TRAC-PD2 posttest analysis of CCTF Test C1-16 (Run 025). [Cylindrical Core Test Facility
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sugimoto, J.
The TRAC-PD2 code version was used to analyze CCTF Test C1-16 (Run 025). The results indicate that the core heater rod temperatures, the liquid mass in the vessel, and differential pressures in the primary loop are predicted well, but the void fraction distribution in the core and water accumulation in the upper plenum are not in good agreement with the data.
TRAC-PD2 posttest analysis of the CCTF Evaluation-Model Test C1-19 (Run 38). [PWR
DOE Office of Scientific and Technical Information (OSTI.GOV)
Motley, F.
The results of a Transient Reactor Analysis Code posttest analysis of the Cylindral Core Test Facility Evaluation-Model Test agree very well with the results of the experiment. The good agreement obtained verifies the multidimensional analysis capability of the TRAC code. Because of the steep radial power profile, the importance of using fine noding in the core region was demonstrated (as compared with poorer results obtained from an earlier pretest prediction that used a coarsely noded model).
Posttest TRAC-PD2/MOD1 predictions for FLECHT SEASET test 31504. [PWR
DOE Office of Scientific and Technical Information (OSTI.GOV)
Booker, C.P.
TRAC-PD2/MOD1 is a publicly released version of TRAC that is used primarily to analyze large-break loss-of-coolant accidents in pressurized-water reactors (PWRs). TRAC-PD2 can calculate, among other things, reflood phenomena. TRAC posttest predictions are compared with test 31504 reflood data from the Full-Length Emergency Core Heat Transfer (FLECHT) System Effects and Separate Effects Tests (SEASET) facility. A false top-down quench is predicted near the top of the core and the subcooling is underpredicted at the bottom of the core. However, the overall TRAC predictions are good, especially near the center of the core.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liao, J.; Kucukboyaci, V. N.; Nguyen, L.
2012-07-01
The Westinghouse Small Modular Reactor (SMR) is an 800 MWt (> 225 MWe) integral pressurized water reactor (iPWR) with all primary components, including the steam generator and the pressurizer located inside the reactor vessel. The reactor core is based on a partial-height 17x17 fuel assembly design used in the AP1000{sup R} reactor core. The Westinghouse SMR utilizes passive safety systems and proven components from the AP1000 plant design with a compact containment that houses the integral reactor vessel and the passive safety systems. A preliminary loss of coolant accident (LOCA) analysis of the Westinghouse SMR has been performed using themore » WCOBRA/TRAC-TF2 code, simulating a transient caused by a double ended guillotine (DEG) break in the direct vessel injection (DVI) line. WCOBRA/TRAC-TF2 is a new generation Westinghouse LOCA thermal-hydraulics code evolving from the US NRC licensed WCOBRA/TRAC code. It is designed to simulate PWR LOCA events from the smallest break size to the largest break size (DEG cold leg). A significant number of fluid dynamics models and heat transfer models were developed or improved in WCOBRA/TRAC-TF2. A large number of separate effects and integral effects tests were performed for a rigorous code assessment and validation. WCOBRA/TRAC-TF2 was introduced into the Westinghouse SMR design phase to assist a quick and robust passive cooling system design and to identify thermal-hydraulic phenomena for the development of the SMR Phenomena Identification Ranking Table (PIRT). The LOCA analysis of the Westinghouse SMR demonstrates that the DEG DVI break LOCA is mitigated by the injection and venting from the Westinghouse SMR passive safety systems without core heat up, achieving long term core cooling. (authors)« less
TRAC posttest calculations of Semiscale Test S-06-3. [PWR
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ireland, J.R.; Bleiweis, P.B.
A comparison of Transient Reactor Analysis Code (TRAC) steady-state and transient results with Semiscale Test S-06-3 (US Standard Problem 8) experimental data is discussed. The TRAC model used employs fewer mesh cells than normal data comparison models so that TRAC's ability to obtain reasonable results with less computer time can be assessed. In general, the TRAC results are in good agreement with the data and the major phenomena found in the experiment are reproduced by the code with a substantial reduction in computing times.
Constitutive relations in TRAC-P1A
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rohatgi, U.S.; Saha, P.
1980-08-01
The purpose of this document is to describe the basic thermal-hydraulic models and correlations that are in the TRAC-P1A code, as released in March 1979. It is divided into two parts, A and B. Part A describes the models in the three-dimensional vessel module of TRAC, whereas Part B focuses on the loop components that are treated by one-dimensional formulations. The report follows the format of the questions prepared by the Analysis Development Branch of USNRC and the questionnaire has been attached to this document for completeness. Concerted efforts have been made in understanding the present models in TRAC-P1A bymore » going through the FORTRAN listing of the code. Some discrepancies between the code and the TRAC-P1A manual have been found. These are pointed out in this document. Efforts have also been made to check the TRAC references for the range of applicability of the models and correlations used in the code. 26 refs., 5 figs., 1 tab.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liao, J.; Cao, L.; Ohkawa, K.
2012-07-01
The non-condensable gases condensation suppression model is important for a realistic LOCA safety analysis code. A condensation suppression model for direct contact condensation was previously developed by Westinghouse using first principles. The model is believed to be an accurate description of the direct contact condensation process in the presence of non-condensable gases. The Westinghouse condensation suppression model is further revised by applying a more physical model. The revised condensation suppression model is thus implemented into the WCOBRA/TRAC-TF2 LOCA safety evaluation code for both 3-D module (COBRA-TF) and 1-D module (TRAC-PF1). Parametric study using the revised Westinghouse condensation suppression model ismore » conducted. Additionally, the performance of non-condensable gases condensation suppression model is examined in the ACHILLES (ISP-25) separate effects test and LOFT L2-5 (ISP-13) integral effects test. (authors)« less
TRAC-PF1/MOD1 support calculations for the MIST/OTIS program
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fujita, R.K.; Knight, T.D.
1984-01-01
We are using the Transient Reactor Analysis Code (TRAC), specifically version TRAC-PF1/MOD1, to perform analyses in support of the MultiLoop Integral-System Test (MIST) and the Once-Through Integral-System (OTIS) experiment program. We have analyzed Geradrohr Dampferzeuger Anlage (GERDA) Test 1605AA to benchmark the TRAC-PF1/MOD1 code against phenomena expected to occur in a raised-loop B and W plant during a small-break loss-of-coolant accident (SBLOCA). These results show that the code can calculate both single- and two-phase natural circulation, flow interruption, boiler-condenser-mode (BCM) heat transfer, and primary-system refill in a B and W-type geometry with low-elevation auxiliary feedwater. 19 figures, 7 tables.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hall, D.G.: Watkins, J.C.
This report documents an evaluation of the TRAC-PF1/MOD1 reactor safety analysis computer code during computer simulations of feedwater line break transients. The experimental data base for the evaluation included the results of three bottom feedwater line break tests performed in the Semiscale Mod-2C test facility. The tests modeled 14.3% (S-FS-7), 50% (S-FS-11), and 100% (S-FS-6B) breaks. The test facility and the TRAC-PF1/MOD1 model used in the calculations are described. Evaluations of the accuracy of the calculations are presented in the form of comparisons of measured and calculated histories of selected parameters associated with the primary and secondary systems. In additionmore » to evaluating the accuracy of the code calculations, the computational performance of the code during the simulations was assessed. A conclusion was reached that the code is capable of making feedwater line break transient calculations efficiently, but there is room for significant improvements in the simulations that were performed. Recommendations are made for follow-on investigations to determine how to improve future feedwater line break calculations and for code improvements to make the code easier to use.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1978-05-01
The Transient Reactor Analysis Code (TRAC) is being developed at the Los Alamos Scientific Laboratory (LASL) to provide an advanced ''best estimate'' predictive capability for the analysis of postulated accidents in light water reactors (LWRs). TRAC-Pl provides this analysis capability for pressurized water reactors (PWRs) and for a wide variety of thermal-hydraulic experimental facilities. It features a three-dimensional treatment of the pressure vessel and associated internals; two-phase nonequilibrium hydrodynamics models; flow-regime-dependent constitutive equation treatment; reflood tracking capability for both bottom flood and falling film quench fronts; and consistent treatment of entire accident sequences including the generation of consistent initial conditions.more » The TRAC-Pl User's Manual is composed of two separate volumes. Volume I gives a description of the thermal-hydraulic models and numerical solution methods used in the code. Detailed programming and user information is also provided. Volume II presents the results of the developmental verification calculations.« less
Precision-Guided Munitions Effects Representation
2017-01-03
Center for Army Analysis (CAA) by the TRADOC Analysis Center, Monterey (TRAC-MTRY). The focus of the research is to improve the current methodology ... Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A-2 Timeline... Methodology . . . . . . . . . . . . . . . . . . . . C-1 MATLAB Code . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C-49 Damage
Coupling of TRAC-PF1/MOD2, Version 5.4.25, with NESTLE
DOE Office of Scientific and Technical Information (OSTI.GOV)
Knepper, P.L.; Hochreiter, L.E.; Ivanov, K.N.
1999-09-01
A three-dimensional (3-D) spatial kinetics capability within a thermal-hydraulics system code provides a more correct description of the core physics during reactor transients that involve significant variations in the neutron flux distribution. Coupled codes provide the ability to forecast safety margins in a best-estimate manner. The behavior of a reactor core and the feedback to the plant dynamics can be accurately simulated. For each time step, coupled codes are capable of resolving system interaction effects on neutronics feedback and are capable of describing local neutronics effects caused by the thermal hydraulics and neutronics coupling. With the improvements in computational technology,more » modeling complex reactor behaviors with coupled thermal hydraulics and spatial kinetics is feasible. Previously, reactor analysis codes were limited to either a detailed thermal-hydraulics model with simplified kinetics or multidimensional neutron kinetics with a simplified thermal-hydraulics model. The authors discuss the coupling of the Transient Reactor Analysis Code (TRAC)-PF1/MOD2, Version 5.4.25, with the NESTLE code.« less
Validating the FOCUS Model Through an Analysis of Identity Fragmentation in Nigerian Social Media
2015-09-01
TRAC-M-TM-15-032 September 2015 Validating the FOCUS Model Through an Analysis of Identity Fragmentation in Nigerian Social Media ...an Analysis of Identity Fragmentation in Nigerian Social Media Authors MAJ Adam Haupt Dr. Camber Warren...Identity Fragmentation in Nigerian Social Media 5. PROJECT NUMBERS TRAC Project Code 060113 6. AUTHOR(S) MAJ Haupt, Dr. Warren 7. PERFORMING
TRAC-PF1 code verification with data from the OTIS test facility. [Once-Through Intergral System
DOE Office of Scientific and Technical Information (OSTI.GOV)
Childerson, M.T.; Fujita, R.K.
1985-01-01
A computer code (TRAC-PF1/MOD1) developed for predicting transient thermal and hydraulic integral nuclear steam supply system (NSSS) response was benchmarked. Post-small break loss-of-coolant accident (LOCA) data from a scaled, experimental facility, designated the One-Through Integral System (OTIS), were obtained for the Babcock and Wilcox NSSS and compared to TRAC predictions. The OTIS tests provided a challenging small break LOCA data set for TRAC verification. The major phases of a small break LOCA observed in the OTIS tests included pressurizer draining and loop saturation, intermittent reactor coolant system circulation, boiler-condenser mode, and the initial stages of refill. The TRAC code wasmore » successful in predicting OTIS loop conditions (system pressures and temperatures) after modification of the steam generator model. In particular, the code predicted both pool and auxiliary-feedwater initiated boiler-condenser mode heat transfer.« less
TOOKUIL: A case study in user interface development for safety code application
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gray, D.L.; Harkins, C.K.; Hoole, J.G.
1997-07-01
Traditionally, there has been a very high learning curve associated with using nuclear power plant (NPP) analysis codes. Even for seasoned plant analysts and engineers, the process of building or modifying an input model for present day NPP analysis codes is tedious, error prone, and time consuming. Current cost constraints and performance demands place an additional burden on today`s safety analysis community. Advances in graphical user interface (GUI) technology have been applied to obtain significant productivity and quality assurance improvements for the Transient Reactor Analysis Code (TRAC) input model development. KAPL Inc. has developed an X Windows-based graphical user interfacemore » named TOOKUIL which supports the design and analysis process, acting as a preprocessor, runtime editor, help system, and post processor for TRAC. This paper summarizes the objectives of the project, the GUI development process and experiences, and the resulting end product, TOOKUIL.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Steiner, J.L.; Lime, J.F.; Elson, J.S.
One dimensional TRAC transient calculations of the process inherent ultimate safety (PIUS) advanced reactor design were performed for a pump-trip SCRAM. The TRAC calculations showed that the reactor power response and shutdown were in qualitative agreement with the one-dimensional analyses presented in the PIUS Preliminary Safety Information Document (PSID) submitted by Asea Brown Boveri (ABB) to the US Nuclear Regulatory Commission for preapplication safety review. The PSID analyses were performed with the ABB-developed RIGEL code. The TRAC-calculated phenomena and trends were also similar to those calculated with another one-dimensional PIUS model, the Brookhaven National Laboratory developed PIPA code. A TRACmore » pump-trip SCRAM transient has also been calculated with a TRAC model containing a multi-dimensional representation of the PIUS intemal flow structures and core region. The results obtained using the TRAC fully one-dimensional PIUS model are compared to the RIGEL, PIPA, and TRAC multi-dimensional results.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Spindler, B.; Pellissier, M.
1990-01-01
Independent assessment of the TRAC code was conducted at the Centre d'Etudes Nucleaires de Grenoble of the Commissariate a l'Energie Atomique (France) in the frame of the ICAP. This report presents the results of the assessment of TRAC-PF1/MOD1 version 14.3 using critical flow steady state tests (MOBY-DICK, SUPER-MOBY-DICK), and blowdown tests (CANON, SUPER-CANON, VERTICAL-CANON, MARVIKEN, OMEGA-TUBE, OMEGA-BUNDLE). This document, Volume 2, presents the experimental data and figures from the assessment.
Posttest analysis of MIST Test 330302 using TRAC-PF1/MOD1
DOE Office of Scientific and Technical Information (OSTI.GOV)
Boyack, B E
This report discusses a posttest analysis of Multi-Loop Integral System Test (MIST) 330302 which has been performed using TRAC-PF1/MOD1. This test was one of group performed in the MIST facility to investigate high-pressure injection (HPI)-power-operated relief valve (PORV) cooling, also known as feed-and-bleed cooling. In Test 330302, HPI cooling was delayed 20 min after opening and locking the PORV open to induce extensive system voiding. We have concluded that the TRAC-calculated results are in reasonable overall agreement with the data for Test 330302. All major trends and phenomena were correctly predicted. Differences observed between the measured and calculated results havemore » been traced and related, in part, to deficiencies in our knowledge of the facility configuration and operation. We have identified two models forwhich additional review is appropriate. However, in general, the TRAC closure models and correlations appear to be adequate for the prediction of the phenomena expected to occur during feed-and-bleed transientsin the MIST facility. We believe that the correct conclusions about trends and phenomena will be reached if the code is used in similar applications. Conclusions reached regarding use of the code to calculate similar phenomena in full-size plants (scaling implications) and regulatory implications of this work are also presented.« less
Tiltrotor Aeroacoustic Code (TRAC) Prediction Assessment and Initial Comparisons with Tram Test Data
NASA Technical Reports Server (NTRS)
Burley, Casey L.; Brooks, Thomas F.; Charles, Bruce D.; McCluer, Megan
1999-01-01
A prediction sensitivity assessment to inputs and blade modeling is presented for the TiltRotor Aeroacoustic Code (TRAC). For this study, the non-CFD prediction system option in TRAC is used. Here, the comprehensive rotorcraft code, CAMRAD.Mod1, coupled with the high-resolution sectional loads code HIRES, predicts unsteady blade loads to be used in the noise prediction code WOPWOP. The sensitivity of the predicted blade motions, blade airloads, wake geometry, and acoustics is examined with respect to rotor rpm, blade twist and chord, and to blade dynamic modeling. To accomplish this assessment, an interim input-deck for the TRAM test model and an input-deck for a reference test model are utilized in both rigid and elastic modes. Both of these test models are regarded as near scale models of the V-22 proprotor (tiltrotor). With basic TRAC sensitivities established, initial TRAC predictions are compared to results of an extensive test of an isolated model proprotor. The test was that of the TiltRotor Aeroacoustic Model (TRAM) conducted in the Duits-Nederlandse Windtunnel (DNW). Predictions are compared to measured noise for the proprotor operating over an extensive range of conditions. The variation of predictions demonstrates the great care that must be taken in defining the blade motion. However, even with this variability, the predictions using the different blade modeling successfully capture (bracket) the levels and trends of the noise for conditions ranging from descent to ascent.
Tiltrotor Aeroacoustic Code (TRAC) Prediction Assessment and Initial Comparisons With TRAM Test Data
NASA Technical Reports Server (NTRS)
Burley, Casey L.; Brooks, Thomas F.; Charles, Bruce D.; McCluer, Megan
1999-01-01
A prediction sensitivity assessment to inputs and blade modeling is presented for the TiltRotor Aeroacoustic Code (TRAC). For this study, the non-CFD prediction system option in TRAC is used. Here, the comprehensive rotorcraft code, CAMRAD.Mod 1, coupled with the high-resolution sectional loads code HIRES, predicts unsteady blade loads to be used in the noise prediction code WOPWOP. The sensitivity of the predicted blade motions, blade airloads, wake geometry, and acoustics is examined with respect to rotor rpm, blade twist and chord, and to blade dynamic modeling. To accomplish this assessment. an interim input-deck for the TRAM test model and an input-deck for a reference test model are utilized in both rigid and elastic modes. Both of these test models are regarded as near scale models of the V-22 proprotor (tiltrotor). With basic TRAC sensitivities established, initial TRAC predictions are compared to results of an extensive test of an isolated model proprotor. The test was that of the TiltRotor Aeroacoustic Model (TRAM) conducted in the Duits-Nederlandse Windtunnel (DNW). Predictions are compared to measured noise for the proprotor operating over an extensive range of conditions. The variation of predictions demonstrates the great care that must be taken in defining the blade motion. However, even with this variability, the predictions using the different blade modeling successfully capture (bracket) the levels and trends of the noise for conditions ranging from descent to ascent.
Numerical simulation of fiber and wire array Z-pinches with Trac-II
NASA Astrophysics Data System (ADS)
Reisman, David Barton
Trac-II is a two dimensional axisymmetric resistive MHD code. It simulates all three spatial components (r, z, φ) of the magnetic field and fluid velocity vectors, and the plasma is treated as a single fluid with two temperatures (Te,Ti). In addition, it can optionally include a self-consistent external circuit. Recent modifications to the code include the addition of the 3-T radiation model, a 4-phase (solid- liquid-vapor-plasma) equation of state model (QEOS), a 4- phase electrical/thermal conductivity model, and an implicit solution of poloidal (Bz,Br) magnetic field diffusion. These changes permit a detailed study of fiber and wire array Z-pinches. Specifically, Trac-II is used to study the wire array Z-pinch at the PBFA-Z pulse power generator at Sandia National Laboratory. First, in 1-D we examine the behavior of a single wire in the Z-pinch. Then, using these results as initial radial conditions in 2-D, we investigate the dynamics of wire array configurations in the r-z and r-θ plane. In the r- z plane we examine the growth of the m = 0 or ``sausage'' instability in single wires within the array. In the r-θ plane we examine the merging behavior between neighboring wires. Special emphasis is placed on trying to explain how instability growth affects the performance of the Z-pinch. Lastly, we introduce Trac-III, a 3-D MHD code, and illustrate the m = 1 or ``kink'' instability. We also discuss how Trac-III can be modified to simulate the wire array Z-pinch.
Assessment of MSIV full closure for Santa Maria de Garona Nuclear Power Plant using TRAC-BF1 (G1J1)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Crespo, J.L.; Fernandez, R.A.
1993-06-01
This document presents a spurious Main Steam Isolation Value (MSIV) closure analysis for Santa Maria de Garorta Nuclear Power Plan describing the problems found when comparing calculated and real data. The plant is a General Electric Boiling Water Reactor 3, containment type Mark 1. It is operated by NUCLENOR, S.A. and was connected to the grid in 1971. The analysis has been performed by the Apphed Physics Department from the University of Cantabria and the Analysis and Operation Section from NUCLENOR, S.A. as a part of an agreement for developing an engineering simulator of operational transients and accidents for Santamore » Maria de Gamma Power Plant. The analysis was performed using the frozen version of TRAC-BFI (GlJl) code and is the second of two NUCLENOR contributions to the International Code Applications and Assessment Program (ICAP). The code was run in a Cyber 932 with operating system NOS/VE, property of NUCLENOR, S.A.. A programming effort was carried out in order to provide suitable graphics from the output file.« less
George, Daniel J; Martini, Jean-François; Staehler, Michael; Motzer, Robert J; Magheli, Ahmed; Escudier, Bernard; Gerletti, Paola; Li, Sherry; Casey, Michelle; Laguerre, Brigitte; Pandha, Hardev S; Pantuck, Allan J; Patel, Anup; Lechuga, Maria J; Ravaud, Alain
2018-04-01
Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free survival (DFS) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov number NCT00375674). A prospectively designed exploratory analysis of tissue biomarkers was conducted to identify predictors of treatment benefit. Experimental Design: Tissue blocks were used for immunohistochemistry (IHC) staining of programmed cell death ligand 1 (PD-L1), CD4, CD8, and CD68. DFS was compared between < versus ≥ median IHC parameter using the Kaplan-Meier method. For biomarkers with predictive potential, receiver operating characteristics curves were generated. Results: Baseline characteristics were similar in patients with ( n = 191) and without ( n = 419) IHC analysis. Among patients with IHC, longer DFS was observed in patients with tumor CD8 + T-cell density ≥ versus < median [median (95% CI), not reached (6.83-not reached) versus 3.47 years (1.73-not reached); hazard ratio (HR) 0.40 (95% CI, 0.20-0.81); P = 0.009] treated with sunitinib ( n = 101), but not with placebo ( n = 90). The sensitivity and specificity for CD8 + T-cell density in predicting DFS were 0.604 and 0.658, respectively. Shorter DFS was observed in placebo-treated patients with PD-L1 + versus PD-L1 - tumors (HR 1.75; P = 0.103). Among all patients with PD-L1 + tumors, DFS was numerically longer with sunitinib versus placebo (HR 0.58; P = 0.175). Conclusions: Greater CD8 + T-cell density in tumor tissue was associated with longer DFS with sunitinib but not placebo, suggesting predictive treatment effect utility. Further independent cohort validation studies are warranted. The prognostic value of PD-L1 expression in primary tumors from patients with high-risk nonmetastatic RCC should also be further explored. Clin Cancer Res; 24(7); 1554-61. ©2018 AACR . ©2018 American Association for Cancer Research.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Spindler, B.; Pellissier, M.
1990-01-01
Independent assessment of the TRAC code was conducted at the Centre d'Etudes Nucleaires de Grenoble of the Commissariate a l'Energie Atomique (France) in the frame of the ICAP. This report presents the results of the assessment of TRAC-PF1/MOD1 version 14.3 using critical flow steady state tests (MOBY-DICK, SUPER-MOBY-DICK), and blowdown tests (CANON, SUPER-CANON, VERTICAL-CANON, MARVIKEN, OMEGA-TUBE, OMEGA-BUNDLE). This document, Volume 1, presents the text and tables from this assessment.
Maeda, Takuma; Hattori, Kohshi; Sumiyoshi, Miho; Kanazawa, Hiroko; Ohnishi, Yoshihiko
2018-06-01
The fourth-generation FloTrac/Vigileo™ improved its algorithm to follow changes in systemic vascular resistance index (SVRI). This revision may improve the accuracy and trending ability of CI even in patients who undergo abdominal aortic aneurysm (AAA) surgery which cause drastic change of SVRI by aortic clamping. The purpose of this study is to elucidate the accuracy and trending ability of the fourth-generation FloTrac/Vigileo™ in patients with AAA surgery by comparing the FloTrac/Vigileo™-derived CI (CI FT ) with that measured by three-dimensional echocardiography (CI 3D ). Twenty-six patients undergoing elective AAA surgery were included in this study. CI FT and CI3 D were determined simultaneously in eight points including before and after aortic clamp. We used CI 3D as the reference method. In the Bland-Altman analysis, CI FT had a wide limit of agreement with CI 3D showing a percentage error of 46.7%. Subgroup analysis showed that the percentage error between CO 3D and CO FT was 56.3% in patients with cardiac index < 2.5 L/min/m 2 and 28.4% in patients with cardiac index ≥ 2.5 L/min/m 2 . SVRI was significantly higher in patients with cardiac index < 2.5 L/min/m 2 (1703 ± 330 vs. 2757 ± 798; p < 0.001). The tracking ability of fourth generation of FloTrac/Vigileo™ after aortic clamp was not clinically acceptable (26.9%). The degree of accuracy of the fourth-generation FloTrac/Vigileo™ in patients with AAA surgery was not acceptable. The tracking ability of the fourth-generation FloTrac/Vigileo™ after aortic clamp was below the acceptable limit.
TRAC-Monterey FY16 Work Program Development and Report of Research Elicitation
2016-01-01
any changes to priorities or additional projects that require immediate research. Work Program; Research Elicitation Unclassified UU UU UU UU 35 MAJ...conduct analysis for the Army. 1 Marks, Chris, Nesbitt, Peter. TRAC FY14 Research Requirements Elicitation . Technical Report TRAC-M-TM-13-059. 700 Dyer... Requirements Elicitation Interviews Interview Guide: 1. Describe a research requirement in the areas of topics, techniques, and methodologies. 2
Pretest and posttest calculations of Semiscale Test S-07-10D with the TRAC computer program. [PWR
DOE Office of Scientific and Technical Information (OSTI.GOV)
Duerre, K.H.; Cort, G.E.; Knight, T.D.
The Transient Reactor Analysis Code (TRAC) developed at the Los Alamos National Laboratory was used to predict the behavior of the small-break experiment designated Semiscale S-07-10D. This test simulates a 10 per cent communicative cold-leg break with delayed Emergency Core Coolant injection and blowdown of the broken-loop steam generator secondary. Both pretest calculations that incorporated measured initial conditions and posttest calculations that incorporated measured initial conditions and measured transient boundary conditions were completed. The posttest calculated parameters were generally between those obtained from pretest calculations and those from the test data. The results are strongly dependent on depressurization rate and,more » hence, on break flow.« less
Posttest analysis of MIST Test 3109AA using TRAC-PF1/MOD1
DOE Office of Scientific and Technical Information (OSTI.GOV)
Steiner, J.L.; Siebe, D.A.; Boyack, B.E.
This document discusses a posttest calculation and analysis of Multi-loop Integral System Test (MIST) 3109AA as the nominal test for the MIST program. It is a test of a small-break loss-of-coolant accident (SBLOCA) with a scaled 10-cm{sup 2} break in the B1 cold leg. The test exhibited the major post-SBLOCA phenomena, as expected, including depressurization to saturation, intermittent and interrupted loop flow, boiler-condenser mode cooling, refill, and postrefill cooldown. Full high-pressure injection and auxiliary feedwater were available, reactor coolant pumps were not available, and reactor-vessel vent valves and guard heaters were automatically controlled. Constant level control in the steam-generator secondariesmore » was used after steam-generator secondary refill and symmetric steam-generator pressure control was used. We performed the calculation using TRAC-PF1/MODI. Agreement between test data and the calculation was generally reasonable. All major trends and phenomena were correctly predicted. It is believed that the correct conclusions about trends and phenomena will be reached if the code is used in similar applications.« less
Posttest analysis of MIST Test 3109AA using TRAC-PF1/MOD1
DOE Office of Scientific and Technical Information (OSTI.GOV)
Steiner, J.L.; Siebe, D.A.; Boyack, B.E.
This document discusses a posttest calculation and analysis of Multi-loop Integral System Test (MIST) 3109AA as the nominal test for the MIST program. It is a test of a small-break loss-of-coolant accident (SBLOCA) with a scaled 10-cm[sup 2] break in the B1 cold leg. The test exhibited the major post-SBLOCA phenomena, as expected, including depressurization to saturation, intermittent and interrupted loop flow, boiler-condenser mode cooling, refill, and postrefill cooldown. Full high-pressure injection and auxiliary feedwater were available, reactor coolant pumps were not available, and reactor-vessel vent valves and guard heaters were automatically controlled. Constant level control in the steam-generator secondariesmore » was used after steam-generator secondary refill and symmetric steam-generator pressure control was used. We performed the calculation using TRAC-PF1/MODI. Agreement between test data and the calculation was generally reasonable. All major trends and phenomena were correctly predicted. It is believed that the correct conclusions about trends and phenomena will be reached if the code is used in similar applications.« less
Ji, Fuhai; Li, Jian; Fleming, Neal; Rose, David; Liu, Hong
2015-08-01
Phenylephrine is often used to treat intra-operative hypotension. Previous studies have shown that the FloTrac cardiac monitor may overestimate cardiac output (CO) changes following phenylephrine administration. A new algorithm (4th generation) has been developed to improve performance in this setting. We performed a prospective observational study to assess the effects of phenylephrine administration on CO values measured by the 3rd and 4th generation FloTrac algorithms. 54 patients were enrolled in this study. We used the Nexfin, a pulse contour method shown to be insensitive to vasopressor administration, as the reference method. Radial arterial pressures were recorded continuously in patients undergoing surgery. Phenylephrine administration times were documented. Arterial pressure recordings were subsequently analyzed offline using three different pulse contour analysis algorithms: FloTrac 3rd generation (G3), FloTrac 4th generation (G4), and Nexfin (nf). One minute of hemodynamic measurements was analyzed immediately before phenylephrine administration and then repeated when the mean arterial pressure peaked. A total of 157 (4.6 ± 3.2 per patient, range 1-15) paired sets of hemodynamic recordings were analyzed. Phenylephrine induced a significant increase in stroke volume (SV) and CO with the FloTrac G3, but not with FloTrac G4 or Nexfin algorithms. Agreement between FloTrac G3 and Nexfin was: 0.23 ± 1.19 l/min and concordance was 51.1%. In contrast, agreement between FloTrac G4 and Nexfin was: 0.19 ± 0.86 l/min and concordance was 87.2%. In conclusion, the pulse contour method of measuring CO, as implemented in FloTrac 4th generation algorithm, has significantly improved its ability to track the changes in CO induced by phenylephrine.
Crowd Behavior Algorithm Development for COMBAT XXI
2017-05-30
This study cost the Department of Defense approximately $176,000 expended by TRAC in Fiscal Years 15-17. Prepared on 30 May 2017 TRAC Project Code...modeling to study impacts of military operations in urban terrain. Impacts of crowds on military operations can include those lethality, mobility...de- pendent on the particular socio-economic, political, and cultural environment of the region being studied in the scenario. Our research has found
NASA Technical Reports Server (NTRS)
Hammond, Dana P.
1991-01-01
The Technical Requirements Analysis and Control Systems (TRACS) software package is described. TRACS offers supplemental tools for the analysis, control, and interchange of project requirements. This package provides the fundamental capability to analyze and control requirements, serves a focal point for project requirements, and integrates a system that supports efficient and consistent operations. TRACS uses relational data base technology (ORACLE) in a stand alone or in a distributed environment that can be used to coordinate the activities required to support a project through its entire life cycle. TRACS uses a set of keyword and mouse driven screens (HyperCard) which imposes adherence through a controlled user interface. The user interface provides an interactive capability to interrogate the data base and to display or print project requirement information. TRACS has a limited report capability, but can be extended with PostScript conventions.
Ho, Cheng-Hsun; Frommer, Wolf B
2014-01-01
To monitor nitrate and peptide transport activity in vivo, we converted the dual-affinity nitrate transceptor CHL1/NRT1.1/NPF6.3 and four related oligopeptide transporters PTR1, 2, 4, and 5 into fluorescence activity sensors (NiTrac1, PepTrac). Substrate addition to yeast expressing transporter fusions with yellow fluorescent protein and mCerulean triggered substrate-dependent donor quenching or resonance energy transfer. Fluorescence changes were nitrate/peptide-specific, respectively. Like CHL1, NiTrac1 had biphasic kinetics. Mutation of T101A eliminated high-affinity transport and blocked the fluorescence response to low nitrate. NiTrac was used for characterizing side chains considered important for substrate interaction, proton coupling, and regulation. We observed a striking correlation between transport activity and sensor output. Coexpression of NiTrac with known calcineurin-like proteins (CBL1, 9; CIPK23) and candidates identified in an interactome screen (CBL1, KT2, WNKinase 8) blocked NiTrac1 responses, demonstrating the suitability for in vivo analysis of activity and regulation. The new technology is applicable in plant and medical research. DOI: http://dx.doi.org/10.7554/eLife.01917.001 PMID:24623305
Long range targeting for space based rendezvous
NASA Technical Reports Server (NTRS)
Everett, Louis J.; Redfield, R. C.
1995-01-01
The work performed under this grant supported the Dexterous Flight Experiment one STS-62 The project required developing hardware and software for automating a TRAC sensor on orbit. The hardware developed by for the flight has been documented through standard NASA channels since it has to pass safety, environmental, and other issues. The software has not been documented previously, therefore, this report provides a software manual for the TRAC code developed for the grant.
TRAC-PF1/MOD1 pretest predictions of MIST experiments
DOE Office of Scientific and Technical Information (OSTI.GOV)
Boyack, B.E.; Steiner, J.L.; Siebe, D.A.
Los Alamos National Laboratory is a participant in the Integral System Test (IST) program initiated in June 1983 to provide integral system test data on specific issues and phenomena relevant to post small-break loss-of-coolant accidents (SBLOCAs) in Babcock and Wilcox plant designs. The Multi-Loop Integral System Test (MIST) facility is the largest single component in the IST program. During Fiscal Year 1986, Los Alamos performed five MIST pretest analyses. The five experiments were chosen on the basis of their potential either to approach the facility limits or to challenge the predictive capability of the TRAC-PF1/MOD1 code. Three SBLOCA tests weremore » examined which included nominal test conditions, throttled auxiliary feedwater and asymmetric steam-generator cooldown, and reduced high-pressure-injection (HPI) capacity, respectively. Also analyzed were two ''feed-and-bleed'' cooling tests with reduced HPI and delayed HPI initiation. Results of the tests showed that the MIST facility limits would not be approached in the five tests considered. Early comparisons with preliminary test data indicate that the TRAC-PF1/MOD1 code is correctly calculating the dominant phenomena occurring in the MIST facility during the tests. Posttest analyses are planned to provide a quantitative assessment of the code's ability to predict MIST transients.« less
TRAC Innovative Visualization Techniques
2016-11-14
Therefore, TRAC analysts need a way to analyze the effectiveness of their visualization design choices. Currently, TRAC does not have a methodology ...to analyze visualizations used to support an analysis story. Our research team developed a visualization design methodology to create effective...visualizations that support an analysis story. First, we based our methodology on the latest research on design thinking, cognitive learning, and
Fostering Team Awareness in Earth System Modeling Communities
NASA Astrophysics Data System (ADS)
Easterbrook, S. M.; Lawson, A.; Strong, S.
2009-12-01
Existing Global Climate Models are typically managed and controlled at a single site, with varied levels of participation by scientists outside the core lab. As these models evolve to encompass a wider set of earth systems, this central control of the modeling effort becomes a bottleneck. But such models cannot evolve to become fully distributed open source projects unless they address the imbalance in the availability of communication channels: scientists at the core site have access to regular face-to-face communication with one another, while those at remote sites have access to only a subset of these conversations - e.g. formally scheduled teleconferences and user meetings. Because of this imbalance, critical decision making can be hidden from many participants, their code contributions can interact in unanticipated ways, and the community loses awareness of who knows what. We have documented some of these problems in a field study at one climate modeling centre, and started to develop tools to overcome these problems. We report on one such tool, TracSNAP, which analyzes the social network of the scientists contributing code to the model by extracting the data in an existing project code repository. The tool presents the results of this analysis to modelers and model users in a number of ways: recommendation for who has expertise on particular code modules, suggestions for code sections that are related to files being worked on, and visualizations of team communication patterns. The tool is currently available as a plugin for the Trac bug tracking system.
Managing Information On Technical Requirements
NASA Technical Reports Server (NTRS)
Mauldin, Lemuel E., III; Hammond, Dana P.
1993-01-01
Technical Requirements Analysis and Control Systems/Initial Operating Capability (TRACS/IOC) computer program provides supplemental software tools for analysis, control, and interchange of project requirements so qualified project members have access to pertinent project information, even if in different locations. Enables users to analyze and control requirements, serves as focal point for project requirements, and integrates system supporting efficient and consistent operations. TRACS/IOC is HyperCard stack for use on Macintosh computers running HyperCard 1.2 or later and Oracle 1.2 or later.
Study of the TRAC Airfoil Table Computational System
NASA Technical Reports Server (NTRS)
Hu, Hong
1999-01-01
The report documents the study of the application of the TRAC airfoil table computational package (TRACFOIL) to the prediction of 2D airfoil force and moment data over a wide range of angle of attack and Mach number. The TRACFOIL generates the standard C-81 airfoil table for input into rotorcraft comprehensive codes such as CAM- RAD. The existing TRACFOIL computer package is successfully modified to run on Digital alpha workstations and on Cray-C90 supercomputers. A step-by-step instruction for using the package on both computer platforms is provided. Application of the newer version of TRACFOIL is made for two airfoil sections. The C-81 data obtained using the TRACFOIL method are compared with those of wind-tunnel data and results are presented.
Amin, Amit P; Nathan, Sandeep; Vassallo, Patricia; Calvin, James E
2009-05-20
To emphasize the importance of troponin in the context of a new score for risk stratifying acute coronary syndromes (ACS) patients. Although troponins have powerful prognostic value, current ACS scores do not fully capitalize this prognostic ability. Here, we weigh troponin status in a multiplicative manner to develop the TRACS score from previously published Rush score risk factors (RRF). 2,866 ACS patients (46.7% troponin positive) from 9 centers comprising the TRACS registry, were randomly split into derivation (n=1,422) and validation (n=1,444) cohorts. In the derivation sample, RRF sum was multiplied by 3 if troponins were positive to yield the TRACS score, which was grouped into five categories of 0-2, 3-5, 6-8, 9-11, 12-15 (multiples of 3). Predictive performance of this score to predict hospital death was ascertained in the validation sample. The TRACS score had ROC AUC of 0.71 in the validation cohort. Logistic regression, Kaplan-Meier analysis, likelihood-ratio and Bayesian Information Criterion (BIC) test indicated that weighing troponin status with 3 in the TRACS score improved the prediction of mortality. Hosmer-Lemeshow test indicated sound model fit. We demonstrate that weighing troponin as a multiple of 3 yields robust prognostication of hospital mortality in ACS patients, when used in the context of the TRACS score.
Amin, Amit P; Nathan, Sandeep; Vassallo, Patricia; Calvin, James E
2009-01-01
Structured Abstract Objective: To emphasize the importance of troponin in the context of a new score for risk stratifying acute coronary syndromes (ACS) patients. Although troponins have powerful prognostic value, current ACS scores do not fully capitalize this prognostic ability. Here, we weigh troponin status in a multiplicative manner to develop the TRACS score from previously published Rush score risk factors (RRF). Methods: 2,866 ACS patients (46.7% troponin positive) from 9 centers comprising the TRACS registry, were randomly split into derivation (n=1,422) and validation (n=1,444) cohorts. In the derivation sample, RRF sum was multiplied by 3 if troponins were positive to yield the TRACS score, which was grouped into five categories of 0-2, 3-5, 6-8, 9-11, 12-15 (multiples of 3). Predictive performance of this score to predict hospital death was ascertained in the validation sample. Results: The TRACS score had ROC AUC of 0.71 in the validation cohort. Logistic regression, Kaplan-Meier analysis, likelihood-ratio and Bayesian Information Criterion (BIC) test indicated that weighing troponin status with 3 in the TRACS score improved the prediction of mortality. Hosmer-Lemeshow test indicated sound model fit. Conclusions: We demonstrate that weighing troponin as a multiple of 3 yields robust prognostication of hospital mortality in ACS patients, when used in the context of the TRACS score. PMID:19557150
Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease.
Ibanez, Laura; Dube, Umber; Davis, Albert A; Fernandez, Maria V; Budde, John; Cooper, Breanna; Diez-Fairen, Monica; Ortega-Cubero, Sara; Pastor, Pau; Perlmutter, Joel S; Cruchaga, Carlos; Benitez, Bruno A
2018-01-01
Background: The prevalence of dementia in Parkinson disease (PD) increases dramatically with advancing age, approaching 80% in patients who survive 20 years with the disease. Increasing evidence suggests clinical, pathological and genetic overlap between Alzheimer disease, dementia with Lewy bodies and frontotemporal dementia with PD. However, the contribution of the dementia-causing genes to PD risk, cognitive impairment and dementia in PD is not fully established. Objective: To assess the contribution of coding variants in Mendelian dementia-causing genes on the risk of developing PD and the effect on cognitive performance of PD patients. Methods: We analyzed the coding regions of the amyloid-beta precursor protein ( APP ), Presenilin 1 and 2 ( PSEN1, PSEN2 ), and Granulin ( GRN ) genes from 1,374 PD cases and 973 controls using pooled-DNA targeted sequence, human exome-chip and whole-exome sequencing (WES) data by single variant and gene base (SKAT-O and burden tests) analyses. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). The effect of coding variants in dementia-causing genes on cognitive performance was tested by multiple regression analysis adjusting for gender, disease duration, age at dementia assessment, study site and APOE carrier status. Results: Known AD pathogenic mutations in the PSEN1 (p.A79V) and PSEN2 (p.V148I) genes were found in 0.3% of all PD patients. There was a significant burden of rare, likely damaging variants in the GRN and PSEN1 genes in PD patients when compared with frequencies in the European population from the ExAC database. Multiple regression analysis revealed that PD patients carrying rare variants in the APP, PSEN1, PSEN2 , and GRN genes exhibit lower cognitive tests scores than non-carrier PD patients ( p = 2.0 × 10 -4 ), independent of age at PD diagnosis, age at evaluation, APOE status or recruitment site. Conclusions: Pathogenic mutations in the Alzheimer disease-causing genes ( PSEN1 and PSEN2) are found in sporadic PD patients. PD patients with cognitive decline carry rare variants in dementia-causing genes. Variants in genes causing Mendelian neurodegenerative diseases exhibit pleiotropic effects.
Interactive web-based identification and visualization of transcript shared sequences.
Azhir, Alaleh; Merino, Louis-Henri; Nauen, David W
2018-05-12
We have developed TraC (Transcript Consensus), a web-based tool for detecting and visualizing shared sequences among two or more mRNA transcripts such as splice variants. Results including exon-exon boundaries are returned in a highly intuitive, data-rich, interactive plot that permits users to explore the similarities and differences of multiple transcript sequences. The online tool (http://labs.pathology.jhu.edu/nauen/trac/) is free to use. The source code is freely available for download (https://github.com/nauenlab/TraC). Copyright © 2018 Elsevier Inc. All rights reserved.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-03
... be found at: http://www2.mar.dfo-mpo.gc.ca/science/trac/tsr.html . The 2012 TRAC noted that, in... the 2012 TRAC assessment can be found at: http://www2.mar.dfo-mpo.gc.ca/science/trac/tsr.html . The... available from the Northeast Fisheries Science Center (NEFSC) at: http://www.nefsc.noaa.gov/saw/saw55...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hirano, Masashi
1997-07-01
This paper describes the results of a scoping study on seismically induced resonance of nuclear-coupled thermal-hydraulic instability in BWRs, which was conducted by using TRAC-BF1 within a framework of a point kinetics model. As a result of the analysis, it is shown that a reactivity insertion could occur accompanied by in-surge of coolant into the core resulted from the excitation of the nuclear-coupled instability by the external acceleration. In order to analyze this phenomenon more in detail, it is necessary to couple a thermal-hydraulic code with a three-dimensional nuclear kinetics code.
Su, Lining; Wang, Chunjie; Zheng, Chenqing; Wei, Huiping; Song, Xiaoqing
2018-04-13
Parkinson's disease (PD) is a long-term degenerative disease that is caused by environmental and genetic factors. The networks of genes and their regulators that control the progression and development of PD require further elucidation. We examine common differentially expressed genes (DEGs) from several PD blood and substantia nigra (SN) microarray datasets by meta-analysis. Further we screen the PD-specific genes from common DEGs using GCBI. Next, we used a series of bioinformatics software to analyze the miRNAs, lncRNAs and SNPs associated with the common PD-specific genes, and then identify the mTF-miRNA-gene-gTF network. Our results identified 36 common DEGs in PD blood studies and 17 common DEGs in PD SN studies, and five of the genes were previously known to be associated with PD. Further study of the regulatory miRNAs associated with the common PD-specific genes revealed 14 PD-specific miRNAs in our study. Analysis of the mTF-miRNA-gene-gTF network about PD-specific genes revealed two feed-forward loops: one involving the SPRK2 gene, hsa-miR-19a-3p and SPI1, and the second involving the SPRK2 gene, hsa-miR-17-3p and SPI. The long non-coding RNA (lncRNA)-mediated regulatory network identified lncRNAs associated with PD-specific genes and PD-specific miRNAs. Moreover, single nucleotide polymorphism (SNP) analysis of the PD-specific genes identified two significant SNPs, and SNP analysis of the neurodegenerative disease-specific genes identified seven significant SNPs. Most of these SNPs are present in the 3'-untranslated region of genes and are controlled by several miRNAs. Our study identified a total of 53 common DEGs in PD patients compared with healthy controls in blood and brain datasets and five of these genes were previously linked with PD. Regulatory network analysis identified PD-specific miRNAs, associated long non-coding RNA and feed-forward loops, which contribute to our understanding of the mechanisms underlying PD. The SNPs identified in our study can determine whether a genetic variant is associated with PD. Overall, these findings will help guide our study of the complex molecular mechanism of PD.
Analysis of internal flows relative to the space shuttle main engine
NASA Technical Reports Server (NTRS)
1987-01-01
Cooperative efforts between the Lockheed-Huntsville Computational Mechanics Group and the NASA-MSFC Computational Fluid Dynamics staff has resulted in improved capabilities for numerically simulating incompressible flows generic to the Space Shuttle Main Engine (SSME). A well established and documented CFD code was obtained, modified, and applied to laminar and turbulent flows of the type occurring in the SSME Hot Gas Manifold. The INS3D code was installed on the NASA-MSFC CRAY-XMP computer system and is currently being used by NASA engineers. Studies to perform a transient analysis of the FPB were conducted. The COBRA/TRAC code is recommended for simulating the transient flow of oxygen into the LOX manifold. Property data for modifying the code to represent LOX/GOX flow was collected. The ALFA code was developed and recommended for representing the transient combustion in the preburner. These two codes will couple through the transient boundary conditions to simulate the startup and/or shutdown of the fuel preburner. A study, NAS8-37461, is currently being conducted to implement this modeling effort.
Posttest analysis of MIST Test 320201 using TRAC-PF1/MOD1
DOE Office of Scientific and Technical Information (OSTI.GOV)
Siebe, D.A.; Steiner, J.L.; Boyack, B.E.
A posttest calculation and analysis of Multi-Loop Integral System Test 320201, a small-break loss-of-coolant accident (SBLOCA) test with a scaled 50-cm{sup 2} cold-leg pump discharge leak, has been completed and is reported herein. It was one in a series of tests, with leak size varied parametrically. Scaled leak sizes included 5, 10, (the nominal, Test 3109AA), and 50 cm{sub 2}. The test exhibited the major post-SBLOCA phenomena, as expected, including depressurization to saturation, interruption of loop flow, boiler-condenser mode cooling, refill, and postrefill cooldown. Full high-pressure injection and auxiliary feedwater were available, reactor coolant pumps were not available, and reactor-vesselmore » vent valves and guard heaters were automatically controlled. Constant level control in the steam-generator (SG) secondaries was used after SG-secondary refill; and symmetric SG pressure control was also used. The sequence of events seen in this test was similar to the sequence of events for much of the nominal test except that events occurred in a shorter time frame as the system inventory was reduced and the system depressurized at a faster rate. The calculation was performed using TRAC-PFL/MOD 1. Agreement between test data and the calculation was generally reasonable. All major trends and phenomena were correctly predicted. We believe that the correct conclusions about trends and phenomena will be reached if the code is used in similar applications.« less
Posttest analysis of MIST Test 320201 using TRAC-PF1/MOD1
DOE Office of Scientific and Technical Information (OSTI.GOV)
Siebe, D.A.; Steiner, J.L.; Boyack, B.E.
A posttest calculation and analysis of Multi-Loop Integral System Test 320201, a small-break loss-of-coolant accident (SBLOCA) test with a scaled 50-cm[sup 2] cold-leg pump discharge leak, has been completed and is reported herein. It was one in a series of tests, with leak size varied parametrically. Scaled leak sizes included 5, 10, (the nominal, Test 3109AA), and 50 cm[sub 2]. The test exhibited the major post-SBLOCA phenomena, as expected, including depressurization to saturation, interruption of loop flow, boiler-condenser mode cooling, refill, and postrefill cooldown. Full high-pressure injection and auxiliary feedwater were available, reactor coolant pumps were not available, and reactor-vesselmore » vent valves and guard heaters were automatically controlled. Constant level control in the steam-generator (SG) secondaries was used after SG-secondary refill; and symmetric SG pressure control was also used. The sequence of events seen in this test was similar to the sequence of events for much of the nominal test except that events occurred in a shorter time frame as the system inventory was reduced and the system depressurized at a faster rate. The calculation was performed using TRAC-PFL/MOD 1. Agreement between test data and the calculation was generally reasonable. All major trends and phenomena were correctly predicted. We believe that the correct conclusions about trends and phenomena will be reached if the code is used in similar applications.« less
Harford, Thomas C.; Chen, Chiung M.; Saha, Tulshi D.; Smith, Sharon M.; Hasin, Deborah S.; Grant, Bridget F.
2013-01-01
The purpose of this study was to evaluate the psychometric properties of DSM–IV symptom criteria for assessing personality disorders (PDs) in a national population and to compare variations in proposed symptom coding for social and/or occupational dysfunction. Data were obtained from a total sample of 34,653 respondents from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). For each personality disorder, confirmatory factor analysis (CFA) established a 1-factor latent factor structure for the respective symptom criteria. A 2-parameter item response theory (IRT) model was applied to the symptom criteria for each PD to assess the probabilities of symptom item endorsements across different values of the underlying trait (latent factor). Findings were compared with a separate IRT model using an alternative coding of symptom criteria that requires distress/impairment to be related to each criterion. The CFAs yielded a good fit for a single underlying latent dimension for each PD. Findings from the IRT indicated that DSM–IV PD symptom criteria are clustered in the moderate to severe range of the underlying latent dimension for each PD and are peaked, indicating high measurement precision only within a narrow range of the underlying trait and lower measurement precision at lower and higher levels of severity. Compared with the NESARC symptom coding, the IRT results for the alternative symptom coding are shifted toward the more severe range of the latent trait but generally have lower measurement precision for each PD. The IRT findings provide support for a reliable assessment of each PD for both NESARC and alternative coding for distress/impairment. The use of symptom dysfunction for each criterion, however, raises a number of issues and implications for the DSM-5 revision currently proposed for Axis II disorders (American Psychiatric Association, 2010). PMID:22449066
Posttest data analysis of FIST experimental TRAC-BD1/MOD1 power transient experiment
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wheatley, P.D.; Wagner, K.C.
The FIST power transient test 6PMC2 was analyzed to further the understanding of the FIST facility and provide an assessment of TRAC-BD1/MOD1. FIST power transient 6PMC2 investigated the thermal-hydraulic response following inadvertent closure of the main steam isolation valve and the subsequent failure of the reactor to scram. Failure of the high pressure core spray system was also assumed, resulting in only the reactor core isolation cooling flow for inventory makeup during the transient. The experiment was a sensitivity study with relatively high core power and low makeup rates. This study provides one of the first opportunities to assess TRAC-BD1/MOD1more » under power transient and natural circulation conditions with data from a facility with prototypical BWR geometry. The power transient test was analyzed with emphasis on the following phenomena: (a) the system pressure response, (b) the natural circulation flows and rates, and (c) the heater rod cladding temperature response. Based on the results of this study, TRAC-BD1/MOD1 can be expected to calculate the thermal-hydraulic behavior of a BWR during a power transient.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Boyack, B.E.; Steiner, J.L.; Harmony, S.C.
The PIUS advanced reactor is a 640-MWe pressurized water reactor developed by Asea Brown Boveri (ABB). A unique feature of the PIUS concept is the absence of mechanical control and shutdown rods. Reactivity is normally controlled by coolant boron concentration and the temperature of the moderator coolant. ABB submitted the PIUS design to the US Nuclear Regulatory Commission (NRC) for preapplication review, and Los Alamos supported the NRC`s review effort. Baseline analyses of small-break initiators at two locations were performed with the system neutronic and thermal-hydraulic analysis code TRAC-PF1/MOD2. In addition, sensitivity studies were performed to explore the robustness ofmore » the PIUS concept to severe off-normal conditions having a very low probability of occurrence.« less
Cross Service Fixed-Wing Cost Estimation
2016-05-17
TRAC-M-TR-16-021 May 2016 Cross Service Fixed-Wing Cost Estimation TRADOC Analysis Center 700 Dyer Road Monterey, California 93943-0692 This study...Service Fixed-Wing Cost Estimation MAJ Jarrod S. Shingleton TRADOC Analysis Center 700 Dyer Road Monterey, California 93943-0692 DISTRIBUTION STATEMENT...Wing Cost Estimation MAJ Jarrod Shingleton 060312 TRADOC Analysis Center, TRAC-MTRY Naval Postgraduate School 700 Dyer Road Bldg 246 Monterey, CA 93943
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wheatley, P.D.; Wagner, K.C.
The FIST power transient test 6PMC2 was analyzed to further the understanding of the FIST facility and provide an assessment of TRAC-BD1/MOD1. FIST power transient 6PMC2 investigated the thermal-hydraulic response following inadvertent closure of the main steam isolation valve and the subsequent failure of the reactor to scram. Failure of the high pressure core spray system was also assumed, resulting on only the reactor core isolation cooling flow for inventory makeup during the transient. The experiment was a sensitivity study with relatively high core power and low makeup rates. This study provides one of the first opportunities to assess TRAC-BD1/MOD1more » under power transient and natural circulation conditions with data from a facility with prototypical BWR geometry. The power transient test was analyzed with emphasis on the following phenomena; (a) the system pressure response, (b) the natural circulation flows and rates, and (c) the heater rod cladding temperature response. Based on the results of this study, TRAC-BD1/MOD1 can be expected to calculate the thermal-hydraulic behavior of a BWR during a power transient.« less
SU-E-J-48: Imaging Origin-Radiation Isocenter Coincidence for Linac-Based SRS with Novalis Tx
DOE Office of Scientific and Technical Information (OSTI.GOV)
Geraghty, C; Workie, D; Hasson, B
Purpose To implement and evaluate an image-based Winston-Lutz (WL) test to measure the displacement between ExacTrac imaging origin and radiation isocenter on a Novalis Tx system using RIT V6.2 software analysis tools. Displacement between imaging and radiation isocenters was tracked over time. The method was applied for cone-based and MLC-based WL tests. Methods The Brainlab Winston-Lutz phantom was aligned to room lasers. The ExacTrac imaging system was then used to detect the Winston- Lutz phantom and obtain the displacement between the center of the phantom and the imaging origin. EPID images of the phantom were obtained at various gantry andmore » couch angles and analyzed with RIT calculating the phantom center to radiation isocenter displacement. The RIT and Exactrac displacements were combined to calculate the displacement between imaging origin and radiation isocenter. Results were tracked over time. Results Mean displacements between ExacTrac origin and radiation isocenter were: VRT: −0.1mm ± 0.3mm, LNG: 0.5mm ± 0.2mm, LAT: 0.2mm ± 0.2mm (vector magnitude of 0.7 ± 0.2mm). Radiation isocenter was characterized by the mean of the standard deviations of the WL phantom displacements: σVRT: 0.2mm, σLNG: 0.4mm, σLAT: 0.6mm. The linac couch base was serviced to reduce couch walkout. This reduced σLAT to 0.2mm. These measurements established a new baseline of radiation isocenter-imaging origin coincidence. Conclusion The image-based WL test has ensured submillimeter localization accuracy using the ExacTrac imaging system. Standard deviations of ExacTrac-radiation isocenter displacements indicate that average agreement within 0.3mm is possible in each axis. This WL test is a departure from the tradiational WL in that imaging origin/radiation isocenter agreement is the end goal not lasers/radiation isocenter.« less
Data and animal management software for large-scale phenotype screening.
Ching, Keith A; Cooke, Michael P; Tarantino, Lisa M; Lapp, Hilmar
2006-04-01
The mouse N-ethyl-N-nitrosourea (ENU) mutagenesis program at the Genomics Institute of the Novartis Research Foundation (GNF) uses MouseTRACS to analyze phenotype screens and manage animal husbandry. MouseTRACS is a Web-based laboratory informatics system that electronically records and organizes mouse colony operations, prints cage cards, tracks inventory, manages requests, and reports Institutional Animal Care and Use Committee (IACUC) protocol usage. For efficient phenotype screening, MouseTRACS identifies mutants, visualizes data, and maps mutations. It displays and integrates phenotype and genotype data using likelihood odds ratio (LOD) plots of genetic linkage between genotype and phenotype. More detailed mapping intervals show individual single nucleotide polymorphism (SNP) markers in the context of phenotype. In addition, dynamically generated pedigree diagrams and inventory reports linked to screening results summarize the inheritance pattern and the degree of penetrance. MouseTRACS displays screening data in tables and uses standard charts such as box plots, histograms, scatter plots, and customized charts looking at clustered mice or cross pedigree comparisons. In summary, MouseTRACS enables the efficient screening, analysis, and management of thousands of animals to find mutant mice and identify novel gene functions. MouseTRACS is available under an open source license at http://www.mousetracs.sourceforge.net.
