et al. (1990). Results are presented applying the experimental data sent to the participants of two intercomparisons organized by the ICRM-GSWG and coordinated by Dr. Marie-Cristine Lépy from the Laboratoire National Henri Becquerel (LNE-LNHB), CEA, in 2008 and 2010, respectively and compared to the other participants in the intercomparisons. Copyright © 2017 Elsevier Ltd. All rights reserved.

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 comments on the outline and drafts from a core group of 174 external reviewers and more broadly from the membership of ISPOR at two ISPOR meetings and via the ISPOR web site. Drug cost measurements should be fully transparent and reflect the net payment most relevant to the user's perspective. The Task Force recommends that for CEAs of brand name drugs performed from a societal perspective, either 1) CEA analysts use a cost that more accurately reflects true societal drug costs (e.g., 20-60% of average sales price), or when that is too unrealistic to be meaningful for decision-makers, 2) refer to their analyses as from a "limited societal perspective." CEAs performed from a payer perspective should use drug prices actually paid by the relevant payer net of all rebates, copays, or other adjustments. When such price adjustments are confidential, the analyst should apply a typical or average discount that preserves this confidentiality. Drug transaction prices not only ration current use of medication but also ration future biomedical research and development. CEA researchers should tailor the appropriate measure of drug costs to the analytic perspective, maintain clarity and transparency on drug cost measurement, and report the sensitivity of CEA results to reasonable drug cost measurement alternatives.

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

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...

Qualification of APOLLO2 BWR calculation scheme on the BASALA mock-up

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

Vaglio-Gaudard, C.; Santamarina, A.; Sargeni, A.

2006-07-01

A new neutronic APOLLO2/MOC/SHEM/CEA2005 calculation scheme for BWR applications has been developed by the French 'Commissariat a l'Energie Atomique'. This scheme is based on the latest calculation methodology (accurate mutual and self-shielding formalism, MOC treatment of the transport equation) and the recent JEFF3.1 nuclear data library. This paper presents the experimental validation of this new calculation scheme on the BASALA BWR mock-up The BASALA programme is devoted to the measurements of the physical parameters of high moderation 100% MOX BWR cores, in hot and cold conditions. The experimental validation of the calculation scheme deals with core reactivity, fission rate maps,more » reactivity worth of void and absorbers (cruciform control blades and Gd pins), as well as temperature coefficient. Results of the analysis using APOLLO2/MOC/SHEM/CEA2005 show an overestimation of the core reactivity by 600 pcm for BASALA-Hot and 750 pcm for BASALA-Cold. Reactivity worth of gadolinium poison pins and hafnium or B{sub 4}C control blades are predicted by APOLLO2 calculation within 2% accuracy. Furthermore, the radial power map is well predicted for every core configuration, including Void configuration and Hf / B{sub 4}C configurations: fission rates in the central assembly are calculated within the {+-}2% experimental uncertainty for the reference cores. The C/E bias on the isothermal Moderator Temperature Coefficient, using the CEA2005 library based on JEFF3.1 file, amounts to -1.7{+-}03 pcm/ deg. C on the range 10 deg. C-80 deg. C. (authors)« less

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

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.

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.

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.

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 otherwise improve carotid stenosis management guidelines. © 2015 American Heart Association, Inc.

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.

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.

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.

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.

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.

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

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. To implement this onto the Internet, I will need to develop an XML input/output format and learn how to write HTML.

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

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.

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.

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

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.

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.

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

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 carotid atherosclerosis must account for the impact of surgeon characteristics on patient outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

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 additional colorectal cancer patients with modifications to enhance T cell responses. ClinicalTrials.gov (identifier NCT00154713 ), September 8, 2005.

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.

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.

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.

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

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

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...

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...

Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET in Diagnosing Patients With CEA Positive Cancer

ClinicalTrials.gov

2018-06-15

Breast Cancer; Colon Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastrointestinal Cancer; Liver and Intrahepatic Biliary Tract Cancer; Lung Cancer; Metastatic Cancer; Pancreatic Cancer; Rectal Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

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

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

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.