DOT National Transportation Integrated Search
1996-12-10
THIS STUDY WAS UNDERTAKEN TO IDENTIFY AND EVALUATE CRITERIA BY WHICH THE PUBLIC, AND CERTAIN STAKEHOLDER GROUPS WITHIN THE PUBLIC, WILL JUDGE THE MERITS OF THE FAST-TRAC SYSTEM. OVER A PERIOD OF TWO YEARS, THREE SURVEYS WERE CONDUCTED TO OBTAIN SPECI...
Tyurin with TRAC experiment in Destiny laboratory
2007-01-02
ISS014-E-11047 (2 Jan. 2007) --- Cosmonaut Mikhail Tyurin, Expedition 14 flight engineer representing Russia's Federal Space Agency, works with the Test of Reaction and Adaptation Capabilities (TRAC) experiment in the Destiny laboratory of the International Space Station. The TRAC investigation will test the theory of brain adaptation during space flight by testing hand-eye coordination before, during and after the space flight.
Lopez-Alegria with TRAC experiment in Destiny laboratory
2007-01-02
ISS014-E-11061 (2 Jan. 2007) --- Astronaut Michael E. Lopez-Alegria, Expedition 14 commander and NASA space station science officer, works with the Test of Reaction and Adaptation Capabilities (TRAC) experiment in the Destiny laboratory of the International Space Station. The TRAC investigation will test the theory of brain adaptation during space flight by testing hand-eye coordination before, during and after the space flight.
DOT National Transportation Integrated Search
1996-01-01
FAST-TRAC : SELECTING THE MOST APPROPRIATE TRAFFIC CONTROL STRATEGY FOR INCIDENT CONGESTION MANAGEMENT CAN HAVE A MAJOR IMPACT ON THE EXTENT AND DURATION OF THE RESULTING CONGESTION. THIS RESEARCH INVESTIGATED THE EFFECTIVENESSES OF SEVERAL CONTRO...
Comparing the Incidence of Falls/Fractures in Parkinson's Disease Patients in the US Population.
Kalilani, Linda; Asgharnejad, Mahnaz; Palokangas, Tuire; Durgin, Tracy
2016-01-01
Patients with Parkinson's disease (PD) may experience falls and/or fractures as a result of disease symptoms. There are limited data available from long-term studies estimating the incidence of falls/fractures in patients with PD. The objective was to compare the incidence rate of falls/fractures in PD patients with non-PD patients in a US population. This was a retrospective study using a US-based claims database (Truven Health MarketScan®) that compared the incidence rate of falls/fractures in PD subjects with non-PD subjects. The study period included the 12 months prior to index date (defined as earliest PD diagnosis [International Classification of Diseases, Ninth Revision, Clinical Modification code 332.0]) and a postindex period to the end of data availability. Fractures were defined by inpatient/outpatient claims as a principal or secondary diagnosis and accompanying procedure codes during the postindex period. Incidence rates and 95% CIs for falls/fractures were calculated as the number of events per 10,000 person-years of follow-up using negative binomial or Poisson regression models. Twenty-eight thousand two hundred and eighty PD subjects were matched to non-PD subjects for the analysis (mean [SD] age, 71.4 [11.8] years; 53% male). A higher incidence rate (adjusted for comorbidities and medications) of all fall/fracture cases and by fall and fracture types was observed for PD subjects versus non-PD subjects; the overall adjusted incidence rate ratio comparing PD to non-PD subjects was 2.05; 95% CI, 1.88-2.24. The incidence rate of falls/fractures was significantly higher in subjects with PD compared with non-PD subjects in a US population.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Boyack, B.E.; Steiner, J.L.; Harmony, S.C.
The PIUS Advanced Reactor is a 640-MW(e) pressurized-water reactor developed by Asea Brown Boveri. A unique feature of the PIUS concept is the absence of mechanical control and shutdown rods. Reactivity normally is controlled by the boron concentration in the coolant and the temperature of the moderator coolant. Analyses of five initiating events have been completed on the basis of calculations performed with the system neutronic and thermal-hydraulic analysis code TRAC-PF1/MOD2. The initiating events analyzed are (1) reactor scram, (2) loss of off-site power (3) main steam-line break, (4) small-break loss of coolant, and (5) large-break loss of coolant. Inmore » addition to the baseline calculation for each sequence, sensitivity studies were performed to explore the response of the PIUS reactor to severe off-normal conditions having a very low probability of occurrence. The sensitivity studies provide insights into the robustness of the design.« less
de Ramón-Carbonell, Marta; Sánchez-Torres, Paloma
2017-12-01
The Slt2 mitogen-activated protein (MAP) kinase homologue of Penicillium digitatum, the most relevant pathogen-producing citrus green mould decay during postharvest, was identified and explored. The P. digitatum Slt2-MAPK coding gene (PdSlt2) was functionally characterized by homologous gene elimination and transcriptomic evaluation. The absence of PdSlt2 gene resulted in significantly reduced virulence during citrus infection. The ΔPdSlt2 mutants were also defective in asexual reproduction, showing impairment of sporulation during citrus infection. Gene expression analysis revealed that PdSlt2 was highly induced during citrus fruit infection at early stages (1 dpi). Moreover, PdSlt2 deletion altered gene expression profiles. The relative gene expression (RGE) of fungicide resistance- and fungal virulence-related genes showed that PdSlt2 acts as negative regulator of several transporter encoding genes (ABC and MFS transporters) and a positive regulator of two sterol demethylases. This study indicates that PdSlt2 MAPK is functionally preserved in P. digitatum and highlights the relevant role of the PdSlt2 MAP kinase-mediated signalling pathway in regulating diverse genes crucial for infection and asexual reproduction. Copyright © 2017 British Mycological Society. Published by Elsevier Ltd. All rights reserved.
SU-E-J-34: Setup Accuracy in Spine SBRT Using CBCT 6D Image Guidance in Comparison with 6D ExacTrac
DOE Office of Scientific and Technical Information (OSTI.GOV)
Han, Z; Yip, S; Lewis, J
2015-06-15
Purpose Volumetric information of the spine captured on CBCT can potentially improve the accuracy in spine SBRT setup that has been commonly performed through 2D radiographs. This work evaluates the setup accuracy in spine SBRT using 6D CBCT image guidance that recently became available on Varian systems. Methods ExacTrac radiographs have been commonly used for Spine SBRT setup. The setup process involves first positioning patients with lasers followed by localization imaging, registration, and repositioning. Verification images are then taken providing the residual errors (ExacTracRE) before beam on. CBCT verification is also acquired in our institute. The availability of both ExacTracmore » and CBCT verifications allows a comparison study. 41 verification CBCT of 16 patients were retrospectively registered with the planning CT enabling 6D corrections, giving CBCT residual errors (CBCTRE) which were compared with ExacTracRE. Results The RMS discrepancies between CBCTRE and ExacTracRE are 1.70mm, 1.66mm, 1.56mm in vertical, longitudinal and lateral directions and 0.27°, 0.49°, 0.35° in yaw, roll and pitch respectively. The corresponding mean discrepancies (and standard deviation) are 0.62mm (1.60mm), 0.00mm (1.68mm), −0.80mm (1.36mm) and 0.05° (0.58°), 0.11° (0.48°), −0.16° (0.32°). Of the 41 CBCT, 17 had high-Z surgical implants. No significant difference in ExacTrac-to-CBCT discrepancy was observed between patients with and without the implants. Conclusion Multiple factors can contribute to the discrepancies between CBCT and ExacTrac: 1) the imaging iso-centers of the two systems, while calibrated to coincide, can be different; 2) the ROI used for registration can be different especially if ribs were included in ExacTrac images; 3) small patient motion can occur between the two verification image acquisitions; 4) the algorithms can be different between CBCT (volumetric) and ExacTrac (radiographic) registrations.« less
SU-F-P-40: Analysis of Pelvic Lymph Node Margin Using Prostate Fiducial Markers, for SBRT Treatments
DOE Office of Scientific and Technical Information (OSTI.GOV)
Torres, J; Castro Pena, P; Garrigo, E
2016-06-15
Purpose: The use of fiducials markers in prostate treatment allows a precise localization of this volume. Typical prostate SBRT margins with fiducials markers are 5mm in all directions, except toward the rectum, where 3mm is used. For some patients nearby pelvic lymph nodes with 5mm margin need to be irradiate assuming that its localization is linked to the prostate fiducial markers instead of bony anatomy. The purpose of this work was to analyze the geometric impact of locate the lymph node regions through the patient positioning by prostate fiducial markers. Methods: 10 patients with prostate SBRT with lymph nodes irradiationmore » were selected. Each patient had 5 implanted titanium fiducial markers. A Novalis TX (BrainLAB-Varian) with ExacTrac and aSi1000 portal image was used. Treatment plan uses 11 beams with a dose prescription (D95%) of 40Gy to the prostate and 25Gy to the lymph node in 5 fractions. Daily positioning was carried out by ExacTrac system based on the implanted fiducials as the reference treatment position; further position verification was performed using the ExacTrac and two portal images (gantry angle 0 and 90) based on bony structures. Comparison between reference position with bony based ExacTrac and portal image localization, was done for each treatment fraction Results: A total of 50 positioning analysis were done. The average discrepancy between reference treatment position and ExacTrac based on bony anatomy (pubic area) was 4.2mm [0.3; 11.2]. The discrepancy was <5mm in 61% of the cases and <9mm in 92%. Using portal images the average discrepancy was 3.7mm [0.0; 11.1]. The discrepancy was <5mm in 69% of the cases and <9mm in 96%. Conclusion: Localizing lymph node by prostate fiducial markers may produce large discrepancy as large as 11mm compared to bony based localization. Dosimetric impact of this discrepancy should be studied.« less
Analysis of PANDA Passive Containment Cooling Steady-State Tests with the Spectra Code
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stempniewicz, Marek M
2000-07-15
Results of post test simulation of the PANDA passive containment cooling (PCC) steady-state tests (S-series tests), performed at the PANDA facility at the Paul Scherrer Institute, Switzerland, are presented. The simulation has been performed using the computer code SPECTRA, a thermal-hydraulic code, designed specifically for analyzing containment behavior of nuclear power plants.Results of the present calculations are compared to the measurement data as well as the results obtained earlier with the codes MELCOR, TRAC-BF1, and TRACG. The calculated PCC efficiencies are somewhat lower than the measured values. Similar underestimation of PCC efficiencies had been obtained in the past, with themore » other computer codes. To explain this difference, it is postulated that condensate coming into the tubes forms a stream of liquid in one or two tubes, leaving most of the tubes unaffected. The condensate entering the water box is assumed to fall down in the form of droplets. With these assumptions, the results calculated with SPECTRA are close to the experimental data.It is concluded that the SPECTRA code is a suitable tool for analyzing containments of advanced reactors, equipped with passive containment cooling systems.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, J; Shi, W; Andrews, D
2015-06-15
Purpose To compare online image registrations of TrueBeam cone-beam CT (CBCT) and BrainLab ExacTrac imaging systems. Methods Tests were performed on a Varian TrueBeam STx linear accelerator (Version 2.0), which is integrated with a BrainLab ExacTrac imaging system (Version 6.0.5). The study was focused on comparing the online image registrations for translational shifts. A Rando head phantom was placed on treatment couch and immobilized with a BrainLab mask. The phantom was shifted by moving the couch translationally for 8 mm with a step size of 1 mm, in vertical, longitudinal, and lateral directions, respectively. At each location, the phantom wasmore » imaged with CBCT and ExacTrac x-ray. CBCT images were registered with TrueBeam and ExacTrac online registration algorithms, respectively. And ExacTrac x-ray image registrations were performed. Shifts calculated from different registrations were compared with nominal couch shifts. Results The averages and ranges of absolute differences between couch shifts and calculated phantom shifts obtained from ExacTrac x-ray registration, ExacTrac CBCT registration with default window, ExaxTrac CBCT registration with adjusted window (bone), Truebeam CBCT registration with bone window, and Truebeam CBCT registration with soft tissue window, were: 0.07 (0.02–0.14), 0.14 (0.01–0.35), 0.12 (0.02–0.28), 0.09 (0–0.20), and 0.06 (0–0.10) mm, in vertical direction; 0.06 (0.01–0.12), 0.27 (0.07–0.57), 0.23 (0.02–0.48), 0.04 (0–0.10), and 0.08 (0– 0.20) mm, in longitudinal direction; 0.05 (0.01–0.21), 0.35 (0.14–0.80), 0.25 (0.01–0.56), 0.19 (0–0.40), and 0.20 (0–0.40) mm, in lateral direction. Conclusion The shifts calculated from ExacTrac x-ray and TrueBeam CBCT registrations were close to each other (the differences between were less than 0.40 mm in any direction), and had better agreements with couch shifts than those from ExacTrac CBCT registrations. There were no significant differences between TrueBeam CBCT registrations using different windows. In ExacTrac CBCT registrations, using bone window led to better agreements than using default window.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Keeling, V; Jin, H; Hossain, S
2014-06-15
Purpose: To evaluate setup accuracy and quantify individual systematic and random errors for the various hardware and software components of the frameless 6D-BrainLAB ExacTrac system. Methods: 35 patients with cranial lesions, some with multiple isocenters (50 total lesions treated in 1, 3, 5 fractions), were investigated. All patients were simulated with a rigid head-and-neck mask and the BrainLAB localizer. CT images were transferred to the IPLAN treatment planning system where optimized plans were generated using stereotactic reference frame based on the localizer. The patients were setup initially with infrared (IR) positioning ExacTrac system. Stereoscopic X-ray images (XC: X-ray Correction) weremore » registered to their corresponding digitally-reconstructed-radiographs, based on bony anatomy matching, to calculate 6D-translational and rotational (Lateral, Longitudinal, Vertical, Pitch, Roll, Yaw) shifts. XC combines systematic errors of the mask, localizer, image registration, frame, and IR. If shifts were below tolerance (0.7 mm translational and 1 degree rotational), treatment was initiated; otherwise corrections were applied and additional X-rays were acquired to verify patient position (XV: X-ray Verification). Statistical analysis was used to extract systematic and random errors of the different components of the 6D-ExacTrac system and evaluate the cumulative setup accuracy. Results: Mask systematic errors (translational; rotational) were the largest and varied from one patient to another in the range (−15 to 4mm; −2.5 to 2.5degree) obtained from mean of XC for each patient. Setup uncertainty in IR positioning (0.97,2.47,1.62mm;0.65,0.84,0.96degree) was extracted from standard-deviation of XC. Combined systematic errors of the frame and localizer (0.32,−0.42,−1.21mm; −0.27,0.34,0.26degree) was extracted from mean of means of XC distributions. Final patient setup uncertainty was obtained from the standard deviations of XV (0.57,0.77,0.67mm,0.39,0.35,0.30degree). Conclusion: Statistical analysis was used to calculate cumulative and individual systematic errors from the different hardware and software components of the 6D-ExacTrac-system. Patients were treated with cumulative errors (<1mm,<1degree) with XV image guidance.« less
Callaghan, Russell C; Cunningham, James K; Sykes, Jenna; Kish, Stephen J
2012-01-01
Since methamphetamine and other amphetamine-type stimulants (meth/amphetamine) can damage dopaminergic neurons, researchers have long speculated that these drugs may predispose users to develop Parkinson's disease (PD), a dopamine deficiency neurological disorder. We employed a retrospective population-based cohort study using all linked statewide California inpatient hospital episodes and death records from January 1, 1990 through December 31, 2005. Patients at least 30 years of age were followed for up to 16 years. Competing risks analysis was used to determine whether the meth/amphetamine cohort had elevated risk of developing PD (ICD-9 332.0; ICD-10 G20) in comparison to a matched population-proxy appendicitis group and a matched cocaine drug control group. Individuals admitted to hospital with meth/amphetamine-related conditions (n=40,472; ICD-9 codes 304.4, 305.7, 969.7, E854.2) were matched on age, race, sex, date of index admission, and patterns of hospital admission with patients with appendicitis conditions (n=207,831; ICD-9 codes 540-542) and also individuals with cocaine-use disorders (n=35,335; ICD-9 codes 304.2, 305.6, 968.5). The meth/amphetamine cohort showed increased risk of PD compared to both that of the matched appendicitis group [hazard ratio (HR)=1.76, 95% CI: 1.12-2.75, p=0.017] and the matched cocaine group [HR=2.44, 95% CI: 1.32-4.41, p=0.004]. The cocaine group did not show elevated hazard of PD compared to the matched appendicitis group [HR=1.04, 95% CI: 0.56-1.93, p=0.80]. These data provide evidence that meth/amphetamine users have above-normal risk for developing PD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Assessment of the TRACE Reactor Analysis Code Against Selected PANDA Transient Data
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zavisca, M.; Ghaderi, M.; Khatib-Rahbar, M.
2006-07-01
The TRACE (TRAC/RELAP Advanced Computational Engine) code is an advanced, best-estimate thermal-hydraulic program intended to simulate the transient behavior of light-water reactor systems, using a two-fluid (steam and water, with non-condensable gas), seven-equation representation of the conservation equations and flow-regime dependent constitutive relations in a component-based model with one-, two-, or three-dimensional elements, as well as solid heat structures and logical elements for the control system. The U.S. Nuclear Regulatory Commission is currently supporting the development of the TRACE code and its assessment against a variety of experimental data pertinent to existing and evolutionary reactor designs. This paper presents themore » results of TRACE post-test prediction of P-series of experiments (i.e., tests comprising the ISP-42 blind and open phases) conducted at the PANDA large-scale test facility in 1990's. These results show reasonable agreement with the reported test results, indicating good performance of the code and relevant underlying thermal-hydraulic and heat transfer models. (authors)« less
Progression Rate Associated Peripheral Blood Biomarkers of Parkinson's Disease.
Fan, Yanxia; Xiao, Shuping
2018-06-23
Parkinson disease (PD) is one of the most frequent neurodegenerative disorders. The aim of this study was to identify blood biomarkers capable to discriminate PD patients with different progression rates. Differentially expressed genes (DEGs) were acquired by comparing the expression profiles of PD patients with rapid and slow progression rates, using an expression dataset from Gene Expression Omnibus (GEO) under accession code of GSE80599. Altered biological processes and pathways were revealed by functional annotation. Potential biomarkers of PD were identified by protein-protein interaction (PPI) network analysis. Critical transcription factors (TFs) and miRNAs regulating DEGs were predicted by TF analysis and miRNA analysis. A total of 225 DEGs were identified between PD patients with rapid and slow progression profiles. These genes were significantly enriched in biological processes and pathways related to fatty acid metabolism. Among these DEGs, ZFAND4, SRMS, UBL4B, PVALB, DIRAS1, PDP2, LRCH1, and MYL4 were potential progression rate associated biomarkers of PD. Additionally, these DEGs may be regulated by miRNAs of the miR-30 family and TFs STAT1 and GRHL3. Our results may contribute to our understanding of the molecular mechanisms underlying different PD progression profiles.
ERIC Educational Resources Information Center
Bloomquist, Carroll R.
The TRANSCOM (Transportation Command) Regulating Command and Control Evacuation System (TRAC2ES), which applies state-of-the-art technology to manage global medical regulating (matching patients to clinical availability) and medical evacuation processes, will be installed at all Department of Defense medical locations globally. A combination of…
ERIC Educational Resources Information Center
Higher Education Funding Council for England, 2015
2015-01-01
This report provides an overview of the financial health of the Higher Education Funding Council for England (HEFCE)-funded higher education sector in England. The analysis covers financial results for the academic year 2013-14, as submitted to HEFCE in December 2014, as well as the outcomes from the sector's Transparent Approach to Costing (TRAC)…
Conflict Prediction Through Geo-Spatial Interpolation of Radicalization in Syrian Social Media
2015-09-24
TRAC-M-TM-15-031 September 2015 Conflict Prediction Through Geo-Spatial Interpolation of Radicalization in Syrian Social Media ...Spatial Interpolation of Radicalization in Syrian Social Media Authors MAJ Adam Haupt Dr. Camber Warren...Spatial Interpolation of Radicalization in Syrian Social 1RAC Project Code 060114 Media 6. AUTHOR(S) MAJ Haupt, Dr. Warren 7. PERFORMING OR
DOT National Transportation Integrated Search
1999-02-12
This report focuses on the system integration aspect of the Transportation Information Management System (TIMS), a component of the FAST-TRAC project. The TIMS functions as the center of a communications network which integrates advanced traffic cont...
1982-04-12
A RC ..... sl6 3i4 ~ N0 A.o 0 o2 *I A3 05 .7 0 to TRACE A 5S :S TRAC .29 .0.0 *2.. *,.j st16 &TRC T ACt la S4 :01 o Ŕ TRAC risAc *4 ?P.TAC *I .0 .02...2l 046 t.2 145 .14 TRACE TRACI T*A TRI 004....~ 60 A001. sOJa .. , 46 .31 .04 .01 6 at .0 .2 .10 47 1_ 1_ - -A .121 __ 48 1.2 .61 .0 TRAC 2.9 l.9 al...r - sea--vu 6s 23.6 *7.6 20 1 9 26 1.9 7 02__1 wo 10mS 0 .5 02U*1*7 9 w 91 "m,. om .4FVC%. LA ~im wm ul 19 292 Ze* ~ U -A- GLiCBAL CLIMATOLOGY
Li, Jun; Shi, Wenyin; Andrews, David; Werner-Wasik, Maria; Lu, Bo; Yu, Yan; Dicker, Adam; Liu, Haisong
2017-06-01
The study was aimed to compare online 6 degree-of-freedom image registrations of TrueBeam cone-beam computed tomography and BrainLab ExacTrac X-ray imaging systems for intracranial radiosurgery. Phantom and patient studies were performed on a Varian TrueBeam STx linear accelerator (version 2.5), which is integrated with a BrainLab ExacTrac imaging system (version 6.1.1). The phantom study was based on a Rando head phantom and was designed to evaluate isocenter location dependence of the image registrations. Ten isocenters at various locations representing clinical treatment sites were selected in the phantom. Cone-beam computed tomography and ExacTrac X-ray images were taken when the phantom was located at each isocenter. The patient study included 34 patients. Cone-beam computed tomography and ExacTrac X-ray images were taken at each patient's treatment position. The 6 degree-of-freedom image registrations were performed on cone-beam computed tomography and ExacTrac, and residual errors calculated from cone-beam computed tomography and ExacTrac were compared. In the phantom study, the average residual error differences (absolute values) between cone-beam computed tomography and ExacTrac image registrations were 0.17 ± 0.11 mm, 0.36 ± 0.20 mm, and 0.25 ± 0.11 mm in the vertical, longitudinal, and lateral directions, respectively. The average residual error differences in the rotation, roll, and pitch were 0.34° ± 0.08°, 0.13° ± 0.09°, and 0.12° ± 0.10°, respectively. In the patient study, the average residual error differences in the vertical, longitudinal, and lateral directions were 0.20 ± 0.16 mm, 0.30 ± 0.18 mm, 0.21 ± 0.18 mm, respectively. The average residual error differences in the rotation, roll, and pitch were 0.40°± 0.16°, 0.17° ± 0.13°, and 0.20° ± 0.14°, respectively. Overall, the average residual error differences were <0.4 mm in the translational directions and <0.5° in the rotational directions. ExacTrac X-ray image registration is comparable to TrueBeam cone-beam computed tomography image registration in intracranial treatments.
A Tangled Web – Tau and Sporadic Parkinson's Disease
Wray, Selina; Lewis, Patrick A.
2010-01-01
Parkinson's disease (PD) represents a major challenge for health care systems around the world: it is the most common degenerative movement disorder of old age, affecting over 100,000 people in the UK alone (Schrag et al., 2000). Despite the remarkable success of treatments directed at potentiating or replacing dopamine within the brain, which can relieve symptoms for over a decade, PD remains an incurable and invariably fatal disorder. As such, efforts to understand the processes that lead to cell death in the brains of patients with PD are a priority for neurodegenerative researchers. A great deal of progress has been made in this regard by taking advantage of advances in genetics, initially by the identification of genes responsible for rare Mendelian forms of PD (outlined in Table 1), and more recently by applying genome wide association studies (GWAS) to the sporadic form of the disease (Hardy et al., 2009). Several such GWAS have now been carried out, with a meta-analysis currently under way. Using over 6000 cases and 10,000 controls, two of these studies have identified variation at a number of loci as being associated with an increased risk of disease (Satake et al., 2009; Simon-Sanchez et al., 2009). Three genes stand out as candidates from these studies – the SNCA gene, coding for α-synuclein, the LRRK2 gene, coding for leucine rich repeat kinase 2, and MAPT, coding for the microtubule-associated protein tau. Mutations at all three of these loci have been associated with Mendelian forms of disease presenting with the clinical syndrome of Parkinsonism, however only SNCA and LRRK2 have been previously associated with pathologically defined PD (Hardy et al., 2009). Point mutations in α-synuclein, along with gene multiplication events, result in autosomal dominant PD, often with a significant dementia component. In addition to this, α-synuclein is the principle component of the main pathological hallmark of idiopathic PD, the Lewy body, making it an unsurprising hit in the GWAS (Spillantini et al., 1997). Mutations in LRRK2 are the most common genetic cause of PD, and so again made this gene a likely candidate as a susceptibility locus for the sporadic form of disease (Kumari and Tan, 2009). More surprising, perhaps, was the identification of tau as a susceptibility factor for Parkinson's. In this review we will outline the role of tau in neurodegeneration and in different forms of Parkinsonism, and speculate as to what the functional basis of the association between MAPT and PD might be. PMID:21423457
A tangled web - tau and sporadic Parkinson's disease.
Wray, Selina; Lewis, Patrick A
2010-01-01
Parkinson's disease (PD) represents a major challenge for health care systems around the world: it is the most common degenerative movement disorder of old age, affecting over 100,000 people in the UK alone (Schrag et al., 2000). Despite the remarkable success of treatments directed at potentiating or replacing dopamine within the brain, which can relieve symptoms for over a decade, PD remains an incurable and invariably fatal disorder. As such, efforts to understand the processes that lead to cell death in the brains of patients with PD are a priority for neurodegenerative researchers. A great deal of progress has been made in this regard by taking advantage of advances in genetics, initially by the identification of genes responsible for rare Mendelian forms of PD (outlined in Table 1), and more recently by applying genome wide association studies (GWAS) to the sporadic form of the disease (Hardy et al., 2009). Several such GWAS have now been carried out, with a meta-analysis currently under way. Using over 6000 cases and 10,000 controls, two of these studies have identified variation at a number of loci as being associated with an increased risk of disease (Satake et al., 2009; Simon-Sanchez et al., 2009). Three genes stand out as candidates from these studies - the SNCA gene, coding for α-synuclein, the LRRK2 gene, coding for leucine rich repeat kinase 2, and MAPT, coding for the microtubule-associated protein tau. Mutations at all three of these loci have been associated with Mendelian forms of disease presenting with the clinical syndrome of Parkinsonism, however only SNCA and LRRK2 have been previously associated with pathologically defined PD (Hardy et al., 2009). Point mutations in α-synuclein, along with gene multiplication events, result in autosomal dominant PD, often with a significant dementia component. In addition to this, α-synuclein is the principle component of the main pathological hallmark of idiopathic PD, the Lewy body, making it an unsurprising hit in the GWAS (Spillantini et al., 1997). Mutations in LRRK2 are the most common genetic cause of PD, and so again made this gene a likely candidate as a susceptibility locus for the sporadic form of disease (Kumari and Tan, 2009). More surprising, perhaps, was the identification of tau as a susceptibility factor for Parkinson's. In this review we will outline the role of tau in neurodegeneration and in different forms of Parkinsonism, and speculate as to what the functional basis of the association between MAPT and PD might be.
Are hospitalized Parkinson's disease patients more likely to carry a do-not-resuscitate order?
Mahajan, Abhimanyu; Patel, Achint; Nadkarni, Girish; Sidiropoulos, Christos
2017-03-01
While DNR utilization is a complex subjective phenomenon, the effect of such a decision can collectively influence attitudes of care. The role of palliative care in advanced PD has been under appreciated. We reviewed the Healthcare Cost and Utilization Project's National Inpatient Sample (NIS) database from 2012 for all hospitalizations ⩾65years. We identified PD by using ICD-9-CM code 332.0 and DNR status with ICD code - V49.86 entered during the same admission as a secondary diagnosis. We estimated risk of mortality by the 3M™ All Patient Refined DRG (APR DRG) classification System and generated multivariate regression models to assess associations between DNR and PD after adjusting for confounders. Finally, we tested for interaction by risk of mortality. We analyzed 12,700,000 hospitalizations with age ⩾65years in 2012, of which 246625 (1.94%) pts had PD. Proportion of DNR utilization was higher among PD patients vs. those without, 20895 (8.47%) vs. 723090 (5.8%) (p<0.01). In multivariable regression analysis, PD patients were associated with higher odds of DNR utilization [Adjusted Odds ratio (aOR): 1.26, 95% CI: 1.21, 1.30, p<0.001]. Finally, the odds of DNR utilization increased significantly with APR-DRG stage [aOR: 1 vs. 1.61 (Stage 2) vs. 2.46 (Stage 3) vs. 3.61 (Stage 4); p<0.0001]. PD patients have higher odds of DNR utilization than the general population, which worsens with increasing objective risk of mortality. This is likely correlated with perception of end of life and importance of QOL with increasing severity of overall illness. Copyright © 2016 Elsevier Ltd. All rights reserved.
TRAC FY15 Research Planning and Elicitation
2014-09-30
Wargaming and Simulation Directorate . . . . . . . . . . . . . C-2 Table C–7. FLVN-Operations Directorate . . . . . . . . . . . . . . . . . . . . . . C...Studies and Analysis III Directorate . . . . . . . . . . . . . . C-4 Table C–14.WSMR - Modeling and Simulation Directorate...Directorate - Mr. Decker • Wargaming and Simulation Directorate - Mr. Johnson • Operations Directorate - Ms. Fratzel • Scenarios and Data Directorate - Mr
Federal Register 2010, 2011, 2012, 2013, 2014
2011-04-27
... augment the TRACS' existing knowledge base with professionals who have done academic research in the... TRACS. From that solicitation, 21 members were chosen, each representing a broad base of expertise...
Modeling Off-Nominal Recovery in NextGen Terminal-Area Operations
NASA Technical Reports Server (NTRS)
Callantine, Todd J.
2011-01-01
Robust schedule-based arrival management requires efficient recovery from off-nominal situations. This paper presents research on modeling off-nominal situations and plans for recovering from them using TRAC, a route/airspace design, fast-time simulation, and analysis tool for studying NextGen trajectory-based operations. The paper provides an overview of a schedule-based arrival-management concept and supporting controller tools, then describes TRAC implementations of methods for constructing off-nominal scenarios, generating trajectory options to meet scheduling constraints, and automatically producing recovery plans.
Wartime critical care air transport.
Bridges, Elizabeth; Evers, Karen
2009-04-01
Describe the characteristics/enroute care of casualties transported by USAF Critical Care Air Transport Teams (CCATT) during Operation Enduring Freedom/Iraqi Freedom (OEF/OIF). Retrospective review of TRAC2ES and CCATT Mission Reports (Oct 2001-May 2006). 3492 patient moves (2439 patients). Moves by route: within Area of Responsibility (AOR) (n = 261); AOR-Landstuhl (LRMC) (n = 1995), Germany-CONUS (n = 1188). For AOR-LRMC: BI (64%), NBI (8%), Disease (25%). Among injured (n = 1491), 69% suffered polytrauma, primarily d/t explosions. Injury area: extremities (63%), head (55%), thorax (46%), abdomen (31%), neck (17%). Injury type: soft tissue (64%), orthopedic (45%), thoracic (35%), skull fracture (27%), brain injury (25%). Disease diagnoses: cardiac (15%) and pulmonary (8%). This is the first analysis of OEF/OIF CCATT patients. Phase 1 of this study demonstrates the strengths and limitations of TRAC2ES and CCATT Mission Reports to describe the characteristics/enroute care of this unique population.
Tacchino, Andrea; Pedullà, Ludovico; Bonzano, Laura; Vassallo, Claudio; Battaglia, Mario Alberto; Mancardi, Gianluigi; Bove, Marco; Brichetto, Giampaolo
2015-08-31
Cognitive impairment is common in people with neurological diseases and severely affects their social and professional life. It has been shown that intensive and personalized cognitive rehabilitation (CR), based on working memory exercises, leads to improved cognitive status of healthy and cognitive-impaired subjects. New technologies would help to promote accessible, at-home, and self-managed CR interventions. The aim of this paper is to describe the design of Cognitive Training Kit (COGNI-TRAcK), an app for mobile devices, to self-administer an at-home, intensive, and personalized CR intervention based on working memory exercises, and test its disposability-to-use (usability, motivation to use, compliance to treatment) on cognitive-impaired patients with multiple sclerosis (MS). COGNI-TRAcK includes user-friendly interfaces for personal data input and management and for CR intervention configurations. Inner routines automatically implement adaptive working load algorithms and allow data processing and analysis. A dedicated team developed COGNI-TRAcK with C# programming language, by using the platform Xamarin Studio 4.0.10 for Android (API level 15 and following). Three exercises based on working memory are now available. To assess the disposability-to-use of the system, patients with MS were selected as likely users due to the young age of disease onset. Cognitive-impaired patients with MS (N=16) with a mean age of 49.06 years (SD 9.10) and a mean score of 3.75 (SD 1.92) on the Expanded Disability Status Scale (EDSS) were submitted to an 8-week at-home intervention administered by the app. The intervention consisted of 5 daily scheduled 30-minute sessions per week. Disposability-to-use of COGNI-TRAcK was investigated by means of a questionnaire administered to patients at the end of the training. The adherence to the treatment was 84% (33.4/40). Of the patients with MS, 94% (15/16) understood the instructions given, 100% (16/16) felt independent to use COGNI-TRAcK at home, 75% (12/16) found the exercises interesting, and 81% (13/16) found the exercises useful and were motivated to use the app again. Moreover, during the exercises, patients with MS were highly motivated to perform well (mean score 3.19/4, SE 0.16), experienced rather low levels of stress (mean score 2.19/4, SE 0.26), were not bored (mean score 1.81/4, SE 0.30), and felt amusement (mean score 2.25/4, SE 0.23). As COGNI-TRAcK is highly usable, motivating, and well-accepted by patients with MS, its effectiveness can now be investigated. To improve COGNI-TRAcK, new releases should contain more working memory exercises, have enhanced perceived amusement, and promote Internet communication procedures for data transfer and fostering remote control of the intervention.
Bonzano, Laura; Vassallo, Claudio; Battaglia, Mario Alberto; Mancardi, Gianluigi; Bove, Marco
2015-01-01
Background Cognitive impairment is common in people with neurological diseases and severely affects their social and professional life. It has been shown that intensive and personalized cognitive rehabilitation (CR), based on working memory exercises, leads to improved cognitive status of healthy and cognitive-impaired subjects. New technologies would help to promote accessible, at-home, and self-managed CR interventions. Objective The aim of this paper is to describe the design of Cognitive Training Kit (COGNI-TRAcK), an app for mobile devices, to self-administer an at-home, intensive, and personalized CR intervention based on working memory exercises, and test its disposability-to-use (usability, motivation to use, compliance to treatment) on cognitive-impaired patients with multiple sclerosis (MS). Methods COGNI-TRAcK includes user-friendly interfaces for personal data input and management and for CR intervention configurations. Inner routines automatically implement adaptive working load algorithms and allow data processing and analysis. A dedicated team developed COGNI-TRAcK with C# programming language, by using the platform Xamarin Studio 4.0.10 for Android (API level 15 and following). Three exercises based on working memory are now available. To assess the disposability-to-use of the system, patients with MS were selected as likely users due to the young age of disease onset. Cognitive-impaired patients with MS (N=16) with a mean age of 49.06 years (SD 9.10) and a mean score of 3.75 (SD 1.92) on the Expanded Disability Status Scale (EDSS) were submitted to an 8-week at-home intervention administered by the app. The intervention consisted of 5 daily scheduled 30-minute sessions per week. Disposability-to-use of COGNI-TRAcK was investigated by means of a questionnaire administered to patients at the end of the training. Results The adherence to the treatment was 84% (33.4/40). Of the patients with MS, 94% (15/16) understood the instructions given, 100% (16/16) felt independent to use COGNI-TRAcK at home, 75% (12/16) found the exercises interesting, and 81% (13/16) found the exercises useful and were motivated to use the app again. Moreover, during the exercises, patients with MS were highly motivated to perform well (mean score 3.19/4, SE 0.16), experienced rather low levels of stress (mean score 2.19/4, SE 0.26), were not bored (mean score 1.81/4, SE 0.30), and felt amusement (mean score 2.25/4, SE 0.23). Conclusions As COGNI-TRAcK is highly usable, motivating, and well-accepted by patients with MS, its effectiveness can now be investigated. To improve COGNI-TRAcK, new releases should contain more working memory exercises, have enhanced perceived amusement, and promote Internet communication procedures for data transfer and fostering remote control of the intervention. PMID:26323749
Status of thermalhydraulic modelling and assessment: Open issues
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bestion, D.; Barre, F.
1997-07-01
This paper presents the status of the physical modelling in present codes used for Nuclear Reactor Thermalhydraulics (TRAC, RELAP 5, CATHARE, ATHLET,...) and attempts to list the unresolved or partially resolved issues. First, the capabilities and limitations of present codes are presented. They are mainly known from a synthesis of the assessment calculations performed for both separate effect tests and integral effect tests. It is also interesting to list all the assumptions and simplifications which were made in the establishment of the system of equations and of the constitutive relations. Many of the present limitations are associated to physical situationsmore » where these assumptions are not valid. Then, recommendations are proposed to extend the capabilities of these codes.« less
Analyses of 1/15 scale Creare bypass transient experiments. [PWR
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kmetyk, L.N.; Buxton, L.D.; Cole, R.K. Jr.
1982-09-01
RELAP4 analyses of several 1/15 scale Creare H-series bypass transient experiments have been done to investigate the effect of using different downcomer nodalizations, physical scales, slip models, and vapor fraction donoring methods. Most of the analyses were thermal equilibrium calculations performed with RELAP4/MOD5, but a few such calculations were done with RELAP4/MOD6 and RELAP4/MOD7, which contain improved slip models. In order to estimate the importance of nonequilibrium effects, additional analyses were performed with TRAC-PD2, RELAP5 and the nonequilibrium option of RELAP4/MOD7. The purpose of these studies was to determine whether results from Westinghouse's calculation of the Creare experiments, which weremore » done with a UHI-modified version of SATAN, were sufficient to guarantee SATAN would be conservative with respect to ECC bypass in full-scale plant analyses.« less
Calculation of design load for the MOD-5A 7.3 mW wind turbine system
NASA Technical Reports Server (NTRS)
Mirandy, L.; Strain, J. C.
1995-01-01
Design loads are presented for the General Electric MOD-SA wind turbine. The MOD-SA system consists of a 400 ft. diameter, upwind, two-bladed, teetered rotor connected to a 7.3 mW variable-speed generator. Fatigue loads are specified in the form of histograms for the 30 year life of the machine, while limit (or maximum) loads have been derived from transient dynamic analysis at critical operating conditions. Loads prediction was accomplished using state of the art aeroelastic analyses developed at General Electric. Features of the primary predictive tool - the Transient Rotor Analysis Code (TRAC) are described in the paper. Key to the load predictions are the following wind models: (1) yearly mean wind distribution; (2) mean wind variations during operation; (3) number of start/shutdown cycles; (4) spatially large gusts; and (5) spatially small gusts (local turbulence). The methods used to develop statistical distributions from load calculations represent an extension of procedures used in past wind programs and are believed to be a significant contribution to Wind Turbine Generator analysis. Test/theory correlations are presented to demonstrate code load predictive capability and to support the wind models used in the analysis. In addition MOD-5A loads are compared with those of existing machines. The MOD-5A design was performed by the General Electric Company, Advanced Energy Program Department, under Contract DEN3-153 with NASA Lewis Research Center and sponsored by the Department of Energy.
DOT National Transportation Integrated Search
2004-06-01
The DelTrac deployment experience included both successes and unmet challenges. Programmatically, the DelTrac approach to managing ITS has been successful at creating a great deal of integration and cooperation between organizations at DelDOT. Stakeh...
Bordalo, Alvaro D B; Nobre, Angelo L; Silva, Fernanda; Serpa, Carlos; Cravino, João
2011-01-01
In spite of the strong criticism elicited thereafter, the results of a multicentric study on the consequences of several perioperative anti-hemorrhagic strategies in cardiac surgery, published five years ago, led to the aprotinin (Aprot) withdrawal from the market and its progressive replacement by tranexamic acid (TrAc) in many surgical departments. To evaluate the hemostatic effects and clinical consequences of TrAc use or non-use in off-pump coronary bypass surgery (CABG) and compare them with those of Aprot use or non-use in conventional (conv) CABG. Retrospective analysis of 2 groups (Gr) of patients (pts): GrA - 252 pts undergoing isolated conv CABG (GrA1 - 185 pts submitted to an intra-operative full-dose Aprot protocol; GrA2 - 67 pts operated without Aprot); GrB - 383 pts undergoing isolated off-pump CABG (GrB1 - 136 pts submitted to an intra-operative low-dose TrAc protocol; GrB2 - 247 pts operated in absence of TrAc). Pre-operative clinical characteristics (GrA1 vs GrA2, GrB1 vs GrB2): mean age (years) - 65 vs 64 (NS), 64 vs 64; female gender - 20% vs 21% (NS), 23% vs 20% (NS); logistic Euroscore - 5.1% vs 6.2% (NS), 6.3% vs 5.5% (NS); chronic renal failure - 21% vs 27% (NS), 27% vs 25% (NS); diffuse coronary artery disease - 34% vs 42% (NS), 36% vs 30% (NS); pre-operative betablocker treatment - 64% vs 55% (NS), 74% vs 71% (NS); statin therapy for > 3 months - 78% vs 82% (NS), 81% vs 85% (NS). Pts have been operated by 4 surgeons largely experienced in both CABG modalities. Antiplatelet therapy was stopped => 4 days prior to surgery (but aspirin was maintained in high-risk pts). Results (GrA1 vs GrA2, GrB1 vs GrB2): 1) Bleeding (mL/pt - mean): 783 vs 1375 (p < 0.001), 1061 vs 1368 (p < 0.001); blood loss > 1500 mL (%pts) - 5.4% vs 34% (p < 0.0001), 12% vs 28% (p < 0.001); surgical re-exploration for bleeding - 1.1% vs 3.0% (NS), 2.2% vs 2.0% (NS). 2) Transfusion of blood products (U/pt - mean): plasma - 0.56 vs 2.19 (p < 0.001), 1.45 vs 1.03 (p < 0.05); platelets - 0.09 vs 0.22 (p < 0.02), 0.24 vs 0.15 (NS). 3) Renal function (%pts): increased serum cre- atinine - 56% vs 56%, 55% vs 38% (p < 0.001); hemofiltration use - 1.1% vs 1.5% (NS), 1.5% vs 0.4% (NS). 4) Perioperative myocardial infarction - 21.6% vs 17.9% (NS), 17.6% vs 14.6% (NS); other ischemic events - 3.2% vs 3.0% (NS), 1.5% vs 1.2% (NS). 5) Hospital mortality: 4.8% vs 4.5% (NS), 4.4% vs 1.6% (NS). 1) TrAc does not reduce the risk of surgical re-exploration for bleeding. 2) Taking into account the differences between conv CABG and off-pump CABG, TrAc hemostatic effect seems to be inferior to that of Aprot, without offering a better safety profile in terms of lesser renal or ischemic risk as a counterpart.
Luukkonen, Jani; Pascual, Laia Mira; Patlaka, Christina; Lång, Pernilla; Turunen, Sanna; Halleen, Jussi; Nousiainen, Tomi; Valkealahti, Maarit; Tuukkanen, Juha; Andersson, Göran; Lehenkari, Petri
2017-01-01
Osteopontin (OPN) is an immunoregulatory protein which production increases in both rheumatoid arthritis (RA) and osteoarthritis (OA). Phosphorylated osteopontin (Phospho-OPN) is known to increase macrophage and osteoclast activation, this process is controlled by extracellular tartrate-resistant acid phosphatase (TRAcP), also a biomarker for RA. Here, we evaluated the phosphorylation status of OPN in RA and OA synovia, as well as its correlation with TRAcP isoforms. Synovial tissue and fluid were obtained from 24 RA (14 seropositive and 10 seronegative) and 24 OA patients. Western blotting was used to analyze the extent of OPN phosphorylation. TRAcP isoforms were measured in synovial fluid using ELISA; immunohistochemistry assessed the distribution of OPN and TRAcP expressing cells in the synovial tissue, especially distinguishing between the TRAcP isoforms. Full-length OPN was more phosphorylated in RA than in OA (p<0.05). The thrombin cleaved C-terminal end of OPN was also more phosphorylated in RA (p<0.05). RA patients had a lower concentration of TRAcP 5B and higher concentration of less active 5A in their synovial fluid compared to OA patients. The TRAcP 5B/5A ratio was decreased in RA and correlated negatively with the amount of phospho-OPN (p<0.05). TRAcP positive cells for both isoforms were found all along the synovial lining; OPN antibody staining was localized in the extracellular matrix. Our data suggests that in RA the synovial fluid contains insufficient amounts of TRAcP 5B which increase levels of the proinflammatory phospho-OPN. This may lead to increased macrophage and osteoclast activation, resulting in the increased local inflammation and bone resorption present in RA joints.
Generating realistic environments for cyber operations development, testing, and training
NASA Astrophysics Data System (ADS)
Berk, Vincent H.; Gregorio-de Souza, Ian; Murphy, John P.
2012-06-01
Training eective cyber operatives requires realistic network environments that incorporate the structural and social complexities representative of the real world. Network trac generators facilitate repeatable experiments for the development, training and testing of cyber operations. However, current network trac generators, ranging from simple load testers to complex frameworks, fail to capture the realism inherent in actual environments. In order to improve the realism of network trac generated by these systems, it is necessary to quantitatively measure the level of realism in generated trac with respect to the environment being mimicked. We categorize realism measures into statistical, content, and behavioral measurements, and propose various metrics that can be applied at each level to indicate how eectively the generated trac mimics the real world.
Comparison of two methods for cardiac output measurement in critically ill patients.
Saraceni, E; Rossi, S; Persona, P; Dan, M; Rizzi, S; Meroni, M; Ori, C
2011-05-01
The aim of recent haemodynamic monitoring has been to obtain continuous and reliable measures of cardiac output (CO) and indices of preload responsiveness. Many of these methods are based on the arterial pressure waveform analysis. The aim of our study was to assess the accuracy of CO measurements obtained by FloTrac/Vigileo, software version 1.07 and the new version 1.10 (Edwards Lifesciences LLC, Irvine, CA, USA), compared with CO measurements obtained by bolus thermodilution by pulmonary artery catheterization (PAC) in the intensive care setting. In 21 critically ill patients (enrolled in two University Hospitals), requiring invasive haemodynamic monitoring, PAC and FloTrac/Vigileo transducers connected to the arterial pressure line were placed. Simultaneous measurements of CO by two methods (FloTrac/Vigileo and thermodilution) were obtained three times a day for 3 consecutive days, when possible. The level of concordance between the two methods was assessed by the procedure suggested by Bland and Altman. One hundred and forty-one pairs of measurements (provided by thermodilution and by both 1.07 and 1.10 FloTrac/Vigileo versions) were obtained in 21 patients (seven of them were trauma patients) with a mean (sd) age of 59 (16) yr. The Pearson product moment coefficient was 0.62 (P<0.001). The bias was -0.18 litre min(-1). The limits of agreement were 4.54 and -4.90 litre min(-1), respectively. Our data show a poor level of concordance between measures provided by the two methods. We found an underestimation of CO values measured with the 1.07 software version of FloTrac for supranormal values of CO. The new software (1.10) has been improved in order to correct this bias; however, its reliability is still poor. On the basis of our data, we can therefore conclude that both software versions of FloTrac/Vigileo did not still provide reliable estimation of CO in our intensive care unit setting.
2015-12-01
Army Training and Doctrine Command (TRADOC) Analysis Center (TRAC) to the Philippines for Operation ENDURING FREEDOM – Philippines (OEF-P). PROJECT...management, doctrine and force development, training management, system testing, system acquisition, decision analysis, and resource management, as...influenced procurement decisions and reshaped Army doctrine . Additionally, CAA itself has benefited in numerous ways. Combat experience provides analysts
Hamza, Taye H; Zabetian, Cyrus P; Tenesa, Albert; Laederach, Alain; Montimurro, Jennifer; Yearout, Dora; Kay, Denise M; Doheny, Kimberly F; Paschall, Justin; Pugh, Elizabeth; Kusel, Victoria I; Collura, Randall; Roberts, John; Griffith, Alida; Samii, Ali; Scott, William K; Nutt, John; Factor, Stewart A; Payami, Haydeh
2010-01-01
Parkinson disease (PD) is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study (GWAS) with 2000 PD and 1986 control Caucasian subjects from NeuroGenetics Research Consortium.1–5 We confirmed SNCA2,6–8 and MAPT3,7–9; replicated GAK9 (PPankratz+NGRC=3.2×10−9); and detected a novel association with HLA (PNGRC=2.9×10−8) which replicated in two datasets (PMeta-analysis=1.9×10−10). We designate the new PD genes PARK17 (GAK) and PARK18 (HLA). PD-HLA association was uniform across genetic and environmental risk strata, and strong in sporadic (P=5.5×10−10) and late-onset (P=2.4×10−8) PD. The association peak was at rs3129882, a non-coding variant in HLA-DRA. Two studies suggested rs3129882 influences expression of HLA-DR and HLA-DQ.10,11 PD brains exhibit up-regulation of DR antigens and presence of DR-positive reactive microglia.12 Moreover, non-steroidal anti-inflammatory drugs (NSAID) reduce PD risk.4,13 The genetic association with HLA coalesces the evidence for involvement of the immune system and offers new targets for drug development and pharmacogenetics. PMID:20711177
Preliminary calculations related to the accident at Three Mile Island
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kirchner, W.L.; Stevenson, M.G.
This report discusses preliminary studies of the Three Mile Island Unit 2 (TMI-2) accident based on available methods and data. The work reported includes: (1) a TRAC base case calculation out to 3 hours into the accident sequence; (2) TRAC parametric calculations, these are the same as the base case except for a single hypothetical change in the system conditions, such as assuming the high pressure injection (HPI) system operated as designed rather than as in the accident; (3) fuel rod cladding failure, cladding oxidation due to zirconium metal-steam reactions, hydrogen release due to cladding oxidation, cladding ballooning, cladding embrittlement,more » and subsequent cladding breakup estimates based on TRAC calculated cladding temperatures and system pressures. Some conclusions of this work are: the TRAC base case accident calculation agrees very well with known system conditions to nearly 3 hours into the accident; the parametric calculations indicate that, loss-of-core cooling was most influenced by the throttling of High-Pressure Injection (HPI) flows, given the accident initiating events and the pressurizer electromagnetic-operated valve (EMOV) failing to close as designed; failure of nearly all the rods and gaseous fission product gas release from the failed rods is predicted to have occurred at about 2 hours and 30 minutes; cladding oxidation (zirconium-steam reaction) up to 3 hours resulted in the production of approximately 40 kilograms of hydrogen.« less
DOT National Transportation Integrated Search
1999-02-12
FAST-TRAC : THIS REPORT DESCRIBES THE CHOICE MODEL STUDY OF THE FAST-TRAC (FASTER AND SAFER TRAVEL THROUGH TRAFFIC ROUTING AND ADVANCED CONTROLS) OPERATIONAL TEST IN SOUTHEAST MICHIGAN. CHOICE MODELING IS A STATED-PREFERENCE APPROACH IN WHICH RESP...
NASA Technical Reports Server (NTRS)
Everett, Louis J.
1994-01-01
The work reported here demonstrates how to automatically compute the position and attitude of a targeting reflective alignment concept (TRAC) camera relative to the robot end effector. In the robotics literature this is known as the sensor registration problem. The registration problem is important to solve if TRAC images need to be related to robot position. Previously, when TRAC operated on the end of a robot arm, the camera had to be precisely located at the correct orientation and position. If this location is in error, then the robot may not be able to grapple an object even though the TRAC sensor indicates it should. In addition, if the camera is significantly far from the alignment it is expected to be at, TRAC may give incorrect feedback for the control of the robot. A simple example is if the robot operator thinks the camera is right side up but the camera is actually upside down, the camera feedback will tell the operator to move in an incorrect direction. The automatic calibration algorithm requires the operator to translate and rotate the robot arbitrary amounts along (about) two coordinate directions. After the motion, the algorithm determines the transformation matrix from the robot end effector to the camera image plane. This report discusses the TRAC sensor registration problem.
GPS-based Microenvironment Tracker (MicroTrac) Model to ...
A critical aspect of air pollution exposure assessment is the estimation of the time spent by individuals in various microenvironments (ME). Accounting for the time spent in different ME with different pollutant concentrations can reduce exposure misclassifications, while failure to do so can add uncertainty and bias to risk estimates. In this study, a classification model, called MicroTrac, was developed to estimate time of day and duration spent in eight ME (indoors and outdoors at home, work, school; inside vehicles; other locations) from global positioning system (GPS) data and geocoded building boundaries. Based on a panel study, MicroTrac estimates were compared to 24 h diary data from 7 participants on workdays and 2 participants on nonworkdays, with corresponding GPS data and building boundaries of home, school, and work. MicroTrac correctly classified the ME for 99.5% of the daily time spent by the participants. The capability of MicroTrac could help to reduce the time-location uncertainty in air pollution exposure models and exposure metrics for individuals in health studies. The National Exposure Research Laboratory’s (NERL’s) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA’s mission to protect human health and the environment. HEASD’s research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA’s strategic plan. More specifically, our division conducts research to characterize
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, J; Shi, W; Andrews, D
2016-06-15
Purpose: To compare online image registrations of TrueBeam cone-beam CT (CBCT) and BrainLab ExacTrac x-ray imaging systems for cranial radiotherapy. Method: Phantom and patient studies were performed on a Varian TrueBeam STx linear accelerator (Version 2.5), which is integrated with a BrainLab ExacTrac imaging system (Version 6.1.1). The phantom study was based on a Rando head phantom, which was designed to evaluate isocenter-location dependence of the image registrations. Ten isocenters were selected at various locations in the phantom, which represented clinical treatment sites. CBCT and ExacTrac x-ray images were taken when the phantom was located at each isocenter. The patientmore » study included thirteen patients. CBCT and ExacTrac x-ray images were taken at each patient’s treatment position. Six-dimensional image registrations were performed on CBCT and ExacTrac, and residual errors calculated from CBCT and ExacTrac were compared. Results: In the phantom study, the average residual-error differences between CBCT and ExacTrac image registrations were: 0.16±0.10 mm, 0.35±0.20 mm, and 0.21±0.15 mm, in the vertical, longitudinal, and lateral directions, respectively. The average residual-error differences in the rotation, roll, and pitch were: 0.36±0.11 degree, 0.14±0.10 degree, and 0.12±0.10 degree, respectively. In the patient study, the average residual-error differences in the vertical, longitudinal, and lateral directions were: 0.13±0.13 mm, 0.37±0.21 mm, 0.22±0.17 mm, respectively. The average residual-error differences in the rotation, roll, and pitch were: 0.30±0.10 degree, 0.18±0.11 degree, and 0.22±0.13 degree, respectively. Larger residual-error differences (up to 0.79 mm) were observed in the longitudinal direction in the phantom and patient studies where isocenters were located in or close to frontal lobes, i.e., located superficially. Conclusion: Overall, the average residual-error differences were within 0.4 mm in the translational directions and were within 0.4 degree in the rotational directions.« less
Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-10
... Reporting Alternative Commitment Agreement (TRAC) for Use in Industries Other Than the Food and Beverage... Use in Industries Other Than the Food and Beverage Industry and the Cosmetology and Barber Industry... Alternative Commitment Agreement (TRAC) for Use in Industries Other Than the Food and Beverage Industry and...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-10
... Reporting Alternative Commitment Agreement (TRAC) for Use in the Food and Beverage Industry AGENCY: Internal... Reporting Alternative Commitment Agreement (TRAC) for Use in the Food and Beverage Industry. DATES: Written... in the Food and Beverage Industry. OMB Number: 1545-1549. Abstract: Announcement 2000-22, 2000-19 I.R...
An integrated decision support system for TRAC: A proposal
NASA Technical Reports Server (NTRS)
Mukkamala, Ravi
1991-01-01
Optimal allocation and usage of resources is a key to effective management. Resources of concern to TRAC are: Manpower (PSY), Money (Travel, contracts), Computing, Data, Models, etc. Management activities of TRAC include: Planning, Programming, Tasking, Monitoring, Updating, and Coordinating. Existing systems are insufficient, not completely automated, manpower intensive, and has the potential for data inconsistency exists. A system is proposed which suggests a means to integrate all project management activities of TRAC through the development of a sophisticated software and by utilizing the existing computing systems and network resources. The systems integration proposal is examined in detail.
Williams with TRAC experiment in Destiny
2007-03-08
ISS014-E-16215 (8 March 2007) --- Astronaut Sunita L. Williams, Expedition 14 flight engineer, works with the Test of Reaction and Adaptation Capabilities (TRAC) experiment in the Destiny laboratory of the International Space Station. The TRAC investigation will test the theory of brain adaptation during space flight by testing hand-eye coordination before, during and after the space flight.
Williams with TRAC experiment in Destiny
2007-03-08
ISS014-E-16210 (8 March 2007) --- Astronaut Sunita L. Williams, Expedition 14 flight engineer, works with the Test of Reaction and Adaptation Capabilities (TRAC) experiment in the Destiny laboratory of the International Space Station. The TRAC investigation will test the theory of brain adaptation during space flight by testing hand-eye coordination before, during and after the space flight.
Williams with TRAC experiment in Destiny
2007-03-08
ISS014-E-16214 (8 March 2007) --- Astronaut Sunita L. Williams, Expedition 14 flight engineer, works with the Test of Reaction and Adaptation Capabilities (TRAC) experiment in the Destiny laboratory of the International Space Station. The TRAC investigation will test the theory of brain adaptation during space flight by testing hand-eye coordination before, during and after the space flight.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-03
... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-75,192; TA-W-75,192A] Core... Leased Workers From Aerotek, Helpmates, Mattson, and Empire Staffing, Irvine, CA; Core Industries, Inc... Eligibility to Apply for Worker Adjustment Assistance on February 15, 2011, applicable to workers of Core...