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.

Multispecies breath analysis faster than a single respiratory cycle by optical-feedback cavity-enhanced absorption spectroscopy

NASA Astrophysics Data System (ADS)

Ventrillard-Courtillot, Irene; Gonthiez, Thierry; Clerici, Christine; Romanini, Daniel

2009-11-01

We demonstrate a first application, of optical-feedback cavity-enhanced absorption spectroscopy (OF-CEAS) to breath analysis in a medical environment. Noninvasive monitoring of trace species in exhaled air was performed simultaneous to spirometric measurements on patients at Bichat Hospital (Paris). The high selectivity of the OF-CEAS spectrometer and a time response of 0.3 s (limited by sample flow rate) allowed following the evolution of carbon monoxide and methane concentrations during individual respiratory cycles, and resolving variations among different ventilatory patterns. The minimum detectable absorption on this time scale is about 3×10-10 cm-1. At the working wavelength of the instrument (2.326 μm), this translates to concentration detection limits of ~1 ppbv (45 picomolar, or ~1.25 μg/m3) for CO and 25 ppbv for CH4, well below concentration values found in exhaled air. This same instrument is also able to provide measurement of NH3 concentrations with a detection limit of ~10 ppbv however, at present, memory effects do not allow its measurement on fast time scales.

Experimental validation of photon-heating calculation for the Jules Horowitz Reactor

NASA Astrophysics Data System (ADS)

Lemaire, M.; Vaglio-Gaudard, C.; Lyoussi, A.; Reynard-Carette, C.; Di Salvo, J.; Gruel, A.

2015-04-01

The Jules Horowitz Reactor (JHR) is the next Material-Testing Reactor (MTR) under construction at CEA Cadarache. High values of photon heating (up to 20 W/g) are expected in this MTR. As temperature is a key parameter for material behavior, the accuracy of photon-heating calculation in the different JHR structures is an important stake with regard to JHR safety and performances. In order to experimentally validate the calculation of photon heating in the JHR, an integral experiment called AMMON was carried out in the critical mock-up EOLE at CEA Cadarache to help ascertain the calculation bias and its associated uncertainty. Nuclear heating was measured in different JHR-representative AMMON core configurations using ThermoLuminescent Detectors (TLDs) and Optically Stimulated Luminescent Detectors (OSLDs). This article presents the interpretation methodology and the calculation/experiment (C/E) ratio for all the TLD and OSLD measurements conducted in AMMON. It then deals with representativeness elements of the AMMON experiment regarding the JHR and establishes the calculation biases (and its associated uncertainty) applicable to photon-heating calculation for the JHR.

Lectin-Based Assay for Glycoform-Specific Detection of α2,6-sialylated Transferrin and Carcinoembryonic Antigen in Tissue and Body Fluid.

PubMed

Ito, Hiromi; Hoshi, Kyoka; Honda, Takashi; Hashimoto, Yasuhiro

2018-05-30

Antibodies are useful for detecting glycoprotein antigens, but a conventional antibody recognizes only a protein epitope rather than a glycan. Thus, glycan isoform detection generally requires time- and labor-consuming processes such as lectin affinity column chromatography followed by sandwich ELISA. We recently found antigen-antibody reactions that were inhibited by lectin binding to glycans on the glycoprotein antigen, leading to a convenient glycoform-specific assay. Indeed, Sambucus sieboldiana agglutinin (SSA) lectin, a binder to sialylα2,6galactose residue, inhibited antibody binding to α2,6-sialylated transferrin (Tf) (SSA inhibition). SSA inhibition was not observed with other glycoforms, such as periodate-treated, sialidase-treated and sialidase/galactosidase-treated Tf, suggesting that the assay was glycoform-specific. SSA inhibition was also applicable for visualizing localization of α2,6-sialylated-Tf in a liver section. This is the first immunohistochemical demonstration of glycoform localization in a tissue section. SSA inhibition was utilized for establishing ELISA to quantify α2,6-sialylated carcinoembryonic antigen (CEA), a marker for various cancers. In addition, α2,6-sialylated-CEA was visualized in a colonic adenocarcinoma section by SSA inhibition. The method would further be applicable to a simple and rapid estimation of other α2,6-sialylated glycoproteins and have a potential aid to histopathological diagnosis.

Discrete Event Simulation-Based Resource Modelling in Health Technology Assessment.

PubMed

Salleh, Syed; Thokala, Praveen; Brennan, Alan; Hughes, Ruby; Dixon, Simon

2017-10-01

The objective of this article was to conduct a systematic review of published research on the use of discrete event simulation (DES) for resource modelling (RM) in health technology assessment (HTA). RM is broadly defined as incorporating and measuring effects of constraints on physical resources (e.g. beds, doctors, nurses) in HTA models. Systematic literature searches were conducted in academic databases (JSTOR, SAGE, SPRINGER, SCOPUS, IEEE, Science Direct, PubMed, EMBASE) and grey literature (Google Scholar, NHS journal library), enhanced by manual searchers (i.e. reference list checking, citation searching and hand-searching techniques). The search strategy yielded 4117 potentially relevant citations. Following the screening and manual searches, ten articles were included. Reviewing these articles provided insights into the applications of RM: firstly, different types of economic analyses, model settings, RM and cost-effectiveness analysis (CEA) outcomes were identified. Secondly, variation in the characteristics of the constraints such as types and nature of constraints and sources of data for the constraints were identified. Thirdly, it was found that including the effects of constraints caused the CEA results to change in these articles. The review found that DES proved to be an effective technique for RM but there were only a small number of studies applied in HTA. However, these studies showed the important consequences of modelling physical constraints and point to the need for a framework to be developed to guide future applications of this approach.

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 ...

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...

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-profile meteorology versus higher-fidelity three-dimensional gridded weather forecast for regional-scale analysis. Tradeoffs between computation time and the fidelity of the results are discussed for both scales. LES, for example, requires nearly 100 times more processor time than the mass-consistent diagnostic model or the RANS model, and seems better able to capture flow entrainment behind tall buildings. As anticipated, results obtained by LLNL and CEA at regional scale around Chicago and Paris look very similar in terms of both atmospheric dispersion of the radiological release and total effective dose. Both LLNL and CEA used the same meteorological data, Lagrangian particle dispersion models, and the same dose coefficients. LLNL and CEA urban-scale modeling results show consistent phenomenological behavior and predict similar impacted areas even though the detailed 3D flow patterns differ, particularly for the Chicago cases where differences in vertical entrainment behind tall buildings are particularly notable. Although RANS and LES (LLNL) models incorporate more detailed physics than do mass-consistent diagnostic flow models (CEA), it is not possible to reach definite conclusions about the prediction fidelity of the various models as experimental measurements were not available for comparison. Stronger conclusions about the relative performances of the models involved and evaluation of the tradeoffs involved in model simplification could be made with a systematic benchmarking of urban-scale modeling. This could be the purpose of a future US / French collaborative exercise.« less

Etude des performances de solveurs deterministes sur un coeur rapide a caloporteur sodium

NASA Astrophysics Data System (ADS)

Bay, Charlotte

The reactors of next generation, in particular SFR model, represent a true challenge for current codes and solvers, used mainly for thermic cores. There is no guarantee that their competences could be straight adapted to fast neutron spectrum, or to major design differences. Thus it is necessary to assess the validity of solvers and their potential shortfall in the case of fast neutron reactors. As part of an internship with CEA (France), and at the instigation of EPM Nuclear Institute, this study concerns the following codes : DRAGON/DONJON, ERANOS, PARIS and APOLLO3. The precision assessment has been performed using Monte Carlo code TRIPOLI4. Only core calculation was of interest, namely numerical methods competences in precision and rapidity. Lattice code was not part of the study, that is to say nuclear data, self-shielding, or isotopic compositions. Nor was tackled burnup or time evolution effects. The study consists in two main steps : first evaluating the sensitivity of each solver to calculation parameters, and obtain its optimal calculation set ; then compare their competences in terms of precision and rapidity, by collecting usual quantities (effective multiplication factor, reaction rates map), but also more specific quantities which are crucial to the SFR design, namely control rod worth and sodium void effect. The calculation time is also a key factor. Whatever conclusion or recommendation that could be drawn from this study, they must first of all be applied within similar frameworks, that is to say small fast neutron cores with hexagonal geometry. Eventual adjustments for big cores will have to be demonstrated in developments of this study.