A mobile trauma database with charge capture.
Moulton, Steve; Myung, Dan; Chary, Aron; Chen, Joshua; Agarwal, Suresh; Emhoff, Tim; Burke, Peter; Hirsch, Erwin
2005-11-01
Charge capture plays an important role in every surgical practice. We have developed and merged a custom mobile database (DB) system with our trauma registry (TRACS), to better understand our billing methods, revenue generators, and areas for improved revenue capture. The mobile database runs on handheld devices using the Windows Compact Edition platform. The front end was written in C# and the back end is SQL. The mobile database operates as a thick client; it includes active and inactive patient lists, billing screens, hot pick lists, and Current Procedural Terminology and International Classification of Diseases, Ninth Revision code sets. Microsoft Information Internet Server provides secure data transaction services between the back ends stored on each device. Traditional, hand written billing information for three of five adult trauma surgeons was averaged over a 5-month period. Electronic billing information was then collected over a 3-month period using handheld devices and the subject software application. One surgeon used the software for all 3 months, and two surgeons used it for the latter 2 months of the electronic data collection period. This electronic billing information was combined with TRACS data to determine the clinical characteristics of the trauma patients who were and were not captured using the mobile database. Total charges increased by 135%, 148%, and 228% for each of the three trauma surgeons who used the mobile DB application. The majority of additional charges were for evaluation and management services. Patients who were captured and billed at the point of care using the mobile DB had higher Injury Severity Scores, were more likely to undergo an operative procedure, and had longer lengths of stay compared with those who were not captured. Total charges more than doubled using a mobile database to bill at the point of care. A subsequent comparison of TRACS data with billing information revealed a large amount of uncaptured patient revenue. Greater familiarity and broader use of mobile database technology holds the potential for even greater revenue capture.
Rini, Brian I; Escudier, Bernard; Martini, Jean-Francois; Magheli, Ahmed; Svedman, Christer; Lopatin, Margarita; Knezevic, Dejan; Goddard, Audrey D; Febbo, Phillip G; Li, Rachel; Lin, Xun; Valota, Olga; Staehler, Michael; Motzer, Robert J; Ravaud, Alain
2018-05-17
Adjuvant sunitinib prolonged disease-free survival (DFS) (hazard ratio [HR] 0.76) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov NCT00375674). The 16-gene Recurrence Score (RS) assay was previously developed and validated to estimate risk for disease recurrence in patients with RCC post-nephrectomy. This analysis further validated the prognostic value of RS assay in patients from S-TRAC and explored association of RS results with prediction of sunitinib benefit. The analysis was prospectively designed with prespecified genes, algorithm, endpoints, and analytical methods. Primary RCC was available from 212 patients with informed consent; primary analysis focused on patients with T3 RCC. Gene expression was quantitated by RT-PCR. Time to recurrence (TTR), DFS, and renal cancer-specific survival (RCSS) were analyzed using Cox proportional hazards regression. Results: Baseline characteristics were similar between patients with and without RS results, and between the sunitinib and placebo arms among patients with RS results. RS results predicted TTR, DFS, and RCSS in both arms, with the strongest results observed in the placebo arm. When high versus low RS groups were compared, HR for recurrence was 9.18 (95% CI, 2.15-39.24; P < 0.001) in the placebo arm; interaction of RS results with treatment was not significant. Conclusions: The strong prognostic performance of the 16-gene RS assay was confirmed in S-TRAC, and the RS assay is now supported by level IB evidence. RS results may help identify patients at high risk for recurrence who may derive higher absolute benefit from adjuvant therapy. Copyright ©2018, American Association for Cancer Research.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, S; Oh, S; Yea, J
Purpose: This study evaluated the setup uncertainties for brain sites when using BrainLAB’s ExacTrac X-ray 6D system for daily pretreatment to determine the optimal planning target volume (PTV) margin. Methods: Between August 2012 and April 2015, 28 patients with brain tumors were treated by daily image-guided radiotherapy using the BrainLAB ExacTrac 6D image guidance system of the Novalis-Tx linear accelerator. DUONTM (Orfit Industries, Wijnegem, Belgium) masks were used to fix the head. The radiotherapy was fractionated into 27–33 treatments. In total, 844 image verifications were performed for 28 patients and used for the analysis. The setup corrections along with themore » systematic and random errors were analyzed for six degrees of freedom in the translational (lateral, longitudinal, and vertical) and rotational (pitch, roll, and yaw) dimensions. Results: Optimal PTV margins were calculated based on van Herk et al.’s [margin recipe = 2.5∑ + 0.7σ − 3 mm] and Stroom et al.’s [margin recipe = 2∑ + 0.7σ] formulas. The systematic errors (∑) were 0.72, 1.57, and 0.97 mm in the lateral, longitudinal, and vertical translational dimensions, respectively, and 0.72°, 0.87°, and 0.83° in the pitch, roll, and yaw rotational dimensions, respectively. The random errors (σ) were 0.31, 0.46, and 0.54 mm in the lateral, longitudinal, and vertical rotational dimensions, respectively, and 0.28°, 0.24°, and 0.31° in the pitch, roll, and yaw rotational dimensions, respectively. According to van Herk et al.’s and Stroom et al.’s recipes, the recommended lateral PTV margins were 0.97 and 1.66 mm, respectively; the longitudinal margins were 1.26 and 3.47 mm, respectively; and the vertical margins were 0.21 and 2.31 mm, respectively. Conclusion: Therefore, daily setup verifications using the BrainLAB ExacTrac 6D image guide system are very useful for evaluating the setup uncertainties and determining the setup margin.∑σ.« less
Inflammatory bowel disease and risk of Parkinson's disease in Medicare beneficiaries.
Camacho-Soto, Alejandra; Gross, Anat; Searles Nielsen, Susan; Dey, Neelendu; Racette, Brad A
2018-05-01
Gastrointestinal (GI) dysfunction precedes the motor symptoms of Parkinson's disease (PD) by several years. PD patients have abnormal aggregation of intestinal α-synuclein, the accumulation of which may be promoted by inflammation. The relationship between intestinal α-synuclein aggregates and central nervous system neuropathology is unknown. Recently, we observed a possible inverse association between inflammatory bowel disease (IBD) and PD as part of a predictive model of PD. Therefore, the objective of this study was to examine the relationship between PD risk and IBD and IBD-associated conditions and treatment. Using a case-control design, we identified 89,790 newly diagnosed PD cases and 118,095 population-based controls >65 years of age using comprehensive Medicare data from 2004-2009 including detailed claims data. We classified IBD using International Classification of Diseases version 9 (ICD-9) diagnosis codes. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between PD and IBD. Covariates included age, sex, race/ethnicity, smoking, Elixhauser comorbidities, and health care use. PD was inversely associated with IBD overall (OR = 0.85, 95% CI 0.80-0.91) and with both Crohn's disease (OR = 0.83, 95% CI 0.74-0.93) and ulcerative colitis (OR = 0.88, 95% CI 0.82-0.96). Among beneficiaries with ≥2 ICD-9 codes for IBD, there was an inverse dose-response association between number of IBD ICD-9 codes, as a potential proxy for IBD severity, and PD (p-for-trend = 0.006). IBD is associated with a lower risk of developing PD. Copyright © 2018 Elsevier Ltd. All rights reserved.
Yao, Q; Fischer, K P; Tyrrell, D L; Gutfreund, K S
2015-04-01
Programmed death ligand-1 (PD-L1) plays an important role in the attenuation of adaptive immune responses in higher vertebrates. Here, we describe the identification of the Pekin duck PD-L1 orthologue (duPD-L1) and its gene structure. The duPD-L1 cDNA encodes a 311-amino acid protein that has an amino acid identity of 78% and 42% with chicken and human PD-L1, respectively. Mapping of the duPD-L1 cDNA with duck genomic sequences revealed an exonic structure of its coding sequence similar to those of other vertebrates but lacked a noncoding exon 1. Homology modelling of the duPD-L1 extracellular domain was compatible with the tandem IgV-like and IgC-like IgSF domain structure of human PD-L1 (PDB ID: 3BIS). Residues known to be important for receptor binding of human PD-L1 were mostly conserved in duPD-L1 within the N-terminus and the G sheet, and partially conserved within the F sheet but not within sheets C and C'. DuPD-L1 mRNA was constitutively expressed in all tissues examined with highest expression levels in lung and spleen and very low levels of expression in muscle, kidney and brain. Mitogen stimulation of duck peripheral blood mononuclear cells transiently increased duPD-L1 mRNA expression. Our observations demonstrate evolutionary conservation of the exonic structure of its coding sequence, the extracellular domain structure and residues implicated in receptor binding, but the role of the longer cytoplasmic tail in avian PD-L1 proteins remains to be determined. © 2014 John Wiley & Sons Ltd.
Investigation of genes coding for inflammatory components in Parkinson's disease.
Håkansson, Anna; Westberg, Lars; Nilsson, Staffan; Buervenich, Silvia; Carmine, Andrea; Holmberg, Björn; Sydow, Olof; Olson, Lars; Johnels, Bo; Eriksson, Elias; Nissbrandt, Hans
2005-05-01
Several findings obtained recently indicate that inflammation may contribute to the pathogenesis in Parkinson's disease (PD). Genetic variants of genes coding for components involved in immune reactions in the brain might therefore influence the risk of developing PD or the age of disease onset. Five single nucleotide polymorphisms (SNPs) in the genes coding for interferon-gamma (IFN-gamma; T874A in intron 1), interferon-gamma receptor 2 (IFN-gamma R2; Gln64Arg), interleukin-10 (IL-10; G1082A in the promoter region), platelet-activating factor acetylhydrolase (PAF-AH; Val379Ala), and intercellular adhesion molecule 1 (ICAM-1; Lys469Glu) were genotyped, using pyrosequencing, in 265 patients with PD and 308 controls. None of the investigated SNPs was found to be associated with PD; however, the G1082A polymorphism in the IL-10 gene promoter was found to be related to the age of disease onset. Linear regression showed a significantly earlier onset with more A-alleles (P = 0.0095; after Bonferroni correction, P = 0.048), resulting in a 5-year delayed age of onset of the disease for individuals having two G-alleles compared with individuals having two A-alleles. The results indicate that the IL-10 G1082A SNP could possibly be related to the age of onset of PD. Copyright 2005 Movement Disorder Society.
Simulation of Rotary-Wing Near-Wake Vortex Structures Using Navier-Stokes CFD Methods
NASA Technical Reports Server (NTRS)
Kenwright, David; Strawn, Roger; Ahmad, Jasim; Duque, Earl; Warmbrodt, William (Technical Monitor)
1997-01-01
This paper will use high-resolution Navier-Stokes computational fluid dynamics (CFD) simulations to model the near-wake vortex roll-up behind rotor blades. The locations and strengths of the trailing vortices will be determined from newly-developed visualization and analysis software tools applied to the CFD solutions. Computational results for rotor nearwake vortices will be used to study the near-wake vortex roll up for highly-twisted tiltrotor blades. These rotor blades typically have combinations of positive and negative spanwise loading and complex vortex wake interactions. Results of the computational studies will be compared to vortex-lattice wake models that are frequently used in rotorcraft comprehensive codes. Information from these comparisons will be used to improve the rotor wake models in the Tilt-Rotor Acoustic Code (TRAC) portion of NASA's Short Haul Civil Transport program (SHCT). Accurate modeling of the rotor wake is an important part of this program and crucial to the successful design of future civil tiltrotor aircraft. The rotor wake system plays an important role in blade-vortex interaction noise, a major problem for all rotorcraft including tiltrotors.
Irie, Koichiro; Yamazaki, Toru; Yoshii, Saori; Takeyama, Hideo; Shimazaki, Yoshihiro
2017-02-01
Development of periodontal disease (PD) may be affected by socioeconomic status. This study examined the relationship between occupational status and PD in a 5-year prospective cohort of Japanese workers. In total, 19,633 participants had initial examinations at the Aichi Health Promotion Foundation, of whom 8210 participants aged 20 years or older did not have PD. Follow-up examinations were conducted for 3757 participants, accounting for 45.8% of baseline participants. Ultimately, 3390 participants were analyzed according to the criterion of job classification at baseline, which was based on the International Standard Classification of Occupations, 1987. Oral examinations were performed using the Community Periodontal Index (CPI). The CPI scores were coded as follows: healthy (score of 0); bleeding after probing (1); dental calculus (2); shallow pockets (3); and deep pockets (4). Participants with one or more sextants with a score >2 were diagnosed with PD. Poisson regression analysis was performed to adjust for age and other potential confounders. Overall, 31.6% of men and 23.8% of women had developed PD (CPI scores of 3 or 4). The adjusted relative risk (RR) for PD (CPI scores of 3 or 4) in men was not significant. On the other hand, the adjusted RRs for PD (CPI score of 4) in men were 2.52-, 2.39-, and 2.74-fold higher for skilled workers, sales persons, and drivers, respectively, than for professionals. In contrast, we found no gradient in women. We found a gradient related to the risk of developing PD according to occupational status among men in a Japanese worker population. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sattarivand, Mike; Summers, Clare; Robar, James
Purpose: To evaluate the validity of using spine as a surrogate for tumor positioning with ExacTrac stereoscopic imaging in lung stereotactic body radiation therapy (SBRT). Methods: Using the Novalis ExacTrac x-ray system, 39 lung SBRT patients (182 treatments) were aligned before treatment with 6 degrees (6D) of freedom couch (3 translations, 3 rotations) based on spine matching on stereoscopic images. The couch was shifted to treatment isocenter and pre-treatment CBCT was performed based on a soft tissue match around tumor volume. The CBCT data were used to measure residual errors following ExacTrac alignment. The thresholds for re-aligning the patients basedmore » on CBCT were 3mm shift or 3° rotation (in any 6D). In order to evaluate the effect of tumor location on residual errors, correlations between tumor distance from spine and individual residual errors were calculated. Results: Residual errors were up to 0.5±2.4mm. Using 3mm/3° thresholds, 80/182 (44%) of the treatments required re-alignment based on CBCT soft tissue matching following ExacTrac spine alignment. Most mismatches were in sup-inf, ant-post, and roll directions which had larger standard deviations. No correlation was found between tumor distance from spine and individual residual errors. Conclusion: ExacTrac stereoscopic imaging offers a quick pre-treatment patient alignment. However, bone matching based on spine is not reliable for aligning lung SBRT patients who require soft tissue image registration from CBCT. Spine can be a poor surrogate for lung SBRT patient alignment even for proximal tumor volumes.« less
Summary of papers on current and anticipated uses of thermal-hydraulic codes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Caruso, R.
1997-07-01
The author reviews a range of recent papers which discuss possible uses and future development needs for thermal/hydraulic codes in the nuclear industry. From this review, eight common recommendations are extracted. They are: improve the user interface so that more people can use the code, so that models are easier and less expensive to prepare and maintain, and so that the results are scrutable; design the code so that it can easily be coupled to other codes, such as core physics, containment, fission product behaviour during severe accidents; improve the numerical methods to make the code more robust and especiallymore » faster running, particularly for low pressure transients; ensure that future code development includes assessment of code uncertainties as integral part of code verification and validation; provide extensive user guidelines or structure the code so that the `user effect` is minimized; include the capability to model multiple fluids (gas and liquid phase); design the code in a modular fashion so that new models can be added easily; provide the ability to include detailed or simplified component models; build on work previously done with other codes (RETRAN, RELAP, TRAC, CATHARE) and other code validation efforts (CSAU, CSNI SET and IET matrices).« less
Forrester works with the TRAC Experiment in the U.S Laboratory during Joint Operations
2007-06-12
S117-E-07092 (12 June 2007) --- Astronaut Patrick Forrester, STS-117 mission specialist, works with the Test of Reaction and Adaptation Capabilities (TRAC) experiment in the Destiny laboratory of the International Space Station while Space Shuttle Atlantis was docked with the station. The TRAC investigation will test the theory of brain adaptation during space flight by testing hand-eye coordination before, during and after the space flight.
Anderson works with the TRAC experiment in the U.S. Laboratory during Joint Operations
2007-06-12
S117-E-07031 (12 June 2007) --- Astronaut Clayton Anderson, Expedition 15 flight engineer, works with the Test of Reaction and Adaptation Capabilities (TRAC) experiment in the Destiny laboratory of the International Space Station while Space Shuttle Atlantis was docked with the station. The TRAC investigation will test the theory of brain adaptation during space flight by testing hand-eye coordination before, during and after the space flight.
Structure and chromosomal localization of the human PD-1 gene (PDCD1)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shinohara, T.; Ishida, Y.; Kawaichi, M.
1994-10-01
A cDNA encoding mouse PD-1, a member of the immunoglobulin superfamily, was previously isolated from apoptosis-induced cells by subtractive hybridization. To determine the structure and chromosomal location of the human PD-1 gene, we screened a human T cell cDNA library by mouse PD-1 probe and isolated a cDNA coding for the human PD-1 protein. The deduced amino acid sequence of human PD-1 was 60% identical to the mouse counterpart, and a putative tyrosine kinase-association motif was well conserved. The human PD-1 gene was mapped to 2q37.3 by chromosomal in situ hybridization. 7 refs., 3 figs.
Epitope enhancement for immunohistochemical demonstration of tartrate-resistant acid phosphatase.
Janckila, A J; Lear, S C; Martin, A W; Yam, L T
1996-03-01
We have developed a monoclonal antibody (9C5) for immunohistochemical localization of tartrate-resistant acid phosphatase (TRAcP). This antibody reacts with a denatured epitope of TRAcP and requires enhancement methods to promote antigenicity in paraffin-embedded tissues. We used this antibody to systematically examine proteolytic digestion and heat denaturation conditions for epitope enhancement in both paraffin sections and fixed smears. The goal was to increase the sensitivity of the immunohistochemical stain for TRAcP. Optimal conditions for proteolytic digestion were established. Denaturation in a conventional boiling water bath was compared to microwave irradiation in several commonly used solutions. Immunohistochemistry was compared directly to TRAcP cytochemistry in fixed smears from hairy cell leukemia specimens to gauge the level of sensitivity of our improved method. Attempts were made to "retrieve" the 9C5 epitope from overfixed tissues and aged smears. Maximal immunoreactivity of TRAcP was achieved by microwave irradiation in a citrate or Tris buffer of pH 6.0-8.0 without the need for a subsequent protease digestion step. With this method of epitope enhancement, immunohistochemistry with antibody 9C5 was as sensitive as direct cytochemical staining of TRAcP activity. However, once a tissue specimen had been overfixed or a smear stored for a year or more, the 9C5 epitope was no longer retrievable. The key element in epitope enhancement for 9C5 immunohistochemistry is heat denaturation of the target epitope. Immunohistochemistry of TRAcP in paraffin sections would be a great asset to the study of specialized forms of the monocyte/macrophage lineage and to the process of macrophage activation. It would also provide another means for more precise evaluation of residual disease in bone marrow of patients treated for hairy cell leukemia.
Zhang, Q; Baldwin, V J; Acland, G M; Parshall, C J; Haskel, J; Aguirre, G D; Ray, K
1999-01-01
Photoreceptor dysplasia (pd) is one of a group of at least six distinct autosomal and one X-linked retinal disorders identified in dogs which are collectively known as progressive retinal atrophy (PRA). It is an early onset retinal disease identified in miniature schnauzer dogs, and pedigree analysis and breeding studies have established autosomal recessive inheritance of the disease. Using a gene-based approach, a number of retina-expressed genes, including some members of the phototransduction pathway, have been causally implicated in retinal diseases of humans and other animals. Here we examined seven such potential candidate genes (opsin, RDS/peripherin, ROM1, rod cGMP-gated cation channel alpha-subunit, and three subunits of transducin) for their causal association with the pd locus by testing segregation of intragenic markers with the disease locus, or, in the absence of informative polymorphisms, sequencing of the coding regions of the genes. Based on these results, we have conclusively excluded four photoreceptor-specific genes as candidates for pd by linkage analysis. For three other photoreceptor-specific genes, we did not find any mutation in the coding sequences of the genes and have excluded them provisionally. Formal exclusion would require investigation of the levels of expression of the candidate genes in pd-affected dogs relative to age-matched controls. At present we are building suitable informative pedigrees for the disease locus with a sufficient number of meiosis to be useful for genomewide screening. This should identify markers linked to the disease locus and eventually permit progress toward the identification of the photoreceptor dysplasia gene and the disease-causing mutation.
Thermal Deformation of Very Slender Triangular Rollable and Collapsible Booms
NASA Technical Reports Server (NTRS)
Stohlman, Olive R.; Loper, Erik R.
2016-01-01
Metallic triangular rollable and collapsible (TRAC) booms have deployed two Cubesat-based solar sails in low Earth orbit, making TRAC booms the most popular solar sail deployment method in practice. This paper presents some concerns and solutions surrounding the behavior of these booms in the space thermal environment. A 3.5-cm-tall, 4-meter-long TRAC boom of Elgiloy cobalt alloy, when exposed to direct sunlight in a 1 AU deep space environment, has a predicted tip motion of as much as 0.5 meters. Such large thermal deflections could generate unacceptable distortions in the shape of a supported solar sail, making attitude control of the solar sail spacecraft difficult or impossible. As a possible means of mitigating this issue, the thermal distortion behaviors of three alternative material TRAC booms are investigated and compared with the uncoated Elgiloy baseline boom. A tenfold decrease in induced curvature is shown to be possible relative to the baseline boom. Potential thermal distortions of the LightSail-A solar sail TRAC booms are also examined and compared, although inconclusively, with available on-orbit camera imagery.
Breen, Michael S.; Long, Thomas C.; Schultz, Bradley D.; Crooks, James; Breen, Miyuki; Langstaff, John E.; Isaacs, Kristin K.; Tan, Yu-Mei; Williams, Ronald W.; Cao, Ye; Geller, Andrew M.; Devlin, Robert B.; Batterman, Stuart A.; Buckley, Timothy J.
2014-01-01
A critical aspect of air pollution exposure assessment is the estimation of the time spent by individuals in various microenvironments (ME). Accounting for the time spent in different ME with different pollutant concentrations can reduce exposure misclassifications, while failure to do so can add uncertainty and bias to risk estimates. In this study, a classification model, called MicroTrac, was developed to estimate time of day and duration spent in eight ME (indoors and outdoors at home, work, school; inside vehicles; other locations) from global positioning system (GPS) data and geocoded building boundaries. Based on a panel study, MicroTrac estimates were compared with 24-h diary data from nine participants, with corresponding GPS data and building boundaries of home, school, and work. MicroTrac correctly classified the ME for 99.5% of the daily time spent by the participants. The capability of MicroTrac could help to reduce the time–location uncertainty in air pollution exposure models and exposure metrics for individuals in health studies. PMID:24619294
Trace Assessment for BWR ATWS Analysis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cheng, L.Y.; Diamond, D.; Arantxa Cuadra, Gilad Raitses, Arnold Aronson
2010-04-22
A TRACE/PARCS input model has been developed in order to be able to analyze anticipated transients without scram (ATWS) in a boiling water reactor. The model is based on one developed previously for the Browns Ferry reactor for doing loss-of-coolant accident analysis. This model was updated by adding the control systems needed for ATWS and a core model using PARCS. The control systems were based on models previously developed for the TRAC-B code. The PARCS model is based on information (e.g., exposure and moderator density (void) history distributions) obtained from General Electric Hitachi and cross sections for GE14 fuel obtainedmore » from an independent source. The model is able to calculate an ATWS, initiated by the closure of main steam isolation valves, with recirculation pump trip, water level control, injection of borated water from the standby liquid control system and actuation of the automatic depres-surization system. The model is not considered complete and recommendations are made on how it should be improved.« less
1978-09-01
SNAPSHOT PICTURE VIDEO TAPE 35-MM PHOTO TRANSPARENCY MICROFILM Figure 2 - Gross Area Information Density other across the organization. Then we developed...the finite element In the modeling of a tor- method. The torpedo hull is divided pedo for shock and vibration analysis, ,. into primary structural...length of the tor- 16. Figure 15 presents the magnitude pedo with several circumferential trac- and phase of motor motion, and Fig. 16 ings at
Wang, He; Wang, Congjun; Tung, Samuel; Dimmitt, Andrew Wilson; Wong, Pei Fong; Edson, Mark A.; Garden, Adam S.; Rosenthal, David I.; Fuller, Clifton D.; Gunn, Gary B.; Takiar, Vinita; Wang, Xin A.; Luo, Dershan; Yang, James N.; Wong, Jennifer
2016-01-01
The purpose of this study was to investigate the setup and positioning uncertainty of a custom cushion/mask/bite‐block (CMB) immobilization system and determine PTV margin for image‐guided head and neck stereotactic ablative radiotherapy (HN‐SABR). We analyzed 105 treatment sessions among 21 patients treated with HN‐SABR for recurrent head and neck cancers using a custom CMB immobilization system. Initial patient setup was performed using the ExacTrac infrared (IR) tracking system and initial setup errors were based on comparison of ExacTrac IR tracking system to corrected online ExacTrac X‐rays images registered to treatment plans. Residual setup errors were determined using repeat verification X‐ray. The online ExacTrac corrections were compared to cone‐beam CT (CBCT) before treatment to assess agreement. Intrafractional positioning errors were determined using prebeam X‐rays. The systematic and random errors were analyzed. The initial translational setup errors were −0.8±1.3 mm, −0.8±1.6 mm, and 0.3±1.9 mm in AP, CC, and LR directions, respectively, with a three‐dimensional (3D) vector of 2.7±1.4 mm. The initial rotational errors were up to 2.4° if 6D couch is not available. CBCT agreed with ExacTrac X‐ray images to within 2 mm and 2.5°. The intrafractional uncertainties were 0.1±0.6 mm, 0.1±0.6 mm, and 0.2±0.5 mm in AP, CC, and LR directions, respectively, and 0.0∘±0.5°, 0.0∘±0.6°, and −0.1∘±0.4∘ in yaw, roll, and pitch direction, respectively. The translational vector was 0.9±0.6 mm. The calculated PTV margins mPTV(90,95) were within 1.6 mm when using image guidance for online setup correction. The use of image guidance for online setup correction, in combination with our customized CMB device, highly restricted target motion during treatments and provided robust immobilization to ensure minimum dose of 95% to target volume with 2.0 mm PTV margin for HN‐SABR. PACS number(s): 87.55.ne PMID:27167275
MODFLOW 2.0: A program for predicting moderator flow patterns
NASA Astrophysics Data System (ADS)
Peterson, P. F.; Paik, I. K.
1991-07-01
Sudden changes in the temperature of flowing liquids can result in transient buoyancy forces which strongly impact the flow hydrodynamics via flow stratification. These effects have been studied for the case of potential flow of stratified liquids to line sinks, but not for moderator flow in SRS reactors. Standard codes, such as TRAC and COMMIX, do not have the capability to capture the stratification effect, due to strong numerical diffusion which smears away the hot/cold fluid interface. A related problem with standard codes is the inability to track plumes injected into the liquid flow, again due to numerical diffusion. The combined effects of buoyant stratification and plume dispersion have been identified as being important in the operation of the Supplementary Safety System which injects neutron-poison ink into SRS reactors to provide safe shutdown in the event of safety rod failure. The MODFLOW code discussed here provides transient moderator flow pattern information with stratification effects, and tracks the location of ink plumes in the reactor. The code, written in Fortran, is compiled for Macintosh II computers, and includes subroutines for interactive control and graphical output. Removing the graphics capabilities, the code can also be compiled on other computers. With graphics, in addition to the capability to perform safety related computations, MODFLOW also provides an easy tool for becoming familiar with flow distributions in SRS reactors.
Pawcatuck and Woonasquatucket River Basins and Narragansett Bay Local Drainage Area. Main Report.
1981-10-01
building and housing codes are recommended. Flood warning systems, urban renewal, tax incentives, and public open space acquisition will also help...RIVER GROUP WATERSHEDLD LOCAL DRAINAGE PD, WOONASQUATUCKET - MOSI4ASSUCK - PROVIDENCE RIVERS SUB-BASIN PD2 BLACKSTONE RIVER SUB-BASIN orPD 3 TENMiLE...of the Taunton River Basin in Massachusetts, 1979 PNB Water Supply Study, January 1979 Big River Reservoir Project, July 1981 Blackstone River
FAST-TRAC evaluation : evaluation summary report
DOT National Transportation Integrated Search
FAST-TRAC is an Intelligent Transportation System (ITS) that integrates advanced traffic control with a variety of advanced traffic information systems through centralized collection, processing, and dissemination of traffic data. The Road Commission...
Oh, Se An; Park, Jae Won; Yea, Ji Woon; Kim, Sung Kyu
2017-01-01
The objective of this study was to evaluate the setup discrepancy between BrainLAB 6 degree-of-freedom (6D) ExacTrac and cone-beam computed tomography (CBCT) used with the imaging guidance system Novalis Tx for intracranial stereotactic radiosurgery. We included 107 consecutive patients for whom white stereotactic head frame masks (R408; Clarity Medical Products, Newark, OH) were used to fix the head during intracranial stereotactic radiosurgery, between August 2012 and July 2016. The patients were immobilized in the same state for both the verification image using 6D ExacTrac and online 3D CBCT. In addition, after radiation treatment, registration between the computed tomography simulation images and the CBCT images was performed with offline 6D fusion in an offline review. The root-mean-square of the difference in the translational dimensions between the ExacTrac system and CBCT was <1.01 mm for online matching and <1.10 mm for offline matching. Furthermore, the root-mean-square of the difference in the rotational dimensions between the ExacTrac system and the CBCT were <0.82° for online matching and <0.95° for offline matching. It was concluded that while the discrepancies in residual setup errors between the ExacTrac 6D X-ray and the CBCT were minor, they should not be ignored.
Kaut, Oliver; Schmitt, Ina; Tost, Jörg; Busato, Florence; Liu, Yi; Hofmann, Per; Witt, Stephanie H; Rietschel, Marcella; Fröhlich, Holger; Wüllner, Ullrich
2017-01-01
Numerous studies have elucidated the genetics of Parkinson's disease; however, the aetiology of the majority of sporadic cases has not yet been resolved. We hypothesized that epigenetic variations could be associated with PD and evaluated the DNA methylation pattern in PD patients compared to brothers or twins without PD. The methylation of DNA from peripheral blood mononuclear cells of 62 discordant siblings including 24 monozygotic twins was characterized with Illumina DNA Methylation 450K bead arrays and subsequently validated in two independent cohorts: 221 PD vs. 227 healthy individuals (cohort 1) applying Illumina's VeraCode and 472 PD patients vs. 487 controls (cohort 2) using pyrosequencing. We choose a delta beta of >15 % and selected 62 differentially methylated CpGs in 51 genes from the discordant siblings. Among them, three displayed multiple CpGs per gene: microRNA 886 (MIR886, 10 CpGs), phosphodiesterase 4D (PDE4D, 2 CpGs) and tripartite motif-containing 34 (TRIM34, 2 CpGs). PDE4D was confirmed in both cohorts (p value 2.44e-05). In addition, for biomarker construction, we used the penalized logistic regression model, resulting in a signature of eight CpGs with an AUC of 0.77. Our findings suggest that a distinct level of PD susceptibility stems from individual, epigenetic modifications of specific genes. We identified a signature of CpGs in blood cells that could separate control from disease with a reasonable discriminatory power, holding promise for future epigenetically based biomarker development.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-11
... Decree in United States v. Highview Gardens, Inc., Civil Action No. 2:09-cv-02827-PD was lodged with the... States v. Highview Gardens, Inc., Civil Action No. 2:09-cv- 02827-PD, D.J. Ref. 90-11-2-902/4. The..., Environment and Natural Resources Division. [FR Doc. 2010-175 Filed 1-8-10; 8:45 am] BILLING CODE 4410-15-P ...
Microenvironment Tracker (MicroTrac) Model helps track air quality
MicroTrac is a model that uses global positioning system (GPS) data to estimate time of day and duration that people spend in different microenvironments (e.g., indoors and outdoors at home, work, school).
Microenvironment Tracker (MicroTrac) Factsheet
MicroTrac is a model developed by EPA that uses GPS data to estimate time of day and duration that people spend in different microenvironments, such as indoors and outdoors at home, work, school, and inside vehicles.
Cytochrome P450 2D6 and Parkinson's Disease: Polymorphism, Metabolic Role, Risk and Protection.
Ur Rasheed, Mohd Sami; Mishra, Abhishek Kumar; Singh, Mahendra Pratap
2017-12-01
Cytochrome P450 (CYP) 2D6 is one of the most highly active, oxidative and polymorphic enzymes known to metabolize Parkinsonian toxins and clinically established anti-Parkinson's disease (PD) drugs. Albeit CYP2D6 gene is not present in rodents, its orthologs perform almost the similar function with imprecise substrate and inhibitor specificity. CYP2D6 expression and catalytic activity are found to be regulated at every stage of the central dogma except replication as well as at the epigenetic level. CYP2D6 gene codes for a set of alternate splice variants that give rise to a range of enzymes possessing variable catalytic activity. Case-control studies, meta-analysis and systemic reviews covering CYP2D6 polymorphism and PD risk have demonstrated that poor metabolizer phenotype possesses a considerable genetic susceptibility. Besides, ultra-rapid metabolizer offers protection against the risk in some populations while lack of positive or inverse association is also reported in other inhabitants. CYP2D6 polymorphisms resulting into deviant protein products with differing catalytic activity could lead to inter-individual variations, which could be explained to certain extent on the basis of sample size, life style factors, food habits, ethnicity and tools used for statistical analysis across various studies. Current article describes the role played by polymorphic CYP2D6 in the metabolism of anti-PD drugs/Parkinsonian toxins and how polymorphisms determine PD risk or protection. Moreover, CYP2D6 orthologs and their roles in rodent models of Parkinsonism have also been mentioned. Finally, a perspective on inconsistency in the findings and futuristic relevance of CYP2D6 polymorphisms in disease diagnosis and treatment has also been highlighted.
Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma
Jusakul, Apinya; Cutcutache, Ioana; Yong, Chern Han; Lim, Jing Quan; Huang, Mi Ni; Padmanabhan, Nisha; Nellore, Vishwa; Kongpetch, Sarinya; Ng, Alvin Wei Tian; Ng, Ley Moy; Choo, Su Pin; Myint, Swe Swe; Thanan, Raynoo; Nagarajan, Sanjanaa; Lim, Weng Khong; Ng, Cedric Chuan Young; Boot, Arnoud; Liu, Mo; Ong, Choon Kiat; Rajasegaran, Vikneswari; Lie, Stefanus; Lim, Alvin Soon Tiong; Lim, Tse Hui; Tan, Jing; Loh, Jia Liang; McPherson, John R.; Khuntikeo, Narong; Bhudhisawasdi, Vajaraphongsa; Yongvanit, Puangrat; Wongkham, Sopit; Totoki, Yasushi; Nakamura, Hiromi; Arai, Yasuhito; Yamasaki, Satoshi; Chow, Pierce Kah-Hoe; Chung, Alexander Yaw Fui; Ooi, London Lucien Peng Jin; Lim, Kiat Hon; Dima, Simona; Duda, Dan G.; Popescu, Irinel; Broet, Philippe; Hsieh, Sen-Yung; Yu, Ming-Chin; Scarpa, Aldo; Lai, Jiaming; Luo, Di-Xian; Carvalho, André Lopes; Vettore, André Luiz; Rhee, Hyungjin; Park, Young Nyun; Alexandrov, Ludmil B.; Gordân, Raluca; Rozen, Steven G.; Shibata, Tatsuhiro; Pairojkul, Chawalit; Teh, Bin Tean; Tan, Patrick
2017-01-01
Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analysed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined four CCA clusters – Fluke-Positive CCAs (Clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations, conversely Fluke-Negative CCAs (Clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3′UTR deletion as a mechanism of FGFR2 upregulation. Integration of non-coding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores – mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Our results exemplify how genetics, epigenetics and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer. PMID:28667006
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jusakul, Apinya; Cutcutache, Ioana; Yong, Chern Han
Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analysed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined four CCA clusters - Fluke- Positive CCAs (Clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations, conversely Fluke-Negative CCAs (Clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3’UTR deletion as a mechanism of FGFR2 upregulation. Integration of non-coding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation ofmore » H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores - mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Lastly, our results exemplify how genetics, epigenetics and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer.« less
Spontaneous and posed facial expression in Parkinson's disease.
Smith, M C; Smith, M K; Ellgring, H
1996-09-01
Spontaneous and posed emotional facial expressions in individuals with Parkinson's disease (PD, n = 12) were compared with those of healthy age-matched controls (n = 12). The intensity and amount of facial expression in PD patients were expected to be reduced for spontaneous but not posed expressions. Emotional stimuli were video clips selected from films, 2-5 min in duration, designed to elicit feelings of happiness, sadness, fear, disgust, or anger. Facial movements were coded using Ekman and Friesen's (1978) Facial Action Coding System (FACS). In addition, participants rated their emotional experience on 9-point Likert scales. The PD group showed significantly less overall facial reactivity than did controls when viewing the films. The predicted Group X Condition (spontaneous vs. posed) interaction effect on smile intensity was found when PD participants with more severe disease were compared with those with milder disease and with controls. In contrast, ratings of emotional experience were similar for both groups. Depression was positively associated with emotion rating but not with measures of facial activity. Spontaneous facial expression appears to be selectively affected in PD, whereas posed expression and emotional experience remain relatively intact.
Ma, Haijie; Sun, Xuepeng; Wang, Mingshuang; Gai, Yunpeng; Chung, Kuang-Ren; Li, Hongye
2016-11-07
The postharvest pathogen Penicillium digitatum causes green mold decay on citrus fruit, resulting in severe economic losses. To explore possible factors involved in fungal pathogenesis, phenotypic characterization of the budding yeast Fus3/Kiss1 mitogen-activated protein (MAP) kinase homolog was carried out. The P. digitatum MAP kinase B coding gene, designated PdMpkB, was functionally inactivated via homologous recombination. The fungal strain (∆PdMpkB) carrying a PdMpkBdeletion demonstrated altered gene expression profiles, reduced growth and conidiogenesis, elevated resistance to osmotic stress, and failed to induce green mold decay on citrus fruit. ∆PdMpkB was more resistant to CaCl2, NaCl and sorbitol than its progenitor strain, indicating a negative regulatory function of PdMpkB in osmotic stress adaptation. Fungal infection assays on citrus fruit revealed that ∆PdMpkB proliferated poorly within host tissues, induced water-soaking lesions, failed to break through host cuticle layers and thus, failed to produce aerial hyphae and conidia. Introduction of a functional copy of PdMpkB into a null mutant restored all defective phenotypes. Transcriptome analysis revealed that inactivation of PdMpkB impacted expression of the genes associated with cell wall-degrading enzyme activities, carbohydrate and amino acid metabolisms, conidial formation, and numerous metabolic processes. Our results define pivotal roles of the PdMpkB-mediated signaling pathway in developmental and pathological functions in the citrus postharvest pathogen P. digitatum. Copyright © 2016 Elsevier B.V. All rights reserved.
Hoeck, W G
1994-06-01
InfoTrac TFD provides a graphical user interface (GUI) for viewing and manipulating datasets in the Transcription Factor Database, TFD. The interface was developed in Filemaker Pro 2.0 by Claris Corporation, which provides cross platform compatibility between Apple Macintosh computers running System 7.0 and higher and IBM-compatibles running Microsoft Windows 3.0 and higher. TFD ASCII-tables were formatted to fit data into several custom data tables using Add/Strip, a shareware utility and Filemaker Pro's lookup feature. The lookup feature was also put to use to allow TFD data tables to become linked within a flat-file database management system. The 'Navigator', consisting of several pop-up menus listing transcription factor abbreviations, facilitates the search for transcription factor entries. Data are presented onscreen in several layouts, that can be further customized by the user. InfoTrac TFD makes the transcription factor database accessible to a much wider community of scientists by making it available on two popular microcomputer platforms.
TRAC PAC : the next generation
DOT National Transportation Integrated Search
1999-05-01
The Transportation and Civil Engineering (TRAC) PAC is a toolkit of instructional aids originally built in 1994 to attract middle and high school students to the transportation field. Since that time, users have noted difficulties arising from the PA...
Zaker, Neda; Zehtabian, Mehdi; Sina, Sedigheh; Koontz, Craig; Meigooni, Ali S
2016-03-08
Monte Carlo simulations are widely used for calculation of the dosimetric parameters of brachytherapy sources. MCNP4C2, MCNP5, MCNPX, EGS4, EGSnrc, PTRAN, and GEANT4 are among the most commonly used codes in this field. Each of these codes utilizes a cross-sectional library for the purpose of simulating different elements and materials with complex chemical compositions. The accuracies of the final outcomes of these simulations are very sensitive to the accuracies of the cross-sectional libraries. Several investigators have shown that inaccuracies of some of the cross section files have led to errors in 125I and 103Pd parameters. The purpose of this study is to compare the dosimetric parameters of sample brachytherapy sources, calculated with three different versions of the MCNP code - MCNP4C, MCNP5, and MCNPX. In these simulations for each source type, the source and phantom geometries, as well as the number of the photons, were kept identical, thus eliminating the possible uncertainties. The results of these investigations indicate that for low-energy sources such as 125I and 103Pd there are discrepancies in gL(r) values. Discrepancies up to 21.7% and 28% are observed between MCNP4C and other codes at a distance of 6 cm for 103Pd and 10 cm for 125I from the source, respectively. However, for higher energy sources, the discrepancies in gL(r) values are less than 1.1% for 192Ir and less than 1.2% for 137Cs between the three codes.
Logistics Support Analysis Techniques Guide
1985-03-15
LANGUAGE (DATA RECORDS) FORTRAN CDC 6600 D&V FSD P/D A H REMA-RKS: Program n-s-ists of F PLIATIffIONS, approx 4000 line of coding , 3 Safegard, AN/FSC... FORTRAN IV -EW-RAK9-- The model consz.sts of IT--k-LIC- I-U-0NS: approximately 367 lines of SiNCGARS, PERSHING II coding . %.’. ~ LSA TASK INTERFACE...system supported by Computer’ Systems Command. The current version of LADEN is coded totally in FORTRAN for virtual memory operating system
Applied Computational Electromagnetics Society Journal and Newletter, Volume 14 No. 1
1999-03-01
code validation, performance analysis, and input/output standardization; code or technique optimization and error minimization; innovations in...SOUTH AFRICA Alamo, CA, 94507-0516 USA Washington, DC 20330 USA MANAGING EDITOR Kueichien C. Hill Krishna Naishadham Richard W. Adler Wright Laboratory...INSTITUTIONAL MEMBERS ALLGON DERA Nasvagen 17 Common Road, Funtington INNOVATIVE DYNAMICS Akersberga, SWEDEN S-18425 Chichester, P018 9PD UK 2560 N. Triphammer
78 FR 22034 - Proposed Collection; Comment Request for Notice 2001-1
Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-12
... Notice 2001-1, Employer-designed Tip Reporting Program for the Food and Beverage Industry (EmTRAC). DATES... Program for the Food and Beverage Industry (EmTRAC). OMB Number: 1545-1716. Notice Number: Notice 2001-1...
IVHS Institutional and Legal Issues Program: Review of the FAST-TRAC Operational Test
DOT National Transportation Integrated Search
1994-06-01
The FAST-TRAC (Faster and Safer Travel through Traffic Routing and Advanced Controls) operational test attempted to integrate advanced traveler information systems (ATIS) and advanced traffic management system (ATMS) technologies in Oakland County, M...
Ebe, Kazuyu; Sugimoto, Satoru; Utsunomiya, Satoru; Kagamu, Hiroshi; Aoyama, Hidefumi; Court, Laurence; Tokuyama, Katsuichi; Baba, Ryuta; Ogihara, Yoshisada; Ichikawa, Kosuke; Toyama, Joji
2015-08-01
To develop and evaluate a new video image-based QA system, including in-house software, that can display a tracking state visually and quantify the positional accuracy of dynamic tumor tracking irradiation in the Vero4DRT system. Sixteen trajectories in six patients with pulmonary cancer were obtained with the ExacTrac in the Vero4DRT system. Motion data in the cranio-caudal direction (Y direction) were used as the input for a programmable motion table (Quasar). A target phantom was placed on the motion table, which was placed on the 2D ionization chamber array (MatriXX). Then, the 4D modeling procedure was performed on the target phantom during a reproduction of the patient's tumor motion. A substitute target with the patient's tumor motion was irradiated with 6-MV x-rays under the surrogate infrared system. The 2D dose images obtained from the MatriXX (33 frames/s; 40 s) were exported to in-house video-image analyzing software. The absolute differences in the Y direction between the center of the exposed target and the center of the exposed field were calculated. Positional errors were observed. The authors' QA results were compared to 4D modeling function errors and gimbal motion errors obtained from log analyses in the ExacTrac to verify the accuracy of their QA system. The patients' tumor motions were evaluated in the wave forms, and the peak-to-peak distances were also measured to verify their reproducibility. Thirteen of sixteen trajectories (81.3%) were successfully reproduced with Quasar. The peak-to-peak distances ranged from 2.7 to 29.0 mm. Three trajectories (18.7%) were not successfully reproduced due to the limited motions of the Quasar. Thus, 13 of 16 trajectories were summarized. The mean number of video images used for analysis was 1156. The positional errors (absolute mean difference + 2 standard deviation) ranged from 0.54 to 1.55 mm. The error values differed by less than 1 mm from 4D modeling function errors and gimbal motion errors in the ExacTrac log analyses (n = 13). The newly developed video image-based QA system, including in-house software, can analyze more than a thousand images (33 frames/s). Positional errors are approximately equivalent to those in ExacTrac log analyses. This system is useful for the visual illustration of the progress of the tracking state and for the quantification of positional accuracy during dynamic tumor tracking irradiation in the Vero4DRT system.
Lin, Chien-Ming; Fan, Hueng-Chuen; Chao, Tsu-Yi; Chu, Der-Ming; Lai, Chi-Chieh; Wang, Chih-Chien; Chen, Shyi-Jou
2016-05-03
Children with longstanding use of antiepileptic drugs (AEDs) are susceptible to developing low bone mineral density and an increased fracture risk. However, the literature regarding the effects of AEDs on growth in epileptic children is limited. The aim of this study was to investigate the potential effects of valproate (VPA) and/or oxcarbazepine (OXC) therapy on growth velocity and bone metabolism. Seventy-three ambulatory children (40 boys and 33 girls) with epilepsy, aged between 1 and 18 years (mean age 9.8 ± 4.1 years), were evaluated for growth velocity before and for 1 year after VPA and/or OXC treatment. The bone resorption marker serum tartrate-resistant acid phosphatase 5b (TRAcP5b) and the bone formation marker serum bone-specific alkaline phosphatase (BAP) were measured post-AEDs therapy for 1 year. The difference in growth velocity (ΔHt) and body weight change (ΔWt) between pre- and post-AEDs treatment were -1.0 ± 2.8 cm/year (P < 0.05) and 0.1 ± 3.9 kg/year (P = 0.84), respectively. The study population had serum TRAcP5b-SDS of -1.6 ± 1.2 and BAP-SDS of 1.7 ± 3.7 compared with sex- and age-matched healthy children. Significant correlation between serum TRAcP 5b and BAP activities was noted (r = 0.60, p < 0.001). There was a positive correlation between growth velocity and serum TRAcP 5b activity after AED treatment (r = 0.42, p < 0.01). No correlation was found between ΔHt, ΔWt, serum TRAcP 5b, BAP activity and types of AEDs. Growth velocity was significantly decreased in epileptic children after 1 year of VPA and/or OXC treatment. The effect of VPA and/or OXC therapy on dysregulation of bone metabolism might play a crucial role in physical growth.
A model of systems integration to facilitate ITS deployment : FAST-TRAC phase IV deliverable
DOT National Transportation Integrated Search
2003-04-01
The FAST-TRAC (Faster and Safer Travel through Traffic Routing and Advanced Controls) Intelligent Transportation Systems (ITS) Field Test in Oakland County, an urbanized county in metropolitan Detroit, represents a large and successful systems integr...
Hazardous chemical tracking system (HAZ-TRAC)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bramlette, J D; Ewart, S M; Jones, C E
Westinghouse Idaho Nuclear Company, Inc. (WINCO) developed and implemented a computerized hazardous chemical tracking system, referred to as Haz-Trac, for use at the Idaho Chemical Processing Plant (ICPP). Haz-Trac is designed to provide a means to improve the accuracy and reliability of chemical information, which enhances the overall quality and safety of ICPP operations. The system tracks all chemicals and chemical components from the time they enter the ICPP until the chemical changes form, is used, or becomes a waste. The system runs on a Hewlett-Packard (HP) 3000 Series 70 computer. The system is written in COBOL and uses VIEW/3000,more » TurboIMAGE/DBMS 3000, OMNIDEX, and SPEEDWARE. The HP 3000 may be accessed throughout the ICPP, and from remote locations, using data communication lines. Haz-Trac went into production in October, 1989. Currently, over 1910 chemicals and chemical components are tracked on the system. More than 2500 personnel hours were saved during the first six months of operation. Cost savings have been realized by reducing the time needed to collect and compile reporting information, identifying and disposing of unneeded chemicals, and eliminating duplicate inventories. Haz-Trac maintains information required by the Superfund Amendment Reauthorization Act (SARA), the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) and the Occupational Safety and Health Administration (OSHA).« less
Is ExacTrac x-ray system an alternative to CBCT for positioning patients with head and neck cancers?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Clemente, Stefania; Chiumento, Costanza; Fiorentino, Alba
Purpose: To evaluate the usefulness of a six-degrees-of freedom (6D) correction using ExacTrac robotics system in patients with head-and-neck (HN) cancer receiving radiation therapy.Methods: Local setup accuracy was analyzed for 12 patients undergoing intensity-modulated radiation therapy (IMRT). Patient position was imaged daily upon two different protocols, cone-beam computed tomography (CBCT), and ExacTrac (ET) images correction. Setup data from either approach were compared in terms of both residual errors after correction and punctual displacement of selected regions of interest (Mandible, C2, and C6 vertebral bodies).Results: On average, both protocols achieved reasonably low residual errors after initial correction. The observed differences inmore » shift vectors between the two protocols showed that CBCT tends to weight more C2 and C6 at the expense of the mandible, while ET tends to average more differences among the different ROIs.Conclusions: CBCT, even without 6D correction capabilities, seems preferable to ET for better consistent alignment and the capability to see soft tissues. Therefore, in our experience, CBCT represents a benchmark for positioning head and neck cancer patients.« less
Whole exome sequencing of rare variants in EIF4G1 and VPS35 in Parkinson disease
Nuytemans, Karen; Bademci, Guney; Inchausti, Vanessa; Dressen, Amy; Kinnamon, Daniel D.; Mehta, Arpit; Wang, Liyong; Züchner, Stephan; Beecham, Gary W.; Martin, Eden R.; Scott, William K.
2013-01-01
Objective: Recently, vacuolar protein sorting 35 (VPS35) and eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) have been identified as 2 causal Parkinson disease (PD) genes. We used whole exome sequencing for rapid, parallel analysis of variations in these 2 genes. Methods: We performed whole exome sequencing in 213 patients with PD and 272 control individuals. Those rare variants (RVs) with <5% frequency in the exome variant server database and our own control data were considered for analysis. We performed joint gene-based tests for association using RVASSOC and SKAT (Sequence Kernel Association Test) as well as single-variant test statistics. Results: We identified 3 novel VPS35 variations that changed the coded amino acid (nonsynonymous) in 3 cases. Two variations were in multiplex families and neither segregated with PD. In EIF4G1, we identified 11 (9 nonsynonymous and 2 small indels) RVs including the reported pathogenic mutation p.R1205H, which segregated in all affected members of a large family, but also in 1 unaffected 86-year-old family member. Two additional RVs were found in isolated patients only. Whereas initial association studies suggested an association (p = 0.04) with all RVs in EIF4G1, subsequent testing in a second dataset for the driving variant (p.F1461) suggested no association between RVs in the gene and PD. Conclusions: We confirm that the specific EIF4G1 variation p.R1205H seems to be a strong PD risk factor, but is nonpenetrant in at least one 86-year-old. A few other select RVs in both genes could not be ruled out as causal. However, there was no evidence for an overall contribution of genetic variability in VPS35 or EIF4G1 to PD development in our dataset. PMID:23408866
NASA Astrophysics Data System (ADS)
Jellali, Nabiha; Najjar, Monia; Ferchichi, Moez; Rezig, Houria
2017-07-01
In this paper, a new two-dimensional spectral/spatial codes family, named two dimensional dynamic cyclic shift codes (2D-DCS) is introduced. The 2D-DCS codes are derived from the dynamic cyclic shift code for the spectral and spatial coding. The proposed system can fully eliminate the multiple access interference (MAI) by using the MAI cancellation property. The effect of shot noise, phase-induced intensity noise and thermal noise are used to analyze the code performance. In comparison with existing two dimensional (2D) codes, such as 2D perfect difference (2D-PD), 2D Extended Enhanced Double Weight (2D-Extended-EDW) and 2D hybrid (2D-FCC/MDW) codes, the numerical results show that our proposed codes have the best performance. By keeping the same code length and increasing the spatial code, the performance of our 2D-DCS system is enhanced: it provides higher data rates while using lower transmitted power and a smaller spectral width.
Impact of glucocerebrosidase mutations on motor and nonmotor complications in Parkinson's disease.
Oeda, Tomoko; Umemura, Atsushi; Mori, Yuko; Tomita, Satoshi; Kohsaka, Masayuki; Park, Kwiyoung; Inoue, Kimiko; Fujimura, Harutoshi; Hasegawa, Hiroshi; Sugiyama, Hiroshi; Sawada, Hideyuki
2015-12-01
Homozygous mutations of the glucocerebrosidase gene (GBA) cause Gaucher disease (GD), and heterozygous mutations of GBA are a major risk factor for Parkinson's disease (PD). This study examined the impact of GBA mutations on the longitudinal clinical course of PD patients by retrospective cohort design. GBA-coding regions were fully sequenced in 215 PD patients and GD-associated GBA mutations were identified in 19 (8.8%) PD patients. In a retrospective cohort study, time to develop dementia, psychosis, wearing-off, and dyskinesia were examined. Survival time analysis followed a maximum 12-year observation (median 6.0 years), revealing that PD patients with GD-associated mutations developed dementia and psychosis significantly earlier than those without mutations (p < 0.001 and p = 0.017, respectively). Adjusted hazard ratios of GBA mutations were 8.3 for dementia (p < 0.001) and 3.1 for psychosis (p = 0.002). No statistically significant differences were observed for wearing-off and dyskinesia between the groups. N-isopropyl-p[(123)I] iodoamphetamine single-photon emission tomography pixel-by-pixel analysis revealed that regional cerebral blood flow was reduced in the bilateral parietal cortex, including the precuneus of GD-associated mutant PD patients, compared with matched PD controls without mutations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Variation in GIGYF2 is not associated with Parkinson disease.
Nichols, W C; Kissell, D K; Pankratz, N; Pauciulo, M W; Elsaesser, V E; Clark, K A; Halter, C A; Rudolph, A; Wojcieszek, J; Pfeiffer, R F; Foroud, T
2009-06-02
A recent study reported that mutations in a gene on chromosome 2q36-37, GIGYF2, result in Parkinson disease (PD). We have previously reported linkage to this chromosomal region in a sample of multiplex PD families, with the strongest evidence of linkage obtained using the subset of the sample having the strongest family history of disease and meeting the strictest diagnostic criteria. We have tested whether mutations in GIGYF2 may account for the previously observed linkage finding. We sequenced the GIGYF2 coding region in 96 unrelated patients with PD used in our original study that contributed to the chromosome 2q36-37 linkage signal. Subsequently, we genotyped the entire sample of 566 multiplex PD kindreds as well as 1,447 controls to test whether variants in GIGYF2 are causative or increase susceptibility for PD. We detected three novel variants as well as one of the previously reported seven variants in a total of five multiple PD families; however, there was no consistent evidence that these variants segregated with PD in these families. We also did not find a significant increase in risk for PD among those inheriting variants in GIGYF2 (p = 0.28). We believe that variation in a gene other than GIGYF2 accounts for the previously reported linkage finding on chromosome 2q36-37.
PD5: a general purpose library for primer design software.
Riley, Michael C; Aubrey, Wayne; Young, Michael; Clare, Amanda
2013-01-01
Complex PCR applications for large genome-scale projects require fast, reliable and often highly sophisticated primer design software applications. Presently, such applications use pipelining methods to utilise many third party applications and this involves file parsing, interfacing and data conversion, which is slow and prone to error. A fully integrated suite of software tools for primer design would considerably improve the development time, the processing speed, and the reliability of bespoke primer design software applications. The PD5 software library is an open-source collection of classes and utilities, providing a complete collection of software building blocks for primer design and analysis. It is written in object-oriented C(++) with an emphasis on classes suitable for efficient and rapid development of bespoke primer design programs. The modular design of the software library simplifies the development of specific applications and also integration with existing third party software where necessary. We demonstrate several applications created using this software library that have already proved to be effective, but we view the project as a dynamic environment for building primer design software and it is open for future development by the bioinformatics community. Therefore, the PD5 software library is published under the terms of the GNU General Public License, which guarantee access to source-code and allow redistribution and modification. The PD5 software library is downloadable from Google Code and the accompanying Wiki includes instructions and examples: http://code.google.com/p/primer-design.
78 FR 37877 - Request for Transit Rail Advisory Committee for Safety (TRACS) Nominations
Federal Register 2010, 2011, 2012, 2013, 2014
2013-06-24
... transportation as FTA implements new statutory authority for public transportation safety oversight. FOR FURTHER... public transportation. Therefore, TRACS membership will be reconfigured to reflect a broader range of... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Request for Transit Rail Advisory...
NASA Technical Reports Server (NTRS)
Everett, L.
1992-01-01
This report documents the performance characteristics of a Targeting Reflective Alignment Concept (TRAC) sensor. The performance will be documented for both short and long ranges. For long ranges, the sensor is used without the flat mirror attached to the target. To better understand the capabilities of the TRAC based sensors, an engineering model is required. The model can be used to better design the system for a particular application. This is necessary because there are many interrelated design variables in application. These include lense parameters, camera, and target configuration. The report presents first an analytical development of the performance, and second an experimental verification of the equations. In the analytical presentation it is assumed that the best vision resolution is a single pixel element. The experimental results suggest however that the resolution is better than 1 pixel. Hence the analytical results should be considered worst case conditions. The report also discusses advantages and limitations of the TRAC sensor in light of the performance estimates. Finally the report discusses potential improvements.