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.

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 in standard effluents resulting from nuclear activities; - To develop reversible solid adsorbents for cartridge-type applications in order to minimize wastes. (authors)« less

[Application of (125)I seeds combined with biliary stent implantation in the treatment of malignant obstructive jaundice].

PubMed

Wang, T; Liu, S; Zheng, Y B; Song, X P; Jiang, W J; Sun, B L; Wang, L G

2016-03-23

To study the feasibility and therapeutic effect of the application of (125)I seeds combined with biliary stent implantation on the treatment of malignant obstructive jaundice. Fifty patients with malignant obstructive jaundice treated from September 2010 to February 2013 in Yantai Yuhuangding Hospital were included in this study. Among them, 24 patients received biliary stent implantation combined with (125)I seeds intraluminal brachytherapy as experimental group, and 26 were treated by biliary stent implantation as control group.The total bilirubin, direct bilirubin and tumor markers (CA-199, CA-242, CEA) before and after surgery, the biliary stent patency status was assessed, and the survival time was evaluated. The 24 patients in experimental group were implanted with 30 (125)I seeds successfully in a total of 450 seeds. Jaundice was improved greatly in both groups. The CA-199 and CA-242 after treatment in the experimental group were significantly decreased than that before treatment (P=0.003 and P=0.004). CEA was also decreased, but showed no statistical significance (P>0.05). There were no significant improvement comparing the CA-199, CA-242 and CEA before and 2 months after surgery in the control group (P>0.05). The rate of biliary stent patency was 83.3% (20/24) in the experimental group and 57.7% (15/26) in the control group (P=0.048). The mean biliary stent patency time in the experimental group was 9.84 months (range 1-15.5 months). The mean biliary stent patency time in the control group was 5.57 months (range 0.8-9 months). There was a significant difference between the two groups (P=0.018). The median survival time was 10.2 months in the experimental group and 5.4 months in the control group (P<0.05). (125)I seeds combined with biliary stent implantation can inhibit the proliferation of vascular endothelial cells and the growth of tumor effectively, and can prolong the biliary stent patency time and the survival time obviously for patients with malignant obstructive jaundice, therefore, is a safe and effective treatment in this malignancy.

Big Data Solution for CTBT Monitoring Using Global Cross Correlation

NASA Astrophysics Data System (ADS)

Gaillard, P.; Bobrov, D.; Dupont, A.; Grenouille, A.; Kitov, I. O.; Rozhkov, M.

2014-12-01

Due to the mismatch between data volume and the performance of the Information Technology infrastructure used in seismic data centers, it becomes more and more difficult to process all the data with traditional applications in a reasonable elapsed time. To fulfill their missions, the International Data Centre of the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO/IDC) and the Département Analyse Surveillance Environnement of Commissariat à l'Energie atomique et aux énergies alternatives (CEA/DASE) collect, process and produce complex data sets whose volume is growing exponentially. In the medium term, computer architectures, data management systems and application algorithms will require fundamental changes to meet the needs. This problem is well known and identified as a "Big Data" challenge. To tackle this major task, the CEA/DASE takes part during two years to the "DataScale" project. Started in September 2013, DataScale gathers a large set of partners (research laboratories, SMEs and big companies). The common objective is to design efficient solutions using the synergy between Big Data solutions and the High Performance Computing (HPC). The project will evaluate the relevance of these technological solutions by implementing a demonstrator for seismic event detections thanks to massive waveform correlations. The IDC has developed an expertise on such techniques leading to an algorithm called "Master Event" and provides a high-quality dataset for an extensive cross correlation study. The objective of the project is to enhance the Master Event algorithm and to reanalyze 10 years of waveform data from the International Monitoring System (IMS) network thanks to a dedicated HPC infrastructure operated by the "Centre de Calcul Recherche et Technologie" at the CEA of Bruyères-le-Châtel. The dataset used for the demonstrator includes more than 300,000 seismic events, tens of millions of raw detections and more than 30 terabytes of continuous seismic data from the primary IMS stations. In this talk, we will present the Master Event algorithm and the associated workflow, we will give an overview of the designed technical solutions (from the building blocks to the global infrastructure), and we will show the preliminary results at a regional scale.

Part per trillion nitric oxide measurement by optical feedback cavity-enhanced absorption spectroscopy in the mid-infrared

NASA Astrophysics Data System (ADS)

Ventrillard, Irène; Gorrotxategi-Carbajo, Paula; Romanini, Daniele

2017-06-01

While nitric oxide (NO) is being monitored in various fields of application, there is still a lack of available instruments at a sub-ppb level of sensitivity. We report on the first application of Optical Feedback Cavity-Enhanced Absorption Spectroscopy (OF-CEAS) to NO trace gas analysis, with a room-temperature quantum-cascade laser at 5.26 µm (1900.5 cm^{-1}). A detection limit of 60 ppt is reached in a single measurement performed in 140 ms. The stability of the instrument allows to average for 10 s down to 8.3 ppt, limited by drift of etalon fringes in the spectra. This work opens the path towards new applications notably in breath analysis and environment sciences.

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…

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.

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.

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.

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.

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.

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.

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

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 Technical Assistance program at Sandia. Despite lack of optimization with the project system, initial results show the dramatic water savings potential of hydroponic forage production compared with traditional irrigated open field practice. This project produced forage using only about 4.5% of the water required for equivalent open field production. Improved operation could bring water use to 2% or less. The hydroponic forage production system and process used in this project are labor intensive and not optimized for minimum water usage. Freshly harvested hydroponic forage has high moisture content that dilutes its nutritional value by requiring that livestock consume more of it to get the same nutritional content as conventional forage. In most other aspects the nutritional content compares well on a dry weight equivalent basis with other conventional forage. More work is needed to further explore and quantify the opportunities, limitations, and viability of this technique for broader use. Collection of greenhouse environmental data in this project was uniquely facilitated through the implementation and use of a self-organizing, wirelessly networked, multi-modal sensor system array with remote cell phone data link capability. Applications of wirelessly networked sensing with improved modeling/simulation and other Sandia technologies (e.g., advanced sensing and control, embedded reasoning, modeling and simulation, materials, robotics, etc.) can potentially contribute to significant improvement across a broad range of CEA applications.« less

All-in-one bioprobe devised with hierarchical-ordered magnetic NiCo2O4 superstructure for ultrasensitive dual-readout immunosensor for logic diagnosis of tumor marker.

PubMed

Dai, Hong; Gong, Lingshan; Zhang, Shupei; Xu, Guifang; Li, Yilin; Hong, Zhensheng; Lin, Yanyu