2011-01-01
and G. Armitage. Dening and evaluating greynets (sparse darknets ). In LCN: Proceedings of the IEEE Conference on Local Computer Networks 30th...analysis of distributed darknet trac. In IMC: Proceedings of the USENIX/ACM Internet Measurement Conference, 2005. Indexing Full Packet Capture Data
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tseng, T; Sheu, R; Todorov, B
2014-06-15
Purpose: To evaluate initial setup accuracy for stereotactic radiosurgery (SRS) between Brainlab frame-based and frameless immobilization system, also to discern the magnitude frameless system has on setup parameters. Methods: The correction shifts from the original setup were compared for total 157 SRS cranial treatments (69 frame-based vs. 88 frameless). All treatments were performed on a Novalis linac with ExacTrac positioning system. Localization box with isocenter overlay was used for initial setup and correction shift was determined by ExacTrac 6D auto-fusion to achieve submillimeter accuracy for treatment. For frameless treatments, mean time interval between simulation and treatment was 5.7 days (rangemore » 0–13). Pearson Chi-Square was used for univariate analysis. Results: The correctional radial shifts (mean±STD, median) for the frame and frameless system measured by ExacTrac were 1.2±1.2mm, 1.1mm and 3.1±3.3mm, 2.0mm, respectively. Treatments with frameless system had a radial shift >2mm more often than those with frames (51.1% vs. 2.9%; p<.0001). To achieve submillimeter accuracy, 85.5% frame-based treatments did not require shift and only 23.9% frameless treatment could succeed with initial setup. There was no statistical significant system offset observed in any direction for either system. For frameless treatments, those treated ≥ 3 days from simulation had statistically higher rates of radial shifts between 1–2mm and >2mm compared to patients treated in a shorter amount of time from simulation (34.3% and 56.7% vs. 28.6% and 33.3%, respectively; p=0.006). Conclusion: Although image-guided positioning system can also achieve submillimeter accuracy for frameless system, users should be cautious regarding the inherent uncertainty of its capability of immobilization. A proper quality assurance procedure for frameless mask manufacturing and a protocol for intra-fraction imaging verification will be crucial for frameless system. Time interval between simulation and treatment was influential to initial setup accuracy. A shorter time frame for frameless SRS treatment could be helpful in minimizing uncertainties in localization.« less
Zaker, Neda; Sina, Sedigheh; Koontz, Craig; Meigooni1, Ali S.
2016-01-01
Monte Carlo simulations are widely used for calculation of the dosimetric parameters of brachytherapy sources. MCNP4C2, MCNP5, MCNPX, EGS4, EGSnrc, PTRAN, and GEANT4 are among the most commonly used codes in this field. Each of these codes utilizes a cross‐sectional library for the purpose of simulating different elements and materials with complex chemical compositions. The accuracies of the final outcomes of these simulations are very sensitive to the accuracies of the cross‐sectional libraries. Several investigators have shown that inaccuracies of some of the cross section files have led to errors in 125I and 103Pd parameters. The purpose of this study is to compare the dosimetric parameters of sample brachytherapy sources, calculated with three different versions of the MCNP code — MCNP4C, MCNP5, and MCNPX. In these simulations for each source type, the source and phantom geometries, as well as the number of the photons, were kept identical, thus eliminating the possible uncertainties. The results of these investigations indicate that for low‐energy sources such as 125I and 103Pd there are discrepancies in gL(r) values. Discrepancies up to 21.7% and 28% are observed between MCNP4C and other codes at a distance of 6 cm for 103Pd and 10 cm for 125I from the source, respectively. However, for higher energy sources, the discrepancies in gL(r) values are less than 1.1% for 192Ir and less than 1.2% for 137Cs between the three codes. PACS number(s): 87.56.bg PMID:27074460
Ditrói, F; Tárkányi, F; Takács, S; Hermanne, A; Ignatyuk, A V
2017-10-01
Excitation functions were measured in the 31-49.2MeV energy range for the nat Pd(d,xn) 111,110m,106m,105,104g,103 Ag, nat Pd(d,x) 111m,109,101,100 Pd, nat Pd(d,x), 105,102m,102g,101m,101g,100,99m,99g Rh and nat Pd(d,x) 103,97 Ru nuclear reactions by using the stacked foil irradiation technique. The experimental results are compared with our previous results and with the theoretical predictions calculated with the ALICE-D, EMPIRE-D and TALYS (TENDL libraries) codes. Copyright © 2017 Elsevier Ltd. All rights reserved.
Evaluation of user perceptions and behaviors of Fast-Trac : pilot study results
DOT National Transportation Integrated Search
1996-01-01
The purpose of the User Perceptions and Behaviors evaluation component of FAST-TRAC is to understand how users perceive and value the in-vehicle navigation system, ALI-SCOUT, and to determine how the system is used in the Oakland County study area. S...
TRAC, a collaborative computer tool for tracer-test interpretation
NASA Astrophysics Data System (ADS)
Gutierrez, A.; Klinka, T.; Thiéry, D.; Buscarlet, E.; Binet, S.; Jozja, N.; Défarge, C.; Leclerc, B.; Fécamp, C.; Ahumada, Y.; Elsass, J.
2013-05-01
Artificial tracer tests are widely used by consulting engineers for demonstrating water circulation, proving the existence of leakage, or estimating groundwater velocity. However, the interpretation of such tests is often very basic, with the result that decision makers and professionals commonly face unreliable results through hasty and empirical interpretation. There is thus an increasing need for a reliable interpretation tool, compatible with the latest operating systems and available in several languages. BRGM, the French Geological Survey, has developed a project together with hydrogeologists from various other organizations to build software assembling several analytical solutions in order to comply with various field contexts. This computer program, called TRAC, is very light and simple, allowing the user to add his own analytical solution if the formula is not yet included. It aims at collaborative improvement by sharing the tool and the solutions. TRAC can be used for interpreting data recovered from a tracer test as well as for simulating the transport of a tracer in the saturated zone (for the time being). Calibration of a site operation is based on considering the hydrodynamic and hydrodispersive features of groundwater flow as well as the amount, nature and injection mode of the artificial tracer. The software is available in French, English and Spanish, and the latest version can be downloaded from the web site http://trac.brgm.fr">http://trac.brgm.fr.
Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jusakul, Apinya; Cutcutache, Ioana; Yong, Chern Han
Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analysed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined four CCA clusters - Fluke- Positive CCAs (Clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations, conversely Fluke-Negative CCAs (Clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3’UTR deletion as a mechanism of FGFR2 upregulation. Integration of non-coding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation ofmore » H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores - mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Lastly, our results exemplify how genetics, epigenetics and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer.« less
Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma
Jusakul, Apinya; Cutcutache, Ioana; Yong, Chern Han; ...
2017-06-30
Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analysed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined four CCA clusters - Fluke- Positive CCAs (Clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations, conversely Fluke-Negative CCAs (Clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3’UTR deletion as a mechanism of FGFR2 upregulation. Integration of non-coding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation ofmore » H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores - mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Lastly, our results exemplify how genetics, epigenetics and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer.« less
Identifying autism early: The Toddlers at Risk of Autism Clinic model.
Davis, Tessa; Clifton, Deirdre; Papadopoulos, Con
2015-07-01
This paper describes the Toddlers at Risk of Autism Clinic (TRAC), which utilises the Social Attention and Communication Study (SACS) and/or Autism Detection in Early Childhood (ADEC) play-based assessments to facilitate the early diagnosis of autism. A retrospective audit was conducted of all 42 children assessed over a 3-year period in the TRAC. A semi-structured interview and play-based assessment (SACS and ADEC) were used to aid experienced clinicians in diagnosing autism. Intervention was recommended, and families were routinely followed up. Analysis was conducted on the tools used, the outcomes of assessment, diagnosis and stability of diagnosis on follow-up. During this period, 35 boys and 7 girls were assessed, with a mean age of 25 months. The average waiting time for clinic was 11.6 weeks. Twenty-five patients were diagnosed with autism; 90.5% of toddlers given an initial diagnosis retained that diagnosis at follow-up. Out of the 17 children who were not diagnosed with autism in the TRAC, one child was later diagnosed with autism. Experienced clinicians can use the SACS and/or ADEC to assist with a Diagnostic and Statistical Manual diagnosis of autism in toddlers. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
Analysis of corridor delay under SCATS control : FAST-TRAC Phase III deliverable
DOT National Transportation Integrated Search
1998-04-01
The study was designed to determine the change in travel time following the implementation of the Sydney Coordinated Adaptive Traffic System (SCATS) in Oakland County, Michigan. A before/after comparison was used to examine the change in travel time ...
Mutations in the GIGYF2 (TNRC15) Gene at the PARK11 Locus in Familial Parkinson Disease
Lautier, Corinne; Goldwurm, Stefano; Dürr, Alexandra; Giovannone, Barbara; Tsiaras, William G.; Pezzoli, Gianni; Brice, Alexis; Smith, Robert J.
2008-01-01
The genetic basis for association of the PARK11 region of chromosome 2 with familial Parkinson disease (PD) is unknown. This study examined the GIGYF2 (Grb10-Interacting GYF Protein-2) (TNRC15) gene, which contains the PARK11 microsatellite marker with the highest linkage score (D2S206, LOD 5.14). The 27 coding exons of the GIGYF2 gene were sequenced in 123 Italian and 126 French patients with familial PD, plus 131 Italian and 96 French controls. A total of seven different GIGYF2 missense mutations resulting in single amino acid substitutions were present in 12 unrelated PD index patients (4.8%) and not in controls. Three amino acid insertions or deletions were found in four other index patients and absent in controls. Specific exon sequencing showed that these ten sequence changes were absent from a further 91 controls. In four families with amino acid substitutions in which at least one other PD case was available, the GIGYF2 mutations (Asn56Ser, Thr112Ala, and Asp606Glu) segregated with PD. There were, however, two unaffected carriers in one family, suggesting age-dependent or incomplete penetrance. One index case (PD onset age 33) inherited a GIGYF2 mutation (Ile278Val) from her affected father (PD onset age 66) and a previously described PD-linked mutation in the LRRK2 gene (Ile1371Val) from her affected mother (PD onset age 61). The earlier onset and severe clinical course in the index patient suggest additive effects of the GIGYF2 and LRRK2 mutations. These data strongly support GIGYF2 as a PARK11 gene with a causal role in familial PD. PMID:18358451
75 FR 51523 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)
Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-20
... Administration (FTA) on matters pertaining to the safety of public transportation systems. TRACS is composed of... Administration Eric Cheng, Utah Department of Transportation Richard W. Clark, California Public Utilities... Grizard, American Public Transportation Association Leonard Hardy, Bay Area Transit Authority Henry...
76 FR 16854 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)
Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-25
... Secretary and the Federal Transit Administrator on matters relating to the safety of public transportation... to the safety of public transportation systems. TRACS is composed of 21 members representing a broad... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Notice of Meeting of the Transit Rail...
A Comparison of Measured and Predicted XV-15 Tiltrotor Surface Acoustic Pressures
NASA Technical Reports Server (NTRS)
Lyle, Karen H.; Burley, Casey L.; Prichard, Devon S.
1997-01-01
Predicted XV-15 exterior surface acoustic pressures are compared with previously published experimental data. Surface acoustic pressure transducers were concentrated near the tip-path-plane of the rotor in airplane mode. The comparison emphasized cruise conditions which are of interest for tiltrotor interior noise - level flight for speeds ranging from 72 m/s to 113 m/s. The predictions were produced by components of the NASA Langley Tiltrotor Aeroacoustic Code (TRAC) system of computer codes. Comparisons between measurements and predictions were made in both the time and frequency domains, as well as overall sound pressure levels. In general, the predictions replicated the measured data well. Discrepancies between measurements and predictions were noted. Some of the discrepancies were due to poor correlation of the measured data with the rotor tach signal. In other cases limitations of the predictive methodology have been indicated.
DOT National Transportation Integrated Search
1996-12-01
This report contains the results of an analysis of : traffic accidents in the City of Troy, Michigan, where : the Sydney Coordinated Adaptive Traffic System : (SCATS) was deployed as part of a federal demonstration : program. The analyses includes a ...
Soreq, Lilach; Guffanti, Alessandro; Salomonis, Nathan; Simchovitz, Alon; Israel, Zvi; Bergman, Hagai; Soreq, Hermona
2014-01-01
The continuously prolonged human lifespan is accompanied by increase in neurodegenerative diseases incidence, calling for the development of inexpensive blood-based diagnostics. Analyzing blood cell transcripts by RNA-Seq is a robust means to identify novel biomarkers that rapidly becomes a commonplace. However, there is lack of tools to discover novel exons, junctions and splicing events and to precisely and sensitively assess differential splicing through RNA-Seq data analysis and across RNA-Seq platforms. Here, we present a new and comprehensive computational workflow for whole-transcriptome RNA-Seq analysis, using an updated version of the software AltAnalyze, to identify both known and novel high-confidence alternative splicing events, and to integrate them with both protein-domains and microRNA binding annotations. We applied the novel workflow on RNA-Seq data from Parkinson's disease (PD) patients' leukocytes pre- and post- Deep Brain Stimulation (DBS) treatment and compared to healthy controls. Disease-mediated changes included decreased usage of alternative promoters and N-termini, 5′-end variations and mutually-exclusive exons. The PD regulated FUS and HNRNP A/B included prion-like domains regulated regions. We also present here a workflow to identify and analyze long non-coding RNAs (lncRNAs) via RNA-Seq data. We identified reduced lncRNA expression and selective PD-induced changes in 13 of over 6,000 detected leukocyte lncRNAs, four of which were inversely altered post-DBS. These included the U1 spliceosomal lncRNA and RP11-462G22.1, each entailing sequence complementarity to numerous microRNAs. Analysis of RNA-Seq from PD and unaffected controls brains revealed over 7,000 brain-expressed lncRNAs, of which 3,495 were co-expressed in the leukocytes including U1, which showed both leukocyte and brain increases. Furthermore, qRT-PCR validations confirmed these co-increases in PD leukocytes and two brain regions, the amygdala and substantia-nigra, compared to controls. This novel workflow allows deep multi-level inspection of RNA-Seq datasets and provides a comprehensive new resource for understanding disease transcriptome modifications in PD and other neurodegenerative diseases. PMID:24651478
77 FR 5876 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)
Federal Register 2010, 2011, 2012, 2013, 2014
2012-02-06
... the safety of public transportation systems. TRACS is comprised of 26 members, including 7 new members... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Notice of Meeting of the Transit Rail... meeting. SUMMARY: This notice announces a public meeting of the Transit Rail Advisory Committee for Safety...
78 FR 28285 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)
Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-14
... the safety of public transportation systems. TRACS is composed of 24 members representing a broad base... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Notice of Meeting of the Transit Rail... meeting. SUMMARY: This notice announces a public meeting of the Transit Rail Advisory Committee for Safety...
78 FR 67212 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)
Federal Register 2010, 2011, 2012, 2013, 2014
2013-11-08
... the safety of public transportation systems. DATES: The TRACS meeting will be held on November 21... Letter Report on the Development of the National Public Transportation Safety Plan (4) Review of the Draft Letter Report on Public Transportation Agency Plans (5) Public Comments (6) Wrap Up As previously...
A comparison of two types of running wheel in terms of mouse preference, health, and welfare.
Walker, Michael; Mason, Georgia
2018-07-01
Voluntary wheel running occurs in mice of all strains, sexes, and ages. Mice find voluntary wheel running rewarding, and it leads to numerous health benefits. For this reason wheels are used both to enhance welfare and to create models of exercise. However, many designs of running wheel are used. This makes between-study comparisons difficult, as this variability could potentially affect the amount, pattern, and/or intensity of running behaviour, and thence the wheels' effects on welfare and exercise-related changes in anatomy and physiology. This study therefore evaluated two commercially available models, chosen because safe for group-housed mice: Bio Serv®'s "fast-trac" wheel combo and Ware Manufacturing Inc.'s stainless steel mesh 5″ upright wheel. Working with a total of three hundred and fifty one female C57BL/6, DBA/2 and BALB/c mice, we assessed these wheels' relative utilization by mice when access was free; the strength of motivation for each wheel-type when access required crossing an electrified grid; and the impact each wheel had on mouse well-being (inferred from acoustic startle responses and neophobia) and exercise-related anatomical changes (BMI; heart and hind limb masses). Mice ran more on the "fast-trac" wheel regardless of whether both wheel-types were available at once, or only if one was present. In terms of motivation, subjects required to work to access a single wheel worked equally hard for both wheel-types (even if locked and thus not useable for running), but if provided with one working wheel for free and the other type of wheel (again unlocked) accessible via crossing the electrified grid, the "fast-trac" wheel emerged as more motivating, as the Maximum Price Paid for the Ware metal wheel was lower than that paid for the "fast-trac" plastic wheel, at least for C57BL/6s and DBA/2s. No deleterious consequences were noted with either wheel in terms of health and welfare, but only mice with plastic wheels developed significantly larger hearts and hind limbs than control animals with locked wheels. Thus, where differences emerged, Bio Serv®'s "fast-trac" wheel combos appeared to better meet the aims of exercise provision than Ware Manufacturing's steel upright wheels. Copyright © 2018 Elsevier Inc. All rights reserved.
Keeping Track Every Step of the Way
NASA Technical Reports Server (NTRS)
2001-01-01
Knowledge Sharing Systems, Inc., a producer of intellectual assets management software systems for the federal government, universities, non-profit laboratories, and private companies, constructed and presently manages the NASA Technology Tracking System, also known as TechTracS. Under contract to Langley Research Center, TechTracS identifies and captures all NASA technologies, manages the patent prosecution process, and then tracks their progress en route to commercialization. The system supports all steps involved in various technology transfer activities, and is considered the premier intellectual asset management system used in the federal government today. NASA TechTracS consists of multiple relational databases and web servers, located at each of the 10 field centers, as well as NASA Headquarters. The system is capable of supporting the following functions: planning commercial technologies; commercialization activities; reporting new technologies and inventions; and processing and tracking intellectual property rights, licensing, partnerships, awards, and success stories. NASA TechTracS is critical to the Agency's ongoing mission to commercialize its revolutionary technologies in a variety of sectors within private industry, both aerospace and non- aerospace.
Role of LRRK2 and SNCA in autosomal dominant Parkinson's disease in Turkey.
Kessler, Christoph; Atasu, Burcu; Hanagasi, Hasmet; Simón-Sánchez, Javier; Hauser, Ann-Kathrin; Pak, Meltem; Bilgic, Basar; Erginel-Unaltuna, Nihan; Gurvit, Hakan; Gasser, Thomas; Lohmann, Ebba
2018-03-01
Mutations in the LRRK2 and alpha-synuclein (SNCA) genes are well-established causes of autosomal dominant Parkinson's disease (PD). However, their frequency differs widely between ethnic groups. Only three studies have screened all coding regions of LRRK2 and SNCA in European samples so far. In Turkey, the role of LRRK2 in Parkinson's disease has been studied fragmentarily, and the incidence of SNCA copy number variations is unknown. The purpose of this study is to determine the frequency of LRRK2 and SNCA mutations in autosomal dominant PD in Turkey. We performed Sanger sequencing of all coding LRRK2 and SNCA exons in a sample of 91 patients with Parkinsonism. Copy number variations in SNCA, PRKN, PINK1, DJ1 and ATP13A2 were assessed using the MLPA method. All patients had a positive family history compatible with autosomal dominant inheritance. Known mutations in LRRK2 and SNCA were found in 3.3% of cases: one patient harbored the LRRK2 G2019S mutation, and two patients carried a SNCA gene duplication. Furthermore, we found a heterozygous deletion of PRKN exon 2 in one patient, and four rare coding variants of unknown significance (LRRK2: A211V, R1067Q, T2494I; SNCA: T72T). Genetic testing in one affected family identified the LRRK2 R1067Q variant as a possibly pathogenic substitution. Point mutations in LRRK2 and SNCA are a rare cause of autosomal dominant PD in Turkey. However, copy number variations should be considered. The unclassified variants, especially LRRK2 R1067Q, demand further investigation. Copyright © 2017. Published by Elsevier Ltd.
NASA Astrophysics Data System (ADS)
Bano, Amreen; Gaur, N. K.
2018-05-01
Ab-initio calculations are carried out to study the electronic and chemical bonding properties of Intermetallic full Heusler compound Pd2HfIn which crystallizes in F-43m structure. All calculations are performed by using density functional theory (DFT) based code Quantum Espresso. Generalized gradient approximations (GGA) of Perdew- Burke- Ernzerhof (PBE) have been adopted for exchange-correlation potential. Calculated electronic band structure reveals the metallic character of the compound. From partial density of states (PDoS), we found the presence of relatively high intensity electronic states of 4d-Pd atom at Fermi level. We have found a pseudo-gap just abouve the Fermi level and N(E) at Fermi level is observed to be 0.8 states/eV, these finding indicates the existence of superconducting character in Pd2HfIn.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ebe, Kazuyu, E-mail: nrr24490@nifty.com; Tokuyama, Katsuichi; Baba, Ryuta
Purpose: To develop and evaluate a new video image-based QA system, including in-house software, that can display a tracking state visually and quantify the positional accuracy of dynamic tumor tracking irradiation in the Vero4DRT system. Methods: Sixteen trajectories in six patients with pulmonary cancer were obtained with the ExacTrac in the Vero4DRT system. Motion data in the cranio–caudal direction (Y direction) were used as the input for a programmable motion table (Quasar). A target phantom was placed on the motion table, which was placed on the 2D ionization chamber array (MatriXX). Then, the 4D modeling procedure was performed on themore » target phantom during a reproduction of the patient’s tumor motion. A substitute target with the patient’s tumor motion was irradiated with 6-MV x-rays under the surrogate infrared system. The 2D dose images obtained from the MatriXX (33 frames/s; 40 s) were exported to in-house video-image analyzing software. The absolute differences in the Y direction between the center of the exposed target and the center of the exposed field were calculated. Positional errors were observed. The authors’ QA results were compared to 4D modeling function errors and gimbal motion errors obtained from log analyses in the ExacTrac to verify the accuracy of their QA system. The patients’ tumor motions were evaluated in the wave forms, and the peak-to-peak distances were also measured to verify their reproducibility. Results: Thirteen of sixteen trajectories (81.3%) were successfully reproduced with Quasar. The peak-to-peak distances ranged from 2.7 to 29.0 mm. Three trajectories (18.7%) were not successfully reproduced due to the limited motions of the Quasar. Thus, 13 of 16 trajectories were summarized. The mean number of video images used for analysis was 1156. The positional errors (absolute mean difference + 2 standard deviation) ranged from 0.54 to 1.55 mm. The error values differed by less than 1 mm from 4D modeling function errors and gimbal motion errors in the ExacTrac log analyses (n = 13). Conclusions: The newly developed video image-based QA system, including in-house software, can analyze more than a thousand images (33 frames/s). Positional errors are approximately equivalent to those in ExacTrac log analyses. This system is useful for the visual illustration of the progress of the tracking state and for the quantification of positional accuracy during dynamic tumor tracking irradiation in the Vero4DRT system.« less
Can dialysis patients be accurately identified using healthcare claims data?
Taneja, Charu; Berger, Ariel; Inglese, Gary W; Lamerato, Lois; Sloand, James A; Wolff, Greg G; Sheehan, Michael; Oster, Gerry
2014-01-01
While health insurance claims data are often used to estimate the costs of renal replacement therapy in patients with end-stage renal disease (ESRD), the accuracy of methods used to identify patients receiving dialysis - especially peritoneal dialysis (PD) and hemodialysis (HD) - in these data is unknown. The study population consisted of all persons aged 18 - 63 years in a large US integrated health plan with ESRD and dialysis-related billing codes (i.e., diagnosis, procedures) on healthcare encounters between January 1, 2005, and December 31, 2008. Using billing codes for all healthcare encounters within 30 days of each patient's first dialysis-related claim ("index encounter"), we attempted to designate each study subject as either a "PD patient" or "HD patient." Using alternative windows of ± 30 days, ± 90 days, and ± 180 days around the index encounter, we reviewed patients' medical records to determine the dialysis modality actually received. We calculated the positive predictive value (PPV) for each dialysis-related billing code, using information in patients' medical records as the "gold standard." We identified a total of 233 patients with evidence of ESRD and receipt of dialysis in healthcare claims data. Based on examination of billing codes, 43 and 173 study subjects were designated PD patients and HD patients, respectively (14 patients had evidence of PD and HD, and modality could not be ascertained for 31 patients). The PPV of codes used to identify PD patients was low based on a ± 30-day medical record review window (34.9%), and increased with use of ± 90-day and ± 180-day windows (both 67.4%). The PPV for codes used to identify HD patients was uniformly high - 86.7% based on ± 30-day review, 90.8% based on ± 90-day review, and 93.1% based on ± 180-day review. While HD patients could be accurately identified using billing codes in healthcare claims data, case identification was much more problematic for patients receiving PD. Copyright © 2014 International Society for Peritoneal Dialysis.
Code of Federal Regulations, 2013 CFR
2013-10-01
... Start field End field Record type 1 Numeric 1=Filing2=Cancellation B 1 1 Insurer number 8 Text FMCSA... Filing type 1 Numeric 1 = BI&PD2 = Cargo 3 = Bond 4 = Trust Fund B 10 10 FMCSA docket number 8 Text FMCSA... 264 265 Insured zip code 9 Numeric (Do not include dash if using 9 digit code) B 266 274 Insured...
Code of Federal Regulations, 2014 CFR
2014-10-01
... Start field End field Record type 1 Numeric 1=Filing2=Cancellation B 1 1 Insurer number 8 Text FMCSA... Filing type 1 Numeric 1 = BI&PD2 = Cargo 3 = Bond 4 = Trust Fund B 10 10 FMCSA docket number 8 Text FMCSA... 264 265 Insured zip code 9 Numeric (Do not include dash if using 9 digit code) B 266 274 Insured...
COMBATXXI: Usage and Analysis at TACOM
2011-06-20
Prescribed by ANSI Std Z39-18 Operational Effectiveness UNCLASSIFIED UNCLASSIFIED Outline Who We Are Our Equipment Our Customers COMBATXXI Model ...Research, Development and Engineering Center Our Customers 5 Operational Effectiveness UNCLASSIFIED UNCLASSIFIED Model Overview Combined Arms...Analysis Tool for the 21st Century (COMBATXXI) - Developed jointly by TRAC- White Sands Missle Range (WSMR) and Marine Corps Combat Development Command
Federal Register 2010, 2011, 2012, 2013, 2014
2012-09-04
..., LLC, Including On-Site Leased Workers From FirstStaff, Trac Staffing, and Worksource, Inc., Fort Smith... Staffing, Worksource, Inc., Fort Smith, Arkansas. The Department's notice of determination was published in... Worksource, Inc. were employed on-site at the Fort Smith, Arkansas location of River Bend Industries, LLC...
Automated Proposition Density Analysis for Discourse in Aphasia.
Fromm, Davida; Greenhouse, Joel; Hou, Kaiyue; Russell, G Austin; Cai, Xizhen; Forbes, Margaret; Holland, Audrey; MacWhinney, Brian
2016-10-01
This study evaluates how proposition density can differentiate between persons with aphasia (PWA) and individuals in a control group, as well as among subtypes of aphasia, on the basis of procedural discourse and personal narratives collected from large samples of participants. Participants were 195 PWA and 168 individuals in a control group from the AphasiaBank database. PWA represented 6 aphasia types on the basis of the Western Aphasia Battery-Revised (Kertesz, 2006). Narrative samples were stroke stories for PWA and illness or injury stories for individuals in the control group. Procedural samples were from the peanut-butter-and-jelly-sandwich task. Language samples were transcribed using Codes for the Human Analysis of Transcripts (MacWhinney, 2000) and analyzed using Computerized Language Analysis (MacWhinney, 2000), which automatically computes proposition density (PD) using rules developed for automatic PD measurement by the Computerized Propositional Idea Density Rater program (Brown, Snodgrass, & Covington, 2007; Covington, 2007). Participants in the control group scored significantly higher than PWA on both tasks. PD scores were significantly different among the aphasia types for both tasks. Pairwise comparisons for both discourse tasks revealed that PD scores for the Broca's group were significantly lower than those for all groups except Transcortical Motor. No significant quadratic or linear association between PD and severity was found. Proposition density is differentially sensitive to aphasia type and most clearly differentiates individuals with Broca's aphasia from the other groups.
Tang, F; Huang, Y L; Jiang, X; Jia, X F; Li, B; Feng, Y; Chen, Q Y; Tang, C F
2018-05-02
Objective: To reveal the molecular epidemiologic characteristics of glucose-6-phosphate dehydrogenase (G6PD) gene and to evaluate based on the genetic analysis the newborn screening program performance and enzymatic diagnosis of G6PD deficiency in Guangzhou. Methods: G6PD enzyme activities were measured by quantitative fluorescence assay in dry blood spots of 16 319 newborns(8 725 males, 7 594 females) 3-7 days after birth in Guangzhou Newborn Center. They were born in Guangzhou form Oct. 1 to 20, 2016. The cutoff value of G6PD was less than 2.6 U/g Hb in dry blood spots. G6PD deficiency was diagnosed when G6PD<1 700 U/L or G6PD/6PGD<1 in red blood cells. Genetic analysis of G6PD gene was performed on the dry blood spot samples of 823 newborns (including positive 346, negative 477)with various levels of G6PD enzyme activities through fluorescence PCR melting curve analysis(FMCA) to detect 15 kinds of mutations reported to be common among Chinese.G6PD gene Sanger sequency was performed in seven highly suspicious patients with negative results by FMCA. Results: (1) Using the cutoff value of G6PD< 2.6 U/g Hb , a total of 687(4.2%) newborns showed positive screening results, including 560 (6.4%) males and 127(1.7%) females. (2) Among the newborns with positive screening results, 214 males and 122 females were randomly chosen for G6PD gene analysis. The results showed that 197 (92.1%) males were hemizygote and 108(88.6%) females were mutation carriers with one to four alleles. Among the newborns with negative screening results, 41 males with G6PD 2.6-2.8 U/g Hb and 436 females with G6PD 2.6-4.5 U/g Hb were chosen for genetic analysis.Mutations were detected in 5(12.2%)boys, and 226(51.8%) girls were carriers.G6PD gene Sanger sequency of seven highly suspicious patients showed that c.406C>T, c.551C>T, c.835A>T hemizygote were found in 3 male's samples, respectively. (3) The estimated prevalence of harboring mutation was 6.0% in males and 13.5% in females according to rates of mutation in samples with various levels of G6PD enzyme activities. Six common mutations were c.1388G>A、c.1376G>T, c.95A> G, c.871G>A, c.1024C>T, c.392G>T, accounting for 95.5% of detected alleles .(4) based on results of G6PD gene analysis, the newborn scereening of G6PD deficiency with cutoff value G6PD<2.6 U/g Hb yielded a positive predict value(PPV) of 93.5%, a false-positive rate of 0.5%, and a sensitivity of 99.0% for males. A PPV of 88.5%, a false-positive rate of 0.2% . The prevalence of severe type G6PD deficiency in females was about 1.5%. Compared with to genetic analysis, the sensitivity and PPV of G6PD activity assay in red blood cells were 95.5%, 97.2%, respectively. Conclusions: The prevalence of G6PD deficiency in males was 6.0% in Guangzhou. Six mutations c.1388G>A, c.1376G>T, c.95A>G, c.871G>A, c.1024C>T, c.392G>T accounted for 95.5%. The cutoff value of G6PD<2.6 U/g Hb innewborn screening program and the criteria of biochemical diagnosis could accurately identify G6PD deficiency . Combined with biochemical and molecular analysis will improve the accuracy of diagnosis of G6PD deficiency and detect more heterozygous females.
Cappariello, Alfredo; Paone, Riccardo; Maurizi, Antonio; Capulli, Mattia; Rucci, Nadia; Muraca, Maurizio; Teti, Anna
2015-01-01
Deficiency of Receptor Activator of NF-κB Ligand (RANKL) prevents osteoclast formation causing osteopetrosis. RANKL is a membrane-bound protein cleaved into active soluble (s)RANKL by metalloproteinase 14 (MMP14). We created a bio-device that harbors primary osteoblasts, cultured on 3D hydroxyapatite scaffolds carrying immobilized MMP14 catalytic domain. Scaffolds were sealed in diffusion chambers and implanted in RANKL-deficient mice. Mice received 1 or 2 diffusion chambers, once or twice and were sacrificed after 1 or 2 months from implants. A progressive increase of body weight was observed in the implanted groups. Histological sections of tibias of non-implanted mice were negative for the osteoclast marker Tartrate-Resistant Acid Phosphatase (TRAcP), consistent with the lack of osteoclasts. In contrast, tibias excised from implanted mice showed TRAcP-positive cells in the bone marrow and on the bone surface, these latter morphologically similar to mature osteoclasts. In mice implanted with 4 diffusion chambers total, we noted the highest number and size of TRAcP-positive cells, with quantifiable eroded bone surface and significant reduction of trabecular bone volume. These data demonstrate that our bio-device delivers effective sRANKL, inducing osteoclastogenesis in RANKL-deficient mice, supporting the feasibility of an innovative experimental strategy to treat systemic cytokine deficiencies. PMID:25678116
Cappariello, Alfredo; Paone, Riccardo; Maurizi, Antonio; Capulli, Mattia; Rucci, Nadia; Muraca, Maurizio; Teti, Anna
2015-04-01
Deficiency of Receptor Activator of NF-κB Ligand (RANKL) prevents osteoclast formation causing osteopetrosis. RANKL is a membrane-bound protein cleaved into active soluble (s)RANKL by metalloproteinase 14 (MMP14). We created a bio-device that harbors primary osteoblasts, cultured on 3D hydroxyapatite scaffolds carrying immobilized MMP14 catalytic domain. Scaffolds were sealed in diffusion chambers and implanted in RANKL-deficient mice. Mice received 1 or 2 diffusion chambers, once or twice and were sacrificed after 1 or 2 months from implants. A progressive increase of body weight was observed in the implanted groups. Histological sections of tibias of non-implanted mice were negative for the osteoclast marker Tartrate-Resistant Acid Phosphatase (TRAcP), consistent with the lack of osteoclasts. In contrast, tibias excised from implanted mice showed TRAcP-positive cells in the bone marrow and on the bone surface, these latter morphologically similar to mature osteoclasts. In mice implanted with 4 diffusion chambers total, we noted the highest number and size of TRAcP-positive cells, with quantifiable eroded bone surface and significant reduction of trabecular bone volume. These data demonstrate that our bio-device delivers effective sRANKL, inducing osteoclastogenesis in RANKL-deficient mice, supporting the feasibility of an innovative experimental strategy to treat systemic cytokine deficiencies. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Land Warrior (LW)/Mounted Warrior (MW) DOTMLPF Assessment
2007-06-01
the DOTMLPF impacts of equipping a Stryker battalion with MW and LW? 3) What is the estimated life cycle cost (LCC) of each LW BOIP alternative? 4...A R E D A T A Assessed costs included: - Support Equipment/Disposal. - Contractor Logistics Support. - Ensemble Hardware...DOTMLPF . 3 - Cost . LUT Navigation Experiment Lethality Experiment AMSAA TRAC-WSMR TRAC-WSMR ATEC LW Test Unit
The study of structures and properties of PdnHm(n=1-10, m=1,2) clusters by density functional theory
NASA Astrophysics Data System (ADS)
Wen, Jun-Qing; Chen, Guo-Xiang; Zhang, Jian-Min; Wu, Hua
2018-04-01
The geometrical evolution, local relative stability, magnetism and charge transfer characteristics of PdnHm(n = 1-10, m = 1,2) have been systematically calculated by using density functional theory. The studied results show that the most stable geometries of PdnH and PdnH2 (n = 1-10) can be got by doping one or two H atoms on the sides of Pdn clusters except Pd6H and Pd6H2. It is found that doping one or two H atoms on Pdn clusters cannot change the basic framework of Pdn. The analysis of stability shows that Pd2H, Pd4H, Pd7H, Pd2H2, Pd4H2 and Pd7H2 clusters have higher local relative stability than neighboring clusters. The analysis of magnetic properties demonstrates that absorption of hydrogen atoms decreases the average atomic magnetic moments compared with pure Pdn clusters. More charges transfer from H atoms to Pd atoms for Pd6H and Pd6H2 clusters, demonstrating the adsorption of hydrogen atoms change from side adsorption to surface adsorption.
Rapid Analysis of Energetic and Geo-Materials Using Laser Induced Breakdown Spectroscopy
2013-04-01
et al ., Anal Bioanal Chem ( 2006 ) 385, 316. 5. Mohamed, W. T. Y., Prog Phys (2007) 2, 42. 6. Elhassan, A., et al ., Spectrochim Acta B (2008) 63...Anal (2005) 5, 21. 20. Anzano, J. M., et al ., Anal Chim Acta ( 2006 ) 575, 230. 21. Rusak, D. A., et al ., TrAC Trend Anal Chem (1998) 17, 453. 22. Martin...Spectrosc Reviews (2004) 39, 27. 25. Winefordner, J. D., et al ., J Anal Atom Spectrom (2004) 19, 1061. 26. Cremers , D. A., and Radziemski, L. J.,
Di Maro, Antimo; Chambery, Angela; Carafa, Vincenzo; Costantini, Susan; Colonna, Giovanni; Parente, Augusto
2009-03-01
The amino acid sequence and glycan structure of PD-L1, PD-L2 and PD-L3, type 1 ribosome-inactivating proteins isolated from Phytolacca dioica L. leaves, were determined using a combined approach based on peptide mapping, Edman degradation and ESI-Q-TOF MS in precursor ion discovery mode. The comparative analysis of the 261 amino acid residue sequences showed that PD-L1 and PD-L2 have identical primary structure, as it is the case of PD-L3 and PD-L4. Furthermore, the primary structure of PD-Ls 1-2 and PD-Ls 3-4 have 81.6% identity (85.1% similarity). The ESI-Q-TOF MS analysis confirmed that PD-Ls 1-3 were glycosylated at different sites. In particular, PD-L1 contained three glycidic chains with the well known paucidomannosidic structure (Man)(3) (GlcNAc)(2) (Fuc)(1) (Xyl)(1) linked to Asn10, Asn43 and Asn255. PD-L2 was glycosylated at Asn10 and Asn43, and PD-L3 was glycosylated only at Asn10. PD-L4 was confirmed to be not glycosylated. Despite an overall high structural similarity, the comparative modeling of PD-L1, PD-L2, PD-L3 and PD-L4 has shown potential influences of the glycidic chains on their adenine polynucleotide glycosylase activity on different substrates.
IJS procedure for RELAP5 to TRACE input model conversion using SNAP
DOE Office of Scientific and Technical Information (OSTI.GOV)
Prosek, A.; Berar, O. A.
2012-07-01
The TRAC/RELAP Advanced Computational Engine (TRACE) advanced, best-estimate reactor systems code developed by the U.S. Nuclear Regulatory Commission comes with a graphical user interface called Symbolic Nuclear Analysis Package (SNAP). Much of efforts have been done in the past to develop the RELAP5 input decks. The purpose of this study is to demonstrate the Institut 'Josef Stefan' (IJS) conversion procedure from RELAP5 to TRACE input model of BETHSY facility. The IJS conversion procedure consists of eleven steps and is based on the use of SNAP. For calculations of the selected BETHSY 6.2TC test the RELAP5/MOD3.3 Patch 4 and TRACE V5.0more » Patch 1 were used. The selected BETHSY 6.2TC test was 15.24 cm equivalent diameter horizontal cold leg break in the reference pressurized water reactor without high pressure and low pressure safety injection. The application of the IJS procedure for conversion of BETHSY input model showed that it is important to perform the steps in proper sequence. The overall calculated results obtained with TRACE using the converted RELAP5 model were close to experimental data and comparable to RELAP5/MOD3.3 calculations. Therefore it can be concluded, that proposed IJS conversion procedure was successfully demonstrated on the BETHSY integral test facility input model. (authors)« less
Kirton, Orlando C; Calabrese, Rebecca C; Staff, Ilene
2015-01-01
Less-invasive hemodynamic monitoring (eg, esophageal doppler monitoring [EDM] and arterial pressure contour analysis, FloTrac) is increasingly used as an alternative to pulmonary artery catheters (PACs) in critically ill intensive care unit (ICU). The decrease in use of PACs is not associated with increased mortality. Five-year retrospective review of 1894 hemodynamically monitored patients admitted to 3 surgical ICUs in a university-affiliate, tertiary care urban hospital. Data included the number of admissions, diagnosis-related group discharge case mix, length of stay, insertion of monitoring devices (PAC, EDM, and FloTrac probes), administered intravenous vasoactive agents (β-predominant agonists--dobutamine, epinephrine, and dopamine; vasopressors--norepinephrine and phenylephrine), and mortality. Data from hospital administrative databases were compiled to create patient characteristic and monitoring variables across a 5-year time period, 2005 to 2009 inclusive. Chi-square for independent proportions, 1-way analysis of variance, and Kruskal-Wallis tests were used; tests for trend were conducted. An α level of .05 was considered significant. Statistical Package for the Social Sciences v14 was used for all statistical testing. There was a significant change in the type of hemodynamic monitors inserted in 2 of the 3 surgical ICUs (in the general surgery and neurointensive care but not in the cardiac ICU) from PACs to less-invasive devices (FloTrac or EDM) during the 5-year study period (P < .001). There was no change in mortality rate over the time period (P = .492). There was an overall increase in the proportion of monitored patients who received intravenous vasoactive agents (P < .001) with a progressive shift from β-agonists to vasopressors (P < .002). Multivariate analyses indicated that age, case mix, and use of vasoactive agents were all independent predictors of inhospital mortality (P = .001) but that type of monitoring was not (P = .638). In a 5-year period, the decreased insertions of PACs were replaced by increased utilization of less-invasive hemodynamic monitoring devices. This change in practice did not adversely impact mortality. © The Author(s) 2013.
Klebe, Stephan; Golmard, Jean-Louis; Nalls, Michael A; Saad, Mohamad; Singleton, Andrew B; Bras, Jose M; Hardy, John; Simon-Sanchez, Javier; Heutink, Peter; Kuhlenbäumer, Gregor; Charfi, Rim; Klein, Christine; Hagenah, Johann; Gasser, Thomas; Wurster, Isabel; Lesage, Suzanne; Lorenz, Delia; Deuschl, Günther; Durif, Franck; Pollak, Pierre; Damier, Philippe; Tison, François; Durr, Alexandra; Amouyel, Philippe; Lambert, Jean-Charles; Tzourio, Christophe; Maubaret, Cécilia; Charbonnier-Beaupel, Fanny; Tahiri, Khadija; Vidailhet, Marie; Martinez, Maria; Brice, Alexis; Corvol, Jean-Christophe
2013-01-01
The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the COMT gene (rs4680) causes a trimodal distribution of high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzyme activity. We tested whether the Val158Met polymorphism is a modifier of the age at onset (AAO) in Parkinson's disease (PD). The rs4680 was genotyped in a total of 16 609 subjects from five independent cohorts of European and North American origin (5886 patients with PD and 10 723 healthy controls). The multivariate analysis for comparing PD and control groups was based on a stepwise logistic regression, with gender, age and cohort origin included in the initial model. The multivariate analysis of the AAO was a mixed linear model, with COMT genotype and gender considered as fixed effects and cohort and cohort-gender interaction as random effects. COMT genotype was coded as a quantitative variable, assuming a codominant genetic effect. The distribution of the COMT polymorphism was not significantly different in patients and controls (p=0.22). The Val allele had a significant effect on the AAO with a younger AAO in patients with the Val/Val (57.1±13.9, p=0.03) than the Val/Met (57.4±13.9) and the Met/Met genotypes (58.3±13.5). The difference was greater in men (1.9 years between Val/Val and Met/Met, p=0.007) than in women (0.2 years, p=0.81). Thus, the Val158Met COMT polymorphism is not associated with PD in the Caucasian population but acts as a modifier of the AAO in PD with a sexual dimorphism: the Val allele is associated with a younger AAO in men with idiopathic PD. PMID:23408064
TRAC based sensing for autonomous rendezvous
NASA Technical Reports Server (NTRS)
Everett, Louis J.; Monford, Leo
1991-01-01
The Targeting Reflective Alignment Concept (TRAC) sensor is to be used in an effort to support an Autonomous Rendezvous and Docking (AR&D) flight experiment. The TRAC sensor uses a fixed-focus, fixed-iris CCD camera and a target that is a combination of active and passive components. The system experiment is anticipated to fly in 1994 using two Commercial Experiment Transporters (COMET's). The requirements for the sensor are: bearing error less than or equal to 0.075 deg; bearing error rate less than 0.3 deg/sec; attitude error less than 0.5 deg.; and attitude rate error less than 2.0 deg/sec. The range requirement depends on the range and the range rate of the vehicle. The active component of the target is several 'kilo-bright' LED's that can emit 2500 millicandela with 40 milliwatts of input power. Flashing the lights in a known pattern eliminates background illumination. The system should be able to rendezvous from 300 meters all the way to capture. A question that arose during the presentation: What is the life time of the LED's and their sensitivity to radiation? The LED's should be manufactured to Military Specifications, coated with silicon dioxide, and all other space qualified precautions should be taken. The LED's will not be on all the time so they should easily last the two-year mission.
Microenvironment Tracker (MicroTrac) | Science Inventory ...
Epidemiologic studies have shown associations between air pollution concentrations measured at central-site ambient monitors and adverse health outcomes. Using central-site concentrations as exposure surrogates, however, can lead to exposure errors due to time spent in various indoor and outdoor microenvironments (ME) with pollutant concentrations that can be substantially different from central-site concentrations. These exposure errors can introduce bias and incorrect confidence intervals in health effect estimates, which diminish the power of such studies to establish correct conclusions about the exposure and health effects association. The significance of this issue was highlighted in the National Research Council (NRC) Report “Research Priorities for Airborne Particulate Matter”, which recommends that EPA address exposure error in health studies. To address this limitation, we developed MicroTrac, an automated classification model that estimates time of day and duration spent in eight ME (indoors and outdoors at home, work, school; inside vehicles; other locations) from personal global positioning system (GPS) data and geocoded boundaries of buildings (e.g., home, work, school). MicroTrac has several innovative design features: (1) using GPS signal quality to account for GPS signal loss inside certain buildings, (2) spatial buffering of building boundaries to account for the spatial inaccuracy of the GPS device, and (3) temporal buffering of GPS positi
Implicit time-integration method for simultaneous solution of a coupled non-linear system
NASA Astrophysics Data System (ADS)
Watson, Justin Kyle
Historically large physical problems have been divided into smaller problems based on the physics involved. This is no different in reactor safety analysis. The problem of analyzing a nuclear reactor for design basis accidents is performed by a handful of computer codes each solving a portion of the problem. The reactor thermal hydraulic response to an event is determined using a system code like TRAC RELAP Advanced Computational Engine (TRACE). The core power response to the same accident scenario is determined using a core physics code like Purdue Advanced Core Simulator (PARCS). Containment response to the reactor depressurization in a Loss Of Coolant Accident (LOCA) type event is calculated by a separate code. Sub-channel analysis is performed with yet another computer code. This is just a sample of the computer codes used to solve the overall problems of nuclear reactor design basis accidents. Traditionally each of these codes operates independently from each other using only the global results from one calculation as boundary conditions to another. Industry's drive to uprate power for reactors has motivated analysts to move from a conservative approach to design basis accident towards a best estimate method. To achieve a best estimate calculation efforts have been aimed at coupling the individual physics models to improve the accuracy of the analysis and reduce margins. The current coupling techniques are sequential in nature. During a calculation time-step data is passed between the two codes. The individual codes solve their portion of the calculation and converge to a solution before the calculation is allowed to proceed to the next time-step. This thesis presents a fully implicit method of simultaneous solving the neutron balance equations, heat conduction equations and the constitutive fluid dynamics equations. It discusses the problems involved in coupling different physics phenomena within multi-physics codes and presents a solution to these problems. The thesis also outlines the basic concepts behind the nodal balance equations, heat transfer equations and the thermal hydraulic equations, which will be coupled to form a fully implicit nonlinear system of equations. The coupling of separate physics models to solve a larger problem and improve accuracy and efficiency of a calculation is not a new idea, however implementing them in an implicit manner and solving the system simultaneously is. Also the application to reactor safety codes is new and has not be done with thermal hydraulics and neutronics codes on realistic applications in the past. The coupling technique described in this thesis is applicable to other similar coupled thermal hydraulic and core physics reactor safety codes. This technique is demonstrated using coupled input decks to show that the system is solved correctly and then verified by using two derivative test problems based on international benchmark problems the OECD/NRC Three mile Island (TMI) Main Steam Line Break (MSLB) problem (representative of pressurized water reactor analysis) and the OECD/NRC Peach Bottom (PB) Turbine Trip (TT) benchmark (representative of boiling water reactor analysis).
An overview of the OmniTRACS: The first operational mobile Ku-band satellite communications
NASA Technical Reports Server (NTRS)
Salmasi, Allen
1988-01-01
The service features of the OmniTRACS system developed by Omninet Communications Services of Los Angeles, California are described. This system is the first operational mobile Ku-band satellite communications system that provides two-way messaging and position determination and reporting services to mobile users on a nationwide basis. The system uses existing Ku-band satellites under a secondary international allocation for mobile satellite services.
NASA Technical Reports Server (NTRS)
Antonio, Franklin P.; Gilhousen, Klein S.; Jacobs, Irwin M.; Weaver, Linday A., Jr.
1988-01-01
The techinical characteristics of the OmniTRACS system are described. The system is the first operational mobile Ku-band satellite communications system and provides two-way message and position determination service to mobile terminals using existing Ku-band satellites. Interference to and from the system is minimized by the use of special spread-spectrum techniques, together with low power and low data rate transmissions.
How the Theory of Computing Can Help in Space Exploration
NASA Technical Reports Server (NTRS)
Kreinovich, Vladik; Longpre, Luc
1997-01-01
The opening of the NASA Pan American Center for Environmental and Earth Sciences (PACES) at the University of Texas at El Paso made it possible to organize the student Center for Theoretical Research and its Applications in Computer Science (TRACS). In this abstract, we briefly describe the main NASA-related research directions of the TRACS center, and give an overview of the preliminary results of student research.
Fink, Joshua; Kwigizile, Valerian; Oh, Jun-Seok
2016-06-01
Despite seeing widespread usage worldwide, adaptive traffic control systems have experienced relatively little use in the United States. Of the systems used, the Sydney Coordinated Adaptive Traffic System (SCATS) is the most popular in America. Safety benefits of these systems are not as well understood nor as commonly documented. This study investigates the safety benefits of adaptive traffic control systems by using the large SCATS-based system in Oakland County, MI known as FAST-TRAC. This study uses data from FAST-TRAC-controlled intersections in Oakland County and compares a wide variety of geometric, traffic, and crash characteristics to similar intersections in metropolitan areas elsewhere in Michigan. Data from 498 signalized intersections are used to conduct a cross-sectional analysis. Negative binomial models are used to estimate models for three dependent crash variables. Multinomial logit models are used to estimate an injury severity model. A variable tracking the presence of FAST-TRAC controllers at intersections is used in all models to determine if a SCATS-based system has an impact on crash occurrences or crash severity. Estimates show that the presence of SCATS-based controllers at intersections is likely to reduce angle crashes by up to 19.3%. Severity results show a statistically significant increase in non-serious injuries, but not a significant reduction in incapacitating injuries or fatal accidents. Copyright © 2016 Elsevier Ltd and National Safety Council. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zehtabian, M; Zaker, N; Sina, S
2015-06-15
Purpose: Different versions of MCNP code are widely used for dosimetry purposes. The purpose of this study is to compare different versions of the MCNP codes in dosimetric evaluation of different brachytherapy sources. Methods: The TG-43 parameters such as dose rate constant, radial dose function, and anisotropy function of different brachytherapy sources, i.e. Pd-103, I-125, Ir-192, and Cs-137 were calculated in water phantom. The results obtained by three versions of Monte Carlo codes (MCNP4C, MCNPX, MCNP5) were compared for low and high energy brachytherapy sources. Then the cross section library of MCNP4C code was changed to ENDF/B-VI release 8 whichmore » is used in MCNP5 and MCNPX codes. Finally, the TG-43 parameters obtained using the MCNP4C-revised code, were compared with other codes. Results: The results of these investigations indicate that for high energy sources, the differences in TG-43 parameters between the codes are less than 1% for Ir-192 and less than 0.5% for Cs-137. However for low energy sources like I-125 and Pd-103, large discrepancies are observed in the g(r) values obtained by MCNP4C and the two other codes. The differences between g(r) values calculated using MCNP4C and MCNP5 at the distance of 6cm were found to be about 17% and 28% for I-125 and Pd-103 respectively. The results obtained with MCNP4C-revised and MCNPX were similar. However, the maximum difference between the results obtained with the MCNP5 and MCNP4C-revised codes was 2% at 6cm. Conclusion: The results indicate that using MCNP4C code for dosimetry of low energy brachytherapy sources can cause large errors in the results. Therefore it is recommended not to use this code for low energy sources, unless its cross section library is changed. Since the results obtained with MCNP4C-revised and MCNPX were similar, it is concluded that the difference between MCNP4C and MCNPX is their cross section libraries.« less
Identification of Developmentally Regulated PCP-Responsive Non-Coding RNA, prt6, in the Rat Thalamus
Umino, Asami; Nishikawa, Toru
2014-01-01
Schizophrenia and similar psychoses induced by NMDA-type glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, usually develop after adolescence. Moreover, adult-type behavioral disturbance following NMDA receptor antagonist application in rodents is observed after a critical period at around 3 postnatal weeks. These observations suggest that the schizophrenic symptoms caused by and psychotomimetic effects of NMDA antagonists require the maturation of certain brain neuron circuits and molecular networks, which differentially respond to NMDA receptor antagonists across adolescence and the critical period. From this viewpoint, we have identified a novel developmentally regulated phencyclidine-responsive transcript from the rat thalamus, designated as prt6, as a candidate molecule involved in the above schizophrenia-related systems using a DNA microarray technique. The transcript is a non-coding RNA that includes sequences of at least two microRNAs, miR132 and miR212, and is expressed strongly in the brain and testis, with trace or non-detectable levels in the spleen, heart, liver, kidney, lung and skeletal muscle, as revealed by Northern blot analysis. The systemic administration of PCP (7.5 mg/kg, subcutaneously (s.c.)) significantly elevated the expression of prt6 mRNA in the thalamus at postnatal days (PD) 32 and 50, but not at PD 8, 13, 20, or 24 as compared to saline-treated controls. At PD 50, another NMDA receptor antagonist, dizocilpine (0.5 mg/kg, s.c.), and a schizophrenomimetic dopamine agonist, methamphetamine (4.8 mg/kg, s.c.), mimicked a significant increase in the levels of thalamic prt6 mRNAs, while a D2 dopmamine receptor antagonist, haloperidol, partly inhibited the increasing influence of PCP on thalamic prt6 expression without its own effects. These data indicate that prt6 may be involved in the pathophysiology of the onset of drug-induced schizophrenia-like symptoms and schizophrenia through the possible dysregulation of target genes of the long non-coding RNA or microRNAs in the transcript. PMID:24886782
TRAC-BF1 thermal-hydraulic, ANSYS stress analysis for core shroud cracking phenomena
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shoop, U.; Feltus, M.A.; Baratta, A.J.
1996-12-31
The U.S. Nuclear Regulatory Commission sent Generic Letter 94-03 informing all licensees about the intergranular stress corrosion cracking (IGSCC) of core shrouds found in both Dresden unit I and Quad Cities unit 1. The letter directed all licensees to perform safety analysis of their boiling water reactor (BWR) units. Two transients of special concern for the core shroud safety analysis include the main steam line break (MSLB) and recirculation line break transient.
Zhao, Na; Xiao, Jianqiu; Zheng, Zhiyong; Fei, Guoqiang; Zhang, Feng; Jin, Lirong; Zhong, Chunjiu
2015-04-01
Our previous studies have demonstrated that ceruloplasmin (CP) dysmetabolism is correlated with Parkinson's disease (PD). However, the causes of decreased serum CP levels in PD patients remain to be clarified. This study aimed to explore the potential association between genetic variants of the CP gene and PD. Clinical features, serum CP levels, and the CP gene (both promoter and coding regions) were analyzed in 60 PD patients and 50 controls. A luciferase reporter system was used to investigate the function of promoter single-nucleotide polymorphisms (SNPs). High-density comparative genomic hybridization microarrays were also used to detect large-scale copy-number variations in CP and an additional 47 genes involved in PD and/or copper/iron metabolism. The frequencies of eight SNPs (one intronic SNP and seven promoter SNPs of the CP gene) and their haplotypes were significantly different between PD patients, especially those with lowered serum CP levels, and controls. However, the luciferase reporter system revealed no significant effect of the risk haplotype on promoter activity of the CP gene. Neither these SNPs nor their haplotypes were correlated with the Hoehn and Yahr staging of PD. The results of this study suggest that common genetic variants of CP are associated with PD and further investigation is needed to explore their functions in PD.
TRAC Searchable Research Library
2016-05-01
network accessible document repository for technical documents and similar document artifacts. We used a model-based approach using the Vector...demonstration and model refinement. 14. SUBJECT TERMS Knowledge Management, Document Repository , Digital Library, Vector Directional Data Model...27 Figure D1. Administrator Repository Upload Page. ................................................................... D-2 Figure D2
Molecular Analysis of Glucose-6-Phosphate Dehydrogenase Gene Mutations in Bangladeshi Individuals.