2016-03-15

A new enzyme-free all-in-one bioprobe, consisted of hematin decorated magnetic NiCo2O4 superstructure (ATS-MNS-Hb), was designed for ultrasensitive photoelectrochemical and electrochemical dual-readout immunosensing of carcinoembryonic antigen (CEA) on carbon nanohorns (CNH) support. Herein, the MNS, possessed hierarchical-ordered structure, good porosity and magnetism, acted as nanocarrier to absorb abundant Hb molecular after functionalization, providing a convenient collection means by magnetic control as well as enhanced dual-readout sensing performances. CNH superstructures were employed as support to immobilize abounding captured antibodies, and then as-designed dual mode bioprobe, covalent binding with secondary antibody of CEA, was introduced for ultrasensitive detection of CEA by sandwich immunosensing. Photoelectrochemical response originated from plentiful hematin molecular, a excellent photosensitizer with good visible light harvesting efficiency, absorbed by functionalized porous MNS. The resultant concentration dependant linear calibration range was from 10 fg/mL to 1 ng/mL with ultralow detection limit of 10 fg/mL. For electrochemical process, catalase-like property of MNS was validated, moreover, MNS-Hb hybrid exhibited much higher mimic enzyme catalytic activity and evidently amplified electrocatalytic signal, performing a wide dynamic linear range from 1 ng/mL to 40 ng/mL with low detection limit of 1 ng/mL. Additionally, due to the improved accuracy of dual signals detection, the exact diagnoses of serum samples were gotten by operating resulting dual signals with AND logic system. This work demonstrated the promising application of MNS in developing ultrasensitive, cost-effective and environment friendly dual-readout immunosensor and accurate diagnoses strategy for tumor markers. Copyright © 2015 Elsevier B.V. All rights reserved.

Generalized cost-effectiveness analysis for national-level priority-setting in the health sector

PubMed Central

Hutubessy, Raymond; Chisholm, Dan; Edejer, Tessa Tan-Torres

2003-01-01

Cost-effectiveness analysis (CEA) is potentially an important aid to public health decision-making but, with some notable exceptions, its use and impact at the level of individual countries is limited. A number of potential reasons may account for this, among them technical shortcomings associated with the generation of current economic evidence, political expediency, social preferences and systemic barriers to implementation. As a form of sectoral CEA, Generalized CEA sets out to overcome a number of these barriers to the appropriate use of cost-effectiveness information at the regional and country level. Its application via WHO-CHOICE provides a new economic evidence base, as well as underlying methodological developments, concerning the cost-effectiveness of a range of health interventions for leading causes of, and risk factors for, disease. The estimated sub-regional costs and effects of different interventions provided by WHO-CHOICE can readily be tailored to the specific context of individual countries, for example by adjustment to the quantity and unit prices of intervention inputs (costs) or the coverage, efficacy and adherence rates of interventions (effectiveness). The potential usefulness of this information for health policy and planning is in assessing if current intervention strategies represent an efficient use of scarce resources, and which of the potential additional interventions that are not yet implemented, or not implemented fully, should be given priority on the grounds of cost-effectiveness. Health policy-makers and programme managers can use results from WHO-CHOICE as a valuable input into the planning and prioritization of services at national level, as well as a starting point for additional analyses of the trade-off between the efficiency of interventions in producing health and their impact on other key outcomes such as reducing inequalities and improving the health of the poor. PMID:14687420

Generalized cost-effectiveness analysis for national-level priority-setting in the health sector.

PubMed

Hutubessy, Raymond; Chisholm, Dan; Edejer, Tessa Tan-Torres

2003-12-19

Cost-effectiveness analysis (CEA) is potentially an important aid to public health decision-making but, with some notable exceptions, its use and impact at the level of individual countries is limited. A number of potential reasons may account for this, among them technical shortcomings associated with the generation of current economic evidence, political expediency, social preferences and systemic barriers to implementation. As a form of sectoral CEA, Generalized CEA sets out to overcome a number of these barriers to the appropriate use of cost-effectiveness information at the regional and country level. Its application via WHO-CHOICE provides a new economic evidence base, as well as underlying methodological developments, concerning the cost-effectiveness of a range of health interventions for leading causes of, and risk factors for, disease.The estimated sub-regional costs and effects of different interventions provided by WHO-CHOICE can readily be tailored to the specific context of individual countries, for example by adjustment to the quantity and unit prices of intervention inputs (costs) or the coverage, efficacy and adherence rates of interventions (effectiveness). The potential usefulness of this information for health policy and planning is in assessing if current intervention strategies represent an efficient use of scarce resources, and which of the potential additional interventions that are not yet implemented, or not implemented fully, should be given priority on the grounds of cost-effectiveness.Health policy-makers and programme managers can use results from WHO-CHOICE as a valuable input into the planning and prioritization of services at national level, as well as a starting point for additional analyses of the trade-off between the efficiency of interventions in producing health and their impact on other key outcomes such as reducing inequalities and improving the health of the poor.