Sarker, Suprovath Kumar; Islam, Md Tarikul; Eckhoff, Grace; Hossain, Mohammad Amir; Qadri, Syeda Kashfi; Muraduzzaman, A K M; Bhuyan, Golam Sarower; Shahidullah, Mohammod; Mannan, Mohammad Abdul; Tahura, Sarabon; Hussain, Manzoor; Akhter, Shahida; Nahar, Nazmun; Shirin, Tahmina; Qadri, Firdausi; Mannoor, Kaiissar
2016-01-01
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked human enzyme defect of red blood cells (RBCs). Individuals with this gene defect appear normal until exposed to oxidative stress which induces hemolysis. Consumption of certain foods such as fava beans, legumes; infection with bacteria or virus; and use of certain drugs such as primaquine, sulfa drugs etc. may result in lysis of RBCs in G6PD deficient individuals. The genetic defect that causes G6PD deficiency has been identified mostly as single base missense mutations. One hundred and sixty G6PD gene mutations, which lead to amino acid substitutions, have been described worldwide. The purpose of this study was to detect G6PD gene mutations in hospital-based settings in the local population of Dhaka city, Bangladesh. Qualitative fluorescent spot test and quantitative enzyme activity measurement using RANDOX G6PDH kit were performed for analysis of blood specimens and detection of G6PD-deficient participants. For G6PD-deficient samples, PCR was done with six sets of primers specific for G6PD gene. Automated Sanger sequencing of the PCR products was performed to identify the mutations in the gene. Based on fluorescence spot test and quantitative enzyme assay followed by G6PD gene sequencing, 12 specimens (11 males and one female) among 121 clinically suspected patient-specimens were found to be deficient, suggesting a frequency of 9.9% G6PD deficiency. Sequencing of the G6PD-deficient samples revealed c.C131G substitution (exon-3: Ala44Gly) in six samples, c.G487A substitution (exon-6:Gly163Ser) in five samples and c.G949A substitution (exon-9: Glu317Lys) of coding sequence in one sample. These mutations either affect NADP binding or disrupt protein structure. From the study it appears that Ala44Gly and Gly163Ser are the most common G6PD mutations in Dhaka, Bangladesh. This is the first study of G6PD mutations in Bangladesh.
Molecular Analysis of Glucose-6-Phosphate Dehydrogenase Gene Mutations in Bangladeshi Individuals
Sarker, Suprovath Kumar; Hossain, Mohammad Amir; Qadri, Syeda Kashfi; Muraduzzaman, A. K. M.; Bhuyan, Golam Sarower; Shahidullah, Mohammod; Mannan, Mohammad Abdul; Tahura, Sarabon; Hussain, Manzoor; Akhter, Shahida; Nahar, Nazmun; Shirin, Tahmina; Qadri, Firdausi; Mannoor, Kaiissar
2016-01-01
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked human enzyme defect of red blood cells (RBCs). Individuals with this gene defect appear normal until exposed to oxidative stress which induces hemolysis. Consumption of certain foods such as fava beans, legumes; infection with bacteria or virus; and use of certain drugs such as primaquine, sulfa drugs etc. may result in lysis of RBCs in G6PD deficient individuals. The genetic defect that causes G6PD deficiency has been identified mostly as single base missense mutations. One hundred and sixty G6PD gene mutations, which lead to amino acid substitutions, have been described worldwide. The purpose of this study was to detect G6PD gene mutations in hospital-based settings in the local population of Dhaka city, Bangladesh. Qualitative fluorescent spot test and quantitative enzyme activity measurement using RANDOX G6PDH kit were performed for analysis of blood specimens and detection of G6PD-deficient participants. For G6PD-deficient samples, PCR was done with six sets of primers specific for G6PD gene. Automated Sanger sequencing of the PCR products was performed to identify the mutations in the gene. Based on fluorescence spot test and quantitative enzyme assay followed by G6PD gene sequencing, 12 specimens (11 males and one female) among 121 clinically suspected patient-specimens were found to be deficient, suggesting a frequency of 9.9% G6PD deficiency. Sequencing of the G6PD-deficient samples revealed c.C131G substitution (exon-3: Ala44Gly) in six samples, c.G487A substitution (exon-6:Gly163Ser) in five samples and c.G949A substitution (exon-9: Glu317Lys) of coding sequence in one sample. These mutations either affect NADP binding or disrupt protein structure. From the study it appears that Ala44Gly and Gly163Ser are the most common G6PD mutations in Dhaka, Bangladesh. This is the first study of G6PD mutations in Bangladesh. PMID:27880809
Electrical conductivity and phase diagram of binary alloys. 21: The system palladium-chromium
NASA Technical Reports Server (NTRS)
Grube, G.; Knabe, R.
1985-01-01
Pd-Cr alloys were investigated by thermal analysis, hardness measurements, X-ray analysis, microscopic examination of etched pieces, and temperature-resistance curves of the solid alloys. Only one compound, Pd2Cr3, m, 1389 deg, is formed. It possesses a cubic face centered lattice and forms with excess Pd a series of solid solutions with a minimum m.p. at 45 atoms% Pd. Hardness maximum appears at the Pd2Cr3 point. Pd2Cr3 forms no solid solutions with Cr but eutectic point appears at 25 atoms% Pd, m. 1320 deg. The sp. resistance of pure Cr in an atom of H, indicates no allotropic forms. Cr2O3 is solid in molten Cr. Pure Cr melts at 1890 plus or minus 10 deg but Cr contg. Cr2O3 starts to melt at 1770 to 1790 deg.
Campos, Michael A; Runken, Michael C; Davis, Angela M; Johnson, Michael P; Stone, Glenda A; Buikema, Ami R
2018-04-01
Alpha 1-antitrypsin deficiency (AATD) is a genetic disorder which reduces serum alpha 1-antitrypsin (AAT or alpha1-proteinase inhibitor, A1PI) and increases the risk of chronic obstructive pulmonary disease (COPD). Management strategies include intravenous A1PI augmentation, and, in some cases, a health management program (Prolastin Direct ® ; PD). This study compared clinical and economic outcomes between patients with and without PD program participation. This retrospective study included commercial and Medicare Advantage health insurance plan members with ≥ 1 claim with diagnosis codes for COPD and ≥ 1 medical or pharmacy claim including A1PI (on index date). Outcomes were compared between patients receiving only Prolastin ® or Prolastin ® -C (PD cohort) and patients who received a different brand without PD (Comparator cohort). Demographic and clinical characteristics were captured during 6 months pre-index. Post-index exacerbation episodes and healthcare utilization and costs were compared between cohorts. The study sample comprised 445 patients (n = 213 in PD cohort; n = 232 in Comparator cohort), with a mean age 55.5 years, 50.8% male, and 78.9% commercially insured. The average follow-up was 822 days (2.25 years), and the average time on A1PI was 747 days (2.04 years). Few differences were observed in demographic or clinical characteristics. Adjusting for differences in patient characteristics, the rate of severe exacerbation episodes was reduced by 36.1% in the PD cohort. Adjusted total annual all-cause costs were 11.4% lower, and adjusted mean respiratory-related costs were 10.6% lower in the PD cohort than the Comparator cohort. Annual savings in all-cause total costs in the PD cohort relative to the Comparator cohort was US$25,529 per patient, largely due to significantly fewer and shorter hospitalizations. These results suggest that comprehensive health management services may improve both clinical and economic outcomes among patients with COPD and AATD who receive augmentation therapy. Grifols Shared Services of North America, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kazantsev, A. A., E-mail: kazantsevanatoly@gmail.com; Sergeev, V. V.; Kochnov, O. Yu.
The temperature regime is calculated for two different designs of containers with uranium-bearing material for the upgraded VVR-Ts research reactor facility (IVV.10M). The containers are to be used in the production of {sup 99}Mo. It is demonstrated that the modification of the container design leads to a considerable temperature reduction and an increase in the near-wall boiling margin and allows one to raise the amount of material loaded into the container. The calculations were conducted using the international thermohydraulic contour code TRAC intended to analyze the technical safety of water-cooled nuclear power units.
Koike, Kazuko; Takaki, Akinobu; Yagi, Takahito; Iwasaki, Yoshiaki; Yasunaka, Tetsuya; Sadamori, Hiroshi; Shinoura, Susumu; Umeda, Yuzo; Yoshida, Ryuichi; Sato, Daisuke; Nobuoka, Daisuke; Utsumi, Masashi; Miyake, Yasuhiro; Ikeda, Fusao; Shiraha, Hidenori; Fujiwara, Toshiyoshi; Yamamoto, Kazuhide
2015-01-01
Background Post orthotopic liver transplantation (OLT) viral hepatitis is an immunological condition where immune cells induce hepatitis during conditions of immune-suppression. The immune-regulatory programmed death-1 (PD-1)/PD-ligand 1 system is acknowledged to play important roles in immune-mediated diseases. However, the PD-1/PD-L2 interaction is not well characterized, with PD-L2 also exhibiting an immunostimulatory function. We hypothesized that this atypical molecule could affect the recurrence of post-OLT hepatitis. To test this hypothesis, we conducted immunohistochemical staining analysis and in vitro analysis of PD-L2. Methods The expression of PD-L2 was evaluated in liver biopsy specimens from patients with chronic hepatitis B (n = 15), post-OLT hepatitis B (n = 8), chronic hepatitis C (n = 48), and post-OLT hepatitis C (CH-C-OLT) (n = 14). The effect of calcineurin inhibitors (CNIs) and hepatitis C virus (HCV) on PD-L2 expression was investigated in hepatoma cell lines. Results The PD-L2 was highly expressed on CH-C-OLT hepatocytes. Treatment of hepatoma cell lines with CNIs resulted in increased PD-L2 expression, especially in combination with HCV core or NS3 protein. Transfection of cell lines with PD-L2 containing plasmid resulted in high intercellular adhesion molecule-1 (ICAM-1) expression, which might enhance hepatitis activity. Conclusions The PD-L2 is highly expressed on CH-C-OLT hepatocytes, whereas HCV proteins, in combination with CNIs, induce high expression of PD-L2 resulting in elevated expression of ICAM-1. These findings demonstrate the effect of CNIs on inducing PD-L2 and subsequent ICAM-1 expression, effects that may produce inflammatory cell infiltration in post-OLT hepatitis C. PMID:25675203
SU-F-J-25: Position Monitoring for Intracranial SRS Using BrainLAB ExacTrac Snap Verification
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jang, S; McCaw, T; Huq, M
2016-06-15
Purpose: To determine the accuracy of position monitoring with BrainLAB ExacTrac snap verification following couch rotations during intracranial SRS. Methods: A CT scan of an anthropomorphic head phantom was acquired using 1.25mm slices. The isocenter was positioned near the centroid of the frontal lobe. The head phantom was initially aligned on the treatment couch using cone-beam CT, then repositioned using ExacTrac x-ray verification with residual errors less than 0.2mm and 0.2°. Snap verification was performed over the full range of couch angles in 15° increments with known positioning offsets of 0–3mm applied to the phantom along each axis. At eachmore » couch angle, the smallest tolerance was determined for which no positioning deviation was detected. Results: For couch angles 30°–60° from the center position, where the longitudinal axis of the phantom is approximately aligned with the beam axis of one x-ray tube, snap verification consistently detected positioning errors exceeding the maximum 8mm tolerance. Defining localization error as the difference between the known offset and the minimum tolerance for which no deviation was detected, the RMS error is mostly less than 1mm outside of couch angles 30°–60° from the central couch position. Given separate measurements of patient position from the two imagers, whether to proceed with treatment can be determined by the criterion of a reading within tolerance from just one (OR criterion) or both (AND criterion) imagers. Using a positioning tolerance of 1.5mm, snap verification has sensitivity and specificity of 94% and 75%, respectively, with the AND criterion, and 67% and 93%, respectively, with the OR criterion. If readings exceeding maximum tolerance are excluded, the sensitivity and specificity are 88% and 86%, respectively, with the AND criterion. Conclusion: With a positioning tolerance of 1.5mm, ExacTrac snap verification can be used during intracranial SRS with sensitivity and specificity between 85% and 90%.« less
Modification of PdO/CeZrO2 doped with transition metals (Y and Fe) for reducibility properties
NASA Astrophysics Data System (ADS)
Shah, M. Nazri Abu; Jai, Junaidah; Faeqah, Nor; Ismail, Kamariah Noor; Hadi, Abdul
2017-12-01
This paper describes the synthesis of modified nanocatalysts of PdO/CeZrYO2(PdO/CZY), PdO/CeZrFeO2(PdO/CZF) and PdO/CeZrO2(PdO/CZ) via microemulsion followed by deposition - precipitation method. The structural, textural and redox properties of the synthesized nanocatalysts were investigated. The diffractogram of XRD showed that all the synthesized nanocatalysts indicate a symmetrical pattern of cubic phase crystallinity. The amount of PdO was detected using EDX analysis and PdO/CZF portrayed the highest Pd contents of about 4.63 %. Therefore it shows a good potential to have reducibility properties and can be manifested active at low temperature reduction.
Comorbid Parkinson's disease, falls and fractures in the 2010 National Emergency Department Sample
Beydoun, Hind A.; Beydoun, May A.; Mishra, Nishant K.; Rostant, Ola S.; Zonderman, Alan B.; Eid, Shaker M.
2017-01-01
Introduction Parkinson's disease (PD) is a progressive, neurodegenerative disorder of multifactorial etiology affecting ~1% of older adults. Research focused on linking PD to falls and bone fractures has been limited in Emergency Department (ED) settings, where most injuries are identified. We assessed whether injured U.S. ED admissions with PD diagnoses were more likely to exhibit comorbid fall- or non-fall related bone fractures and whether a PD diagnosis with a concomitant fall or bone fracture is linked to worse prognosis. Methods We performed secondary analyses of 2010 Healthcare Utilization Project National ED Sample from 4,253,987 admissions to U.S. EDs linked to injured elderly patients. ED discharges with ICD-9-CM code (332.0) were identified as PD and those with ICD-9-CM code (800.0–829.0) were used to define bone fracture location. Linear and logistic regression models were constructed to estimate slopes (B) and odds ratios (OR) with 95% confidence intervals (CI). Results PD admissions had 28% increased adjusted prevalence of bone fracture. Non-fall injuries showed stronger relationship between PD and bone fracture (ORadj = 1.33, 95% CI: 1.22–1.45) than fall injuries (ORadj = 1.06, 95% CI: 1.01–1.10). PD had the strongest impact on hospitalization length when bone fracture and fall co-occurred, and total charges were directly associated with PD only for fall injuries. Finally, PD status was not related to in-hospital death in this population. Conclusions Among injured U.S. ED elderly patient visits, those with PD had higher bone fracture prevalence and more resource utilization especially among fall-related injuries. No association of PD with in-hospital death was noted. PMID:27887896
Chung, Chen-Chih; Kang, Jiunn-Horng; Yuan, Rey-Yue; Wu, Dean; Chen, Chih-Chung; Chi, Nai-Fang; Chen, Po-Chih; Hu, Chaur-Jong
2013-07-01
Sleep disorders are frequently seen in patients with Parkinson disease (PD), including rapid eye movement (REM) behavior disorder and periodic limb movement disorder. However, knowledge about changes in non-REM sleep in patients with PD is limited. This study explored the characteristics of electroencephalography (EEG) during sleep in patients with PD and non-PD controls. We further conducted multiscale entropy (MSE) analysis to evaluate and compare the complexity of sleep EEG for the 2 groups. There were 9 patients with PD (Hoehn-Yahr stage 1 or 2) and 11 non-PD controls. All participants underwent standard whole-night polysomnography (PSG), which included 23 channels, 6 of which were for EEG. The raw data of the EEG were extracted and subjected to MSE analysis. Patients with PD had a longer sleep onset time and a higher spontaneous EEG arousal index. Sleep stage-specific increased MSE was observed in patients with PD during non-REM sleep. The difference was more marked and significant at higher time scale factors (TSFs). In conclusion, increased biosignal complexity, as revealed by MSE analysis, was found in patients with PD during non-REM sleep at high TSFs. This finding might reflect a compensatory mechanism for early defects in neuronal network control machinery in PD.
Minucci, Angelo; Moradkhani, Kamran; Hwang, Ming Jing; Zuppi, Cecilia; Giardina, Bruno; Capoluongo, Ettore
2012-03-15
In the present paper we have updated the G6PD mutations database, including all the last discovered G6PD genetic variants. We underline that the last database has been published by Vulliamy et al. [1] who analytically reported 140 G6PD mutations: along with Vulliamy's database, there are two main sites, such as http://202.120.189.88/mutdb/ and www.LOVD.nl/MR, where almost all G6PD mutations can be found. Compared to the previous mutation reports, in our paper we have included for each mutation some additional information, such as: the secondary structure and the enzyme 3D position involving by mutation, the creation or abolition of a restriction site (with the enzyme involved) and the conservation score associated with each amino acid position. The mutations reported in the present tab have been divided according to the gene's region involved (coding and non-coding) and mutations affecting the coding region in: single, multiple (at least with two bases involved) and deletion. We underline that for the listed mutations, reported in italic, literature doesn't provide all the biochemical or bio-molecular information or the research data. Finally, for the "old" mutations, we tried to verify features previously reported and, when subsequently modified, we updated the specific information using the latest literature data. Copyright © 2012 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stegemann, Frank; Benndorf, Christopher; Touzani, Rachid St.
SrPt{sub 3}Al{sub 2}, a CaCu{sub 5} relative (P6/mmm; a = 566.29(3), c = 389.39(3) pm; wR{sub 2} = 0.0202, 121 F{sup 2} values, 9 parameters), and Sr{sub 2}Pd{sub 2}Al, isostructural to Ca{sub 2}Pt{sub 2}Ge (Fdd2; a = 1041.45(5), b = 1558.24(7), c = 604.37(3) pm; wR{sub 2} = 0.0291, 844 F{sup 2} values, 25 parameters) have been prepared from the elements. The crystal structures have been investigated by single crystal X-ray diffraction. Structural relaxation confirmed the electronic stability of SrPt{sub 3}Al{sub 2}, while orthorhombic Sr{sub 2}Pd{sub 2}Al might be a metastable polymorph as it is energetically competitive to its monoclinicmore » variant. Both compounds are predicted to be metallic conductors as their density-of-states (DOS) are non-zero at the Fermi level. COHP bonding analysis coupled with Bader effective charge analysis suggest that the title compounds are polar intermetallic phases in which strong Pt–Al and Pd–Al covalent bonds are present, while a significant electron transfer from Sr atoms to the [Pt{sub 3}Al{sub 2}]{sup δ–} or [Pd{sub 2}Al]{sup δ–} network is found. - Graphical abstract: Chains of Pd atoms in the crystal structure of Sr{sub 2}Pd{sub 2}Al get connected by Al atoms in the shape of a distorted tetrahedra. The band structure calculations confirm weak Pd–Pd interactions. - Highlights: • SrPt{sub 3}Al{sub 2} and Sr{sub 2}Pd{sub 2}Al discovered and crystallographically investigated. • DFT predicts the here reported orthorhombic Sr{sub 2}Pd{sub 2}Al to be competitive in energy to the presently unknown monoclinic Sr{sub 2}Pd{sub 2}Al. • Bader charge analysis indicates SrPt{sub 3}Al{sub 2} and Sr{sub 2}Pd{sub 2}Al are polar intermetallics.« less
Dual Coding, Reasoning and Fallacies.
ERIC Educational Resources Information Center
Hample, Dale
1982-01-01
Develops the theory that a fallacy is not a comparison of a rhetorical text to a set of definitions but a comparison of one person's cognition with another's. Reviews Paivio's dual coding theory, relates nonverbal coding to reasoning processes, and generates a limited fallacy theory based on dual coding theory. (PD)
EYE-TRAC: monitoring attention and utility for mTBI
NASA Astrophysics Data System (ADS)
Maruta, Jun; Tong, Jianliang; Lee, Stephanie W.; Iqbal, Zarah; Schonberger, Alison; Ghajar, Jamshid
2012-06-01
Attention is a core function in cognition and also the most prevalent cognitive deficit in mild traumatic brain injury (mTBI). Predictive timing is an essential element of attention functioning because sensory processing and execution of goal-oriented behavior are facilitated by temporally accurate prediction. It is hypothesized that impaired synchronization between prediction and external events accounts for the attention deficit in mTBI. Other cognitive and somatic or affective symptoms associated with mTBI may be explained as secondary consequences of impaired predictive timing. Eye-Tracking Rapid Attention Computation (EYE-TRAC) is the quantification of predictive timing with indices of dynamic visuo-motor synchronization (DVS) between the gaze and the target during continuous predictive visual tracking. Such quantification allows for cognitive performance monitoring in comparison to the overall population as well as within individuals over time. We report preliminary results of normative data and data collected from subjects with a history of mTBI within 2 weeks of injury and post-concussive symptoms at the time of recruitment. A substantial proportion of mTBI subjects demonstrated DVS scores worse than 95% of normal subjects. In addition, longitudinal monitoring of acute mTBI subjects showed that initially abnormal DVS scores were followed by improvement toward the normal range. In summary, EYE-TRAC provides fast and objective indices of DVS that allow comparison of attention performance to a normative standard and monitoring of within-individual changes.
ERIC Educational Resources Information Center
Higher Education Funding Council for England, 2016
2016-01-01
This report provides an overview of the current financial health of the Higher Education Funding Council for England (HEFCE) funded higher education sector in England. This does not include directly funded further education or other colleges, or alternative providers of higher education. The analysis covers financial results for the academic year…
Bognar, Stephanie; DeFaria, Anne Marie; O'Dwyer, Casey; Pankiw, Elana; Simic Bogler, Jennifer; Teixeira, Suzanne; Nyhof-Young, Joyce; Evans, Cathy
2017-06-01
To understand why individuals with Parkinson's disease (PD) participate in a community-based therapeutic dance program and to explore its influence on perceived physical, social and emotional well-being of participants. A qualitative descriptive design was employed using one-on-one semi-structured interviews. Individuals with PD who participated in the Dancing with Parkinson's program were recruited from two locations. Interviews were audio-recorded, transcribed, de-identified and then placed into NVivo 10 software for analysis. A content analysis approach was used with an inductive analysis method to generate a coding scheme. Group discussion facilitated development of overarching themes. Ten participants' responses revealed that the dance program allows for self-improvement and regaining identity through disease self-management. Positive influences of socialization arose through the class, decreasing isolation and improving quality of life. Participants communicate through music and dance to enhance connection with others. Dancing with Parkinson's classes allow for re-development of the social self, which can increase sense of enjoyment in life. Dance programs provide opportunities for social interaction, non-verbal communication and self-improvement, reestablishing self-identity and a sense of usefulness. This study provides unique insight into the experience of participating in a dance program from the perspective of individuals with PD. Implications for rehabilitation Dance is emerging as a strategy to address the physical and psychosocial effects of Parkinson's disease (PD), but little is known regarding participants' perceptions of community-based therapeutic dance programs for PD. This study found that Dancing with Parkinson's (DWP) facilitated an improvement in social participation, resulting in decreased isolation and improved quality of life. Participation in the DWP program can facilitate a positive change in perspective and attitude toward a PD diagnosis, thereby increasing feelings of self-efficacy and improving self-management of the disease. Participants of this study emphasized the multifaceted benefits of DWP, suggesting that it has great potential for addressing not only the physical challenges, but also the cognitive and emotional challenges associated with PD.
Stephen, Emma; Blake, Alexander J; Carter, Emma; Collison, David; Davies, E Stephen; Edge, Ruth; Lewis, William; Murphy, Damien M; Wilson, Claire; Gould, Robert O; Holder, Alan J; McMaster, Jonathan; Schröder, Martin
2012-02-06
The Pd(II) complexes [Pd([9]aneS(3))(2)](PF(6))(2)·2MeCN (1) ([9]aneS(3) = 1,4,7-trithiacyclononane) and [Pd([18]aneS(6))](PF(6))(2) (2) ([18]aneS(6) = 1,4,7,10,13,16-hexathiacyclooctadecane) can be oxidized electrochemically or chemically oxidized with 70% HClO(4) to [Pd([9]aneS(3))(2)](3+) and [Pd([18]aneS(6))](3+), respectively. These centers have been characterized by single crystal X-ray diffraction, and by UV/vis and multifrequency electron paramagnetic resonance (EPR) spectroscopies. The single crystal X-ray structures of [Pd(III)([9]aneS(3))(2)](ClO(4))(6)·(H(3)O)(3)·(H(2)O)(4) (3) at 150 K and [Pd([18]aneS(6))](ClO(4))(6)·(H(5)O(2))(3) (4) at 90 K reveal distorted octahedral geometries with Pd-S distances of 2.3695(8), 2.3692(8), 2.5356(9) and 2.3490(6), 2.3454(5), 2.5474(6) Å, respectively, consistent with Jahn-Teller distortion at a low-spin d(7) Pd(III) center. The Pd(II) compound [Pd([9]aneS(3))(2)](PF(6))(2) shows a one-electron oxidation process in MeCN (0.2 M NBu(4)PF(6), 293 K) at E(1/2) = +0.57 V vs. Fc(+)/Fc assigned to a formal Pd(III)/Pd(II) couple. Multifrequency (Q-, X-, S-, and L-band) EPR spectroscopic analysis of [Pd([9]aneS(3))(2)](3+) and [Pd([18]aneS(6))](3+) gives g(iso) = 2.024, |A(iso(Pd))| = 18.9 × 10(-4) cm(-1); g(xx) = 2.046, g(yy) = 2.041, g(zz) = 2.004; |A(xx(Pd))| = 24 × 10(-4) cm(-1), |A(yy(Pd))| = 22 × 10(-4) cm(-1), |A(zz(Pd))| = 14 × 10(-4) cm(-1), |a(xx(H))| = 4 × 10(-4) cm(-1), |a(yy(H))| = 5 × 10(-4) cm(-1), |a(zz(H))| = 5.5 × 10(-4) cm(-1) for [Pd([9]aneS(3))(2)](3+), and g(iso) = 2.015, |A(iso(Pd))| = 18.8× 10(-4) cm(-1); g(xx) = 2.048 g(yy) = 2.036, g(zz) = 1.998; |a(xx(H))| = 5, |a(yy(H))| = 5, |a(zz(H))| = 6 × 10(-4) cm(-1); |A(xx(Pd))| = 23× 10(-4) cm(-1), |A(yy(Pd))| = 22 × 10(-4) cm(-1), |A(zz(Pd))| = 4 × 10(-4) cm(-1) for [Pd([18]aneS(6))](3+). Both [Pd([9]aneS(3))(2)](3+) and [Pd([18]aneS(6))](3+) exhibit five-line superhyperfine splitting in the g(zz) region in their frozen solution EPR spectra. Double resonance spectroscopic measurements, supported by density functional theory (DFT) calculations, permit assignment of this superhyperfine to through-bond coupling involving four (1)H centers of the macrocyclic ring. Analysis of the spin Hamiltonian parameters for the singly occupied molecular orbital (SOMO) in these complexes gives about 20.4% and 25% Pd character in [Pd([9]aneS(3))(2)](3+) and [Pd([18]aneS(6))](3+), respectively, consistent with the compositions calculated from scalar relativistic DFT calculations.
NASA Astrophysics Data System (ADS)
Terashima, Atsunori; Nilsson, Mikael; Ozawa, Masaki; Chiba, Satoshi
2017-09-01
The Aprés ORIENT research program, as a concept of advanced nuclear fuel cycle, was initiated in FY2011 aiming at creating stable, highly-valuable elements by nuclear transmutation from ↓ssion products. In order to simulate creation of such elements by (n, γ) reaction succeeded by β- decay in reactors, a continuous-energy Monte Carlo burnup calculation code MVP-BURN was employed. Then, it is one of the most important tasks to con↓rm the reliability of MVP-BURN code and evaluated neutron cross section library. In this study, both an experiment of neutron activation analysis in TRIGA Mark I reactor at University of California, Irvine and the corresponding burnup calculation using MVP-BURN code were performed for validation of the simulation on transmutation of light platinum group elements. Especially, some neutron capture reactions such as 102Ru(n, γ)103Ru, 104Ru(n, γ)105Ru, and 108Pd(n, γ)109Pd were dealt with in this study. From a comparison between the calculation (C) and the experiment (E) about 102Ru(n, γ)103Ru, the deviation (C/E-1) was signi↓cantly large. Then, it is strongly suspected that not MVP-BURN code but the neutron capture cross section of 102Ru belonging to JENDL-4.0 used in this simulation have made the big di↑erence as (C/E-1) >20%.
SUS Source Level Error Analysis
1978-01-20
RIECIP1IEN’ CATALOG NUMBER * ITLE (and SubaltIe) S. TYP aof REPORT & _V9RCO SUS~ SOURCE LEVEL ERROR ANALYSIS & Fia 1.r,. -. pAURWORONTIUMm N (s)$S...Fourier Transform (FFTl) SUS Signal model ___ 10 TRA&C (CeEOINIMII1& ro"* *140O tidat n9#*#*Y a"d 0e~ntiff 6T 69*.4 apbt The report provides an analysis ...of major terms which contribute to signal analysis error in a proposed experiment to c-librate sourr - I levels of SUS (Signal Underwater Sound). A
De Backer, Daniel; Marx, Gernot; Tan, Andrew; Junker, Christopher; Van Nuffelen, Marc; Hüter, Lars; Ching, Willy; Michard, Frédéric; Vincent, Jean-Louis
2011-02-01
Second-generation FloTrac software has been shown to reliably measure cardiac output (CO) in cardiac surgical patients. However, concerns have been raised regarding its accuracy in vasoplegic states. The aim of the present multicenter study was to investigate the accuracy of the third-generation software in patients with sepsis, particularly when total systemic vascular resistance (TSVR) is low. Fifty-eight septic patients were included in this prospective observational study in four university-affiliated ICUs. Reference CO was measured by bolus pulmonary thermodilution (iCO) using 3-5 cold saline boluses. Simultaneously, CO was computed from the arterial pressure curve recorded on a computer using the second-generation (CO(G2)) and third-generation (CO(G3)) FloTrac software. CO was also measured by semi-continuous pulmonary thermodilution (CCO). A total of 401 simultaneous measurements of iCO, CO(G2), CO(G3), and CCO were recorded. The mean (95%CI) biases between CO(G2) and iCO, CO(G3) and iCO, and CCO and iCO were -10 (-15 to -5)% [-0.8 (-1.1 to -0.4) L/min], 0 (-4 to 4)% [0 (-0.3 to 0.3) L/min], and 9 (6-13)% [0.7 (0.5-1.0) L/min], respectively. The percentage errors were 29 (20-37)% for CO(G2), 30 (24-37)% for CO(G3), and 28 (22-34)% for CCO. The difference between iCO and CO(G2) was significantly correlated with TSVR (r(2) = 0.37, p < 0.0001). A very weak (r(2) = 0.05) relationship was also observed for the difference between iCO and CO(G3). In patients with sepsis, the third-generation FloTrac software is more accurate, as precise, and less influenced by TSVR than the second-generation software.
Supaporn, Pansuwan; Yeom, Sung Ho
2018-04-30
This study investigated the biological conversion of crude glycerol generated from a commercial biodiesel production plant as a by-product to 1,3-propanediol (1,3-PD). Statistical analysis was employed to derive a statistical model for the individual and interactive effects of glycerol, (NH 4 ) 2 SO 4 , trace elements, pH, and cultivation time on the four objectives: 1,3-PD concentration, yield, selectivity, and productivity. Optimum conditions for each objective with its maximum value were predicted by statistical optimization, and experiments under the optimum conditions verified the predictions. In addition, by systematic analysis of the values of four objectives, optimum conditions for 1,3-PD concentration (49.8 g/L initial glycerol, 4.0 g/L of (NH 4 ) 2 SO 4 , 2.0 mL/L of trace element, pH 7.5, and 11.2 h of cultivation time) were determined to be the global optimum culture conditions for 1,3-PD production. Under these conditions, we could achieve high 1,3-PD yield (47.4%), 1,3-PD selectivity (88.8%), and 1,3-PD productivity (2.1/g/L/h) as well as high 1,3-PD concentration (23.6 g/L).
Sato, Tatsuhiko; Watanabe, Ritsuko; Sihver, Lembit; Niita, Koji
2012-01-01
Microdosimetric quantities such as lineal energy are generally considered to be better indices than linear energy transfer (LET) for expressing the relative biological effectiveness (RBE) of high charge and energy particles. To calculate their probability densities (PD) in macroscopic matter, it is necessary to integrate microdosimetric tools such as track-structure simulation codes with macroscopic particle transport simulation codes. As an integration approach, the mathematical model for calculating the PD of microdosimetric quantities developed based on track-structure simulations was incorporated into the macroscopic particle transport simulation code PHITS (Particle and Heavy Ion Transport code System). The improved PHITS enables the PD in macroscopic matter to be calculated within a reasonable computation time, while taking their stochastic nature into account. The microdosimetric function of PHITS was applied to biological dose estimation for charged-particle therapy and risk estimation for astronauts. The former application was performed in combination with the microdosimetric kinetic model, while the latter employed the radiation quality factor expressed as a function of lineal energy. Owing to the unique features of the microdosimetric function, the improved PHITS has the potential to establish more sophisticated systems for radiological protection in space as well as for the treatment planning of charged-particle therapy.
Data-Base Software For Tracking Technological Developments
NASA Technical Reports Server (NTRS)
Aliberti, James A.; Wright, Simon; Monteith, Steve K.
1996-01-01
Technology Tracking System (TechTracS) computer program developed for use in storing and retrieving information on technology and related patent information developed under auspices of NASA Headquarters and NASA's field centers. Contents of data base include multiple scanned still images and quick-time movies as well as text. TechTracS includes word-processing, report-editing, chart-and-graph-editing, and search-editing subprograms. Extensive keyword searching capabilities enable rapid location of technologies, innovators, and companies. System performs routine functions automatically and serves multiple users.
Effect of planecta and ROSE™ on the frequency characteristics of blood pressure-transducer kits.
Fujiwara, Shigeki; Kawakubo, Yoshifumi; Mori, Satoshi; Tachihara, Keiichi; Toyoguchi, Izumi; Yokoyama, Takeshi
2015-12-01
Pressure-transducer kits have frequency characteristics such as natural frequency and damping coefficient, which affect the monitoring accuracy. The aim of the present study was to investigate the effect of planecta ports and a damping device (ROSE™, Argon Medical Devices, TX, USA) on the frequency characteristics of pressure-transducer kits. The FloTrac sensor kit (Edwards Lifesciences, CA, USA) and the DTXplus transducer kit (Argon Medical Devices) were prepared with planecta ports, and their frequency characteristics were tested with or without ROSE™. The natural frequency and damping coefficient of each kit were obtained using frequency characteristics analysis software and evaluated by plotting them on the Gardner's chart. By inserting a planecta port, the natural frequency markedly decreased in both the FloTrac sensor kit (from 40 to 22 Hz) and the DTXplus transducer kit (from 35 to 22 Hz). In both kits with one planecta port, the damping coefficient markedly increased by insertion of ROSE™ from 0.2 to 0.5, optimising frequency characteristics. In both kits with two planecta ports, however, the natural frequency decreased from 22 to 12 Hz. The damping coefficient increased from 0.2 to 0.8 by insertion of ROSE™; however, optimisation was not achieved even by ROSE™ insertion. Planecta ports decrease the natural frequency of the kit. ROSE™ is useful to optimise the frequency characteristics in the kits without or with one planecta port. However, optimisation is difficult with two or more planecta ports, even with the ROSE™ device.
Personality characteristics and motor skills attributed to occupations in Parkinson disease.
Gatto, Nicole M; Bordelon, Yvette; Gatz, Margaret; Ritz, Beate
2011-03-01
It has previously been speculated that a distinct premorbid personality characterized by introversion, rigidity, and over cautiousness might be associated with Parkinson disease (PD). Only 1 previous study has assessed personality before PD onset, and other data collected retrospectively do not exclude reverse causation. We relied on the longest held job reported in an interview to infer personality traits and motor skills for 355 incident PD patients and 335 population controls enrolled in a PD study in California. Jobs were coded according to the 1980 US Census Occupational Code and assigned scores for various demands, skills, and aptitudes required by the job. None of the occupational temperament or interest factors required, expected, or exhibited by workers were related to statistically significantly higher odds of having PD per unit increase in scores, whereas there was some suggestion of differences when the extremes were examined. Analyses of physical aptitude factors showed that PD cases were less likely to have worked in jobs that involved certain motor skills. This study uses a novel approach to assess personality traits using occupational characteristics. Most job attributes thought to reflect conservativeness; risk taking, stress resistance, and flexibility were not associated with PD in a linear manner. Thus, these occupation-derived traits do not seem to support the existence of a distinct parkinsonian personality. However, the negative associations with jobs requiring certain motor skills are intriguing, and may suggest very early premotor features or a lack of continuous motor training as a risk factor for PD.
Wang, Huanbin; Yao, Han; Li, Chushu; Liang, Lunxi; Zhang, Yao; Shi, Hubing; Zhou, Chongzhi; Chen, Yingxuan; Fang, Jing-Yuan; Xu, Jie
2017-01-01
Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46.3 vs 69.1 mo; p = 0.0004). The association remained significant in multivariate COX regression analysis (hazard ratio = 2.778, 95% confidence interval [CI] = 1.668-4.627; p < 0.0001). In the validation CRC data set, significant association between PD-L2 overexpression and poor survival was supported by the univariate analysis (27.1 vs. 88.9 mo; p = 0.0002) and multivariate model (hazard ratio = 7.09, 95%CI 1.78-28.16; p = 0.005). Western Blot revealed strong induction of PD-L2 expression by interferon-γ (IFNγ) in CRC cells, and the mRNA levels of both genes were significantly correlated in CRC tissue samples. Suppression of glycosylation with tunicamycin caused a shift in molecular weight and significant decrease in the expression of PD-L2 protein. In conclusion, PD-L2 overexpression in CRC cells, under the regulation by IFNγ and glycosylation, associates with poor survival of patients with colorectal cancer. These findings highlight PD-L2 as a promising therapeutic target in CRC and suggest potential routes to control PD-L2 expression in CRC cells.
Wang, Huanbin; Yao, Han; Li, Chushu; Liang, Lunxi; Zhang, Yao; Shi, Hubing; Zhou, Chongzhi; Chen, Yingxuan; Fang, Jing-Yuan
2017-01-01
ABSTRACT Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46.3 vs 69.1 mo; p = 0.0004). The association remained significant in multivariate COX regression analysis (hazard ratio = 2.778, 95% confidence interval [CI] = 1.668–4.627; p < 0.0001). In the validation CRC data set, significant association between PD-L2 overexpression and poor survival was supported by the univariate analysis (27.1 vs. 88.9 mo; p = 0.0002) and multivariate model (hazard ratio = 7.09, 95%CI 1.78–28.16; p = 0.005). Western Blot revealed strong induction of PD-L2 expression by interferon-γ (IFNγ) in CRC cells, and the mRNA levels of both genes were significantly correlated in CRC tissue samples. Suppression of glycosylation with tunicamycin caused a shift in molecular weight and significant decrease in the expression of PD-L2 protein. In conclusion, PD-L2 overexpression in CRC cells, under the regulation by IFNγ and glycosylation, associates with poor survival of patients with colorectal cancer. These findings highlight PD-L2 as a promising therapeutic target in CRC and suggest potential routes to control PD-L2 expression in CRC cells. PMID:28811964
Wu, Zhongbiao; Sheng, Zhongyi; Liu, Yue; Wang, Haiqiang; Tang, Nian; Wang, Jie
2009-05-30
Pd-modified TiO(2) prepared by thermal impregnation method was used in this study for photocatalytic oxidation of NO in gas phase. The physico-chemical properties of Pd/TiO(2) catalysts were characterized by X-ray diffraction analysis (XRD), Brunauer-Emmett-Teller measurements (BET), X-ray photoelectron spectrum analysis (XPS), transmission electron microscopy (TEM), high resolution-transmission electron microscopy (HR-TEM), UV-vis diffuse reflectance spectra (UV-vis DRS) and photoluminescence spectra (PL). It was found that Pd dopant existed as PdO particles in as-prepared photocatalysts. The results of PL spectra indicated that the photogenerated electrons and holes were efficiently separated after Pd doping. During in situ XPS study, it was found that the content of hydroxyl groups on the surface of Pd/TiO(2) increased when the catalyst was irradiated by UV light, which could result in the improvement of photocatalytic activity. The activity test showed that the optimum Pd dopant content was 0.05 wt.%. And the maximum conversion of NO was about 72% higher than that of P25 when the initial concentration of NO was 200 ppm, which showed that Pd/TiO(2) photocatalysts could be potentially applied to oxidize higher concentration of NO.
[Detection of gene mutation in glucose-6-phosphate dehydrogenase deficiency by RT-PCR sequencing].
Lyu, Rong-Yu; Chen, Xiao-Wen; Zhang, Min; Chen, Yun-Sheng; Yu, Jie; Wen, Fei-Qiu
2016-07-01
Since glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary hemolytic erythrocyte enzyme deficiency, most cases have single nucleotide mutations in the coding region, and current test methods for gene mutation have some missed detections, this study aimed to investigate the feasibility of RT-PCR sequencing in the detection of gene mutation in G6PD deficiency. According to the G6PD/6GPD ratio, 195 children with anemia of unknown cause or who underwent physical examination between August 2013 and July 2014 were classified into G6PD-deficiency group with 130 children (G6PD/6GPD ratio <1.00) and control group with 65 children (G6PD/6GPD ratio≥1.00). The primer design and PCR amplification conditions were optimized, and RT-PCR sequencing was used to analyze the complete coding sequence and verify the genomic DNA sequence in the two groups. In the G6PD-deficiency group, the detection rate of gene mutation was 100% and 13 missense mutations were detected, including one new mutation. In the control group, no missense mutation was detected in 28 boys; 13 heterozygous missense mutations, 1 homozygous same-sense mutation (C1191T) which had not been reported in China and abroad, and 14 single nucleotide polymorphisms of C1311T were detected in 37 girls. The control group showed a high rate of missed detection of G6PD deficiency (carriers) in the specimens from girls (35%, 13/37). RT-PCR sequencing has a high detection rate of G6PD gene mutation and a certain value in clinical diagnosis of G6PD deficiency.
Applying Subject Matter Expertise (SME) Elicitation Techniques to TRAC Studies
2014-09-30
prioritisation, budgeting and resource allocation with multi-criteria decision analysis and decision conferencing ”. English. In: Annals of Operations... electronically . Typically, in responding to survey items, experts are not expected to elaborate beyond providing responses in the format requested in the...between them, however irrelevant to probability Kynn and Ayyub.84 For example, an electronic jamming device might disrupt a cell phone signal at certain
NASA Astrophysics Data System (ADS)
Geraldes, Adriana Napoleão; Furtunato da Silva, Dionisio; Martins da Silva, Júlio César; Antonio de Sá, Osvaldo; Spinacé, Estevam Vitório; Neto, Almir Oliveira; Coelho dos Santos, Mauro
2015-02-01
Pd and PdSn (Pd:Sn atomic ratios of 90:10), supported on Multi Wall Carbon Nanotubes (MWCNT) or Carbon (C), are prepared by an electron beam irradiation reduction method. The obtained materials are characterized by X-Ray diffraction (XRD), Energy dispersive X-ray analysis (EDX), Transmission electron Microscopy (TEM) and Cyclic Voltammetry (CV). The activity for ethanol electro-oxidation is tested in alkaline medium, at room temperature, using Cyclic Voltammetry and Chronoamperometry (CA) and in a single alkaline direct ethanol fuel cell (ADEFC), in the temperature range of 60-90 °C. CV analysis finds that Pd/MWCNT and PdSn/MWCNT presents onset potentials changing to negative values and high current values, compared to Pd/C and PdSn/C electrocatalysts. ATR-FTIR analysis, performed during the CV, identifies acetate and acetaldehyde as principal products formed during the ethanol electro-oxidation, with low conversion to CO2. In single fuel cell tests, at 85 °C, using 2.0 mol L-1 ethanol in 2.0 mol L-1 KOH solutions, the electrocatalysts supported on MWCNT, also, show higher power densities, compared to the materials supported on carbon: PdSn/MWCNT, presents the best result (36 mW cm-2). The results show that the use of MWCNT, instead of carbon, as support, plus the addition of small amounts of Sn to Pd, improves the electrocatalytic activity for Ethanol Oxidation Reaction (EOR).
Fu, Ching-Feng; Lee, Chun-Chin; Liu, Yi-Hung; Peng, Shie-Ming; Warsink, Stefan; Elsevier, Cornelis J; Chen, Jwu-Ting; Liu, Shiuh-Tzung
2010-03-15
A series of designed palladium biscarbene complexes including saturated and unsaturated N-heterocyclic carbene (NHC) moieties have been prepared by the carbene transfer methods. All of these complexes have been characterized by (1)H and (13)C NMR spectroscopy as well as X-ray diffraction analysis. The reactivity of Pd-C((saturated NHC)) is distinct from that of Pd-C((unsaturated NHC)). The Pd-C((saturated NHC)) bonds are fairly stable toward reagents such as CF(3)COOH, AgBF(4) and I(2), whereas Pd-C((unsaturated NHC)) bonds are readily cleaved under the similar conditions. Notably, the catalytically activity of these palladium complexes on Suzuki-Miyaura coupling follows the order: (sat-NHC)(2)PdCl(2) > (sat-NHC)(unsat-NHC)PdCl(2 )> (unsat-NHC)(2)PdCl(2).
Eltoukhy, Moataz; Kuenze, Christopher; Oh, Jeonghoon; Jacopetti, Marco; Wooten, Savannah; Signorile, Joseph
2017-06-01
Gait patterns differ between healthy elders and those with Parkinson's disease (PD). A simple, low-cost clinical tool that can evaluate kinematic differences between these populations would be invaluable diagnostically; since gait analysis in a clinical setting is impractical due to cost and technical expertise. This study investigated the between group differences between the Kinect and a 3D movement analysis system (BTS) and reported validity and reliability of the Kinect v2 sensor for gait analysis. Nineteen subjects participated, eleven without (C) and eight with PD (PD). Outcome measures included spatiotemporal parameters and kinematics. Ankle range of motion for C was significantly less during ankle swing compared to PD (p=0.04) for the Kinect. Both systems showed significant differences for stride length (BTS (C 1.24±0.16, PD=1.01±0.17, p=0.009), Kinect (C=1.24±0.17, PD=1.00±0.18, p=0.009)), gait velocity (BTS (C=1.06±0.14, PD=0.83±0.15, p=0.01), Kinect (C=1.06±0.15, PD=0.83±0.16, p=0.01)), and swing velocity (BTS (C=2.50±0.27, PD=2.12±0.36, p=0.02), Kinect (C=2.32±0.25, PD=1.95±0.31, p=0.01)) between groups. Agreement (Range ICC =0.93-0.99) and consistency (Range ICC =0.94-0.99) were excellent between systems for stride length, stance duration, swing duration, gait velocity, and swing velocity. The Kinect v2 can was sensitive enough to detect between group differences and consistently produced results similar to the BTS system. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Benson, Michael T.; He, Lingfeng; King, James A.; Mariani, Robert D.
2018-04-01
Palladium is being investigated as a potential additive to metallic fuel to control fuel-cladding chemical interaction (FCCI). A primary cause of FCCI is the lanthanide fission products moving to the fuel periphery and interacting with the cladding. This interaction will lead to wastage of the cladding and, given enough time or burn-up, eventually to a cladding breach. The current study is a scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterization of annealed U-12Zr-4Pd and U-12Zr-4Pd-5Ln, where Ln = 53Nd-25Ce-16Pr-6La. The present study shows that Pd preferentially binds the lanthanides over other fuel constituents, which may prevent lanthanide migration and interaction with the cladding during irradiation. The SEM analysis indicates the 1:1 Pd-Ln compound is being formed, while the TEM analysis, due to higher resolution, found the 1:1 compound, as well as Pd-rich compounds Pd2Ln and Pd3Ln2.
Magnetic characteristics of CoPd and FePd antidot arrays on nanoperforated Al2O3 templates
NASA Astrophysics Data System (ADS)
Maximenko, A.; Fedotova, J.; Marszałek, M.; Zarzycki, A.; Zabila, Y.
2016-02-01
Hard magnetic antidot arrays show promising results in context of designing of percolated perpendicular media. In this work the technology of magnetic FePd and CoPd antidot arrays fabrication is presented and correlation between surface morphology, structure and magnetic properties is discussed. CoPd and FePd antidot arrays were fabricated by deposition of Co/Pd and Fe/Pd multilayers (MLs) on porous anodic aluminum oxide templates with bowl-shape cell structure with inclined intercellular regions. FePd ordered L10 structure was obtained by successive vacuum annealing at elevated temperatures (530 °C) and confirmed by XRD analysis. Systematic analysis of magnetization curves evidenced perpendicular magnetic anisotropy of CoPd antidot arrays, while FePd antidot arrays revealed isotropic magnetic anisotropy with increased out-of-plane magnetic contribution. MFM images of antidots showed more complicated contrast, with alternating magnetic dots oriented parallel and antiparallel to tip magnetization moment.
Genomic analysis of primordial dwarfism reveals novel disease genes.
Shaheen, Ranad; Faqeih, Eissa; Ansari, Shinu; Abdel-Salam, Ghada; Al-Hassnan, Zuhair N; Al-Shidi, Tarfa; Alomar, Rana; Sogaty, Sameera; Alkuraya, Fowzan S
2014-02-01
Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis.
Genomic analysis of primordial dwarfism reveals novel disease genes
Shaheen, Ranad; Faqeih, Eissa; Ansari, Shinu; Abdel-Salam, Ghada; Al-Hassnan, Zuhair N.; Al-Shidi, Tarfa; Alomar, Rana; Sogaty, Sameera; Alkuraya, Fowzan S.
2014-01-01
Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis. PMID:24389050
Differential effects of severe vs mild GBA mutations on Parkinson disease.
Gan-Or, Ziv; Amshalom, Idan; Kilarski, Laura L; Bar-Shira, Anat; Gana-Weisz, Mali; Mirelman, Anat; Marder, Karen; Bressman, Susan; Giladi, Nir; Orr-Urtreger, Avi
2015-03-03
To better define the genotype-phenotype correlations between the type of GBA (glucosidase, beta, acid) mutation, severe or mild, and the risk and age at onset (AAO), and potential mechanism of Parkinson disease (PD). We analyzed 1,000 patients of Ashkenazi-Jewish descent with PD for 7 founder GBA mutations, and conducted a meta-analysis of risk and AAO according to GBA genotype (severe or mild mutation). The meta-analysis included 11,453 patients with PD and 14,565 controls from worldwide populations. The statistical analysis was done with and without continuity correction (constant or empirical), considering biases that could potentially affect the results. Among Ashkenazi-Jewish patients with PD, the odds ratios for PD were 2.2 and 10.3 for mild and severe GBA mutation carriers, respectively. The observed frequency of severe GBA mutation carriers among patients with PD was more than 4-fold than expected (4.4% vs 0.9%, respectively, p < 0.0001, Fisher exact test). In the different models of the meta-analysis, the odds ratios for PD ranged between 2.84 and 4.94 for mild GBA mutation carriers and 9.92 and 21.29 for severe GBA mutation carriers (p < 1 × 10(-6) for all analyses). Pooled analysis demonstrated AAO of 53.1 (±11.2) and 58.1 (±10.6) years for severe and mild GBA mutation carriers, respectively (p = 4.3 × 10(-5)). These data demonstrate that mild and severe heterozygous GBA mutations differentially affect the risk and the AAO of PD. Our results have important implications for genetic counseling and clinical follow-up. © 2015 American Academy of Neurology.
Genetic analysis of SCA2, 3 and 17 in idiopathic Parkinson's disease.
Lim, S W; Zhao, Y; Chua, E; Law, H Y; Yuen, Y; Pavanni, R; Wong, M C; Ng, I S; Yoon, C S; Puong, K Y; Lim, S H; Tan, E K
2006-07-31
Recent reports of SCA2 and SCA3 patients who presented with levodopa responsive parkinsonism have generated considerable interest as they have implications for genetic testing. It is unclear whether ethnic race alone or founder effects within certain geographical region explain such an association. In this study, we conducted genetic analysis of SCA2, 3, 17 in an ethnic Chinese cohort with early onset and familial Parkinson's disease (PD) and healthy controls. A total of 191 subjects comprising of 91 PD and 100 healthy controls were examined. We identified one positive case of SCA2 in an early-onset sporadic PD patient who had CAG 36 repeats, yielding a prevalence of 2.2% in early-onset sporadic PD patients and less than 1.0% in our study PD population. The size of the repeats was lower than the expanded repeats (38-57) in SCA2 patients with ataxia in our population. All the children of the patient were physically normal even though some of them carried the repeat expansion of similar size. No cases and controls were positive for SCA3 and SCA17. We do not think routine screening of SCA2, SCA3 and SCA17 for all idiopathic PD patients is cost-effective in our ethnic Chinese population. However, SCA2 should be a differential diagnosis in young onset sporadic PD when genetic mutations of other known PD genes have been excluded.
Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection
Eyquem, Justin; Mansilla-Soto, Jorge; Giavridis, Theodoros; van der Stegen, Sjoukje J. C.; Hamieh, Mohamad; Cunanan, Kristen M.; Odak, Ashlesha; Gönen, Mithat; Sadelain, Michel
2017-01-01
Chimeric antigen receptors (CARs) are synthetic receptors that redirect and reprogram T cells to mediate tumour rejection1. The most successful CARs used to date are those targeting CD19 (ref. 2), which offer the prospect of complete remission in patients with chemorefractory or relapsed B-cell malignancies3. CARs are typically transduced into the T cells of a patient using γ-retroviral4 vectors or other randomly integrating vectors5, which may result in clonal expansion, oncogenic transformation, variegated transgene expression and transcriptional silencing6–8. Recent advances in genome editing enable efficient sequence-specific interventions in human cells9,10, including targeted gene delivery to the CCR5 and AAVS1 loci11,12. Here we show that directing a CD19-specific CAR to the T-cell receptor α constant (TRAC) locus not only results in uniform CAR expression in human peripheral blood T cells, but also enhances T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in a mouse model of acute lymphoblastic leukaemia. We further demonstrate that targeting the CAR to the TRAC locus averts tonic CAR signalling and establishes effective internalization and re-expression of the CAR following single or repeated exposure to antigen, delaying effector T-cell differentiation and exhaustion. These findings uncover facets of CAR immunobiology and underscore the potential of CRISPR/Cas9 genome editing to advance immunotherapies. PMID:28225754
75 FR 14161 - Agency Information Collection Activities: Submission for OMB Review; Comment Request
Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-24
.... Proposed Project: Transformation Accountability (TRAC) Reporting System --(OMB No. 0930-0285)--Revision... Receiving Mental Health Services. The name of this data collection effort is revised to the Transformation... 2 Education and Employment 4 3 Crime and Criminal Justice........ 1 1 Perception of Care 15 14...
A motif for infinite metal atom wires.
Yin, Xi; Warren, Steven A; Pan, Yung-Tin; Tsao, Kai-Chieh; Gray, Danielle L; Bertke, Jeffery; Yang, Hong
2014-12-15
A new motif for infinite metal atom wires with tunable compositions and properties is developed based on the connection between metal paddlewheel and square planar complex moieties. Two infinite Pd chain compounds, [Pd4(CO)4(OAc)4Pd(acac)2] 1 and [Pd4(CO)4(TFA)4Pd(acac)2] 2, and an infinite Pd-Pt heterometallic chain compound, [Pd4(CO)4(OAc)4Pt(acac)2] 3, are identified by single-crystal X-ray diffraction analysis. In these new structures, the paddlewheel moiety is a Pd four-membered ring coordinated by bridging carboxylic ligands and μ2 carbonyl ligands. The planar moiety is either Pd(acac)2 or Pt(acac)2 (acac = acetylacetonate). These moieties are connected by metallophilic interactions. The results showed that these one-dimensional metal wire compounds have photoluminescent properties that are tunable by changing ligands and metal ions. 3 can also serve as a single source precursor for making Pd4Pt bimetallic nanostructures with precise control of metal composition. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Bogojeski, Jovana; Volbeda, Jeroen; Freytag, Matthias; Tamm, Matthias; Bugarčić, Živadin D
2015-10-21
A series of novel Pd(ii) complexes with chelating mono(imidazolin-2-imine) and bis(imidazolin-2-imine) ligands were synthesized. The crystal structures of [Pd(DMEAIm(iPr))Cl2] and [Pd(DPENIm(iPr))Cl2] were determined by X-ray diffraction analysis. The reactivity of the six Pd(ii) complexes, namely, [Pd(en)Cl2], [Pd(EAIm(iPr))Cl2], [Pd(DMEAIm(iPr))Cl2], [Pd(DPENIm(iPr))Cl2], [Pd(BL(iPr))Cl2] and [Pd(DACH(Im(iPr))2)Cl2], were investigated. Spectrophotometric acid-base titrations were performed to determine the pKa values of the coordinated water molecules in [Pd(en)(H2O)2](2+), [Pd(EAIm(iPr))(H2O)2](2+), [Pd(DMEAIm(iPr))(H2O)2](2+), [Pd(DPENIm(iPr))(H2O)2](2+), [Pd(BL(iPr))(H2O)2](2+) and [Pd(DACH(Im(iPr))2)(H2O)2](2+). The substitution of the chloride ligands in these complexes by TU, l-Met, l-His and Gly was studied under pseudo-first-order conditions as a function of the nucleophile concentration and temperature using stopped-flow techniques; the sulfur-donor nucleophiles have shown better reactivity than nitrogen-donor nucleophiles. The obtained results indicate that there is a clear correlation between the nature of the imidazolin-2-imine ligands and the acid-base characteristics and reactivity of the resulting Pd(ii) complexes; the order of reactivity of the investigated Pd(ii) complexes is: [Pd(en)Cl2] > [Pd(EAIm(iPr))Cl2] > [Pd(DMEAIm(iPr))Cl2] > [Pd(DPENIm(iPr))Cl2] > [Pd(BL(iPr))Cl2] > [Pd(DACH(Im(iPr))2)Cl2]. The solubility measurements revealed good solubility of the studied imidazolin-2-imine complexes in water, despite the fact that these Pd(ii) complexes are neutral complexes. Based on the performed studies, three unusual features of the novel imidazolin-2-imine Pd(ii) complexes are observed, that is, good solubility in water, very low reactivity and high pKa values. The coordination geometries around the palladium atoms are distorted square-planar; the [Pd(DMEAIm(iPr))Cl2] complex displays Pd-N distances of 2.013(2) and 2.076(2) Å, while the [Pd(DPENIm(iPr))Cl2] complex displays similar Pd-N distances of 2.034(4) and 2.038(3) Å. The studied systems are of interest because little is known about the substitution behavior of imidazolin-2-imine Pd(ii) complexes with bio-molecules under physiological conditions.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kwon, Tae-Soon; Yun, Byong-Jo; Euh, Dong-Jin
Multidimensional thermal-hydraulic behavior in the downcomer annulus of a pressurized water reactor (PWR) vessel with a direct vessel injection mode is presented based on the experimental observation in the MIDAS (multidimensional investigation in downcomer annulus simulation) steam-water test facility. From the steady-state test results to simulate the late reflood phase of a large-break loss-of-coolant accident (LBLOCA), isothermal lines show the multidimensional phenomena of a phasic interaction between steam and water in the downcomer annulus very well. MIDAS is a steam-water separate effect test facility, which is 1/4.93 linearly scaled down to a 1400-MW(electric) PWR type of a nuclear reactor, focusedmore » on understanding multidimensional thermal-hydraulic phenomena in a downcomer annulus with various types of safety injection during the refill or reflood phase of an LBLOCA. The initial and the boundary conditions are scaled from the pretest analysis based on the preliminary calculation using the TRAC code. The superheated steam with a superheating degree of 80 K at a given downcomer pressure of 180 kPa is injected equally through three intact cold legs into the downcomer.« less
NASA Astrophysics Data System (ADS)
Długokęcka, Marta; Łuczak, Justyna; Polkowska, Żaneta; Zaleska-Medynska, Adriana
2017-05-01
A series of microemulsion (ME) system, constituted by different water to surfactant molar ratios (Wo) and oil to surfactant mass ratios (S), have been applied for Pd-TiO2 preparation. The effect of ME properties on the morphology of Pd nanoparticles formed at TiO2 surface and an effect of Pd size and distribution on the surface and photocatalytic properties of Pd-TiO2 were investigated. Microemulsion systems were characterized by means of viscosity, density, dynamic light scattering as well as surface tension measurements to find a correlation between the conditions of Pd nanoparticles formation, their morphology and photocatalyst features. The photocatalysts were characterized by transmission electron microscopy (TEM), X-ray diffraction analysis (XRD), UV-vis diffuse-reflectance spectroscopy (DRS), BET surface area and elemental analysis. The photocatalytic properties of Pd-modified TiO2 particles were studied in a model reaction of phenol photodegradation under Vis irradiation, as well as active species involved in the photocatalytic reaction were determined. Microemulsion composition was found to be a crucial parameter in determining the features of the TiO2-based photocatalysts covered by metallic nanoparticles. The highest photocatalytic activity under Vis radiation was observed for the Pd-TiO2 sample (average diameter 2.4 nm) obtained using 0.1 mol% Pd in the ME system containing 1.5 wt% of water and 82.8 wt% of cyclohexane with average droplet size of 2.83 ± 0.18 nm. In this regard, synthesis of such metal-semiconductor composites through the microemulsion route should always be preceded by investigation of ME properties in order to the eliminate the inhibitory effect of ME internal structure.
PD-L1 expression in Xp11.2 translocation renal cell carcinoma: Indicator of tumor aggressiveness.
Chang, Kun; Qu, Yuanyuan; Dai, Bo; Zhao, Jian-Yuan; Gan, Hualei; Shi, Guohai; Zhu, Yiping; Shen, Yijun; Zhu, Yao; Zhang, Hailiang; Ye, Dingwei
2017-05-18
Programmed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies. However, the PD-L1 content of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and its correlation with clinical outcomes remain unclear. This study aimed to investigate PD-L1 expression in Xp11.2 RCC and to assess its prognostic value. Formalin-fixed paraffin-embedded specimens from 36 adult patients that were histologically confirmed (by fluorescence in situ hybridization) were subjected to immunohistochemical analysis. Of the 36 Xp11.2 RCC patients, 9 (25.0%) had tumors with positive PD-L1 expression and 27 (75.0%) had tumors with negative PD-L1 expression. Positive PD-L1 expression correlated with advanced tumor stage (P = 0.001), regional lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). A multivariate analysis identified positive PD-L1 expression was an independent adverse prognostic factor for both progression free survival (hazard ratio: 3.7, P = 0.018) and overall survival (hazard ratio: 4.5, P = 0.034). The median PFS and OS for the whole cohort were 13.0 months (95% confidence interval [CI], 9.4-16.6 months) and 36.0 months (95% CI, 23.9-48.1 months), respectively. Our findings suggest that positive PD-L1 expression is indicative of worse clinical outcome in Xp11.2 RCC. Further studies are needed to explore the potential efficacy of targeting PD-L1 in Xp11.2 RCC.
Complete genomic screen in Parkinson disease: evidence for multiple genes.
Scott, W K; Nance, M A; Watts, R L; Hubble, J P; Koller, W C; Lyons, K; Pahwa, R; Stern, M B; Colcher, A; Hiner, B C; Jankovic, J; Ondo, W G; Allen, F H; Goetz, C G; Small, G W; Masterman, D; Mastaglia, F; Laing, N G; Stajich, J M; Slotterbeck, B; Booze, M W; Ribble, R C; Rampersaud, E; West, S G; Gibson, R A; Middleton, L T; Roses, A D; Haines, J L; Scott, B L; Vance, J M; Pericak-Vance, M A
2001-11-14
The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD. To identify genetic risk factors for idiopathic PD. Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status. Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis. Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients. Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.
Promising SiC support for Pd catalyst in selective hydrogenation of acetylene to ethylene
NASA Astrophysics Data System (ADS)
Guo, Zhanglong; Liu, Yuefeng; Liu, Yan; Chu, Wei
2018-06-01
In this study, SiC supported Pd nanoparticles were found to be an efficient catalyst in acetylene selective hydrogenation reaction. The ethylene selectivity can be about 20% higher than that on Pd/TiO2 catalyst at the same acetylene conversion at 90%. Moreover, Pd/SiC catalyst showed a stable catalytic life at 65 °C with 80% ethylene selectivity. With the detailed characterization using temperature-programmed reduction (H2-TPR), powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), N2 adsorption/desorption analysis, CO-chemisorption and thermo-gravimetric analysis (TGA), it was found that SiC owns a lower surface area (22.9 m2/g) and a broad distribution of meso-/macro-porosity (from 5 to 65 nm), which enhanced the mass transfer during the chemical process at high reaction rate and decreased the residence time of ethylene on catalyst surface. Importantly, SiC support has the high thermal conductivity, which favored the rapid temperature homogenization through the catalyst bed and inhabited the over-hydrogenation of acetylene. The surface electronic density of Pd on Pd/SiC catalyst was higher than that on Pd/TiO2, which could promote desorption of ethylene from surface of the catalyst. TGA results confirmed a much less coke deposition on Pd/SiC catalyst.
Lee, Ya-Ling; Hu, Hsiao-Yun; Huang, Li-Ying; Chou, Pesus; Chu, Dachen
2017-09-01
To determine the magnitude and temporal aspect of the effect of poor dental health and periodontal disease (PD) on dementia. Retrospective cohort study SETTING: Taiwan National Health Insurance Research Database. Individuals with newly diagnosed PD (N = 182,747) MEASUREMENTS: Participants were followed from January 1, 2000, to December 31, 2010. Participants were assigned to dental prophylaxis, intensive periodontal treatment, tooth extraction, or no treatment, according to International Classification of Diseases codes and PD treatment codes. The incidence rate of dementia of the groups was compared. The association between PD and dementia was analyzed using Cox regression, with adjustments for age, sex, monthly income, residential urbanicity, and comorbidities. The incidence of dementia was significantly higher in the group with PD that did not receive treatment (0.76% per year) and in the group that had teeth extracted (0.57% per year) than in the group that underwent intensive PD treatment (0.35% per year) and the group that received dental prophylaxis (0.39% per year) (P < .001). After adjusting for confounders, the Cox proportional hazards model revealed a higher risk of dementia in the group with PD who did not undergo treatment (hazard ratio (HR) = 1.14, 95% confidence interval (CI) = 1.04-1.24) and the group that had teeth extracted (HR = 1.10, 95% CI = 1.04-1.16) than in the group that received dental prophylaxis. Subjects who had more severe PD or did not receive periodontal treatment were at greater risk of developing dementia. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.
Personality Characteristics and Motor Skills Attributed to Occupations in Parkinson Disease
Gatto, Nicole M.; Bordelon, Yvette; Gatz, Margaret; Ritz, Beate
2013-01-01
Background It has previously been speculated that a distinct premorbid personality characterized by introversion, rigidity, and over cautiousness might be associated with Parkinson disease (PD). Only 1 previous study has assessed personality before PD onset, and other data collected retrospectively do not exclude reverse causation. Objective We relied on the longest held job reported in an interview to infer personality traits and motor skills for 355 incident PD patients and 335 population controls enrolled in a PD study in California. Methods Jobs were coded according to the 1980 US Census Occupational Code and assigned scores for various demands, skills, and aptitudes required by the job. Results None of the occupational temperament or interest factors required, expected, or exhibited by workers were related to statistically significantly higher odds of having PD per unit increase in scores, whereas there was some suggestion of differences when the extremes were examined. Analyses of physical aptitude factors showed that PD cases were less likely to have worked in jobs that involved certain motor skills. Conclusions This study uses a novel approach to assess personality traits using occupational characteristics. Most job attributes thought to reflect conservativeness; risk taking, stress resistance, and flexibility were not associated with PD in a linear manner. Thus, these occupation-derived traits do not seem to support the existence of a distinct parkinsonian personality. However, the negative associations with jobs requiring certain motor skills are intriguing, and may suggest very early premotor features or a lack of continuous motor training as a risk factor for PD. PMID:21487260
Sensitivity Analysis of a Cognitive Architecture for the Cultural Geography Model
2011-12-01
developmental inquiry. American Psychologist, 34(10), 906–911. Gazzaniga, M. S . (2004) The cognitive neurosciences III. Cambridge: MIT Press. Greeno, J. G...129 ix LIST OF FIGURES Situation-Based Cognitive Architecture (From Alt et al., 2011) .....................13 Figure 1. Theory of Planned...Harold, CG Model developer at TRAC-MTRY, who spend countless hours explaining to me the implementation of the Cognitive Architecture and CG model
Sociocultural Behavior Research and Engineering in the Department of Defense Context
2011-09-01
return on investment. Section IV provides a set of principles and practices to ensure that DoD investments are cost effective and have high...projects. The U.S. Army Training and Doctrine Command (TRADOC) Analysis Center (TRAC), the Naval Postgraduate School (NPS), the OSD’s Cost Assessment... cost -effectively allocating resources targeted toward relevant problems. The OSD HSCB Modeling Program is using that approach to rapidly implement a
Chern, Yahn-Bor; Ho, Pei-Shan; Kuo, Li-Chueh; Chen, Jin-Bor
2013-01-01
Peritoneal dialysis (PD)-related peritonitis remains an important complication in PD patients, potentially causing technique failure and influencing patient outcome. To date, no comprehensive study in the Taiwanese PD population has used a time-dependent statistical method to analyze the factors associated with PD-related peritonitis. Our single-center retrospective cohort study, conducted in southern Taiwan between February 1999 and July 2010, used time-dependent statistical methods to analyze the factors associated with PD-related peritonitis. The study recruited 404 PD patients for analysis, 150 of whom experienced at least 1 episode of peritonitis during the follow-up period. The incidence rate of peritonitis was highest during the first 6 months after PD start. A comparison of patients in the two groups (peritonitis vs null-peritonitis) by univariate analysis showed that the peritonitis group included fewer men (p = 0.048) and more patients of older age (≥65 years, p = 0.049). In addition, patients who had never received compulsory education showed a statistically higher incidence of PD-related peritonitis in the univariate analysis (p = 0.04). A proportional hazards model identified education level (less than elementary school vs any higher education level) as having an independent association with PD-related peritonitis [hazard ratio (HR): 1.45; 95% confidence interval (CI): 1.01 to 2.06; p = 0.045). Comorbidities measured using the Charlson comorbidity index (score >2 vs ≤2) showed borderline statistical significance (HR: 1.44; 95% CI: 1.00 to 2.13; p = 0.053). A lower education level is a major risk factor for PD-related peritonitis independent of age, sex, hypoalbuminemia, and comorbidities. Our study emphasizes that a comprehensive PD education program is crucial for PD patients with a lower education level.
Whole genome survey of coding SNPs reveals a reproducible pathway determinant of Parkinson disease
Srinivasan, Balaji S; Doostzadeh, Jaleh; Absalan, Farnaz; Mohandessi, Sharareh; Jalili, Roxana; Bigdeli, Saharnaz; Wang, Justin; Mahadevan, Jaydev; Lee, Caroline LG; Davis, Ronald W; William Langston, J; Ronaghi, Mostafa
2009-01-01
It is quickly becoming apparent that situating human variation in a pathway context is crucial to understanding its phenotypic significance. Toward this end, we have developed a general method for finding pathways associated with traits that control for pathway size. We have applied this method to a new whole genome survey of coding SNP variation in 187 patients afflicted with Parkinson disease (PD) and 187 controls. We show that our dataset provides an independent replication of the axon guidance association recently reported by Lesnick et al. [PLoS Genet 2007;3:e98], and also indicates that variation in the ubiquitin-mediated proteolysis and T-cell receptor signaling pathways may predict PD susceptibility. Given this result, it is reasonable to hypothesize that pathway associations are more replicable than individual SNP associations in whole genome association studies. However, this hypothesis is complicated by a detailed comparison of our dataset to the second recent PD association study by Fung et al. [Lancet Neurol 2006;5:911–916]. Surprisingly, we find that the axon guidance pathway does not rank at the very top of the Fung dataset after controlling for pathway size. More generally, in comparing the studies, we find that SNP frequencies replicate well despite technologically different assays, but that both SNP and pathway associations are globally uncorrelated across studies. We thus have a situation in which an association between axon guidance pathway variation and PD has been found in 2 out of 3 studies. We conclude by relating this seeming inconsistency to the molecular heterogeneity of PD, and suggest future analyses that may resolve such discrepancies. PMID:18853455
Ohnleiter, T; Mahé, M-A; Biau, J; Wdowczyk, D; Clavier, J-B; Antoni, D; Noël, G
2016-12-01
This study aimed to analyse the positioning protocols with the ExacTrac ® system, associated with a dedicated linear accelerator such as Novalis ® , for stereotactic treatment of brain metastases in several French centres. A survey, including three questions about the prescription of irradiation and twenty-one questions about how the ExacTrac ® system is used, was sent to nine French centres owning a dedicated Novalis ® accelerator. Five centres have accepted to participate in the study. All centres checked the positioning before each treatment's bow, with residual mismatch tolerances of 0.5 to 0.7mm for the translations and 0.5 to 1° for the rotations. All centres except one also realised orthogonal planar images of classic incidences to help operators ensure proper isocentre positioning. Prescribed doses were 20Gy in one fraction, 30Gy and 33Gy in three fractions or 34Gy in four fractions, mainly depending on the size of the lesion. Finally, a physician validated the images at the treatment station before starting the irradiation. The practices of the different centres concerning the positioning protocols were rather homogeneous, in agreement with the literature data on ExacTrac ® system's accuracy, as well as proposed fractionations. The systematic medical validation at the treatment station may, however, be questioned because of the waiting time between the doctor's call and validation itself and because of its usefulness; indeed, corrections by the radiation oncologist are very rare and in some centres, non-existent. Copyright © 2016. Published by Elsevier SAS.
High-affinity PD-1 molecules deliver improved interaction with PD-L1 and PD-L2.
Li, Yanyan; Liang, Zhaoduan; Tian, Ye; Cai, Wenxuan; Weng, Zhiming; Chen, Lin; Zhang, Huanling; Bao, Yifeng; Zheng, Hongjun; Zeng, Sihai; Bei, Chunhua; Li, Yi
2018-06-11
The inhibitory checkpoint molecule programmed death (PD)-1 plays a vital role in maintaining immune homeostasis upon binding to its ligands, PD-L1 and PD-L2. Several recent studies have demonstrated that soluble PD-1 (sPD-1) can block the interaction between membrane PD-1 and PD-L1 to enhance the anti-tumor capability of T cells. However, the affinity of natural sPD-1 binding to PD-L1 is too low to permit therapeutic applications. Here a PD-1 variant with ~3,000-fold and ~70-fold affinity increase to bind PD-L1 and PD-L2, respectively, was generated through directed molecular evolution and phage display technology. Structural analysis showed that mutations at amino acid positions 124 and 132 of PD-1 played major roles in enhancing the affinity of PD-1 binding to its ligands. The high-affinity PD-1 mutant could compete with the binding of antibodies specific to PD-L1 or PD-L2 on cancer cells or dendritic cells (DCs), and it could enhance the proliferation and IFN-γ release of activated lymphocytes. These features potentially qualify the high-affinity PD-1 variant as a unique candidate for the development of a new class of PD-1 immune checkpoint blockade therapeutics. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Czochralski growth of LaPd2Al2 single crystals
NASA Astrophysics Data System (ADS)
Doležal, P.; Rudajevová, A.; Vlášková, K.; Kriegner, D.; Václavová, K.; Prchal, J.; Javorský, P.
2017-10-01
The present study is focused on the preparation of single crystalline LaPd2Al2 by the Czochralski method. Differential scanning calorimetry (DSC) and energy dispersive X-ray spectroscopy (EDX) analyses reveal that LaPd2Al2 is an incongruently melting phase which causes difficulties for the preparation of single crystalline LaPd2Al2 by the Czochralski method. Therefore several non-stoichiometric polycrystalline samples were studied for its preparation. Finally the successful growth of LaPd2Al2 without foreign phases has been achieved by using a non-stoichiometric precursor with atomic composition 22:39:39 (La:Pd:Al). X-ray powder diffraction, EDX analysis and DSC were used for the characterisation. A single crystalline sample was separated from the ingot prepared by the Czochralski method using the non-stoichiometric precursor. The presented procedure for the preparation of pure single phase LaPd2Al2 could be modified for other incongruently melting phases.
Kimoto, Tetsuya; Ishii, Hirotaka; Higo, Shimpei; Hojo, Yasushi; Kawato, Suguru
2010-12-01
Although sex steroids play a crucial role in the postnatal brain development, the age-related changes in the hippocampal steroidogenesis remain largely unknown. We performed comprehensive investigations for the mRNA expressions of 26 sex steroidogenic enzymes/proteins and three sex steroid receptors in the male rat hippocampus, at the ages of postnatal day (PD) 1, PD4, PD7, PD10, PD14, 4 wk, and 12 wk (adult), by RT-PCR/Southern blotting analysis. The relative expression levels of these enzymes/receptors at PD1 were Srd5a1 > Star > Ar ∼ Hsd17b4 ∼ Hsd17b1 ∼ Hsd17b7 ∼ Esr1 ∼ Srd5a2 > Hsd17b3 > Esr2 > Cyp11a1 > Cyp17a1 > Cyp19a1 ∼ Hsd17b2 > 3β-hydroxysteroid dehydrogenase I. The mRNA levels of essential enzymes for progesterone/testosterone/estradiol metabolisms (Cyp17a1, Hsd17b7, and Cyp19a1) were approximately constant between PD1 and PD14 and then declined toward the adult levels. Cyp11a1 increased during PD4-PD14 and then considerably decreased toward the adult level (∼8% of PD1). Hsd17b1, Hsd17b2, and 3β-hydroxysteroid dehydrogenase I mRNA decreased approximately monotonously. Hsd17b3 increased to approximately 200% of PD1 during PD4-PD14 and was maintained at this high level. The 5α-reductase mRNA was maintained constant (Srd5a1) or decreased monotonically (Srd5a2) toward the adult level. The Esr1 level peaked at PD4 and decreased toward the adult level, whereas Ar greatly increased during PD1-PD14 and was maintained at this high level. The Star and Hsd17b4 levels were maintained constant from neonate to adult. These results suggest that the hippocampal sex steroidogenic properties are substantially altered during the postnatal development processes, which might contribute to brain sexual maturation.
Röver, Lea Kristin; Gevensleben, Heidrun; Dietrich, Jörn; Bootz, Friedrich; Landsberg, Jennifer; Goltz, Diane; Dietrich, Dimo
2018-02-01
Immune checkpoints are important targets for immunotherapies. However, knowledge on the epigenetic modification of immune checkpoint genes is sparse. In the present study, we investigated promoter methylation of CTLA4, PD-L1, PD-L2, and PD-1 in diffuse lower-grade gliomas (LGG) harboring isocitrate dehydrogenase (IDH) mutations with regard to mRNA expression levels, clinicopathological parameters, previously established methylation subtypes, immune cell infiltrates, and survival in a cohort of 419 patients with IDH-mutated LGG provided by The Cancer Genome Atlas. PD-L1, PD-L2, and CTLA-4 mRNA expression levels showed a significant inverse correlation with promoter methylation (PD-L1: p=0.005; PD-L2: p<0.001; CTLA-4: p<0.001). Furthermore, immune checkpoint methylation was significantly associated with age (PD-L2: p=0.003; PD-1: p=0.015), molecular alterations, i.e. MGMT methylation (PD-L1: p<0.001; PD-L2: p<0.001), ATRX mutations (PD-L2: p<0.001, PD-1: p=0.001), and TERT mutations (PD-L1: p=0.035, PD-L2: p<0.001, PD-1: p<0.001, CTLA4: p<0.001) as well as methylation subgroups and immune cell infiltrates. In multivariate Cox proportional hazard analysis, PD-1 methylation qualified as strong prognostic factor (HR=0.51 [0.34-0.76], p=0.001). Our findings suggest an epigenetic regulation of immune checkpoint genes via DNA methylation in LGG. PD-1 methylation may assist the identification of patients that might benefit from an alternative treatment, particularly in the context of emerging immunotherapies. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.
Schuck, Edgar; Bohnert, Tonika; Chakravarty, Arijit; Damian-Iordache, Valeriu; Gibson, Christopher; Hsu, Cheng-Pang; Heimbach, Tycho; Krishnatry, Anu Shilpa; Liederer, Bianca M; Lin, Jing; Maurer, Tristan; Mettetal, Jerome T; Mudra, Daniel R; Nijsen, Marjoleen Jma; Raybon, Joseph; Schroeder, Patricia; Schuck, Virna; Suryawanshi, Satyendra; Su, Yaming; Trapa, Patrick; Tsai, Alice; Vakilynejad, Majid; Wang, Shining; Wong, Harvey
2015-03-01
The application of modeling and simulation techniques is increasingly common in preclinical stages of the drug discovery and development process. A survey focusing on preclinical pharmacokinetic/pharmacodynamics (PK/PD) analysis was conducted across pharmaceutical companies that are members of the International Consortium for Quality and Innovation in Pharmaceutical Development. Based on survey responses, ~68% of companies use preclinical PK/PD analysis in all therapeutic areas indicating its broad application. An important goal of preclinical PK/PD analysis in all pharmaceutical companies is for the selection/optimization of doses and/or dose regimens, including prediction of human efficacious doses. Oncology was the therapeutic area with the most PK/PD analysis support and where it showed the most impact. Consistent use of more complex systems pharmacology models and hybrid physiologically based pharmacokinetic models with PK/PD components was less common compared to traditional PK/PD models. Preclinical PK/PD analysis is increasingly being included in regulatory submissions with ~73% of companies including these data to some degree. Most companies (~86%) have seen impact of preclinical PK/PD analyses in drug development. Finally, ~59% of pharmaceutical companies have plans to expand their PK/PD modeling groups over the next 2 years indicating continued growth. The growth of preclinical PK/PD modeling groups in pharmaceutical industry is necessary to establish required resources and skills to further expand use of preclinical PK/PD modeling in a meaningful and impactful manner.
Henninger, B; Raithel, E; Kranewitter, C; Steurer, M; Jaschke, W; Kremser, C
2018-05-01
To prospectively evaluate a prototypical 3D turbo-spin-echo proton-density-weighted sequence with compressed sensing and free-stop scan mode for preventing motion artefacts (3D-PD-CS-SPACE free-stop) for knee imaging in a clinical setting. 80 patients underwent 3T magnetic resonance imaging (MRI) of the knee with our 2D routine protocol and with 3D-PD-CS-SPACE free-stop. In case of a scan-stop caused by motion (images are calculated nevertheless) the sequence was repeated without free-stop mode. All scans were evaluated by 2 radiologists concerning image quality of the 3D-PD-CS-SPACE (with and without free-stop). Important knee structures were further assessed in a lesion based analysis and compared to our reference 2D-PD-fs sequences. Image quality of the 3D-PD-CS-SPACE free-stop was found optimal in 47/80, slightly compromised in 21/80, moderately in 10/80 and severely in 2/80. In 29/80, the free-stop scan mode stopped the 3D-PD-CS-SPACE due to subject motion with a slight increase of image quality at longer effective acquisition times. Compared to the 3D-PD-CS-SPACE with free-stop, the image quality of the acquired 3D-PD-CS-SPACE without free-stop was found equal in 6/29, slightly improved in 13/29, improved with equal contours in 8/29, and improved with sharper contours in 2/29. The lesion based analysis showed a high agreement between the results from the 3D-PD-CS-SPACE free-stop and our 2D-PD-fs routine protocol (overall agreement 96.25%-100%, Cohen's Kappa 0.883-1, p < 0.001). 3D-PD-CS-SPACE free-stop is a reliable alternative for standard 2D-PD-fs protocols with acceptable acquisition times. Copyright © 2018 Elsevier B.V. All rights reserved.
Matchett, Gerald; Ryan, Timothy J; Sunna, Mary C; Lee, Simon C; Pepe, Paul E
2018-04-30
U.S. federal regulations for research involving exception from informed consent (EFIC) include stipulations for community consultation (CC) and public disclosure (PD) (FDA 21 CFR 50.24). Published descriptions of PD campaigns include letters to community leaders, media outreach, paid advertising, and community meetings. Whether or not these activities provide measurable impact is unknown, as few prior works have evaluated PD activities with probabilistic polling. The aim of this study is to use polling to assess how much public awareness PD efforts generate. A 3-month PD campaign similar in scope and scale to PD campaigns described in several recent publications was implemented across a large urban county (pop. 2.55 million). PD included a study website (www.evktrial.org), letters to 300 community leaders/organizations, bilingual media outreach and also phased roll-outs, weeks apart, of newspaper advertisements, mass e-mail messaging, and paid advertising in Facebook ® and Twitter ® augmented by volunteer social media outreach. During PD we used repeated zip code-targeted online polling via Google Consumer Surveys ® to assess community awareness of the proposed EFIC study. Over 3-months all-source exposures to >1 million individuals were estimated, generating ∼5,000 website visits (12-month cumulative, ∼9000). However, general community awareness evaluated through repeated county-wide polling never rose above baseline measurements. CC/PD campaign costs were estimated at $60,000 (USD). A PD campaign in scope and scale common for EFIC studies may not provide measurable impact in a community. Investigators, review boards and regulators could consider these findings when re-examining and/or creating policies for PD for EFIC studies. Copyright © 2018 Elsevier B.V. All rights reserved.
Lu, Yanjun; Liu, Wei; Tan, Kun; Peng, Jing; Zhu, Yaowu; Wang, Xiong
2015-09-03
Recent studies investigating the association of the Ras-like without CAAX 2 (RIT2) polymorphism, rs12456492, with Parkinson's disease (PD) are controversial. We performed a meta-analysis to study the association between rs12456492 and PD susceptibility in Asian populations. Literature searches of PubMed and Embase were performed up to June 3, 2015, and the strength of the association between rs12456492 and PD was evaluated by odds ratios (OR) and 95% confidence intervals (CI). Four studies conducted between 2013 and 2015, comprising 2017 PD cases and 2010 controls, were included in the meta-analysis. Significant association of rs12456492 with PD was found in the dominant (GG + AG vs. AA: OR = 1.26, 95% CI = 1.20-1.44, P = 0.00) and additive models (GG vs. AA: OR = 1.38, 95% CI = 1.03-1.83, P = 0.030). Although sensitivity analysis found that the overall result was stable only in the dominant genetic model, a publication bias was also detected. Therefore, the results should be treated with caution. The current meta-analysis suggested that rs12456492 might be associated with increased PD risk in Asian populations, but studies using larger sample sizes and different ethnic populations will be needed to further confirm this association.
Glucose-6-phosphate dehydrogenase variants associated with favism in Thai children.
Laosombat, Vichai; Sattayasevana, Benjamas; Chotsampancharoen, Teerachit; Wongchanchailert, Malai
2006-02-01
In a study conducted at Songklanagarind Hospital in the south of Thailand, the subjects were 225 patients (210 boys and 15 girls) with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Favism was found in 3.6% of the G6PD-deficient children. Approximately one half of the G6PD-deficient patients with favism were younger than 2 years. Sudden onset of anemia was found within 1 to 3 days after ingestion of dried fava beans. The classic features of favism, which are pallor, hemoglobinuria, and jaundice, were detected in all cases. To characterize the known G6PD mutations in Thai children, molecular analysis was performed for 8 G6PD-deficient children with favism by a combination of polymerase chain reaction-restriction fragment length polymorphism analysis and amplification refractory mutation system analysis. The G6PD variants in these children were G6PD Kaiping 1388,G-->A; G6PD Mahidol 487,G-->A; G6PD Viangchan 871,G-->A; and uncharacterized mutation with silent mutation 1311,C-->T.
Okabayashi, Toshiaki; Yamamoto, Takuya; Okabayashi, Emi Y; Tanimoto, Mitsutoshi
2011-03-17
The rotational spectra of NiCO and PdCO in the ground and ν(2) excited vibrational states were observed by employing a source-modulated microwave spectrometer. The NiCO and PdCO molecules were generated in a free space cell by the sputtering reaction of nickel and palladium sheets, respectively, lining the inner surface of a stainless steel cathode with a dc glow plasma of CO and Ar. The molecular constants of NiCO and PdCO were determined by least-squares analysis. By force field analysis for the molecular constants of not only NiCO and PdCO but also of PtCO as previously reported, the harmonic force constants were determined for these three group 10 metal monocarbonyls. The vibrational wavenumbers derived for the lower M-C stretching vibrations were in good agreement with those obtained from the IR spectra in noble gas matrices and those predicted by several quantum chemical calculations published in the past. The bending vibrational wavenumbers derived by the force field analysis were also consistent with most quantum chemical calculations previously reported, but showed systematic discrepancies from the matrix IR values by about 40 cm(-1), even after reassignment (ν(2) band → 2ν(2) band) of the matrix IR spectra of PdCO and PtCO.
Nakayama, Masaaki; Zhu, Wan-Jun; Watanabe, Kimio; Gibo, Ayano; Sherif, Ali M; Kabayama, Shigeru; Ito, Sadayoshi
2017-10-31
Peritoneal dialysis (PD) is used as renal replacement therapy in patients with end-stage kidney disease. However, peritoneal membrane failure remains problematic and constitutes a critical cause of PD discontinuation. Recent studies have revealed the unique biological action of molecular hydrogen (H 2 ) as an anti-oxidant, which ameliorates tissue injury. In the present study, we aimed to examine the effects of H 2 on the peritoneal membrane of experimental PD rats. Eight-week-old male Sprague-Dawley rats were divided into the following groups (n = 8-11 each) receiving different test solutions: control group (no treatment), PD group (commercially available lactate-based neutral 2.5% glucose PD solution), and H 2 PD group (PD solution with dissolved H 2 at 400 ppb). Furthermore, the influence of iron (FeCl 3 : 5 μM: inducer of oxidative cellular injury) in the respective PD solutions was also examined (Fe-PD and Fe-H 2 PD groups). The H 2 PD solution was manufactured by bathing a PD bag in H 2 -oversaturated water created by electrolysis of the water. Twenty mL of the test solutions were intraperitoneally injected once a day for 10 days. Parietal peritoneum samples and cells collected from the peritoneal surface following treatment with trypsin were subjected to analysis. In the PD group as compared to controls, a mild but significant sub-mesothelial thickening was observed, with increase in the number of cells in the peritoneal surface tissue that were positive for apoptosis, proliferation and vimentin, as seen by immunostaining. There were significantly fewer of such changes in the H 2 PD group, in which there was a dominant presence of M2 (CD163+) macrophages in the peritoneum. The Fe-PD group showed a significant loss of mesothelial cells with sub-mesothelial thickening, these changes being ameliorated in the Fe-H 2 PD group. H 2 -dissolved PD solutions could preserve mesothelial cells and peritoneal membrane integrity in PD rats. Clinical application of H 2 in PD could be a novel strategy for protection of peritoneal tissue during PD treatment.
Finkelstein, Murray M; Jerrett, Michael
2007-07-01
There is concern that industrial emissions of manganese (Mn) and the use of Mn-containing compounds as fuel additives might increase the population risk of Parkinson's disease (PD)-like disorders. We investigated associations between the diagnosis and treatment of PD and markers of exposure to vehicle exhaust and industrial emissions of Mn within a cohort of 110,000 subjects in the cities of Toronto and Hamilton, Canada. Methylcyclopentadienyl manganese tricarbonyl (MMT) has been added to Canadian gasoline since 1976 and steelmaking in Hamilton emits Mn to the air. Using residential postal codes, subjects were mapped to: (1) residence locations close to traffic and to neighbourhood levels of NO2, as markers of traffic-generated air pollution (TGAP); and, (2) neighbourhood levels of ambient Mn in Hamilton, as measured by the Mn fraction of total suspended particulate. Subjects were linked to Ministry of Health administrative databases, 1992-1999, to identify physicians' diagnoses of PD and prescriptions for l-Dopa containing medications. In Toronto, we found no association between PD and the markers of TGAP. In Hamilton, the odds ratio for a physician's diagnosis of PD was 1.034 (1.00-1.07) per 10 ng/m3 increase in Mn in TSP. The estimate of the "doubling exposure" for physician-diagnosed PD was about 150 ng/m3 Mn in TSP. Examination of prevalence curves suggested that exposure to ambient Mn advances the age of diagnosis of PD, consistent with the theory that exposure to Mn adds to the natural loss of neurons attributable to the aging process.
Kadara, H; Choi, M; Zhang, J; Parra, E R; Rodriguez-Canales, J; Gaffney, S G; Zhao, Z; Behrens, C; Fujimoto, J; Chow, C; Yoo, Y; Kalhor, N; Moran, C; Rimm, D; Swisher, S; Gibbons, D L; Heymach, J; Kaftan, E; Townsend, J P; Lynch, T J; Schlessinger, J; Lee, J; Lifton, R P; Wistuba, I I; Herbst, R S
2017-01-01
Abstract Background Lung adenocarcinomas (LUADs) lead to the majority of deaths attributable to lung cancer. We performed whole-exome sequencing (WES) and immune profiling analyses of a unique set of clinically annotated early-stage LUADs to better understand the pathogenesis of this disease and identify clinically relevant molecular markers. Methods We performed WES of 108 paired stage I-III LUADs and normal lung tissues using the Illumina HiSeq 2000 platform. Ten immune markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 and Granzyme B) were profiled by imaging-based immunohistochemistry (IHC) in a subset of LUADs (n = 92). Associations among mutations, immune markers and clinicopathological variables were analyzed using ANOVA and Fisher’s exact test. Cox proportional hazards regression models were used for multivariate analysis of clinical outcome. Results LUADs in this cohort exhibited an average of 243 coding mutations. We identified 28 genes with significant enrichment for mutation. SETD2-mutated LUADs exhibited relatively poor recurrence- free survival (RFS) and mutations in STK11 and ATM were associated with poor RFS among KRAS-mutant tumors. EGFR, KEAP1 and PIK3CA mutations were predictive of poor response to adjuvant therapy. Immune marker analysis revealed that LUADs in smokers and with relatively high mutation burdens exhibited increased levels of immune markers. Analysis of immunophenotypes revealed that LUADs with STK11 mutations exhibited relatively low levels of infiltrating CD4+/CD8+ T-cells indicative of a muted immune response. Tumoral PD-L1 was significantly elevated in TP53 mutant LUADs whereas PIK3CA mutant LUADs exhibited markedly down-regulated PD-L1 expression. LUADs with TP53 or KEAP1 mutations displayed relatively increased CD57 and Granzyme B levels indicative of augmented natural killer (NK) cell infiltration. Conclusion(s) Our study highlights molecular and immune phenotypes that warrant further analysis for their roles in clinical outcomes and personalized immune-based therapy of LUAD. PMID:27687306
Kadara, H; Choi, M; Zhang, J; Parra, E R; Rodriguez-Canales, J; Gaffney, S G; Zhao, Z; Behrens, C; Fujimoto, J; Chow, C; Yoo, Y; Kalhor, N; Moran, C; Rimm, D; Swisher, S; Gibbons, D L; Heymach, J; Kaftan, E; Townsend, J P; Lynch, T J; Schlessinger, J; Lee, J; Lifton, R P; Wistuba, I I; Herbst, R S
2017-01-01
Lung adenocarcinomas (LUADs) lead to the majority of deaths attributable to lung cancer. We performed whole-exome sequencing (WES) and immune profiling analyses of a unique set of clinically annotated early-stage LUADs to better understand the pathogenesis of this disease and identify clinically relevant molecular markers. We performed WES of 108 paired stage I-III LUADs and normal lung tissues using the Illumina HiSeq 2000 platform. Ten immune markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 and Granzyme B) were profiled by imaging-based immunohistochemistry (IHC) in a subset of LUADs (n = 92). Associations among mutations, immune markers and clinicopathological variables were analyzed using ANOVA and Fisher's exact test. Cox proportional hazards regression models were used for multivariate analysis of clinical outcome. LUADs in this cohort exhibited an average of 243 coding mutations. We identified 28 genes with significant enrichment for mutation. SETD2-mutated LUADs exhibited relatively poor recurrence- free survival (RFS) and mutations in STK11 and ATM were associated with poor RFS among KRAS-mutant tumors. EGFR, KEAP1 and PIK3CA mutations were predictive of poor response to adjuvant therapy. Immune marker analysis revealed that LUADs in smokers and with relatively high mutation burdens exhibited increased levels of immune markers. Analysis of immunophenotypes revealed that LUADs with STK11 mutations exhibited relatively low levels of infiltrating CD4+/CD8+ T-cells indicative of a muted immune response. Tumoral PD-L1 was significantly elevated in TP53 mutant LUADs whereas PIK3CA mutant LUADs exhibited markedly down-regulated PD-L1 expression. LUADs with TP53 or KEAP1 mutations displayed relatively increased CD57 and Granzyme B levels indicative of augmented natural killer (NK) cell infiltration. Our study highlights molecular and immune phenotypes that warrant further analysis for their roles in clinical outcomes and personalized immune-based therapy of LUAD. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
NASA Astrophysics Data System (ADS)
Rajesh, Dhanushkotti; Indra Neel, Pulidindi; Pandurangan, Arumugam; Mahendiran, Chinnathambi
2018-06-01
The synthesis of Pd-NiO nanoparticles decorated multiwalled carbon nanotubes (MWCNTs) on reduced graphene oxide (rGO) for ethanol electrooxidation is reported. NiO nanoparticles (NPs) were deposited on functionalized MWCNTs by wet impregnation method. Pd nanoparticles were formed on NiO-MWCNTs by the addition of PdCl2 and its reduction using NaBH4. The Pd-NiO/MWCNTs nanocomposite then deposited on rGO support using ultrasound irradiation which led to the formation of the Pd-NiO/MWCNTs/rGO electrocatalyst. The prepared electrocatalysts were characterized by XRD, SEM, HR-TEM and XPS analysis. Electrochemical measurements demonstrate that as synthesized Pd-NiO/MWCNTs/rGO electrocatalyst exhibit higher catalytic activity (90.89 mA/cm2) than either Pd/MWCNTs/rGO (43.05 mA/cm2) or Pd/C (28.0 mA/cm2) commercial catalyst. Chronoamperometry study of Pd-NiO/MWCNTs/rGO electrocatalyst showed long-term electrochemical stability. The enhanced catalytic activity of Pd-NiO/MWCNTs/rGO electrocatalyst for electrooxidation of ethanol can be attributed to the synergistic effect between Pd & NiO active sites.
Petrova, Nina L; Petrov, Peter K; Edmonds, Michael E; Shanahan, Catherine M
2014-04-01
We hypothesized that newly formed osteoclasts from patients with acute Charcot osteoarthropathy can resorb surfaces of bone more extensively compared with controls. Peripheral blood monocytes, isolated from eight Charcot patients and nine controls, were cultured in vitro on 24-well plates and bovine bone discs in duplicate with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κβ ligand (RANKL). Osteoclast formation was assessed by tartrate-resistant acid phosphatase staining (TRAcP) at day 17. Resorption was measured at day 21 after toluidine blue staining by two methods: (1) area of resorption at the surface by image analysis (%) and (2) area of resorption under the surface (μm(2)) measured by a Dektak 150 Surface Profiler. Ten 1,000 μm-long scans were performed per disc. Pits were classified as unidented, bidented, and multidented according to their shape. Although the number of newly formed TRAcP positive multinucleated cells (>3 nuclei) was similar in M-CSF + RANKL-treated cultures between controls and Charcot patients, the latter exhibited increased resorbing activity. The area of resorption on the surface by image analysis was significantly greater in Charcot patients compared with controls (21.1 % [14.5-26.2] vs. 40.8 % [35.4-46.0], median [25-75th percentile], p < 0.01), as was the area of resorption under the surface (2.7 x 10(3) μm(2) [1.6 x 10(3)- 3.9 x 10(3)] vs. 8.3 x 10(3) μm (2) [5.6 x 10(3)- 10.6 x 10(3), [corrected] p < 0.01) after profilometry. In Charcot patients pits were deeper and wider and more frequently presented as multidented pits. This application of the Dektak 150 Surface Profiler revealed novel differences in resorption pit profile from osteoclasts derived from Charcot patients compared with controls. Resorption in Charcot patients was mediated by highly aggressive newly formed osteoclasts from monocytes eroding large and deep areas of bone.
Polar-Drive--Implosion Physics on OMEGA and the NIF
NASA Astrophysics Data System (ADS)
Radha, P. B.
2012-10-01
Polar drive (PD) permits the execution of direct-drive--ignition experiments on facilities that are configured for x-ray drive such as the National Ignition Facility (NIF) and Laser M'egajoule. Experiments on the OMEGA laser are used to develop and validate models of PD implosions. Results from OMEGA PD shock-timing and warm implosions are presented. Experiments are simulated with the 2-D hydrodynamic code DRACO including full 3-D ray trace to model oblique beams. Excellent agreement is obtained in shock velocity and catch-up in PD geometry in warm, plastic shells. Predicted areal densities are measured in PD implosion experiments. Good agreement between simulation and experiments is obtained in the overall shape of the compressing shell when observed through x-ray backlighting. Simulated images of the hot core, including the effect of magnetic fields, are compared with experiments. Comparisons of simulated and observed scattered light and bang time in PD geometry are presented. Several techniques to increase implosion velocity are presented including beam profile variations and different ablator materials. Results from shimmed-target PD experiments will also be presented. Designs for future PD OMEGA experiments at ignition-relevant intensities will be presented. The implication of these results for NIF-scale plasmas is discussed. Experiments for the NIF in its current configuration, with indirect-drive phase plates, are proposed to study implosion energetics and shell asymmetries. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC52-08NA28302.
Keating, Jonathan; Sankar, Gopinathan; Hyde, Timothy I; Kohara, Shinji; Ohara, Koji
2013-06-14
The PdO-Pd phase transformation in a 4 wt% Pd/Al2O3 catalyst has been investigated using in situ X-ray absorption spectroscopy (XAS) and in situ X-ray total scattering (also known as high-energy X-ray diffraction) techniques. Both the partial and total pair distribution functions (PDF) from these respective techniques have been analysed in depth. New information from PDF analysis of total scattering data has been garnered using the differential PDF (d-PDF) approach where only correlations orginating from PdO and metallic Pd are extracted. This method circumvents problems encountered in characerising the catalytically active components due to the diffuse scattering from the disordered γ-Al2O3 support phase. Quantitative analysis of the palladium components within the catalyst allowed for the phase composition to be established at various temperatures. Above 850 °C it was found that PdO had converted to metallic Pd, however, the extent of reduction was of the order ca. 70% Pd metal and 30% PdO. Complementary in situ XANES and EXAFS were performed, with heating to high temperature and subsequent cooling in air, and the results of the analyses support the observations, that residual PdO is detected at elevated temperatures. Hysteresis in the transformation upon cooling is confirmed from XAS studies where reoxidation occurs below 680 °C.
Microstructures of Pd-containing dispersants for admixed dental amalgams.
Chern Lin, J H; Greener, E H
1991-10-01
Blended Pd-containing dispersants were developed by the utilization of a Ag-Cu eutectic into which Pd was substituted for Ag or Cu in concentrations of up to 20 wt%. Compositions were melted either in argon-filled sealed vycor tubes or in a graphite-linked carbon crucible of an induction furnace with an argon blanket. Ingots of approximately 1.5 cm in diameter were sectioned to 0.2 cm in thickness and polished through standard metallographic polishing procedures. The possible compounds were identified by XRD. The microstructures of the alloys were examined by SEM/EDS. XRD analysis of the alloys revealed the preferential dissolution of Pd in Cu when the Pd concentration was less than or equal to 10 wt%. When the Pd concentration exceeded 20 wt%, Pd was found to be dissolved in both Ag and Pd. No Cu3Pd x-ray diffraction peaks were found for alloys with Pd concentration of up to 20 wt%. SEM/EDS analysis confirmed XRD results; lamellae of Ag and Cu-Pd were found in alloys with Pd concentration less than or equal to 10 wt%.
Mailoa, James; Lin, Guo-Hao; Khoshkam, Vahid; MacEachern, Mark; Chan, Hsun-Liang; Wang, Hom-Lay
2015-10-01
The aim of this systematic review is to evaluate the long term (≥ 2 years) effect of four surgical and non-surgical therapies in treating periodontal disease. An electronic search of four databases and a hand search of peer-reviewed journals for relevant articles were conducted. Prospective human controlled clinical trials were included that compared surgical therapy to non-surgical therapy in ≥ 10 patients diagnosed with chronic periodontitis with a follow-up period of ≥ 2 years and that reported change in probing depth (PD) and clinical attachment level (CAL) after the therapy. Random effect meta-analysis was performed to compare the outcome of surgical and non-surgical therapy in shallow, moderate, and deep PD. Eight human prospective clinical trials were included. In 1- to 3-mm PD, scaling and root planing (SRP), modified Widman flap (MWF), and osseous surgery (OS) resulted in 23.2%, 39.4%, and 61.39% CAL loss, respectively; SRP, MWF, and OS resulted in increased mean PD of 2.5%, 3.3%, and 6.3%, respectively. In 4- to 6-mm PD, SRP, MWF, and OS resulted in 8.4%, 6.5%, and 5.22% CAL gain, respectively; SRP, MWF, and OS resulted in 18.7%, 25.4%, and 30.8% PD reduction, respectively. In PD ≥ 7 mm, SRP, MWF, and OS resulted in 9.8%, 14.2%, and 9.38% CAL gain, respectively; SRP, MWF, and OS resulted in mean PD reduction of 21.6%, 33.1%, and 42.8%, respectively. Surgical therapy had significantly more CAL loss than non-surgical therapy in shallow PD. In moderate PD, MWF had significantly more PD reduction than SRP, and there was significantly less CAL gain with surgical therapy. In deep PD, OS had significantly higher PD reduction than SRP.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thompson, Simon T.; Lamb, H. Henry
The double complex salt [Pd(NH3)4](ReO4)2 was employed as precursor of supported bimetallic catalysts for selective hydrogenation of furfural. Direct reduction of [Pd(NH3)4](ReO4)2 on γ-Al2O3 in flowing H2 at 400 °C yields bimetallic nanoparticles 1–2 nm in size that exhibit significant interaction between the metals, as evidenced by temperature-programmed hydride decomposition (complete suppression of β-PdHx formation), extended X-ray absorption fine structure spectroscopy at the Pd K and Re LIII edges (PdRe distance = 2.72 Å), and scanning transmission electron microscopy with energy dispersive X-ray analysis. In contrast, calcination of [Pd(NH3)4](ReO4)2 on γ-Al2O3 at 350 °C in air and subsequent reduction inmore » H2 at 400 °C results in metal segregation and formation of large (>50 nm) supported Pd particles; Re species cover the Pd particles and γ-Al2O3 support. A PdRe 1:2 catalyst prepared by sequential impregnation and calcination using HReO4 and [Pd(NH3)4](NO3)2 has a similar morphology. The catalyst derived by direct reduction of [Pd(NH3)4](ReO4)2 on γ-Al2O3 exhibits remarkably high activity for selective hydrogenation of furfural to furfuryl alcohol (FAL) at 150 °C and 1 atm. Suppression of H2 chemisorption via elimination of Pd threefold sites, as evidenced by CO diffuse-reflectance infrared Fourier transform spectroscopy, correlates with increased FAL selectivity.« less
NASA Astrophysics Data System (ADS)
Saleem, Junaid; Safdar Hossain, SK.; Al-Ahmed, Amir; Rahman, Ateequr; McKay, Gordon; Hossain, Mohammed M.
2018-04-01
In this work, CeO2-modified Pd/CeO2-carbon nanotube (CNT) electrocatalyst for the electro-oxidation of formic acid has been investigated. The support CNT was first modified with different amounts (5-30 wt.%) of CeO2 using a precipitation-deposition method. The electrocatalysts were developed by dispersing Pd on the CeO2-CNT supports using the borohydride reduction method. The synthesized electrocatalysts were analyzed for composition, morphology and electronic structure using x-ray diffraction (XRD), scanning electron microscopy with energy-dispersive x-ray spectroscopy (SEM/EDX), transmission electron microscopy (TEM), x-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA) techniques. The formation of Pd nanoparticles on the CeO2-CNT support was confirmed using TEM. The activity of Pd/CeO2-CNT and of Pd-CNT samples upon oxidation of formic acid was evaluated by using carbon monoxide stripping voltammetry, cyclic voltammetry, and chronoamperometry. The addition of moderate amounts of cerium oxide (up to 10 wt.%) significantly improved the activity of Pd/CeO2-CNT compared to the unmodified Pd-CNT. Pd/10 wt.% CeO2-CNT showed a current density of 2 A mg-1, which is ten times higher than that of the unmodified Pd-CNT (0.2 A mg-1). Similarly, the power density obtained for Pd/10 wt.% CeO2-CNT in an air-breathing formic acid fuel cell was 6.8 mW/cm2 which is two times higher than Pd-CNT (3.2 mW/cm2), thus exhibiting the promotional effects of CeO2 to Pd/CeO2-CNT. A plausible justification for the improved catalytic performance and stability is provided in the light of the physical characterization results.
Depression and the Subsequent Risk of Parkinson’s Disease in the NIH-AARP Diet and Health Study
Fang, Fang; Xu, Qun; Park, Yikyung; Huang, Xuemei; Hollenbeck, Albert; Blair, Aaron; Schatzkin, Arthur; Kamel, Freya; Chen, Honglei
2010-01-01
We conducted a case-control study to examine the association between depression and Parkinson’s disease (PD). Participants included 992 PD cases diagnosed after 2000 and 279,958 individuals without PD from the NIH-AARP Diet and Health Study Follow-up Survey. Physician-diagnosed depression and PD were self-reported with information on the year of diagnosis in the following categories: before 1985, 1985–1994, 1995–1999, and 2000-present. Only PD cases diagnosed after 2000 were included in the analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models, adjusted for age, gender, educational level, marital status, smoking, and coffee drinking. Individuals with depression diagnosed after 2000 were more likely to report a concurrent diagnosis of PD than those without depression (OR=4.7,95% CI = 3.9,5.7). Depression diagnosed before 2000 was also associated with higher odds of PD diagnosed after 2000(OR= 2.0,95% CI=1.6,2.4). This association was stronger for depression diagnosed in 1995–1999 (OR = 2.7,95% CI = 2.0,3.6), but was also noted for depression diagnosed in 1985–1994 (OR = 1.6,95% CI = 1.1,2.3) or even before 1985 (OR=1.7,95% CI=1.3,2.3). This association was not modified by other factors and persisted in an analysis excluding participants who reported poor health status. The results suggest that depression may either be a very early symptom of PD or share common etiological factors with PD. PMID:20310050
Jiao, Q; Liu, C; Li, W; Li, W; Fang, F; Qian, Q; Zhang, X
2017-06-01
The programmed death-1 (PD-1) receptor ligands, PD-L1 and PD-L2, are co-stimulatory molecules that contribute to the negative regulation of T lymphocyte activation. It is still unclear whether there is correlation between PD-L1 or PD-L2 and tumour-infiltrating dendritic cells (TIDCs) in cutaneous squamous cell carcinoma (CSCC). The aim of this study was to analyse PD-L1 and PD-L2 expression and dendritic cells infiltration in tumour tissue of CSCC patients and investigate their clinical significance. Immunohistochemical analysis was used to evaluate the expression of PD-L1, PD-L2, CD1a and CD83 in 61 CSCC tissues. The immunofluoresence double-labelling technique was performed to detect the co-expression of PD-L1 or PD-L2 and CD1a or CD83 in tumour tissues. We found that 25 of 61 cases CSCC (40·98%) exhibited positivity for PD-L1, whereas 37 of 61 cases CSCC (60·66%) exhibited positivity for PD-L2. A higher percentage of CD1a-positive cases were observed on both PD-L1-positive and PD-L2-positive specimens compared with that of CD83-positive cases (92·29% versus 37·60%, 83·20% versus 33·16%). The expression of PD-L1 and PD-L2 on CD1a + cells was significantly higher than that on CD83 + cells in tumour tissues of CSCC patients. Furthermore, the expression rate of PD-L1 was associated with UICC stage, and the expression rate of PD-L2 was associated with predominant differentiation and tumour size in CSCC. Our results indicated that higher expression of PD-L1 and PD-L2 on CD1a + cells than that on CD83 + cells in CSCC tumour tissues may contribute to negative regulation in anti-tumour immune responses. © 2017 British Society for Immunology.
Establishing the role of rare coding variants in known Parkinson's disease risk loci.
Jansen, Iris E; Gibbs, J Raphael; Nalls, Mike A; Price, T Ryan; Lubbe, Steven; van Rooij, Jeroen; Uitterlinden, André G; Kraaij, Robert; Williams, Nigel M; Brice, Alexis; Hardy, John; Wood, Nicholas W; Morris, Huw R; Gasser, Thomas; Singleton, Andrew B; Heutink, Peter; Sharma, Manu
2017-11-01
Many common genetic factors have been identified to contribute to Parkinson's disease (PD) susceptibility, improving our understanding of the related underlying biological mechanisms. The involvement of rarer variants in these loci has been poorly studied. Using International Parkinson's Disease Genomics Consortium data sets, we performed a comprehensive study to determine the impact of rare variants in 23 previously published genome-wide association studies (GWAS) loci in PD. We applied Prix fixe to select the putative causal genes underneath the GWAS peaks, which was based on underlying functional similarities. The Sequence Kernel Association Test was used to analyze the joint effect of rare, common, or both types of variants on PD susceptibility. All genes were tested simultaneously as a gene set and each gene individually. We observed a moderate association of common variants, confirming the involvement of the known PD risk loci within our genetic data sets. Focusing on rare variants, we identified additional association signals for LRRK2, STBD1, and SPATA19. Our study suggests an involvement of rare variants within several putatively causal genes underneath previously identified PD GWAS peaks. Copyright © 2017 Elsevier Inc. All rights reserved.
PD-L1 expression and prognostic impact in glioblastoma
Nduom, Edjah K.; Wei, Jun; Yaghi, Nasser K.; Huang, Neal; Kong, Ling-Yuan; Gabrusiewicz, Konrad; Ling, Xiaoyang; Zhou, Shouhao; Ivan, Cristina; Chen, Jie Qing; Burks, Jared K.; Fuller, Greg N.; Calin, George A.; Conrad, Charles A.; Creasy, Caitlin; Ritthipichai, Krit; Radvanyi, Laszlo; Heimberger, Amy B.
2016-01-01
Background Therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule-4 (CTLA-4) and PD-1/PD-L1 has demonstrated tumor regression in clinical trials, and phase 2 trials are ongoing in glioblastoma (GBM). Previous reports have suggested that responses are more frequent in patients with tumors that express PD-L1; however, this has been disputed. At issue is the validation of PD-L1 biomarker assays and prognostic impact. Methods Using immunohistochemical analysis, we measured the incidence of PD-L1 expression in 94 patients with GBM. We categorized our results according to the total number of PD-L1-expressing cells within the GBMs and then validated this finding in ex vivo GBM flow cytometry with further analysis of the T cell populations. We then evaluated the association between PD-L1 expression and median survival time using the protein expression datasets and mRNA from The Cancer Genome Atlas. Results The median percentage of PD-L1-expressing cells in GBM by cell surface staining is 2.77% (range: 0%–86.6%; n = 92), which is similar to the percentage found by ex vivo flow cytometry. The majority of GBM patients (61%) had tumors with at least 1% or more PD-L1-positive cells, and 38% had at least 5% or greater PD-L1 expression. PD-L1 is commonly expressed on the GBM-infiltrating T cells. Expression of both PD-L1 and PD-1 are negative prognosticators for GBM outcome. Conclusions The incidence of PD-L1 expression in GBM patients is frequent but is confined to a minority subpopulation, similar to other malignancies that have been profiled for PD-L1 expression. Higher expression of PD-L1 is correlated with worse outcome. PMID:26323609
Parkinson's disease-cognitive rating scale: psychometrics for mild cognitive impairment.