Top-down nanofabrication of silicon nanoribbon field effect transistor (Si-NR FET) for carcinoembryonic antigen detection.

PubMed

Bao, Zengtao; Sun, Jialin; Zhao, Xiaoqian; Li, Zengyao; Cui, Songkui; Meng, Qingyang; Zhang, Ye; Wang, Tong; Jiang, Yanfeng

2017-01-01

Sensitive and quantitative detection of tumor markers is highly required in the clinic for cancer diagnosis and consequent treatment. A field-effect transistor-based (FET-based) nanobiosensor emerges with characteristics of being label-free, real-time, having high sensitivity, and providing direct electrical readout for detection of biomarkers. In this paper, a top-down approach is proposed and implemented to fulfill a novel silicon nano-ribbon FET, which acts as biomarker sensor for future clinical application. Compared with the bottom-up approach, a top-down fabrication approach can confine width and length of the silicon FET precisely to control its electrical properties. The silicon nanoribbon (Si-NR) transistor is fabricated on a Silicon-on-Insulator (SOI) substrate by a top-down approach with complementary metal oxide semiconductor (CMOS)-compatible technology. After the preparation, the surface of Si-NR is functionalized with 3-aminopropyltriethoxysilane (APTES). Glutaraldehyde is utilized to bind the amino terminals of APTES and antibody on the surface. Finally, a microfluidic channel is integrated on the top of the device, acting as a flowing channel for the carcinoembryonic antigen (CEA) solution. The Si-NR FET is 120 nm in width and 25 nm in height, with ambipolar electrical characteristics. A logarithmic relationship between the changing ratio of the current and the CEA concentration is measured in the range of 0.1-100 ng/mL. The sensitivity of detection is measured as 10 pg/mL. The top-down fabricated biochip shows feasibility in direct detecting of CEA with the benefits of real-time, low cost, and high sensitivity as a promising biosensor for tumor early diagnosis.

Vaccination of metastatic colorectal cancer patients with matured dendritic cells loaded with multiple major histocompatibility complex class I peptides.

PubMed

Kavanagh, Brian; Ko, Andrew; Venook, Alan; Margolin, Kim; Zeh, Herbert; Lotze, Michael; Schillinger, Brian; Liu, Weihong; Lu, Ying; Mitsky, Peggie; Schilling, Marta; Bercovici, Nadege; Loudovaris, Maureen; Guillermo, Roy; Lee, Sun Min; Bender, James; Mills, Bonnie; Fong, Lawrence

2007-10-01

Developing a process to generate dendritic cells (DCs) applicable for multicenter trials would facilitate cancer vaccine development. Moreover, targeting multiple antigens with such a vaccine strategy could enhance the efficacy of such a treatment approach. We performed a phase 1/2 clinical trial administering a DC-based vaccine targeting multiple tumor-associated antigens to patients with advanced colorectal cancer (CRC). A qualified manufacturing process was used to generate DC from blood monocytes using granulocyte macrophage colony-stimulating factor and IL-13, and matured for 6 hours with Klebsiella-derived cell wall fraction and interferon-gamma (IFN-gamma). DCs were also loaded with 6 HLA-A*0201 binding peptides derived from carcinoembryonic antigen (CEA), MAGE, and HER2/neu, as well as keyhole limpet hemocyanin protein and pan-DR epitope peptide. Four planned doses of 35x10(6) cells were administered intradermally every 3 weeks. Immune response was assessed by IFN-gamma enzyme-linked immunosorbent spot (ELISPOT). Matured DC possessed an activated phenotype and could prime T cells in vitro. In the trial, 21 HLA-A2+ patients were apheresed, 13 were treated with the vaccine, and 11 patients were evaluable. No significant treatment-related toxicity was reported. T-cell responses to a CEA-derived peptide were detected by ELISPOT in 3 patients. T cells induced to CEA possessed high avidity T-cell receptors. ELISPOT after in vitro restimulation detected responses to multiple peptides in 2 patients. All patients showed progressive disease. This pilot study in advanced CRC patients demonstrates DC-generated granulocyte macrophage colony-stimulating factor and IL-13 matured with Klebsiella-derived cell wall fraction and IFN-gamma can induce immune responses to multiple tumor-associated antigens in patients with advanced CRC.