Fernández de Bobadilla, Ramón; Pagonabarraga, Javier; Martínez-Horta, Saül; Pascual-Sedano, Berta; Campolongo, Antonia; Kulisevsky, Jaime
2013-09-01
Lack of validated data on cutoff scores for mild cognitive impairment (MCI) and sensitivity to change in predementia stages of Parkinson's disease (PD) limit the utility of instruments measuring global cognition as screening and outcome measures in therapeutic trials. Investigators who were blinded to PD-Cognitive Rating Scale (PD-CRS) scores classified a cohort of prospectively recruited, nondemented patients into a PD with normal cognition (PD-NC) group and a PD with MCI (PD-MCI) group using Clinical Dementia Rating (CDR) and the Mattis Dementia Rating Scale-2 (MDRS-2). The discriminative power of the PD-CRS for PD-MCI was examined in a representative sample of 234 patients (145 in the PD-NC group; 89 in the PD-MCI group) and in a control group of 98 healthy individuals. Sensitivity to change in the PD-CRS score (the minimal clinically important difference was examined with the Clinical Global Impression of Change scale and was calculated with a combination of distribution-based and anchor-based approaches) was explored in a 6-month observational multicenter trial involving a subset of 120 patients (PD-NC, 63; PD-MCI, 57). Regression analysis demonstrated that PD-CRS total scores (P < 0.001) and age (P = 0.01) independently differentiated PD-NC from PD-MCI. Area under the receiver operating characteristic curve (AUC) analysis (AUC, 0.85; 95% confidence interval, 0.80-0.90) indicated that a score ≤ 81 of 134 was the optimal cutoff point on the total score for the PD-CRS (sensitivity, 79%; specificity, 80%; positive predictive value, 59%; negative predictive value, 91%). A range of change from 10 to 13 points on the PD-CRS total score was indicative of clinically significant change. These findings suggest that the PD-CRS is a useful tool to identify PD-MCI and to track cognitive changes in nondemented patients with PD. © 2013 International Parkinson and Movement Disorder Society.
Mednikov, Evgueni G; Jewell, Matthew C; Dahl, Lawrence F
2007-09-19
Presented herein are the preparation and crystallographic/microanalytical/magnetic/spectroscopic characterization of the Pt-centered four-shell 165-atom Pd-Pt cluster, (mu(12)-Pt)Pd(164-x)Pt(x)(CO)(72)(PPh(3))(20) (x approximately 7), 1, that replaces the geometrically related capped three-shell icosahedral Pd(145) cluster, Pd(145)(CO)(x)(PEt(3))(30) (x approximately 60), 2, as the largest crystallographically determined discrete transition metal cluster with direct metal-metal bonding. A detailed comparison of their shell-growth patterns gives rise to important stereochemical implications concerning completely unexpected structural dissimilarities as well as similarities and provides new insight concerning possible synthetic approaches for generation of multi-shell metal clusters. 1 was reproducibly prepared in small yields (<10%) from the reaction of Pd(10)(CO)(12)(PPh(3))(6) with Pt(CO)(2)(PPh(3))(2). Its 165-atom metal-core geometry and 20 PPh(3) and 72 CO ligands were established from a low-temperature (100 K) CCD X-ray diffraction study. The well-determined crystal structure is attributed largely to 1 possessing cubic T(h) (2/m3) site symmetry, which is the highest crystallographic subgroup of the noncrystallographic pseudo-icosahedral I(h) (2/m35) symmetry. The "full" four-shell Pd-Pt anatomy of 1 consists of: (a) shell 1 with the centered (mu(12)-Pt) atom encapsulated by the 12-atom icosahedral Pt(x)Pd(12-x) cage, x = 1.2(3); (b) shell 2 with the 42-atom nu(2) icosahedral Pt(x)Pd(42-x) cage, x = 3.5(5); (c) shell 3 with the anti-Mackay 60-atom semi-regular rhombicosidodecahedral Pt(x)Pd(60-x) cage, x = 2.2(6); (d) shell 4 with the 50-atom nu(2) pentagonal dodecahedral Pd(50) cage. The total number of crystallographically estimated Pt atoms, 8 +/- 3, which was obtained from least-squares (Pt(x)/Pd(1-x))-occupancy analysis of the X-ray data that conclusively revealed the central atom to be pure Pt (occupancy factor, x = 1.00(3)), is fortuitously in agreement with that of 7.6(7) found from an X-ray Pt/Pd microanalysis (WDS spectrometer) on three crystals of 1. Our utilization of this site-occupancy (Pt(x)Pd(1-x))-analysis for shells 1-3 originated from the microanalytical results; otherwise, the presumed metal-core composition would have been (mu(12)-Pt)Pd(164). [Alternatively, the (mu(12)-Pt)M(164) core-geometry of 1 may be viewed as a pseudo-Ih Pt-centered six-shell successive nu(1) polyhedral system, each with radially equivalent vertex atoms: Pt@M(12)(icosahedron)@M(30)(icosidodecahedron)@M(12)(icosahedron)@M(60)(rhombicosidodecahedron)@M(30)(icosidodecahedron)@M(20)(pentagonal dodecahedron)]. Completely surprising structural dissimilarities between 1 and 2 are: (1) to date 1 is only reproducibly isolated as a heterometallic Pd-Pt cluster with a central Pt instead of Pd atom; (2) the 50 atoms comprising the outer fourth nu(2) pentagonal dodecahedral shell in 1 are less than the 60 atoms of the inner third shell in 1, in contradistinction to shell-by-shell growth processes in all other known shell-based structures; (3) the 10 fewer PR3 ligands in 1 necessitate larger bulky PPh(3) ligands to protect the Pd-Pt core-geometry; (4) the 72 CO ligands consist of six bridging COs within each of the 12 pentagons in shell 4 that are coordinated to intershell metal atoms. SQUID magnetometry measurements showed a single-crystal sample of 1 to be diamagnetic over the entire temperature range of 10-300 K.
Ali, Omyma A M
2014-01-01
The solid complexes of Pd(II) and Cd(II) with N,N/bis(salicylaldehyde)4,5-dimethyl-1,2-phenylenediamine (H2L(1)), and N,N/bis(salicylaldehyde)4,5-dichloro-1,2-phenylenediamine (H2L(2)) have been synthesized and characterized by several techniques using elemental analysis (CHN), FT-IR, (1)H NMR, UV-Vis spectra and thermal analysis. Elemental analysis data proved 1:1 stoichiometry for the reported complexes while spectroscopic data indicated square planar and octahedral geometries for Pd(II) and Cd(II) complexes, respectively. The prepared ligands, Pd(II) and Cd(II) complexes exhibited intraligand (π-π(∗)) fluorescence and can potentially serve as photoactive materials. Thermal behavior of the complexes was studied and kinetic parameters were determined by Coats-Redfern method. Both the ligands and their complexes have been screened for antimicrobial activities. Copyright © 2013 Elsevier B.V. All rights reserved.
Fayda, Merdan; Isin, Mustafa; Tambas, Makbule; Guveli, Murat; Meral, Rasim; Altun, Musa; Sahin, Dilek; Ozkan, Gozde; Sanli, Yasemin; Isin, Husniye; Ozgur, Emre; Gezer, Ugur
2016-03-01
Long non-coding RNAs (lncRNAs) have been shown to be aberrantly expressed in head and neck cancer (HNC). The aim of the present study was to evaluate plasma levels of three lncRNA molecules (lincRNA-p21, GAS5, and HOTAIR) in the treatment response in HNC patients treated with radical chemoradiotherapy (CRT). Forty-one patients with HNC were enrolled in the study. Most of the patients had nasopharyngeal carcinoma (n = 27, 65.9 %) and locally advanced disease. Blood was drawn at baseline and treatment evaluation 4.5 months after therapy. lncRNAs in plasma were measured by semiquantitative PCR. Treatment response was evaluated according to clinical examination, RECIST and PERCIST criteria based on magnetic resonance imaging (MRI), and positron emission tomography with computed tomography (PET/CT) findings. Complete response (CR) rates were 73.2, 36.6, and 50 % for clinical investigation, PET/CT-, or MRI-based response evaluation, respectively. Predictive value of lncRNAs was investigated in patients with CR vs. those with partial response (PR)/progressive disease (PD). We found that post-treatment GAS5 levels in patients with PR/PD were significantly higher compared with patients with CR based on clinical investigation (p = 0.01). Receiver operator characteristic (ROC) analysis showed that at a cutoff value of 0.3 of GAS5, sensitivity and specificity for clinical tumor response were 82 and 77 %, respectively. Interestingly, pretreatment GAS5 levels were significantly increased in patients with PR/PD compared to those with CR upon MRI-based response evaluation (p = 0.042). In contrast to GAS5, pretreatment or post-treatment lincRNA-p21 and HOTAIR levels were not informative for treatment response. Our results suggest that circulating GAS5 could be a biomarker in predicting treatment response in HNC patients.
Blood biomarker for Parkinson disease: peptoids
Yazdani, Umar; Zaman, Sayed; Hynan, Linda S; Brown, L Steven; Dewey, Richard B; Karp, David; German, Dwight C
2016-01-01
Parkinson disease (PD) is the second most common neurodegenerative disease. Because dopaminergic neuronal loss begins years before motor symptoms appear, a biomarker for the early identification of the disease is critical for the study of putative neuroprotective therapies. Brain imaging of the nigrostriatal dopamine system has been used as a biomarker for early disease along with cerebrospinal fluid analysis of α-synuclein, but a less costly and relatively non-invasive biomarker would be optimal. We sought to identify an antibody biomarker in the blood of PD patients using a combinatorial peptoid library approach. We examined serum samples from 75 PD patients, 25 de novo PD patients, and 104 normal control subjects in the NINDS Parkinson’s Disease Biomarker Program. We identified a peptoid, PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects (P<0.0001) and is 68% accurate in identifying PD. The PD2 peptoid is 84% accurate in identifying de novo PD. Also, IgG3 levels are significantly higher in PD versus control serum (P<0.001). Finally, PD2 levels are positively correlated with the United Parkinson’s Disease Rating Scale score (r=0.457, P<0001), a marker of disease severity. The PD2 peptoid may be useful for the early-stage identification of PD, and serve as an indicator of disease severity. Additional studies are needed to validate this PD biomarker. PMID:27812535
Yang, Jin; Li, Pinhua; Zhang, Yicheng; Wang, Lei
2014-05-21
Six dinuclear N-heterocyclic carbene (NHC) palladium complexes, [PdCl2(IMes)]2(μ-dppe) (1), [PdCl2(IPr)]2(μ-dppe) (2), [PdCl2(IMes)]2(μ-dppb) (3), [PdCl2(IPr)]2(μ-dppb) (4), [PdCl2(IMes)]2(μ-dpph) (5), and [PdCl2(IPr)]2(μ-dpph) (6) [IMes = N,N'-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene; IPr = N,N'-bis-(2,6-di(iso-propyl)phenyl)imidazol-2-ylidene; dppe = 1,2-bis(diphenylphosphino)ethane, dppb = 1,4-bis(diphenylphosphino)butane; and dpph = 1,6-bis(diphenylphosphino)hexane], have been synthesized through bridge-cleavage reactions of chloro-bridged dimeric compounds, [Pd(μ-Cl)(Cl)(NHC)]2, with the corresponding diphosphine ligands. The obtained compounds were fully characterized by (1)H NMR, (13)C NMR and (31)P NMR spectroscopy, FT-IR, elemental analysis and single-crystal X-ray crystallography. Moreover, further explorations of the catalytic potential of the dinuclear carbene palladium complexes as catalysts for the Pd-catalyzed transformations have been performed under microwave irradiation conditions, and the complexes exhibited moderate to good catalytic activity in the Hiyama coupling reaction of trimethoxyphenylsilane with aryl chlorides.
Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Ellinger, Jörg; Landsberg, Jennifer; Kristiansen, Glen; Dietrich, Dimo
2016-01-01
Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 ( PDCD1 ) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn. In the TCGA cohort, the PD-1 promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs. 38.2%, p < 0.001) and PD-1 methylation ( mPD-1 ) inversely correlated with PD-1 mRNA expression in PCa (Spearman's ρ = -0.415, p < 0.001). In both cohorts, mPD-1 significantly correlated with preoperative prostate specific antigen (PSA). In univariate Cox Proportional Hazard analysis, mPD-1 served as a significant prognostic factor for biochemical recurrence (BCR)-free survival (Hazard ratio: HR = 2.35 [1.35-4.10], p = 0.003, n = 410) in the TCGA cohort. In multivariate analysis, mPD-1 was shown to add significant independent prognostic information adjunct to pathologic tumor category (pT) and Gleason grading group (HR = 2.08 [1.16-3.74], p = 0.014, n = 350). PD-1 promoter methylation analyses could thus potentially aid the identification of patients which might benefit from adjuvant treatment after radical prostatectomy. Moreover, our data suggest an intrinsic role of PD-1 in PCa carcinogenesis and disease progression, which needs to be addressed in future studies.
Chen, Si; Li, Yuan; Deng, Chuiwen; Li, Jing; Wen, Xiaoting; Wu, Ziyan; Hu, Chaojun; Zhang, Shulan; Li, Ping; Zhang, Xuan; Zhang, Fengchun; Li, Yongzhe
2016-01-01
Previous surveys had evaluated the effects of the PD-1, CTLA-4 gene polymorphisms on susceptibility to ankylosing spondylitis (AS), but the results remained controversial. To briefly examine these consequences, a comprehensive meta-analysis was conducted to estimate the relationships between PD-1 rs11568821, rs2227982, rs2227981, CTLA-4 +49 A/G and -318 C/T polymorphisms and AS risk. The available articles dated to December 2014 were searched in the PUBMED, MEDLINE and EMBASE databases. The data of the genotypes and/or alleles for the PD-1 rs11568821, rs2227982, rs2227981, CTLA-4 +49 A/G and -318 C/T polymorphisms in the AS and control subjects were extracted, and statistical analysis was conducted by STATA 11.2 software. Summary odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) were calculated to determine the strength of associations with fixed-effects or random-effects models. A total of eight published studies were finally involved in this meta-analysis. Meta-analysis of PD-1 rs2227982 polymorphism under the T allele versus C allele (OR 1.744, 95 % CI 1.477-2.059, P < 0.0001), TT+TC versus CC (OR 2.292, 95 % CI 1.654-3.175, P < 0.0001), TT versus CC (OR 1.883, 95 % CI 1.299-2.729, P = 0.001) revealed a significant association with AS. Our meta-analysis demonstrated that the rs2227982 polymorphism in the PD-1 gene might contribute to AS susceptibility. However, further studies with large sample sizes and among different ethnicity populations should be required to confirm this association.
NASA Astrophysics Data System (ADS)
Jang, Jae-Myung; Kim, Seung-Dai; Park, Tae-Eon; Choe, Han-Cheol
2018-02-01
The biocompatibility structure of an implant surface is of great importance to the formation of new bone tissue around the dental implant and also has a significant chemical reaction in the osseointegration process. Thus, ultra-fine Pd-Ag-HAp nanoparticles have been electrodeposited on protruded TiO2 barrier layer in mixed electrolyte solutions. Unusual protrusions patterns, which are assigned to Pd-Ag-HAp nanoparticles, can be clearly differentiated from a TiO2 nanotube oxide layer formed by an anodizing process. In the chemical bonding state, the surface characteristics of Pd/Ag/HAp compounds have been investigated by FE-SEM, EDS mapping analysis, and XPS analysis. The mapping dots of the elements including Ti, Ca, Pd, Ag, and P showed a homogeneous distribution throughout the entire surface when deposited onto the protruded TiO2 barrier layer. The XPS spectra of Ti-2p, O-1S, Pd-3d, and Ag-3d have been investigated, with the major XPS peak indicating Pd-3d. The Ag-3d level was clearly observed with further scanning of the Ca-2p region. Based on the results of the chemical states, the structural properties of the protrusion patterns were also examined after being deposited onto the barrier oxide film, resulting in the representative protrusion patterns being mainly composed of Pd-Ag-HAp compounds. The results of the soaking evaluation showed that the protrusion patterns and the protruded TiO2 barrier layer were all effective in regards to biocompatibility.
Asymptomatic Effluent Protozoa Colonization in Peritoneal Dialysis Patients.
Simões-Silva, Liliana; Correia, Inês; Barbosa, Joana; Santos-Araujo, Carla; Sousa, Maria João; Pestana, Manuel; Soares-Silva, Isabel; Sampaio-Maia, Benedita
Currently, chronic kidney disease (CKD) is a global health problem. Considering the impaired immunity of CKD patients, the relevance of infection in peritoneal dialysis (PD), and the increased prevalence of parasites in CKD patients, protozoa colonization was evaluated in PD effluent from CKD patients undergoing PD. Overnight PD effluent was obtained from 49 asymptomatic stable PD patients. Protozoa analysis was performed microscopically by searching cysts and trophozoites in direct wet mount of PD effluent and after staining smears. Protozoa were found in PD effluent of 10.2% of evaluated PD patients, namely Blastocystis hominis, in 2 patients, and Entamoeba sp., Giardia sp., and Endolimax nana in the other 3 patients, respectively. None of these patients presented clinical signs or symptoms of peritonitis at the time of protozoa screening. Our results demonstrate that PD effluent may be susceptible to asymptomatic protozoa colonization. The clinical impact of this finding should be further investigated. Copyright © 2016 International Society for Peritoneal Dialysis.
The role of PD-1 in regulation of macrophage apoptosis and its subversion by Leishmania donovani
Roy, Shalini; Gupta, Purnima; Palit, Shreyasi; Basu, Moumita; Ukil, Anindita; Das, Pijush K
2017-01-01
Programmed death-1 receptor (PD-1) expressed in many immune cells is known to trigger T-cell exhaustion but the significance of macrophage-associated PD-1 in relevance to macrophage apoptosis is not known. This study is aimed to delineate whether PD-1 pathway has any role in eliciting macrophage apoptosis and, if so, then how the intra-macrophage parasite, Leishmania donovani modulates PD-1 pathway for protecting its niche. Resting macrophages when treated with H2O2 showed increased PD-1 expression and apoptosis, which was further enhanced on PD-1 agonist treatment. The administration of either PD-1 receptor or PD-1 ligand-blocking antibodies reversed the process thus documenting the involvement of PD-1 in macrophage apoptosis. On the contrary, L. donovani-infected macrophages showed decreased PD-1 expression concurrent with inhibition of apoptosis. The activation of PD-1 pathway was found to negatively regulate the phosphorylation of pro-survival AKT, which was reversed during infection. Infection-induced PD-1 downregulation led to the activation of AKT resulting in phosphorylation and subsequent inhibition of proapoptotic protein BAD. Strong association of SHP2 (a SH2-containing ubiquitously expressed tyrosine-specific protein phosphatase) with PD-1 along with AKT deactivation observed in H2O2-treated macrophages was reversed by L. donovani infection. Kinetic analysis coupled with inhibitor-based approach and knockdown experiments demonstrated that L. donovani infection actively downregulated the PD-1 by deactivating NFATc1 as revealed by its reduced nuclear translocation. The study thus elucidates the detailed mechanism of the role of PD-1 in macrophage apoptosis and its negative modulation by Leishmania for their intracellular survival. PMID:28690843
Su, Qiang; Zhang, Xiaochen; Shen, Xinhua; Hou, Yanli; Sun, Zhigang; Gao, Zu Hua
2018-01-01
Background: We performed a meta-analysis to evaluate the risk of immune-related colitis associated with PD1/PD-L1 inhibitors as compared to chemotherapy in solid tumor patients. Methods: Eligible studies were identified through a comprehensive search of multiple databases and included solid tumor patients in randomized controlled trials (RCTs) with PD-1/PD-L1 inhibitors. The data was analyzed by Stata version 12.0 software. Results: After exclusion of ineligible studies, 11 clinical trials were considered eligible for the meta-analysis, including 5751 patients. Compared with chemotherapy, the risk ratios (RRs) of all-grade colitis were significant for the PD-1 inhibitor subgroup (RR 2.69, 95% confidence interval (CI): 1.15-6.29, p=0.023), and for pembrolizumab subgroup (RR 3.17, 95% CI: 1.08-9.37, p=0.037), but not for nivolumab treatment and PD-L1 inhibitor (atezolizumab) treatment (RR 2.05, 95% CI: 0.52-8.13, p=0.305; RR 4.75,95% CI: 0.56-40.50, p=0.154, respectively). The RR of all-grade colitis was significant for PD-1/PD-L1 inhibitor in NSCLC (RR 4.34, 95% CI: 1.37-13.82, p=0.013), and not significant in melanoma (RR 2.11, 95% CI: 0.54-8.34, p=0.285). Moreover, the RRs of all-grade diarrhea were significant for the PD-1 inhibitor subgroup (RR 0.61, 95% CI: 0.44-0.83, p=0.002), for the nivolumab subgroup (RR 0.54, 95% CI: 0.34-0.87, p=0.012), and for atezolizumab subgroup (RR 0.48, 95% CI: 0.25-0.89, p=0.021). The RR of high-grade diarrhea was significant for atezolizumab subgroup (RR 0.34, 95% CI: 0.12-0.94, p=0.037). Conclusions: Our meta-analysis demonstrates that compared with chemotherapy, pembrolizumab may result in a higher risk of all-grade immune-mediated colitis. PD-1/PD-L1 inhibitor treatment in NSCLC patients, but not in melanoma patients, increases the risk of all-grade colitis incidence.
TechTracS: NASA's commercial technology management system
NASA Astrophysics Data System (ADS)
Barquinero, Kevin; Cannon, Douglas
1996-03-01
The Commercial Technology Mission is a primary NASA mission, comparable in importance to those in aeronautics and space. This paper will discuss TechTracS, NASA Commercial Technology Management System that has been put into place in FY 1995 to implement this mission. This system is designed to identify and capture the NASA technologies which have commercial potential into an off-the-shelf database application, and then track the technologies' progress in realizing the commercial potential through collaborations with industry. The management system consists of four stages. The first is to develop an inventory database of the agency's entire technology portfolio and assess it for relevance to the commercial marketplace. Those technologies that are identified as having commercial potential will then be actively marketed to appropriate industries—this is the second stage. The third stage is when a NASA-industry partnership is entered into for the purposes of commercializing the technology. The final stage is to track the technology's success or failure in the marketplace. The collection of this information in TechTracS enables metrics evaluation and can accelerate the establishment on direct contacts between and NASA technologist and an industry technologist. This connection is the beginning of the technology commercialization process.
Zhang, Hangjun; Jiang, Xiaojun; Lu, Liping; Xiao, Wenfeng
2015-01-01
Polychlorinated biphenyls (PCBs), a class of hazardous pollutants, are difficult to dissipate in the natural environment. In this study, a cyanobacterial strain Anabaena PD-1 showed good resistance against PCB congeners. Compared to a control group, chlorophyll a content decreased 3.7% and 11.7% when Anabaena PD-1 was exposed to 2 and 5 mg/L PCBs for 7 d. This cyanobacterial strain was capable of decomposing PCB congeners which was conclusively proved by determination of chloride ion concentrations in chlorine-free medium. After 7 d, the chloride ion concentrations in PCB-treated groups (1, 2, 5 mg/L) were 3.55, 3.05, and 2.25 mg/L, respectively. The genetic information of strain PD-1 was obtained through 16S rRNA sequencing analysis. The GenBank accession number of 16S rRNA of Anabaena PD-1 was KF201693.1. Phylogenetic tree analysis clearly indicated that Anabaena PD-1 belonged to the genus Anabaena. The degradation half-life of Aroclor 1254 by Anabaena PD-1 was 11.36 d; the total degradation rate for Aroclor 1254 was 84.4% after 25 d. Less chlorinated PCB congeners were more likely to be degraded by Anabaena PD-1 in comparison with highly chlorinated congeners. Meta- and para-chlorines in trichlorodiphenyls and tetrachlorobiphenyls were more susceptible to dechlorination than ortho-chlorines during the PCB-degradation process by Anabaena PD-1. Furthermore, Anabaena PD-1 can decompose dioxin-like PCBs. The percent biodegradation of 12 dioxin-like PCBs by strain PD-1 ranged from 37.4% to 68.4% after 25 days. Results above demonstrate that Anabaena PD-1 is a PCB-degrader with great potential for the in situ bioremediation of PCB-contaminated paddy soils. PMID:26177203
Yoshioka, R; Yasunaga, H; Hasegawa, K; Horiguchi, H; Fushimi, K; Aoki, T; Sakamoto, Y; Sugawara, Y; Kokudo, N
2014-04-01
High morbidity and mortality rates after pancreaticoduodenectomy (PD) have led to concentration of this surgery in high-volume centres, with improved outcomes. The extent to which better outcomes might be apparent in a healthcare system where the mortality rate is already low is unclear. The Japanese Diagnosis Procedure Combination database was used to identify patients undergoing PD between 2007 and 2010. Patient data included age, sex, co-morbidities at admission, type of hospital, type of PD, and the year in which the patient was treated. Hospital volume was defined as the number of PDs performed annually at each hospital, and categorized into quintiles: very low-, low-, medium-, high- and very high-volume groups. The Charlson co-morbidity index was calculated using the International Classification of Diseases, tenth revision, codes of co-morbidities. A total of 10 652 patients who underwent PD in 848 hospitals were identified. The overall in-hospital mortality rate after PD was 3·3 per cent (350 of 10 652), and for the groups ranged from 5·0 per cent for the very low-volume group to 1·4 per cent for the very high-volume group (P < 0·001). Multivariable analysis revealed a significant linear relationship between higher hospital volume and shorter postoperative length of stay compared with the very low-volume group, and between increasing hospital volume and lower total costs. A significant relationship exists between increasing hospital volume, lower in-hospital mortality, shorter length of stay and lower costs for patients undergoing PD in Japan. Centralization of PD in this healthcare system is therefore justified. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
The following are reported: theoretical calculations (configuration interaction, relativistic effective core potentials, polyatomics, CASSCF); proposed theoretical studies (clusters of Cu, Ag, Au, Ni, Pt, Pd, Rh, Ir, Os, Ru; transition metal cluster ions; transition metal carbide clusters; bimetallic mixed transition metal clusters); reactivity studies on transition metal clusters (reactivity with H{sub 2}, C{sub 2}H{sub 4}, hydrocarbons; NO and CO chemisorption on surfaces). Computer facilities and codes to be used, are described. 192 refs, 13 figs.
Solid solutions of platinum(II) and palladium(II) oxalato-complex salt as precursors of nanoalloys
NASA Astrophysics Data System (ADS)
Zadesenets, A. V.; Asanova, T. I.; Vikulova, E. S.; Filatov, E. Yu.; Plyusnin, P. E.; Baidina, I. A.; Asanov, I. P.; Korenev, S. V.
2013-03-01
A solid solution of platinum (II) and palladium (II) oxalato-complex salt, (NH4)2[Pt0.5Pd0.5(C2O4)2]·2H2O, has been synthesized and studied as a precursor for preparing bimetallic PtPd nanoparticles through its thermal decomposition. The smallest homogenous bimetallic PtPd nanoparticles were found to form in hydrogen and helium atmospheres. The annealing temperature and time have low effect on the bimetallic particles size. Comparative analysis of structural and thermal properties of the solid solution and individual Pt, Pd oxalato-complex salts was performed to investigate a mechanism of thermal decomposition of (NH4)2[Pt0.5Pd0.5(C2O4)2]·2H2O. Based on in situ X-ray photoemission spectroscopy investigation it was proposed a mechanism of formation of bimetallic PtPd nanoparticles from the solid-solution oxalato-complex salt during thermal decomposition.
Highly efficient photocatalytic degradation of methylene blue by PoPD/TiO2 nanocomposite
Dong, Wenping; Cui, Guanwei; Ren, Zongming
2017-01-01
The poly-o-phenylenediamine (PoPD)/TiO2 nanocomposite was successfully synthesized via ‘in situ’ oxidative polymerization method. The modified photocatalysts were characterized by BET, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrarad spectra (FT-IR), thermogravimrtic analysis (TGA), X-ray photoelectron spectroscopy (XPS), Ultraviolet-visible diffuse reflectance spectrum (UV-Vis DRS) and Photocurrent Test. The results showed that the PoPD exists on the surface of TiO2, the presence of PoPD does not impact on the lattice structure and grain size of TiO2, and the presence of PoPD enhances the visible response and photoelectric property. The photocatalytic degradation of methylene blue (MB) was chosen as a model reaction to evaluate the photocatalytic activities of TiO2 and PoPD/TiO2. The optimal preparation condition was the molar ratio of oPD to TiO2 = 3:1, HCl concentration = 1.2 mol/L, the molar ratio of APS to oPD = 1:1. The apparent first-order rate constant kapp of PoPD/TiO2 nanocomposite was 0.0098 min-1, which is 6 times higher than TiO2 (0.0016 min-1). Meanwhile, the PoPD/TiO2 nanocomposites showed excellent photocatalytic stability, and the photocatalytic stability was depended on the stability of structure. At last, the photocatalytic mechanism of POPD/TiO2 nanocomposites was also proposed based on the synergetic effect between TiO2 and PoPD. PMID:28329007
Bidirectional active control of structures with type-2 fuzzy PD and PID
NASA Astrophysics Data System (ADS)
Paul, Satyam; Yu, Wen; Li, Xiaoou
2018-03-01
Proportional-derivative and proportional-integral-derivative (PD/PID) controllers are popular algorithms in structure vibration control. In order to maintain minimum regulation error, the PD/PID control require big proportional and derivative gains. The control performances are not satisfied because of the big uncertainties in the buildings. In this paper, type-2 fuzzy system is applied to compensate the unknown uncertainties, and is combined with the PD/PID control. We prove the stability of these fuzzy PD and PID controllers. The sufficient conditions can be used for choosing the gains of PD/PID. The theory results are verified by a two-storey building prototype. The experimental results validate our analysis.
NASA Astrophysics Data System (ADS)
Yasmin, Sabina; Joo, Yuri; Jeon, Seungwon
2017-06-01
The electrochemical deposition of Pd nanoparticles (Pd NPs) on 2,3 diamino pyridine functionalized reduced graphene oxide (2,3 DAP-rGO/Pd) has been investigated for the oxygen reduction reaction (ORR) in alkaline media. First, 2,3 diaminopyridine functionalized graphene oxide (2,3 DAP-rGO) has been synthesized via simple hydrothermal method. Then, palladium is directly incorporated into the 2,3 DAP-rGO by electrochemical deposition method to generate 2,3 DAP-rGO/Pd composites. The as-prepared material 2,3 DAP-rGO/Pd has been characterized by various instrumental methods. The morphological analysis shows the cluster-like Pd nanoparticles are dispersed onto the 2,3 diamino pyridine functionalized reduced graphene oxide (2,3 DAP-rGO). The electrocatalytic activities have been verified using cyclic voltammetry (CV) and hydrodynamic voltammetry and chronoamperometry techniques in 0.1 M KOH electrolyte. The as-synthesized 2,3 DAP-rGO/Pd shows higher catalytic activity toward ORR with more positive onset potential and cathodic current density, superior methanol/ethanol tolerance and excellent stability in alkaline medium. It is also noteworthy that the 2,3 DAP-rGO/Pd exhibits a four-electron transfer pathway for ORR with lower H2O2 yield.
Genetic and epigenetic status of triple exotic consanguinity cotton introgression lines.
He, S P; Sun, J L; Du, X M
2011-10-03
Introgression lines are some of the most important germplasm for breeding applications and other research conducted on cotton crops. The DNA methylation level among 10 introgression lines of cotton (Gossypium hirsutum) and three exotic parental species (G. arboreum, G. thurberi and G. barbadense) were assessed by methylation-sensitive amplified polymorphism (MSAP) technology. The methylation level in the introgression lines ranged from 33.3 to 51.5%. However, the lines PD0111 and PD0113 had the lowest methylation level (34.6 and 33.3%, respectively) due to demethylation of most non-coding sequences. Amplified fragment length polymorphism (AFLP) was used to evaluate the genetic polymorphism in the cotton introgression lines. A high degree of polymorphism was observed in all introgression lines (mean 47.2%) based on AFLP and MSAP analyses. This confirmed the effects of genetic improvement on cotton introgression lines. The low methylation varieties, PD0111 and PD0113 (introgression lines), clustered outside of the introgression lines based on MSAP data, which was incongruent with an AFLP-based dendrogram. This phenomenon could be caused by environmental changes or introgression of exotic DNA fragments.
NASA Astrophysics Data System (ADS)
Leblanc, Sylvain G.
2002-12-01
A plant canopy gap-size analyzer, the Tracing Radiation and Architecture of Canopies (TRAC), developed by Chen and Cihlar [Appl. Opt. 34, 6211 (1995)] and commercialized by 3rd Wave Engineering (Nepean, Canada), has been used around the world to quantify the fraction of photosynthetically active radiation absorbed by plant canopies, the leaf area index (LAI), and canopy architectural parameters. The TRAC is walked under a canopy along transects to measure sunflecks that are converted into a gap-size distribution. A numerical gap-removal technique is performed to remove gaps that are not theoretically possible in a random canopy. The resulting reduced gap-size distribution is used to quantify the heterogeneity of the canopy and to improve LAI measurements. It is explicitly shown here that the original derivation of the clumping index was missing a normalization factor. For a very clumped canopy with a large gap fraction, the resulting LAI can be more than 100% smaller than previously estimated. A test case is used to demonstrate that the new clumping index derivation allows a more accurate change of LAI to be measured.
Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis.
Zhuan-Sun, Yongxun; Huang, Fengting; Feng, Min; Zhao, Xinbao; Chen, Wenying; Zhu, Zhe; Zhang, Shineng
2017-01-01
Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is often activated in cancer and plays a pivotal role in the initiation and progression of cancer. However, the clinicopathologic significance and prognostic value of PD-L1 in pancreatic cancer (PC) remains controversial. In this study, we conducted a meta-analysis to retrospectively evaluate the relationship between PD-L1 and PC. PubMed and other databases were searched for the clinical studies published up to March 21, 2017, to be included in the meta-analysis. Hazard ratios and their 95% CIs were calculated. Risk ratios (RRs) were extracted to assess the correlations between the clinicopathologic parameters and PD-L1 expression. Ten studies including 1,058 patients were included in the meta-analysis. The pooled results indicated that positive PD-L1 expression was correlated with a poor overall survival outcome in PC patients (hazard ratio =1.76, 95% CI: 1.43-2.17, P <0.00001). Interestingly, high PD-L1 expression was correlated with poor pathologic differentiation (RR =1.57, 95% CI: 1.25-1.98, P =0.0001) and neural invasion (RR =1.30, 95% CI: 1.03-1.64, P =0.03). However, there were no significant correlations between PD-L1 expression and other clinicopathologic characteristics. In summary, our meta-analysis implied that PD-L1 could serve as a negative predictor for the overall survival of PC patients, and high expression of PD-L1 was correlated with poor differentiation and neural invasion, indicating that anti-PD-L1 treatments should be evaluated in PC patients, especially in those who exhibit these two characteristics.
Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis
Feng, Min; Zhao, Xinbao; Chen, Wenying; Zhu, Zhe; Zhang, Shineng
2017-01-01
Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is often activated in cancer and plays a pivotal role in the initiation and progression of cancer. However, the clinicopathologic significance and prognostic value of PD-L1 in pancreatic cancer (PC) remains controversial. In this study, we conducted a meta-analysis to retrospectively evaluate the relationship between PD-L1 and PC. PubMed and other databases were searched for the clinical studies published up to March 21, 2017, to be included in the meta-analysis. Hazard ratios and their 95% CIs were calculated. Risk ratios (RRs) were extracted to assess the correlations between the clinicopathologic parameters and PD-L1 expression. Ten studies including 1,058 patients were included in the meta-analysis. The pooled results indicated that positive PD-L1 expression was correlated with a poor overall survival outcome in PC patients (hazard ratio =1.76, 95% CI: 1.43–2.17, P<0.00001). Interestingly, high PD-L1 expression was correlated with poor pathologic differentiation (RR =1.57, 95% CI: 1.25–1.98, P=0.0001) and neural invasion (RR =1.30, 95% CI: 1.03–1.64, P=0.03). However, there were no significant correlations between PD-L1 expression and other clinicopathologic characteristics. In summary, our meta-analysis implied that PD-L1 could serve as a negative predictor for the overall survival of PC patients, and high expression of PD-L1 was correlated with poor differentiation and neural invasion, indicating that anti-PD-L1 treatments should be evaluated in PC patients, especially in those who exhibit these two characteristics. PMID:29081663
Benipal, Neeva; Qi, Ji; Dalian Univ. of Technology, Dalian; ...
2017-03-10
Electro-oxidation of alcohol is the key reaction occurring at the anode of a direct alcohol fuel cell (DAFC), in which both reaction kinetics (rate) and selectivity (to deep oxidation products) need improvement to obtain higher power density and fuel utilization for a more efficient DAFC. We recently found that a PdAg bimetallic nanoparticle catalyst is more efficient than Pd for alcohol oxidation: Pd can facilitate deprotonation of alcohol in a base electrolyte, while Ag can promote intermediate aldehyde oxidation and cleavage of C-single bondC bond of C 3 species to C 2 species. Furthermore, a combination of the two activemore » sites (Pd and Ag) with two different functions, can simultaneously improve the reaction rates and deeper oxidation products of alcohols. In this continuing work, Pd, Ag mono, and bimetallic nanoparticles supported on carbon nanotubes (Ag/CNT, Pd/CNT, Pd 1Ag 1/CNT, and Pd 1Ag 3/CNT) were prepared using an aqueous-phase reduction method; they served as working catalysts for studying electrocatalytic oxidation of glycerol in an anion-exchange membrane-based direct glycerol fuel cell. Combined XRD, TEM, and HAADF-STEM analyses performed to fully characterize as-prepared catalysts suggested that they have small particle sizes: 2.0 nm for Pd/CNT, 2.3 nm for PdAg/CNT, 2.4 nm for PdAg 3/CNT, and 13.9 nm for Ag/CNT. XPS further shows that alloying with Ag results in more metal state Pd presented on the surface, and this may be related to their higher direct glycerol fuel cell (DGFC) performances. Single DGFC performance and product analysis results show that PdAg bimetallic nanoparticles can not only improve the glycerol reaction rate so that higher power output can be achieved, but also facilitate deep oxidation of glycerol so that a higher faradaic efficiency and fuel utilization can be achieved along with optimal reaction conditions (increased base-to-fuel ratio). Half-cell electrocatalytic activity measurement and single fuel cell product analysis of different glycerol oxidation intermediates, including C 3: glycerate, tartronate, mesoxalate, and lactate; C 2: glycolate and oxalate, over PdAg/CNT catalyst was further conducted and produced deeper insight into the synergistic effects and reaction pathways of bimetallic PdAg catalysts in glycerol electrocatalytic oxidation.« less
Recoil distance lifetime measurements in 122,124Xe
NASA Astrophysics Data System (ADS)
Govil, I. M.; Kumar, A.; Iyer, H.; Li, H.; Garg, U.; Ghugre, S. S.; Johnson, T.; Kaczarowski, R.; Kharraja, B.; Naguleswaran, S.; Walpe, J. C.
1998-02-01
Lifetimes of the lower-excited states in 122,124Xe are measured using the recoil-distance Doppler-shift technique. The reactions 110Pd(16O,4n)122Xe and 110Pd(18O,4n)124Xe at a beam energy of 66 MeV were used for this experiment. The lifetimes of the 2+, 4+, 6+, and 8+ states of the ground state band were extracted using the computer code LIFETIME including the corrections due to the side feeding and the nuclear deorientation effects. The lifetime of the 2+ state in 122Xe agrees with the recoil distance method (RDM) measurements but for the 124Xe it does not agree with the RDM measurements but agrees with the Coulomb-excitation experiment. The measured B(E2) values for both the nuclei are compared with the standard algebraic and the multishell models.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Keeling, V; Jin, H; Hossain, S
2015-06-15
Purpose: To evaluate patient setup accuracy and quantify individual and cumulative positioning uncertainties associated with different hardware and software components of the stereotactic radiotherapy (SRS/SRT) with the frameless-6D-ExacTrac system. Methods: A statistical model was used to evaluate positioning uncertainties of the different components of SRS/SRT treatment with the BrainLAB 6D-ExacTrac system using the positioning shifts of 35 patients having cranial lesions (49 total lesions treated in 1, 3, 5 fractions). All these patients were immobilized with rigid head-and-neck masks, simulated with BrainLAB-localizer and planned with iPlan treatment planning system. Infrared imaging (IR) was used initially to setup patients. Then, stereoscopicmore » x-ray images (XC) were acquired and registered to corresponding digitally-reconstructed-radiographs using bony-anatomy matching to calculate 6D-translational and rotational shifts. When the shifts were within tolerance (0.7mm and 1°), treatment was initiated. Otherwise corrections were applied and additional x-rays were acquired (XV) to verify that patient position was within tolerance. Results: The uncertainties from the mask, localizer, IR-frame, x-ray imaging, MV and kV isocentricity were quantified individually. Mask uncertainty (Translational: Lateral, Longitudinal, Vertical; Rotational: Pitch, Roll, Yaw) was the largest and varied with patients in the range (−1.05−1.50mm, −5.06–3.57mm, −5.51−3.49mm; −1.40−2.40°, −1.24−1.74°, and −2.43−1.90°) obtained from mean of XC shifts for each patient. Setup uncertainty in IR positioning (0.88,2.12,1.40mm, and 0.64,0.83,0.96°) was extracted from standard-deviation of XC. Systematic uncertainties of the localizer (−0.03,−0.01,0.03mm, and −0.03,0.00,−0.01°) and frame (0.18,0.25,−1.27mm,−0.32,0.18, and 0.47°) were extracted from means of all XV setups and mean of all XC distributions, respectively. Uncertainties in isocentricity of the MV radiotherapy machine were (0.27,0.24,0.34mm) and kV-imager (0.15,−0.4,0.21mm). Conclusion: A statistical model was developed to evaluate the individual and cumulative systematic and random uncertainties induced by the different hardware and software components of the 6D-ExacTrac-system. The immobilization mask was associated with the largest positioning uncertainty.« less
Thimmaiah, Srinivasa; Miller, Gordon J.
2015-06-03
A series of pseudo-binary compounds MgZn 2-xPd x (0.15 ≤ x ≤ 1.0) were synthesized and structurally characterized to understand the role of valence electron concentration (vec) on the prototype Laves phase MgZn 2 with Pd-substitution. Three distinctive phase regions were observed with respect to Pd content, all exhibiting fundamental Laves phase structures: 0.1 ≤ x ≤ 0.3 (MgNi 2-type, hP24; MgZn 1.80Pd 0.20(2)), 0.4 ≤ x ≤ 0.6 (MgCu 2-type, cF24; MgZn 1.59Pd 0.41(2)), and 0.62 ≤ x ≤ 0.8 (MgZn 2-type, hP12: MgZn 1.37Pd 0.63(2)). Refinements from single-crystal X-ray diffraction indicated nearly statistical distributions of Pd and Znmore » atoms among the majority atom sites in these structures. Interestingly, the MgZn 2-type structure re-emerges in MgZn 2–xPd x at x ≈ 0.7 with the refined composition MgZn 1.37(2)Pd 0.63 and a c/a ratio of 1.59 compared to 1.64 for binary MgZn 2. Electronic structure calculations on a model “MgZn 1.25Pd 0.75” yielded a density of states (DOS) curve showing enhancement of a pseudogap at the Fermi level as a result of electronic stabilization due to the Pd addition. Moreover, integrated crystal orbital Hamilton population values show significant increases of orbital interactions for (Zn,Pd)–(Zn,Pd) atom pairs within the majority atom substructure, i.e., within the Kagomé nets as well as between a Kagomé net and an apical site, from binary MgZn 2 to the ternary “MgZn 1.25Pd 0.75”. Multi-centered bonding is evident from electron localization function plots for “MgZn 1.25Pd 0.75”, an outcome which is in accordance with analysis of other Laves phases.« less
Electrodermal complexity during the Stroop colour word test.
Svetlak, Miroslav; Bob, Petr; Cernik, Michal; Kukleta, Miloslav
2010-01-15
Several recent studies suggest that quantitative description of signal complexity using algorithms of nonlinear analysis could uncover new information about the autonomic system that is not reflected using common methods applied to measures of autonomic activity. With this aim we have performed complexity analysis of electrodermal activity (EDA) assessed in 106 healthy university students during rest conditions and non-conflicting and conflicting Stroop task. Complexity analysis applied to EDA was performed using Skinner's algorithm for pointwise correlation dimension (PD2). Results have shown that EDA responses during the Stroop Colour Word test are related to significantly increased or decreased complexity. Particularly significant result is that PD2 has a unique ability to predict to an extent the change in EDA response to stress i.e. that subjects with low initial PD2 tended to respond to experimental stress by its increase and subjects with high initial PD2 values tended to respond by its decrease. This response was not found in EDA measures where increase of the EDA presented predominant response to experimental stress in majority of the subjects. These findings suggest that PD2 is more sensitive to subtle aspects of functionally and spatially distributed modulatory influences of various parts of the brain that are involved in the EDA modulation and provides novel information in comparison to traditional methods.
Van Laere, Koen; Clerinx, Kristien; D'Hondt, Eduard; de Groot, Tjibbe; Vandenberghe, Wim
2010-04-01
Striatal dopamine D(2) receptor (D2R) PET has been proposed to differentiate between Parkinson disease (PD) and multiple-system atrophy with predominant parkinsonism (MSA-P). However, considerable overlap in striatal D(2) binding may exist between PD and MSA-P. It has been shown that imaging of neuronal activity, as determined by metabolism or perfusion, can also help distinguish PD from MSA-P. We investigated whether the differential diagnostic value of (11)C-raclopride PET could be improved by dynamic scan analysis combining D2R binding and regional tracer influx. (11)C-raclopride PET was performed in 9 MSA-P patients (mean age +/- SD, 56.2 +/- 10.2 y; disease duration, 2.9 +/- 0.8 y; median Hoehn-Yahr score, 3), 10 PD patients (mean age +/- SD, 65.7 +/- 8.1 y; disease duration, 3.3 +/- 1.5 y; median Hoehn-Yahr score, 1.5), and 10 healthy controls (mean age +/- SD, 61.6 +/- 6.5 y). Diagnosis was obtained after prolonged follow-up (MSA-P, 5.5 +/- 2.0 y; PD, 6.0 +/- 2.3 y) using validated clinical criteria. Spatially normalized parametric images of binding potential (BP) and local influx ratio (R(1) = K(1)/K'(1)) of (11)C-raclopride were obtained using a voxelwise reference tissue model with occipital cortex as reference region. Stepwise forward discriminant analysis with cross-validation, with and without the inclusion of regional R(1) values, was performed using a predefined volume-of-interest template. Using conventional BP values, we correctly classified 65.5% (all values given with cross-validation) of 29 cases only. The combination of BP and R(1) information increased discrimination accuracy to 79.3%. When healthy controls were not included and patients only were considered, BP information alone discriminated PD and MSA-P in 84.2% of cases, but the combination with R(1) data increased accuracy to 100%. Discriminant analysis using combined striatal D2R BP and cerebral influx ratio information of a single dynamic (11)C-raclopride PET scan distinguishes MSA-P and PD patients with high accuracy and is superior to conventional methods of striatal D2R binding analysis.
BRCA1/2 and TP53 mutation status associates with PD-1 and PD-L1 expression in ovarian cancer.
Wieser, Verena; Gaugg, Inge; Fleischer, Martina; Shivalingaiah, Giridhar; Wenzel, Soeren; Sprung, Susanne; Lax, Sigurd F; Zeimet, Alain G; Fiegl, Heidelinde; Marth, Christian
2018-04-03
Checkpoint molecules such as programmed cell death protein-1 (PD-1) and its ligand PD-L1 are critically required for tumor immune escape. The objective of this study was to investigate tumoral PD-1 and PD-L1 mRNA-expression in a cohort of ovarian cancer (OC) patients in relation to tumor mutations. We analyzed mRNA expression of PD-1 , PD-L1 and IFNG by quantitative real-time PCR in tissue of 170 patients with low grade-serous (LGSOC), high-grade serous (HGSOC), endometrioid and clear cell OC compared to 28 non-diseased tissues (ovaries and fallopian tubes) in relation to tumor protein 53 ( TP53 ) and breast cancer gene 1/2 ( BRCA1/2 ) mutation status. TP53 -mutated OC strongly expressed PD-L1 compared to TP53 wild-type OC ( p = 0.028) and BRCA1/2 -mutated OC increasingly expressed PD-1 ( p = 0.024) and PD-L1 ( p = 0.012) compared to BRCA1/2 wild-type OC. For the first time in human, we noted a strong correlation between tumoral IFNG and PD-1 or PD-L1 mRNA-expression, respectively ( p < 0.001). OC tissue increasingly expressed PD-1 compared to healthy controls (vs. ovaries: p < 0.001; vs. tubes: p = 0.018). PD-1 and PD-L1 mRNA-expression increased with higher tumor grade ( p = 0.008 and p = 0.027, respectively) and younger age (< median age, p = 0.001). Finally, in the major subgroup of our cohort, FIGO stage III/IV HGSOC, high PD-1 and PD-L1 mRNA-expression was associated with reduced progression-free ( p = 0.024) and overall survival ( p = 0.049) but only in the univariate analysis. Our study suggests that in OC PD-1 / PD-L1 mRNA-expression is controlled by IFNγ and affected by TP53 and BRCA1/2 mutations. We suggest that these mutations might serve as potential predictive factors that guide anti- PD1 / PD-L1 immunotherapy.
ERIC Educational Resources Information Center
Somech, Lior Y.; Elizur, Yoel
2012-01-01
Research of psychological distress (PD) needs to differentiate between anxiety/depression and hostility/suspiciousness, which are associated with different motivational systems. In this study, structural equation modeling was used to test two hypothesized models for the prediction of each facet of PD. Hypotheses were proposed about the effects of…
Cloudy - simulating the non-equilibrium microphysics of gas and dust, and its observed spectrum
NASA Astrophysics Data System (ADS)
Ferland, Gary J.
2014-01-01
Cloudy is an open-source plasma/spectral simulation code, last described in the open-access journal Revista Mexicana (Ferland et al. 2013, 2013RMxAA..49..137F). The project goal is a complete simulation of the microphysics of gas and dust over the full range of density, temperature, and ionization that we encounter in astrophysics, together with a prediction of the observed spectrum. Cloudy is one of the more widely used theory codes in astrophysics with roughly 200 papers citing its documentation each year. It is developed by graduate students, postdocs, and an international network of collaborators. Cloudy is freely available on the web at trac.nublado.org, the user community can post questions on http://groups.yahoo.com/neo/groups/cloudy_simulations/info, and summer schools are organized to learn more about Cloudy and its use (http://cloud9.pa.uky.edu gary/cloudy/CloudySummerSchool/). The code’s widespread use is possible because of extensive automatic testing. It is exercised over its full range of applicability whenever the source is changed. Changes in predicted quantities are automatically detected along with any newly introduced problems. The code is designed to be autonomous and self-aware. It generates a report at the end of a calculation that summarizes any problems encountered along with suggestions of potentially incorrect boundary conditions. This self-monitoring is a core feature since the code is now often used to generate large MPI grids of simulations, making it impossible for a user to verify each calculation by hand. I will describe some challenges in developing a large physics code, with its many interconnected physical processes, many at the frontier of research in atomic or molecular physics, all in an open environment.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-01-09
... October 1, 1999, and Delegation of Authority No. 236-3 of August 28, 2000 (and, as appropriate, Delegation..., SA-5, L/PD, Fifth Floor (Suite 5H03), Washington, DC 20522-0505. Dated: January 2, 2013. J. Adam... State. [FR Doc. 2013-00246 Filed 1-8-13; 8:45 am] BILLING CODE 4710-05-P ...
Sulzer, Patricia; Becker, Sara; Maetzler, Walter; Kalbe, Elke; van Nueten, Luc; Timmers, Maarten; Machetanz, Gerrit; Streffer, Johannes; Salvadore, Giacomo; Scholz, Erich; Tkaczynska, Zuzanna; Brockmann, Kathrin; Berg, Daniela; Liepelt-Scarfone, Inga
2018-06-23
The early diagnosis of mild cognitive impairment (PD-MCI) in Parkinson's disease (PD) is essential as it increases the future risk for PD dementia (PDD). Recently, a novel weighting algorithm for the Montreal Cognitive Assessment (MoCA) subtests has been reported, to best discriminate between those with and without cognitive impairment in PD. The aim of our study was to validate this scoring algorithm in a large sample of non-demented PD patients, hypothesizing that the weighted MoCA would have a higher diagnostic accuracy for PD-MCI than the original MoCA. In 202 non-demented PD patients, we evaluated cognitive status, clinical and demographic data, as well as the MoCA with a weighted and unweighted score. Receiver operating characteristic (ROC) curve analysis was used to evaluate discriminative ability of the MoCA. Group comparisons and ROC analysis were performed for PD-MCI classifications with a cut-off ≤ 1, 1.5, and 2 standard deviation (SD) below appropriate norms. PD-MCI patients scored lower on the weighted than the original MoCA version (p < 0.001) compared to PD patients with normal cognitive function. Areas under the curve only differed significantly for the 2 SD cut-off, leading to an increased sensitivity of the weighted MoCA score (72.9% vs. 70.5%) and specificity compared to the original version (79.0% vs. 65.4%). Our results indicate better discriminant power for the weighted MoCA compared to the original for more advanced stages of PD-MCI (2 SD cut-off). Future studies are needed to evaluate the predictive value of the weighted MoCA for PDD.
Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Ellinger, Jörg; Landsberg, Jennifer; Kristiansen, Glen; Dietrich, Dimo
2016-01-01
ABSTRACT Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 (PDCD1) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn. In the TCGA cohort, the PD-1 promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs. 38.2%, p < 0.001) and PD-1 methylation (mPD-1) inversely correlated with PD-1 mRNA expression in PCa (Spearman's ρ = −0.415, p < 0.001). In both cohorts, mPD-1 significantly correlated with preoperative prostate specific antigen (PSA). In univariate Cox Proportional Hazard analysis, mPD-1 served as a significant prognostic factor for biochemical recurrence (BCR)-free survival (Hazard ratio: HR = 2.35 [1.35–4.10], p = 0.003, n = 410) in the TCGA cohort. In multivariate analysis, mPD-1 was shown to add significant independent prognostic information adjunct to pathologic tumor category (pT) and Gleason grading group (HR = 2.08 [1.16–3.74], p = 0.014, n = 350). PD-1 promoter methylation analyses could thus potentially aid the identification of patients which might benefit from adjuvant treatment after radical prostatectomy. Moreover, our data suggest an intrinsic role of PD-1 in PCa carcinogenesis and disease progression, which needs to be addressed in future studies. PMID:27853645
Santini, Manuela Favarin; Rosa, Ricardo Abreu da; Ferreira, Maria Beatriz Cardoso; Fischer, Maria Isabel; Souza, Erick Miranda; Só, Marcus Vinícius Reis
2017-01-01
Acute periradicular abscess is a condition characterized by the formation and propagation of pus in the periapical tissues and generally associated with debilitating pain. The aim of this study was to compare the overall analgesic effectiveness of two combinations of opioid and non-opioid analgesics for acute periradicular abscess. This study included 26 patients who sought emergency care in a Brazilian dental school. The patients were randomly divided into two groups: Co/Ac - oral prescription of codeine (30 mg) plus acetaminophen (500 mg), every 4 h, for 3 days or Tr/Ac - oral prescription of tramadol hydrochloride (37.5 mg) plus acetaminophen (500 mg) on the same schedule. Two factors were evaluated: (1) pain scores recorded by the patients in a pain diary 6, 12, 24, 48, and 72 h after treatment, using the Visual Analogue Scale; and (2) the occurrence of adverse effects. In both groups, there was a reduction in pain scores over time. For the Co/Ac group, there was a significant reduction in the scores 12, 24, 48, and 72 hours after treatment (P<0.05). In the Tr/Ac group, the scores significantly decreased over time from time point 6 h (P<0.05). Comparing the pain at each time point, the groups were not significantly different (P>0.05), i.e., both treatments were effective in controlling pain caused by APA; however, the combination of Tr/Ac caused more adverse reactions as two patients had to stop using the medication. This study suggests that, considering both analgesic efficacy and safety, the combination of codeine and acetaminophen is more effective to control moderate to severe pain from acute periradicular abscesses.
Sheong, Fu Kit; Chen, Wen-Jie; Zhang, Jing-Xuan; Li, Yang; Lin, Zhenyang
2017-02-14
In this article, we have presented a computational analysis on the structure and bonding of [Pd 2 Sn 18 ] 4- and illustrated that it serves as an interesting example of OMO-UMO mutual delocalisation with two identical [PdE 9 ] 2- fragments. We have also illustrated the alternative roles that could be played by an [ME 9 ] 2- /[E 9 ] 2- fragment, a simple L-type donor and a lone-pair acceptor.