[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.

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.

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.

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.

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

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

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.

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.

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 generally agree with position statements prepared by other organizations in recent years, and with a January 1995 consensus statement by a group of experts assembled by the American Heart Association.

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.

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 revascularization. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

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.

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

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

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.

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.

[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.

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 this analysis from the MSQC database, there is an associated increased morbidity and resource utilization with GA vs RA for CEA. This has implications for enterprise resource planning initiatives and the CEA value proposition in general, which is of special interest to both hospitals and payers. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

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 Surgery. Published by Elsevier Ltd. All rights reserved.

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 changes were observed for either CEA-BML, STIR-BML or N voxel . Neither the degree nor the volume of contrast enhancement in BMLs seems to add any clinical information compared to BMLs visualized by fluid sensitive sequences. Manual segmentation may be needed to obtain valid CEA-BML measurements.

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). Although hundreds of thousands of patients undergo chemotherapies each year, the neural mechanisms mediating their side effects are unknown. The current data outline a neural circuit activated by cisplatin chemotherapy and demonstrate that glutamate signaling in the amygdala, arising from hindbrain projections, is required for the full expression of cisplatin-induced malaise, anorexia, and body weight loss. Together, these data help to characterize the neural circuits and neurotransmitters mediating chemotherapy-induced energy balance dysregulation, which will ultimately provide an opportunity for the development of well tolerated cancer and anti-emetic treatments. PMID:26245970

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 scoring system (P = 0.26) and there was no difference in the ROC curves (C statistic = 0.74 vs 0.73). This validated scoring system can be a useful tool for determining which patients are likely to benefit most from CEA based on the probability of long-term survival. Given that the 5-year survival of patients in the medical arm of the asymptomatic CEA trials was 60% to 70%, it is reasonable to conclude that patients who score 0 to 8 points are excellent candidates for CEA whereas most patients with ≥12 points should be managed with medical therapy alone.

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 demonstrated that the emergency physician as referral source (P = .0002) was statistically significant for reducing CEA delay. Patients who were investigated as an outpatient (P = .02), first medical contact with a general practitioner (P = .0002), and hospital center I as referral center (P = .045) were also found to be statistically significant to extend CEA delay when the model was adjusted over all covariates. In this center, there was no correlation between ABCD 2 risk score and waiting time for surgery. The majority of our cohort falls short of the recommended 2-week interval to perform CEA. Factors contributing to reduced CEA delay were presentation to an emergency department, in-patient investigations, and a stroke center where a vascular surgeon is available. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

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...

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…

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...

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...

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...

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…

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…

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

HgCdTe APDS for time resolved space applications

NASA Astrophysics Data System (ADS)

Rothman, J.; Lasfargues, G.; Delacourt, B.; Dumas, A.; Gibert, F.; Bardoux, A.; Boutillier, M.

2017-09-01

HgCdTe APDs have opened a new horizon in photon starved applications due to their exceptional performance in terms of high linear gain, low excess noise and high quantum efficiency. Both focal plane arrays (FPAs) and large array single element using HgCdTe (MCT) APDs have been developed at CEA/Leti and Sofradir and high performance devices are at present available to detect without deterioration the spatial and/or temporal information in photon fluxes with a low number of photon in each spatio-temporal bin. The enhancement in performance that can be achieved with MCT has subsequently been demonstrated in a wide scope of applications such as astronomical observations, active imaging, deep space telecommunications, atmospheric LIDAR and mid-IR (MIR) time resolved photoluminescence measurements. Most of these applications can be used in space borne platforms.