Dai, Cong; Wang, Meng; Lu, Jun; Dai, Zhiming; Lin, Shuai; Yang, Pengtao; Tian, Tian; Liu, Xinghan; Min, Weili; Dai, Zhijun
2017-01-01
PD-L1 has been reported to be expressed in diverse human malignancies. However, the prognostic value of PD-L1 in digestive system cancers remains inconclusive. Therefore, we conducted this meta-analysis to evaluate the prognostic impact of PD-L1 expression in digestive system cancers. We searched the PubMed, Embase, and the Chinese National Knowledge Infrastructure for publications concerning PD-L1 expression in digestive system cancers. Correlations of PD-L1 expression level with overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were analyzed. Finally, 32 studies with 7,308 patients were included. Our results show that PD-L1 expression was significantly associated with poorer OS (hazard ratio [HR] =1.44, 95% confidence interval [CI] =1.18-1.76, P <0.001), but not DFS (HR =0.91, 95% CI =0.61-1.37, P =0.657) or RFS (HR =1.27, 95% CI =0.75-2.14, P =0.368). Moreover, in the subgroup analysis, significant associations between PD-L1 expression and OS were found in Asians (HR =1.50, 95% CI =1.19-1.89, P =0.001), gastric cancer (HR =1.43, 95% CI =1.05-1.94, P =0.021), and pancreatic carcinoma (HR =2.64, 95% CI =1.78-3.93, P <0.001). These results suggest that the expression of PD-L1 is associated with worse OS in digestive system cancers, especially in gastric cancer and pancreatic cancer. In addition, PD-L1 may act as a new parameter for predicting poor prognosis and a promising target for anticancer therapy in digestive system cancers.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Benipal, Neeva; Qi, Ji; Dalian Univ. of Technology, Dalian
Electro-oxidation of alcohol is the key reaction occurring at the anode of a direct alcohol fuel cell (DAFC), in which both reaction kinetics (rate) and selectivity (to deep oxidation products) need improvement to obtain higher power density and fuel utilization for a more efficient DAFC. We recently found that a PdAg bimetallic nanoparticle catalyst is more efficient than Pd for alcohol oxidation: Pd can facilitate deprotonation of alcohol in a base electrolyte, while Ag can promote intermediate aldehyde oxidation and cleavage of C-single bondC bond of C 3 species to C 2 species. Furthermore, a combination of the two activemore » sites (Pd and Ag) with two different functions, can simultaneously improve the reaction rates and deeper oxidation products of alcohols. In this continuing work, Pd, Ag mono, and bimetallic nanoparticles supported on carbon nanotubes (Ag/CNT, Pd/CNT, Pd 1Ag 1/CNT, and Pd 1Ag 3/CNT) were prepared using an aqueous-phase reduction method; they served as working catalysts for studying electrocatalytic oxidation of glycerol in an anion-exchange membrane-based direct glycerol fuel cell. Combined XRD, TEM, and HAADF-STEM analyses performed to fully characterize as-prepared catalysts suggested that they have small particle sizes: 2.0 nm for Pd/CNT, 2.3 nm for PdAg/CNT, 2.4 nm for PdAg 3/CNT, and 13.9 nm for Ag/CNT. XPS further shows that alloying with Ag results in more metal state Pd presented on the surface, and this may be related to their higher direct glycerol fuel cell (DGFC) performances. Single DGFC performance and product analysis results show that PdAg bimetallic nanoparticles can not only improve the glycerol reaction rate so that higher power output can be achieved, but also facilitate deep oxidation of glycerol so that a higher faradaic efficiency and fuel utilization can be achieved along with optimal reaction conditions (increased base-to-fuel ratio). Half-cell electrocatalytic activity measurement and single fuel cell product analysis of different glycerol oxidation intermediates, including C 3: glycerate, tartronate, mesoxalate, and lactate; C 2: glycolate and oxalate, over PdAg/CNT catalyst was further conducted and produced deeper insight into the synergistic effects and reaction pathways of bimetallic PdAg catalysts in glycerol electrocatalytic oxidation.« less
2017-01-01
Purpose This study evaluated trends in tooth extraction due to acute and chronic periodontal disease (PD) using data from the National Health Insurance Service-National Sample Cohort for 2002–2013. Methods A random sample of 1,025,340 individuals was selected as a representative sample of the population, and a database (DB) of diagnostic and prescription codes was followed up for 12 years. We used multivariate logistic regression analysis to assess the incidence of total extraction (TE), extraction due to periodontal disease (EPD), and immediate extraction due to periodontal disease (IEPD) according to sociodemographic factors (sex, age, household income, health status, and area of residence). Results The incidence of tooth extraction was found to be increasing, and at a higher rate for TE in PD patients. In 2002, 50.6% of cases of TE were caused by PD, and this increased to 70.8% in 2013, while the number of cases of IEPD increased from 42.8% to 54.9% over the same period. The incidence rates of extraction due to acute and chronic PD increased monotonically. We found that the incidence rates of TE, EPD, and IEPD were all 2-fold higher among patients with high income levels and those who were not beneficiaries of health insurance. Conclusions The rates of TE, EPD, and IEPD have been steadily increasing despite dental healthcare policies to expand public health insurance coverage, increasing the accessibility of dental clinics. Moreover, the effects of these policies were found to vary with both income and education levels. Consistent patient follow-up is required to observe changes in trends regarding tooth extraction according to changes in dental healthcare policies, and meticulous studies of such changes will ensure optimal policy reviews and revisions. PMID:29093985
In situ treatability testing of reductive dechlorination in wetland sediments
Lorah, M.M.; Majcher, E.; Jones, E.; Driedger, G.; Dworatzek, S.; Graves, D.
2005-01-01
In situ treatability testing was conducted in the discharge wetlands along West Branch Canal Creek at Aberdeen Proving Ground, MD. The potential for stimulating reductive dechlorination of 1,1,2,2-tetrachloroethane, tetrachloroethylene, trichloroethylene, and carbon tetrachloride in areas of preferential discharge or seeps was evaluated. Geological Survey that degrades chlorinated ethanes and ethylenes was tested using MICRO-Trac??? devices. At seep 3-4W, results of the C and BA MICRO-Trac??? treatments showed essentially no biodegradation of chlorinated solvents occurring under natural and bioaugmented conditions. Results of geochemical samples at this site indicated predominantly iron- and sulfate-reducing conditions consistent with the rapid discharge rates previously measured. The biostimulated treatment showed stimulation of methanogenic conditions and partial degradation of the parent chlorinated VOC to intermediate chlorinated compounds. The bioaugmented and bistimulated treatment showed the highest production of methane, the highest removal of parent compounds and intermediate daughter products, and the highest production of the non-chlorinated end product ethylene. This is an abstract of a paper presented at the proceedings of the 8th International In Situ and On-Site Bioremediation Symposium (Baltimore, MD 6/6-9/2005).
Types and Frequency of Infusion Pump Alarms: Protocol for a Retrospective Data Analysis.
Glover, Kevin R; Vitoux, Rachel R; Schuster, Catherine; Curtin, Christopher R
2018-06-14
The variety of alarms from all types of medical devices has increased from 6 to 40 in the last three decades, with today's most critically ill patients experiencing as many as 45 alarms per hour. Alarm fatigue has been identified as a critical safety issue for clinical staff that can lead to potentially dangerous delays or nonresponse to actionable alarms, resulting in serious patient injury and death. To date, most research on medical device alarms has focused on the nonactionable alarms of physiological monitoring devices. While there have been some reports in the literature related to drug library alerts during the infusion pump programing sequence, research related to the types and frequencies of actionable infusion pump alarms remains largely unexplored. The objectives of this study protocol are to establish baseline data related to the types and frequency of infusion pump alarms from the B. Braun Outlook 400ES Safety Infusion System with the accompanying DoseTrac Infusion Management Software. The most recent consecutive 60-day period of backup hospital data received between April 2014 and February 2017 from 32 United States-based hospitals will be selected for analysis. Microsoft SQL Server (2012 - 11.0.5343.0 X64) will be used to manage the data with unique code written to sort data and perform descriptive analyses. A validated data management methodology will be utilized to clean and analyze the data. Data management procedures will include blinding, cleaning, and review of existing infusion data within the DoseTrac Infusion Management Software databases at each hospital. Patient-identifying data will be removed prior to merging into a dedicated and secure data repository. This pooled data will then be analyzed. This exploratory study will analyze the aggregate alarm data for each hospital by care area, drug infused, time of day, and day of week, including: overall infusion pump alarm frequency (number of alarms per active infusion), duration of alarms (average, range, median), and type and frequency of alarms distributed by care area. Infusion pump alarm data collected and analyzed in this study will be used to help establish a baseline of infusion pump alarm types and relative frequencies. Understanding the incidences and characteristics of infusion pump alarms will result in more informed quality improvement recommendations to decrease and/or modify infusion pump alarms, and potentially reduce clinical staff alarm fatigue and improve patient safety. . RR1-10.2196/10446. ©Kevin R Glover, Rachel R Vitoux, Catherine Schuster, Christopher R Curtin. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 14.06.2018.
Makani, Ramkrishna; Mansuri, Zeeshan; Patel, Upenkumar; Desai, Rupak; Chopra, Amit
2017-01-01
Background Major Depressive Disorder (MDD) is a common comorbidity that significantly affects the quality of life and disease outcomes in Parkinson’s disease (PD) patients. No studies have been conducted to our knowledge to address the health care utilization and its outcomes in these patients. The aim of this study is to analyze and discern the differences in the hospitalization outcomes, comorbid conditions, and utilization of procedures in PD patients versus patients with comorbid MDD. Methods We used the Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project from year’s 2010-2014. We identified PD and MDD as a primary and secondary diagnosis respectively using validated International Classification of Diseases, 9th Revision, and Clinical Modification codes. Pearson’s chi-square test and independent sample T-test were used for categorical data and continuous data, respectively. All statistical analysis was done by SPSS 22.0 in this study. Results Extensive analysis was performed on 63,912 patients with PD and 1445 patients with PD having MDD. Patients with comorbid depression had three times greater chances of disposition to acute care hospital (3.1% vs. 1.1%, p < 0.001). Median length of hospitalization was higher in Parkinson’s patients with depression (5.85 vs. 4.08 days; p < 0.001) though the median cost of hospitalization was low ($ 31,039 vs. $ 39,464; p < 0.001). This could be because therapeutic procedures performed during the hospitalization were lower in Parkinson’s patients with depression (0.53 vs. 0.89, p < 0.001). Utilization of Deep Brain Stimulation (DBS) was lower in Parkinson’s patients with depression (9.4% vs. 25.6%, p < 0.001). In-hospital mortality was significantly higher in Parkinson’s patients with depression (1.4% vs. 1.1%; p < 0.001). Conclusion Our study establishes the negative impact of depression in PD with regards to hospitalization-related outcomes including the illness severity, comorbid conditions, risk of mortality, utilization of diagnostic and therapeutic procedures, the length of stay and disposition as compared to PD without depression. PMID:29142796
Digital Coding and the Self-Proving Message
ERIC Educational Resources Information Center
Dettering, Richard
1971-01-01
Author suggests that digital Communication", which relies on arbitrary coding elements, like the phones of speech," overshadows the importance of the analogic symbolism people use more extensively than realized. Non-verbal messages can be more convincing than verbal and can be used to predict patterns of future behavior. (Author/PD)
RHEED and EELS study of Pd/Al bimetallic thin film growth on different α-Al 2O 3 substrates
NASA Astrophysics Data System (ADS)
Moroz, V.; Rajs, K.; Mašek, K.
2002-06-01
Pd/Al bimetallic thin films were grown by molecular beam epitaxy on single-crystalline α-Al 2O 3(0 0 0 1) and (1 1 2¯ 0) surfaces. Substrate and deposit crystallographic structures and evolution of deposit lattice parameter during the growth were studied by reflection high-energy electron diffraction. The electron energy loss spectroscopy was used as an auxiliary method for chemical analysis. The bimetallic films were prepared by successive deposition of both Pd and Al metals. The structure of Pd and Al deposits in early stages of the growth and its dependence on the preparation conditions were studied. Two phases of Pd clusters covered by Al overlayer have been found. The formation of Al overlayer strongly influenced the lattice parameter of Pd clusters.
Miao, Jing-Kun; Chen, Qi-Xiong; Bao, Li-Ming; Huang, Yi; Zhang, Juan; Wan, Ke-Xing; Yi, Jing; Wang, Shi-Yi; Zou, Lin; Li, Ting-Yu
2013-09-23
Conventional screening tests to assess G6PD deficiency use a low cutoff value of 2.10 U/gHb which may not be adequate for detecting females with heterozygous deficiency. The aim of present study was to determine an appropriate cutoff value with increased sensitivity in identifying G6PD-deficient heterozygous females. G6PD activity analysis was performed on 51,747 neonates using semi-quantitative fluorescent spot test. Neonates suspected with G6PD deficiency were further analyzed using quantitatively enzymatic assay and for common G6PD mutations. The cutoff values of G6PD activity were estimated using the receiver operating characteristic curve. Our results demonstrated that using 2.10 U/g Hb as a cutoff, the sensitivity of the assay to detect female neonates with G6PD heterozygous deficiency was 83.3%, as compared with 97.6% using 2.55 U/g Hb as a cutoff. The high cutoff identified 21% (8/38) of the female neonates with partial G6PD deficiency which were not detected with 2.10 U/g Hb. Our study found that high cutoffs, 2.35 and 2.55 U/g Hb, would increase assay's sensitivity to identify male and female G6PD deficiency neonates, respectively. We established a reliable cutoff value of G6PD activity with increased sensitivity in identifying female newborns with partial G6PD deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Bakhshetyan, Karen; Melkonyan, Gurgen G.; Galstian, Tigran V.; Saghatelyan, Armen
2015-10-01
Natural or "self" alignment of molecular complexes in living tissue represents many similarities with liquid crystals (LC), which are anisotropic liquids. The orientational characteristics of those complexes may be related to many important functional parameters and their study may reveal important pathologies. The know-how, accumulated thanks to the study of LC materials, may thus be used to this end. One of the traditionally used methods, to characterize those materials, is the polarized light imaging (PLI) that allows for label-free analysis of anisotropic structures in the brain tissue and can be used, for example, for the analysis of myelinated fiber bundles. In the current work, we first attempted to apply the PLI on the mouse histological brain sections to create a map of anisotropic structures using cross-polarizer transmission light. Then we implemented the PLI for comparative study of histological sections of human postmortem brain samples under normal and pathological conditions, such as Parkinson's disease (PD). Imaging the coronal, sagittal and horizontal sections of mouse brain allowed us to create a false color-coded fiber orientation map under polarized light. In human brain datasets for both control and PD groups we measured the pixel intensities in myelin-rich subregions of internal capsule and normalized these to non-myelinated background signal from putamen and caudate nucleus. Quantification of intensities revealed a statistically significant reduction of fiber intensity of PD compared to control subjects (2.801 +/- 0.303 and 3.724 +/- 0.07 respectively; *p < 0.05). Our study confirms the validity of PLI method for visualizing myelinated axonal fibers. This relatively simple technique can become a promising tool for study of neurodegenerative diseases where labeling-free imaging is an important benefit.
Interference removals on Pd, Ru and Au with ICP-QQQ-MS in PGE RM
NASA Astrophysics Data System (ADS)
Nadeem Hussain Bokhari, Syed; Meisel, Thomas; Walkner, Christoph
2015-04-01
Gold and platinum group elements (PGE) are essential industrial precious metals with high world demand due to their unique properties. Struggle for natural exploration of PGE is on great pace and recycling from industrial wastes, electronics and catalytic convertor is on the rise for PGE supply chain. Along with these developments it is becoming more challenging for analytical chemists to determine gold and PGE out of complex matrix which causes severe interferences. The current state of art is online analysis coupled with chromatographic separation of interferences. The ICP-QQQ-MS Agilent 8800 has the capability of using multi tunes and mass shifts. We aim to remove interferences on Pd+ (for direct and isotope dilution analysis) Au+ and Ru+ in lieu of chemical separations. YO+, SrOH+, ZnAr+, NiAr+, ZrO+, CuAr+, MoO+ , Ru+and Cd+ are expected interferences on Pd+ while Au+ is interfered by TaO+, HfOH+, GdAr+ and 102Ru+ ,104Ru+ by 102Pd+ ,104Pd+ etc. Initial test were performed on pure solutions of 1mg/l (interfering elements): 1 ng/l (Pd, Ru & Au) respectively. The outcomes of initial tests were applied on PGE reference material (RM) WMG-1 and SARM-7 (digested with Na2O2 sintering). The results obtained show that YO+, SrOH+ interfere (104Pd,105Pd), 104 Ru+ on (104Pd), ZnAr+ has slight interference on (104Pd and106Pd), ZrO+, NiAr+, CuAr+ interferences are negligible, MoO+ has severe interference on (108Pd, 110Pd) and that Cd+ has severe isobaric interference on (106Pd,108Pd, 110Pd). These interference have been removed by formation of Pd(NH3)3+complex. The TaO+, HfOH+ and GdAr+ interferences on Au+ are best removed by formation of Au(NH3)+ and Au(NH3)2+ complexes. 102Pd+,104Pd+interference on 102Ru+ ,104Ru+ can be removed by formation of Ru(NH3)4+ and RuO+ compounds. The results obtained comply with certified values of RM. The developed method is being tested on low concentration PGE reference materials. References: Sugiyama, N. " Removal of complex spectral interferences on noble metal isotopes." Agilent 8800 ICP-QQQ Application Handbook, 2014, 42-46.
NASA Astrophysics Data System (ADS)
Sabounchei, Seyyed Javad; Hashemi, Ali; Sedghi, Asieh; Bayat, Mehdi; Akhlaghi Bagherjeri, Fateme; Gable, Robert W.
2017-05-01
Reaction of dimethyl sulfide with 2, 3‧-dibromoacetophenone led to formation of sulfonium salt [Me2SCH2C(O)C6H4-m-Br]Br (1). The resulted sulfonium salt was treated with NaOH and gave the α-keto stabilized sulfur ylide Me2SC(H)C(O)C6H4-m-Br (2). This ligand was reacted with [MCl2(cod)] (M = Pd, Pt; cod = 1,5-cyclooctadiene) to form the new cis- and trans-[MCl2(ylide)2] (M = Pd (cis- and trans-3), Pt (cis- and trans-4)) complexes. Characterization of the obtained compounds was performed by elemental analysis, IR, 1H and 13C NMR. Recrystallization of dichlorobis(ylide) palladium(II) and platinum(II) complexes from DMSO solution yielded the crystalline products, which X-ray diffraction data revealed that the both compounds were crystallized as cis-[MCl2(ylide)(DMSO)] (M = Pd (5), Pt (6)) complexes. Also, a theoretical study on structure and nature of the Msbnd C bonding between the Y ligand (ylide) and [MCl2·DMSO] fragments in [YMCl2·DMSO] (M = Pd, Pt) complexes has been reported via NBO and energy-decomposition analysis (EDA). Furthermore, the palladium catalyzed Suzuki-Miyaura reaction of various aryl chlorides with arylboronic acids was performed. The results showed that the Pd(II) complexes cis- and trans-3 catalyzed efficiently coupling reactions at low catalyst loading and short reaction time.
Suja, E; Nancharaiah, Y V; Venugopalan, V P
2014-11-15
Microbial granules cultivated in an aerobic bubble column sequencing batch reactor were used for reduction of Pd(II) and formation of biomass associated Pd(0) nanoparticles (Bio-Pd) for reductive transformation of organic and inorganic contaminants. Addition of Pd(II) to microbial granules incubated under fermentative conditions resulted in rapid formation of Bio-Pd. The reduction of soluble Pd(II) to biomass associated Pd(0) was predominantly mediated by H2 produced through fermentation. X-ray diffraction and scanning electron microscope analysis revealed that the produced Pd nanoparticles were associated with the microbial granules. The catalytic activity of Bio-Pd was determined using p-nitrophenol and Cr(VI) as model compounds. Reductive transformation of p-nitrophenol by Bio-Pd was ∼20 times higher in comparison to microbial granules without Pd. Complete reduction of up to 0.25 mM of Cr(VI) by Bio-Pd was achieved in 24 h. Bio-Pd synthesis using self-immobilized microbial granules is advantageous and obviates the need for nanoparticle encapsulation or use of barrier membranes for retaining Bio-Pd in practical applications. In short, microbial granules offer a dual purpose system for Bio-Pd production and retention, wherein in situ generated H2 serves as electron donor powering biotransformations. Copyright © 2014 Elsevier Ltd. All rights reserved.
Wang, Zhun; Peng, Shuanghe; Xie, Hui; Guo, Linpei; Cai, Qiliang; Shang, Zhiqun; Jiang, Ning; Niu, Yuanjie
2018-05-01
The prognostic significance of PD-L1 in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain controversial. The primary aim of this meta-analysis was to investigate the prognostic and clinicopathological significance of the PD-L1 expression in patients with RCC. Relevant literature was identified form PubMed, Embase, Web of Science and Cochrane library, which compared the prognostic significance between PD-L1 expression and RCC. Hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for clinical parameters associated with PD-L1 were extracted from eligible studies. Heterogeneity was assessed using the I 2 value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Begg's funnel plots and Egger's regression test. A total of 1863 patients from ten eligible studies were analyzed. The results showed that PD-L1 expression is associated with poor overall survival in clear cell RCC (ccRCC) (HR = 2.76, 95%CI: 2.25-3.38, I 2 = 14.4%, P < 0.001) and non-clear cell RCC (non-ccRCC) (HR = 2.77, 95%CI: 1.62-4.72, I 2 = 28.8%, P < 0.001). In addition, PD-L1 expression was found to be significantly associated with primary tumor stage (OR = 1.76, 95%CI: 1.39-2.23; I 2 = 56.3%), regional lymph node involvement (OR = 2.10, 95%CI: 1.48-2.98; I 2 = 14.9%), distant metastases (OR = 2.69, 95%CI: 2.05-3.54; I 2 = 0.0%), nuclear grade (OR = 1.72, 95%CI: 1.32-2.23; I 2 = 79.4%) and histologic tumor necrosis (OR = 2.25, 95%CI: 1.59-3.18; I 2 = 66.1%) in patients with RCC. The outcome stability was confirmed by sensitivity analysis. Both the Begg's funnel plot test (P = 0.276) and the Egger's (P = 0.388) verified that there was no publication bias within the included studies. This study suggests that PD-L1 expression is correlated with poor prognosis and advanced clinicopathological features in RCC patients.
TUSC2 downregulates PD-L1 expression in non-small cell lung cancer (NSCLC).
Cao, Xiaobo; Zhao, Yang; Wang, Jing; Dai, Bingbing; Gentile, Emanuela; Lin, Jing; Pu, Xingxiang; Ji, Lin; Wu, Shuhong; Meraz, Ismail; Majidi, Mourad; Roth, Jack A
2017-12-08
Expression of the TUSC2 tumor-suppressor gene in TUSC2-deficient NSCLC cells decreased PD-L1 expression and inhibited mTOR activity. Overexpressing TUSC2 or treatment with rapamycin resulted in similar inhibition of PD-L1 expression. Both TUSC2 and rapamycin decreased p70 and SK6 phosphorylation, suggesting that TUSC2 and rapamycin share the same mTOR target. Microarray mRNA expression analysis using TUSC2-inducible H1299 showed that genes that negatively regulate the mTOR pathway were significantly upregulated by TUSC2 compared with control. The presence of IFN-γ significantly increased PD-L1 expression in lung cancer cell lines, but overexpressing TUSC2 in these cell lines prevented PD-L1 from increasing in the presence of IFN-γ. Taken together, these findings show that TUSC2 can decrease PD-L1 expression in lung cancer cells. This ability to modify the tumor microenvironment suggests that TUSC2 could be added to checkpoint inhibitors to improve the treatment of lung cancer.
TUSC2 downregulates PD-L1 expression in non-small cell lung cancer (NSCLC)
Cao, Xiaobo; Zhao, Yang; Wang, Jing; Dai, Bingbing; Gentile, Emanuela; Lin, Jing; Pu, Xingxiang; Ji, Lin; Wu, Shuhong; Meraz, Ismail; Majidi, Mourad; Roth, Jack A.
2017-01-01
Expression of the TUSC2 tumor-suppressor gene in TUSC2-deficient NSCLC cells decreased PD-L1 expression and inhibited mTOR activity. Overexpressing TUSC2 or treatment with rapamycin resulted in similar inhibition of PD-L1 expression. Both TUSC2 and rapamycin decreased p70 and SK6 phosphorylation, suggesting that TUSC2 and rapamycin share the same mTOR target. Microarray mRNA expression analysis using TUSC2-inducible H1299 showed that genes that negatively regulate the mTOR pathway were significantly upregulated by TUSC2 compared with control. The presence of IFN-γ significantly increased PD-L1 expression in lung cancer cell lines, but overexpressing TUSC2 in these cell lines prevented PD-L1 from increasing in the presence of IFN-γ. Taken together, these findings show that TUSC2 can decrease PD-L1 expression in lung cancer cells. This ability to modify the tumor microenvironment suggests that TUSC2 could be added to checkpoint inhibitors to improve the treatment of lung cancer. PMID:29296193
Diao, Hongyu; Li, Xinxing; Hu, Sheng; Liu, Yunhui
2012-01-01
Parkinson disease (PD) progresses relentlessly and affects approximately 4% of the population aged over 80 years old. It is difficult to diagnose in its early stages. The purpose of our study is to identify molecular biomarkers for PD initiation using a computational bioinformatics analysis of gene expression. We downloaded the gene expression profile of PD from Gene Expression Omnibus and identified differentially coexpressed genes (DCGs) and dysfunctional pathways in PD patients compared to controls. Besides, we built a regulatory network by mapping the DCGs to known regulatory data between transcription factors (TFs) and target genes and calculated the regulatory impact factor of each transcription factor. As the results, a total of 1004 genes associated with PD initiation were identified. Pathway enrichment of these genes suggests that biological processes of protein turnover were impaired in PD. In the regulatory network, HLF, E2F1 and STAT4 were found have altered expression levels in PD patients. The expression levels of other transcription factors, NKX3-1, TAL1, RFX1 and EGR3, were not found altered. However, they regulated differentially expressed genes. In conclusion, we suggest that HLF, E2F1 and STAT4 may be used as molecular biomarkers for PD; however, more work is needed to validate our result.
Diao, Hongyu; Li, Xinxing; Hu, Sheng; Liu, Yunhui
2012-01-01
Parkinson disease (PD) progresses relentlessly and affects approximately 4% of the population aged over 80 years old. It is difficult to diagnose in its early stages. The purpose of our study is to identify molecular biomarkers for PD initiation using a computational bioinformatics analysis of gene expression. We downloaded the gene expression profile of PD from Gene Expression Omnibus and identified differentially coexpressed genes (DCGs) and dysfunctional pathways in PD patients compared to controls. Besides, we built a regulatory network by mapping the DCGs to known regulatory data between transcription factors (TFs) and target genes and calculated the regulatory impact factor of each transcription factor. As the results, a total of 1004 genes associated with PD initiation were identified. Pathway enrichment of these genes suggests that biological processes of protein turnover were impaired in PD. In the regulatory network, HLF, E2F1 and STAT4 were found have altered expression levels in PD patients. The expression levels of other transcription factors, NKX3-1, TAL1, RFX1 and EGR3, were not found altered. However, they regulated differentially expressed genes. In conclusion, we suggest that HLF, E2F1 and STAT4 may be used as molecular biomarkers for PD; however, more work is needed to validate our result. PMID:23284986
You, Wei; Liu, Mei; Miao, Ji-Dong; Liao, Yu-Qian; Song, Yi-Bing; Cai, Dian-Kun; Gao, Yang; Peng, Hao
2018-01-01
Background : This network meta-analysis aimed at comparing anti-programmed death 1 (anti-PD-1) with anti-programmed death ligand 1(anti-PD-L1) immunotherapy in patients with metastatic, previously treated non-small cell lung cancer (NSCLC) who failed first-line treatment. Methods : We searched electronic databases to identify all eligible clinical trials. End-points included overall survival (OS), progression-free survival (PFS) and objective response. Hazard ratios (HRs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were extracted. Network meta-analysis was performed using the frequentist approach for multiple treatment comparisons. Results : In total, 3024 patients were randomly assigned: 1117 received anti-PD-1 therapy (nivolumab + pembrolizumab), 569 received anti-PD-L1 (atezolizumab) and 1338 received docetaxel. Anti-PD-1 (HR, 0.56; 95% CI, 0.48-0.66) and anti-PD-L1 (HR, 0.64; 95% CI, 0.51-0.79) achieved better OS than docetaxel, and anti-PD-1 was superior to docetaxel in terms of PFS (HR, 0.75; 95% CI, 0.62-0.89). Moreover, anti-PD-1 achieved the highest effect on OS and PFS, with a P-score of 91.2% and 95.5%, respectively. With regard to tumor response, anti-PD-1 group had a higher rate of responders than that in anti-PD-L1 (HR, 0.35; 95% CI, 0.19-0.65) and docetaxel (HR, 0.36; 95% CI, 0.25-0.52) groups. Undoubtedly, anti-PD-1 and anti-PD-L1 obtained less toxicity profile than docetaxel, and no significant difference was observed between anti-PD-1 and anti-PD-L1 groups. Conclusions : Anti-PD-1 may be a better choice for patients with metastatic and previously treated NSCLC who failed first-line treatment in terms of the treatment ranking.
Brabenec, L; Mekyska, J; Galaz, Z; Rektorova, Irena
2017-03-01
Hypokinetic dysarthria (HD) occurs in 90% of Parkinson's disease (PD) patients. It manifests specifically in the areas of articulation, phonation, prosody, speech fluency, and faciokinesis. We aimed to systematically review papers on HD in PD with a special focus on (1) early PD diagnosis and monitoring of the disease progression using acoustic voice and speech analysis, and (2) functional imaging studies exploring neural correlates of HD in PD, and (3) clinical studies using acoustic analysis to evaluate effects of dopaminergic medication and brain stimulation. A systematic literature search of articles written in English before March 2016 was conducted in the Web of Science, PubMed, SpringerLink, and IEEE Xplore databases using and combining specific relevant keywords. Articles were categorized into three groups: (1) articles focused on neural correlates of HD in PD using functional imaging (n = 13); (2) articles dealing with the acoustic analysis of HD in PD (n = 52); and (3) articles concerning specifically dopaminergic and brain stimulation-related effects as assessed by acoustic analysis (n = 31); the groups were then reviewed. We identified 14 combinations of speech tasks and acoustic features that can be recommended for use in describing the main features of HD in PD. While only a few acoustic parameters correlate with limb motor symptoms and can be partially relieved by dopaminergic medication, HD in PD seems to be mainly related to non-dopaminergic deficits and associated particularly with non-motor symptoms. Future studies should combine non-invasive brain stimulation with voice behavior approaches to achieve the best treatment effects by enhancing auditory-motor integration.
Solinas, Cinzia; Garaud, Soizic; De Silva, Pushpamali; Boisson, Anaïs; Van den Eynden, Gert; de Wind, Alexandre; Risso, Paolo; Rodrigues Vitória, Joel; Richard, François; Migliori, Edoardo; Noël, Grégory; Duvillier, Hugues; Craciun, Ligia; Veys, Isabelle; Awada, Ahmad; Detours, Vincent; Larsimont, Denis; Piccart-Gebhart, Martine; Willard-Gallo, Karen
2017-01-01
There is an exponentially growing interest in targeting immune checkpoint molecules in breast cancer (BC), particularly in the triple-negative subtype where unmet treatment needs remain. This study was designed to analyze the expression, localization, and prognostic role of PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM3 in primary BC. Gene expression analysis using the METABRIC microarray dataset found that all six immune checkpoint molecules are highly expressed in basal-like and HER2-enriched compared to the other BC molecular subtypes. Flow cytometric analysis of fresh tissue homogenates from untreated primary tumors show that PD-1 is principally expressed on CD4+ or CD8+ T cells and CTLA-4 is expressed on CD4+ T cells. The global proportion of PD-L1+, PD-L2+, LAG3+, and TIM3+ tumor-infiltrating lymphocytes (TIL) was low and detectable in only a small number of tumors. Immunohistochemically staining fixed tissues from the same tumors was employed to score TIL and tertiary lymphoid structures (TLS). PD-L1+, PD-L2+, LAG3+, and TIM3+ cells were detected in some TLS in a pattern that resembles secondary lymphoid organs. This observation suggests that TLS are important sites of immune activation and regulation, particularly in tumors with extensive baseline immune infiltration. Significantly improved overall survival was correlated with PD-1 expression in the HER2-enriched and PD-L1 or CTLA-4 expression in basal-like BC. PD-1 and CTLA-4 proteins were most frequently detected on TIL, which supports the correlations observed between their gene expression and improved long-term outcome in basal-like and HER2-enriched BC. PD-L1 expression by tumor or immune cells is uncommon in BC. Overall, the data presented here distinguish PD-1 as a marker of T cell activity in both the T and B cell areas of BC associated TLS. We found that immune checkpoint molecule expression parallels the extent of TIL and TLS, although there is a noteworthy amount of heterogeneity between tumors even within the same molecular subtype. These data indicate that assessing the levels of immune checkpoint molecule expression in an individual patient has important implications for the success of therapeutically targeting them in BC. PMID:29163490
MicroRNA alterations in iPSC-derived dopaminergic neurons from Parkinson disease patients.
Tolosa, Eduard; Botta-Orfila, Teresa; Morató, Xavier; Calatayud, Carles; Ferrer-Lorente, Raquel; Martí, María-José; Fernández, Manel; Gaig, Carles; Raya, Ángel; Consiglio, Antonella; Ezquerra, Mario; Fernández-Santiago, Rubén
2018-05-31
MicroRNA (miRNA) misregulation in peripheral blood has been linked to Parkinson disease (PD) but its role in the disease progression remains elusive. We performed an explorative genome-wide study of miRNA expression levels in dopaminergic neurons (DAn) from PD patients generated by somatic cell reprogramming and induced pluripotent stem cells differentiation. We quantified expression levels of 377 miRNAs in DAn from 3 sporadic PD patients (sPD), 3 leucine-rich repeat kinase 2-associated PD patients (L2PD) (total 6 PD), and 4 healthy controls. We identified differential expression of 10 miRNA of which 5 were upregulated in PD (miR-9-5p, miR-135a-5p, miR-135b-5p, miR-449a, and miR-449b-5p) and 5 downregulated (miR-141-3p, miR-199a-5p, miR-299-5p, miR-518e-3p, and miR-519a-3p). Changes were similar in sPD and L2PD. Integrative analysis revealed significant correlations between miRNA/mRNA expression. Moreover, upregulation of miR-9-5p and miR-135b-5p was associated with downregulation of transcription factors related to the DNA hypermethylation of enhancer elements in PD DAn (FOXA1 and NR3C1). In summary, miRNA changes are associated with monogenic L2PD and sPD and co-occur with epigenetic changes in DAn from PD patients. Copyright © 2018 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Babilotte, P.; Dubreuil, M.; Rivet, S.; Lijour, Y.; Sevrain, D.; Martin, L.; Le Brun, G.; Le Grand, Y.; Le Jeune, B.
2011-10-01
Human liver biopsy samples, consisting into a 16 μm thickness biomaterial chemically fixed into a formaldehyde matrix, and stained by red picrosirius dye, are analysed for different states of fibrosis degeneration. Polarimetric methods, and specially Mueller polarimetry based on wavelength coding, have been qualified as an efficient tool to describe many different biological aspects. The polarimetric characteristics of the media, extracted from a Lu and Chipman decomposition1, 2 of their Mueller Matrix (MM), are correlated with the degeneracy level of tissue. Different works and results linked to the clinical analysis will be presented and compared to previous performed works.3 Polarimetric imaging will be presented and compared with SHG measurements. A statistical analysis of the distribution of polarimetric parameters (such as the retardance R and depolarisation Pd) will be presented too, in order to characterise the liver fibrosis level into the biomaterial under study.
Schwarz, Stefan T.; Abaei, Maryam; Gontu, Vamsi; Morgan, Paul S.; Bajaj, Nin; Auer, Dorothee P.
2013-01-01
There is increasing interest in developing a reliable, affordable and accessible disease biomarker of Parkinson's disease (PD) to facilitate disease modifying PD-trials. Imaging biomarkers using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) can describe parameters such as fractional anisotropy (FA), mean diffusivity (MD) or apparent diffusion coefficient (ADC). These parameters, when measured in the substantia nigra (SN), have not only shown promising but also varying and controversial results. To clarify the potential diagnostic value of nigral DTI in PD and its dependency on selection of region-of-interest, we undertook a high resolution DTI study at 3 T. 59 subjects (32 PD patients, 27 age and sex matched healthy controls) were analysed using manual outlining of SN and substructures, and voxel-based analysis (VBA). We also performed a systematic literature review and meta-analysis to estimate the effect size (DES) of disease related nigral DTI changes. We found a regional increase in nigral mean diffusivity in PD (mean ± SD, PD 0.80 ± 0.10 vs. controls 0.73 ± 0.06 · 10− 3 mm2/s, p = 0.002), but no difference using a voxel based approach. No significant disease effect was seen using meta-analysis of nigral MD changes (10 studies, DES = + 0.26, p = 0.17, I2 = 30%). None of the nigral regional or voxel based analyses of this study showed altered fractional anisotropy. Meta-analysis of 11 studies on nigral FA changes revealed a significant PD induced FA decrease. There was, however, a very large variation in results (I2 = 86%) comparing all studies. After exclusion of five studies with unusual high values of nigral FA in the control group, an acceptable heterogeneity was reached, but there was non-significant disease effect (DES = − 0.5, p = 0.22, I2 = 28%). The small PD related nigral MD changes in conjunction with the negative findings on VBA and meta-analysis limit the usefulness of nigral MD measures as biomarker of Parkinson's disease. The negative results of nigral FA measurements at regional, sub-regional and voxel level in conjunction with the results of the meta-analysis of nigral FA changes question the stability and validity of this measure as a PD biomarker. PMID:24273730
Scaife, Courtney L; Hewitt, Kelly C; Mone, Mary C; Hansen, Heidi J; Nelson, Edward T; Mulvihill, Sean J
2014-01-01
The intraoperative placement of an enteral feeding tube (FT) during pancreaticoduodenectomy (PD) is based on the surgeon's perception of need for postoperative nutrition. Published preoperative risk factors predicting postoperative morbidity may be used to predict FT need and associated intraoperative placement. A retrospective review of patients who underwent PD during 2005-2011 was performed by querying the National Surgical Quality Improvement Program (NSQIP) database with specific procedure codes. Patients were categorized based on how many of 10 possible preoperative risk factors they demonstrated. Groups of patients with scores of ≤ 1 (low) and ≥ 2 (high), respectively, were compared for FT need, length of stay (LoS) and organ space surgical site infections (SSIs). Of 138 PD patients, 82 did not have an FT placed intraoperatively, and, of those, 16 (19.5%) required delayed FT placement. High-risk patients were more likely to require a delayed FT (29.3%) compared with low-risk patients (9.8%) (P = 0.026). The 16 patients who required a delayed FT had a median LoS of 15.5 days, whereas the 66 patients who did not require an FT had a median LoS of 8 days (P < 0.001). In this analysis, subjects considered as high-risk patients were more likely to require an FT than low-risk patients. Assessment of preoperative risk factors may improve decision making for selective intraoperative FT placement. © 2013 International Hepato-Pancreato-Biliary Association.
Prognostic Value of PD-L1 in Breast Cancer: A Meta-Analysis.
Wang, Changjun; Zhu, Hanjiang; Zhou, Yidong; Mao, Feng; Lin, Yan; Pan, Bo; Zhang, Xiaohui; Xu, Qianqian; Huang, Xin; Sun, Qiang
2017-07-01
Programmed cell death 1 ligand 1 (PD-L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD-L1 and breast cancer survival remains unclear. Here, we present the first meta-analysis to investigate the prognostic value of PD-L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD-L1 expression and breast cancer survival. Fixed- and random-effect meta-analyses were conducted based on heterogeneity of included studies. Publication bias was evaluated by funnel plot and Begg's test. Overall, nine relevant studies with 8583 patients were included. PD-L1 overexpression was found in 25.8% of breast cancer patients. PD-L1 (+) associated with several high-risk prognostic indicators, such as ductal cancer (p = 0.037), high tumor grade (p = 0.000), ER negativity (p = 0.000), PR negativity (p = 0.000), HER2 positivity (p = 0.001) and aggressive molecular subtypes (HER2-rich and Basal-like p = 0.000). PD-L1 overexpression had no significant impact on metastasis-free survival (HR 0.924, 95% CI = 0.747-1.141, p = 0.462), disease-free survival (HR 1.122, 95% CI = 0.878-1.434, p = 0.357) and overall specific survival (HR 0.837, 95% CI = 0.640-1.093, p = 0.191), but significantly correlated with shortened overall survival (HR 1.573, 95% CI = 1.010-2.451, p = 0.045). PD-L1 overexpression in breast cancer associates with multiple clinicopathological parameters that indicated poor outcome, and may increase the risk for mortality. Further standardization of PD-L1 assessment assay and well-controlled clinical trials are warranted to clarify its prognostic and therapeutic value. © 2017 Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Hosseini-Sarvari, Mona; Razmi, Zahra
2015-01-01
A novel Pd supported on ZnO nanoparticles was readily synthesized and characterized. The amount of palladium on ZnO is 9.84 wt% which was determined by ICP analysis and atomic absorption spectroscopy (AAS). Percentage of accessible Pd as active catalyst is also estimated to 2.72% based on the thermogravimetric (TG) analysis. This nano-sized Pd/ZnO with an average particle size of 20-25 nm and specific surface area 40.61 m2 g-1 was used as a new reusable heterogeneous catalyst for direct hydrogenation and one-pot reductive amidation of nitro compounds without the use of any ligands under atmospheric pressure. The catalyst can be recovered and recycled several times without marked loss of activity.
1981-06-01
into the Wunsch-Bell equation) are P = A R , 1t-0 5 1.2 PD) = A26B2t-.5 (3) JAJ where A,*, A, B1, and B2 are experimentally determined constants and TJ...ATTN CODE 7240, S. N. LICHT’NAN PATRICK AID, FL 32J25 DIV COIMAND SAN DIEGO, CA 92152 ATTN D]PN-ATC AF WEAPONS LABORATORY, AFSC ATTN DRCFN- TDS -DSI
Meyer, Hans Jonas; Höhn, Annekathrin; Surov, Alexey
2018-04-06
Functional imaging modalities like Diffusion-weighted imaging are increasingly used to predict tumor behavior like cellularity and vascularity in different tumors. Histogram analysis is an emergent imaging analysis, in which every voxel is used to obtain a histogram and therefore statistically information about tumors can be provided. The purpose of this study was to elucidate possible associations between ADC histogram parameters and several immunhistochemical features in rectal cancer. Overall, 11 patients with histologically proven rectal cancer were included into the study. There were 2 (18.18%) females and 9 males with a mean age of 67.1 years. KI 67-index, expression of p53, EGFR, VEGF, and Hif1-alpha were semiautomatically estimated. The tumors were divided into PD1-positive and PD1-negative lesions. ADC histogram analysis was performed as a whole lesion measurement using an in-house matlab application. Spearman's correlation analysis revealed a strong correlation between EGFR expression and ADCmax (p=0.72, P=0.02). None of the vascular parameters (VEGF, Hif1-alpha) correlated with ADC parameters. Kurtosis and skewness correlated inversely with p53 expression (p=-0.64, P=0.03 and p=-0.81, P=0.002, respectively). ADCmedian and ADCmode correlated with Ki67 (p=-0.62, P=0.04 and p=-0.65, P=0.03, respectively). PD1-positive tumors showed statistically significant lower ADCmax values in comparison to PD1-negative tumors, 1.93 ± 0.36 vs 2.32 ± 0.47×10 -3 mm 2 /s, p=0.04. Several associations were identified between histogram parameter derived from ADC maps and EGFR, KI 67 and p53 expression in rectal cancer. Furthermore, ADCmax was different between PD1 positive and PD1 negative tumors indicating an important role of ADC parameters for possible future treatment prediction.
Meyer, Hans Jonas; Höhn, Annekathrin; Surov, Alexey
2018-01-01
Functional imaging modalities like Diffusion-weighted imaging are increasingly used to predict tumor behavior like cellularity and vascularity in different tumors. Histogram analysis is an emergent imaging analysis, in which every voxel is used to obtain a histogram and therefore statistically information about tumors can be provided. The purpose of this study was to elucidate possible associations between ADC histogram parameters and several immunhistochemical features in rectal cancer. Overall, 11 patients with histologically proven rectal cancer were included into the study. There were 2 (18.18%) females and 9 males with a mean age of 67.1 years. KI 67-index, expression of p53, EGFR, VEGF, and Hif1-alpha were semiautomatically estimated. The tumors were divided into PD1-positive and PD1-negative lesions. ADC histogram analysis was performed as a whole lesion measurement using an in-house matlab application. Spearman's correlation analysis revealed a strong correlation between EGFR expression and ADCmax (p=0.72, P=0.02). None of the vascular parameters (VEGF, Hif1-alpha) correlated with ADC parameters. Kurtosis and skewness correlated inversely with p53 expression (p=-0.64, P=0.03 and p=-0.81, P=0.002, respectively). ADCmedian and ADCmode correlated with Ki67 (p=-0.62, P=0.04 and p=-0.65, P=0.03, respectively). PD1-positive tumors showed statistically significant lower ADCmax values in comparison to PD1-negative tumors, 1.93 ± 0.36 vs 2.32 ± 0.47×10−3mm2/s, p=0.04. Several associations were identified between histogram parameter derived from ADC maps and EGFR, KI 67 and p53 expression in rectal cancer. Furthermore, ADCmax was different between PD1 positive and PD1 negative tumors indicating an important role of ADC parameters for possible future treatment prediction. PMID:29719621
Determination of glucose-6-phosphate dehydrogenase cut-off values in a Tunisian population.
Laouini, Naouel; Sahli, Chaima Abdelhafidh; Jouini, Latifa; Haloui, Sabrine; Fredj, Sondes Hadj; Daboubi, Rym; Siala, Hajer; Ouali, Faida; Becher, Meriam; Toumi, Nourelhouda; Bibi, Amina; Messsaoud, Taieb
2017-07-26
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest enzymopathy worldwide. The incidence depends essentially on the methods used for the assessment. In this respect, we attempted in this study to set cut-off values of G6PD activity to discriminate among normal, heterozygous, and deficient individuals using the World Health Organization (WHO) classification and the receiver operating characteristics (ROC) curve analysis. Blood samples from 250 female and 302 male subjects were enrolled in this study. The G6PD activity was determined using a quantitative assay. The common G6PD mutations in Tunisia were determined using the amplification refractory mutation system (ARMS-PCR) method. The ROC curve was used to choice the best cut-off. Normal G6PD values were 7.69±2.37, 7.86±2.39, and 7.51±2.35 U/g Hb for the entire, male, and female groups, respectively. Cut-off values for the total, male, and female were determined using the WHO classification and ROC curves analysis. In the male population, both cut-offs established using ROC curve analysis (4.00 U/g Hb) and the 60% level (3.82 U/g Hb), respectively are sensitive and specific resulting in a good efficiency of discrimination between deficient and normal males. For the female group the ROC cut-off (5.84 U/g Hb) seems better than the 60% level cut-off (3.88 U/g Hb) to discriminate between normal and heterozygote or homozygote women with higher Youden Index. The establishment of the normal values for a population is important for a better evaluation of the assay result. The ROC curve analysis is an alternative method to determine the status of patients since it correlates DNA analysis and G6PD activity.
Clinical accuracy of ExacTrac intracranial frameless stereotactic system
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ackerly, T.; Lancaster, C. M.; Geso, M.
2011-09-15
Purpose: In this paper, the authors assess the accuracy of the Brainlab ExacTrac system for frameless intracranial stereotactic treatments in clinical practice. Methods: They recorded couch angle and image fusion results (comprising lateral, longitudinal, and vertical shifts, and rotation corrections about these axes) for 109 stereotactic radiosurgery and 166 stereotactic radiotherapy patient treatments. Frameless stereotactic treatments involve iterative 6D image fusion corrections applied until the results conform to customizable pass criteria, theirs being 0.7 mm and 0.5 deg. for each axis. The planning CT slice thickness was 1.25 mm. It has been reported in the literature that the CT slices'more » thickness impacts the accuracy of localization to bony anatomy. The principle of invariance with respect to patient orientation was used to determine spatial accuracy. Results: The data for radiosurgery comprised 927 image pairs, of which 532 passed (pass ratio of 57.4%). The data for radiotherapy comprised 15983 image pairs, of which 10 050 passed (pass ratio of 62.9%). For stereotactic radiotherapy, the combined uncertainty of ExacTrac calibration, image fusion, and intrafraction motion was (95% confidence interval) 0.290-0.302 and 0.306-0.319 mm in the longitudinal and lateral axes, respectively. The combined uncertainty of image fusion and intrafraction motion in the anterior-posterior coordinates was 0.174-0.182 mm. For stereotactic radiosurgery, the equivalent ranges are 0.323-0.393, 0.337-0.409, and 0.231-0.281 mm. The overall spatial accuracy was 1.24 mm for stereotactic radiotherapy (SRT) and 1.35 mm for stereotactic radiosurgery (SRS). Conclusions: The ExacTrac intracranial frameless stereotactic system spatial accuracy is adequate for clinical practice, and with the same pass criteria, SRT is more accurate than SRS. They now use frameless stereotaxy exclusively at their center.« less
Parker, Katherine M.; Clark, Alexander P.; Goodman, Norman C.; Glover, David K.; Holmes, Jeffrey W.
2015-01-01
Background Quantitative analysis of wall motion from three-dimensional (3D) dobutamine stress echocardiography (DSE) could provide additional diagnostic information not available from qualitative analysis. In this study we compare the effectiveness of 3D fractional shortening (3DFS), a measure of wall motion computed from 3D echocardiography (3DE), to strain and strain rate measured with sonomicrometry for detecting critical stenoses during DSE. Methods Eleven open-chest dogs underwent DSE both with and without a critical stenosis. 3DFS was measured from 3DE images acquired at peak stress. 3DFS was normalized by subtracting average 3DFS during control peak stress (Δ3DFS). Strains in the perfusion defect (PD) were measured from sonomicrometry, and PD size and location were measured with microspheres. Results A Δ3DFS abnormality indicated the presence of a critical stenosis with high sensitivity and specificity (88% and 100%, respectively), and Δ3DFS abnormality size correlated with PD size (R2=0.54). The sensitivity and specificity for Δ3DFS was similar to that for area strain (88%, 100%) and circumferential strain and strain rate (88%, 92% and 88%, 86%, respectively), while longitudinal strain and strain rate were less specific. Δ3DFS correlated significantly with both coronary flow reserve (R2=0.71) and PD size (R2=0.97), while area strain correlated with PD size only (R2=0.67), and other measures were not significantly correlated with flow reserve or PD size. Conclusion Quantitative wall motion analysis using Δ3DFS is effective for detecting critical stenoses during DSE, performing similarly to 3D strain, and provides potentially useful information on the size and location of a perfusion defect. PMID:24815588
Cilia, Roberto; Benfante, Roberta; Asselta, Rosanna; Marabini, Laura; Cereda, Emanuele; Siri, Chiara; Pezzoli, Gianni; Goldwurm, Stefano; Fornasari, Diego
2016-08-01
Impulse control disorders and compulsive medication intake may occur in a minority of patients with Parkinson's disease (PD). We hypothesize that genetic polymorphisms associated with addiction in the general population may increase the risk for addictive behaviors also in PD. Sixteen polymorphisms in candidate genes belonging to five neurotransmitter systems (dopaminergic, catecholaminergic, serotonergic, glutamatergic, opioidergic) and the BDNF were screened in 154 PD patients with addictive behaviors and 288 PD control subjects. Multivariate analysis investigated clinical and genetic predictors of outcome (remission vs. persistence/relapse) after 1 year and at the last follow-up (5.1 ± 2.5 years). Addictive behaviors were associated with tryptophan hydroxylase type 2 (TPH2) and dopamine transporter gene variants. A subsequent analysis within the group of cases showed a robust association between TPH2 genotype and the severity of addictive behaviors, which survived Bonferroni correction for multiple testing. At multivariate analysis, TPH2 genotype resulted the strongest predictor of no remission at the last follow-up (OR[95%CI], 7.4[3.27-16.78] and 13.2[3.89-44.98] in heterozygous and homozygous carriers, respectively, p < 0.001). The extent of medication dose reduction was not a predictor. TPH2 haplotype analysis confirmed the association with more severe symptoms and lower remission rates in the short- and the long-term (p < 0.005 for all analyses). The serotonergic system is likely to be involved in the pathophysiology of addictive behaviors in PD, modulating the severity of symptoms and the rate of remission at follow-up. If confirmed in larger independent cohorts, TPH2 genotype may become a useful biomarker for the identification of at-risk individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.
Bologna, Matteo; Berardelli, Isabella; Paparella, Giulia; Marsili, Luca; Ricciardi, Lucia; Fabbrini, Giovanni; Berardelli, Alfredo
2016-01-01
Altered emotional processing, including reduced emotion facial expression and defective emotion recognition, has been reported in patients with Parkinson's disease (PD). However, few studies have objectively investigated facial expression abnormalities in PD using neurophysiological techniques. It is not known whether altered facial expression and recognition in PD are related. To investigate possible deficits in facial emotion expression and emotion recognition and their relationship, if any, in patients with PD. Eighteen patients with PD and 16 healthy controls were enrolled in this study. Facial expressions of emotion were recorded using a 3D optoelectronic system and analyzed using the facial action coding system. Possible deficits in emotion recognition were assessed using the Ekman test. Participants were assessed in one experimental session. Possible relationship between the kinematic variables of facial emotion expression, the Ekman test scores, and clinical and demographic data in patients were evaluated using the Spearman's test and multiple regression analysis. The facial expression of all six basic emotions had slower velocity and lower amplitude in patients in comparison to healthy controls (all P s < 0.05). Patients also yielded worse Ekman global score and disgust, sadness, and fear sub-scores than healthy controls (all P s < 0.001). Altered facial expression kinematics and emotion recognition deficits were unrelated in patients (all P s > 0.05). Finally, no relationship emerged between kinematic variables of facial emotion expression, the Ekman test scores, and clinical and demographic data in patients (all P s > 0.05). The results in this study provide further evidence of altered emotional processing in PD. The lack of any correlation between altered facial emotion expression kinematics and emotion recognition deficits in patients suggests that these abnormalities are mediated by separate pathophysiological mechanisms.
Liu, Hongmei; Liu, Hongbo; Li, Ting; Cui, Jiayi; Fu, Yingmei; Ren, Juanjuan; Sun, Xiujia; Jiang, Ping; Yu, Shunying; Li, Chunbo
2017-05-22
The homo sapiens nuclear receptor subfamily 4, group A (NR4A2) genetic variation has been implicated as a risk factor for Parkinson's disease (PD). Nevertheless, the results are inconclusive. We conducted a comprehensive systematic review and meta-analysis to quantify the impact of NR4A2 variation on the risk of PD. All eligible case-control studies published up to June 2016 by searching Pubmed, OVID, EBSCO, PsycINFO, ISI Web of Knowledge, Chinese Biomedical Literature Database and China Academic Journals Database were identified. Pooled odds ratio (OR) with 95% confidence interval (CI) were used to access the strength of the association in fixed- or random-effects model. Eighteen studies reported 24 genetic variants with a total of 6150 cases and 5919 controls were included. Twelve studies for NR4A2 rs35479735 polymorphism and 4 studies for rs12803 were available for meta-analysis. A significant association was observed for rs35479735 under the homozygous model (OR=1.31, 95% CI: 1.10-1.56, P=0.003), whereas no significant association for rs12803 was detected. In subgroup analysis stratified by ethnicity, age onset and familial history, we found no significant association except one in sporadic PD subgroup under the recessive (OR=3.30, 95% CI: 1.23-8.84, P=0.02) and homozygous model (OR=3.43, 95% CI: 1.26-9.33, P=0.02) for rs35479735. The study comprehensively evaluated the association of NR4A2 variation with PD, and the results failed to demonstrate that the NR4A2 polymorphisms significantly associated with PD except for rs35479735, suggesting that more studies are needed to elucidate if NR4A2 is a risk of PD. Copyright © 2017 Elsevier B.V. All rights reserved.
Li, Ji; Wang, Ping; Xu, Youliang
2017-01-01
Programmed cell death ligand 1 (PD-L1) expression was reported to be correlated with poor prognosis in various cancers. However, the relationship between PD-L1 expression and the survival of patients with head and neck cancer (HNC) remains inconclusive. In the present study, we aimed to clarify the prognostic value of PD-L1 in HNC patients using meta-analysis techniques. A comprehensive database searching was conducted in the PubMed, EMBASE, Web of Science and Cochrane Library from inception to August 2016. Studies meeting the inclusion criteria were included. The methodological quality of included studies was assessed by the Newcastle-Ottawa quality assessment scale. Hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were pooled by STATA 11.0 for the outcome of overall survival (OS) and disease-free survival (DFS). A total of 17 studies with 2,869 HNC patients were included in the meta-analysis. The results of meta-analysis showed that there was no significant correlation between PD-L1 expression and OS (HR, 1.23; 95% CI, 0.99-1.53; P = 0.065) or DFS (HR, 1.42; 95% CI, 1.00-2.03; P = 0.052) of HNC patients. However, the subgroup analysis suggested that positive expression of PD-L1 was associated with poor OS (HR, 1.38; 95% CI, 1.12, 1.70; P = 0.003) and DFS (HR, 1.99; 95% CI, 1.59, 2.48; P = 0.001) in HNC patients from Asian countries/regions. The subgroup analysis also showed that the correlations between PD-L1 and prognosis are variant among different subtypes of HNC. When performing sensitive analyses, we found that the results of meta-analyses were not robust. The meta-analysis indicated that positive expression of PD-L1 could serve as a good predictor for poor prognosis of Asian patients with HNC. However, the findings still need to be confirmed by large-scale, prospective studies.
Affinity purification mass spectrometry analysis of PD-1 uncovers SAP as a new checkpoint inhibitor.
Peled, Michael; Tocheva, Anna S; Sandigursky, Sabina; Nayak, Shruti; Philips, Elliot A; Nichols, Kim E; Strazza, Marianne; Azoulay-Alfaguter, Inbar; Askenazi, Manor; Neel, Benjamin G; Pelzek, Adam J; Ueberheide, Beatrix; Mor, Adam
2018-01-16
Programmed cell death-1 (PD-1) is an essential inhibitory receptor in T cells. Antibodies targeting PD-1 elicit durable clinical responses in patients with multiple tumor indications. Nevertheless, a significant proportion of patients do not respond to anti-PD-1 treatment, and a better understanding of the signaling pathways downstream of PD-1 could provide biomarkers for those whose tumors respond and new therapeutic approaches for those whose tumors do not. We used affinity purification mass spectrometry to uncover multiple proteins associated with PD-1. Among these proteins, signaling lymphocytic activation molecule-associated protein (SAP) was functionally and mechanistically analyzed for its contribution to PD-1 inhibitory responses. Silencing of SAP augmented and overexpression blocked PD-1 function. T cells from patients with X-linked lymphoproliferative disease (XLP), who lack functional SAP, were hyperresponsive to PD-1 signaling, confirming its inhibitory role downstream of PD-1. Strikingly, signaling downstream of PD-1 in purified T cell subsets did not correlate with PD-1 surface expression but was inversely correlated with intracellular SAP levels. Mechanistically, SAP opposed PD-1 function by acting as a molecular shield of key tyrosine residues that are targets for the tyrosine phosphatase SHP2, which mediates PD-1 inhibitory properties. Our results identify SAP as an inhibitor of PD-1 function and SHP2 as a potential therapeutic target in patients with XLP.
Multiloop integral system test (MIST): Final report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gloudemans, J.R.
1991-04-01
The Multiloop Integral System Test (MIST) is part of a multiphase program started in 1983 to address small-break loss-of-coolant accidents (SBLOCAs) specific to Babcock and Wilcox designed plants. MIST is sponsored by the US Nuclear Regulatory Commission, the Babcock Wilcox Owners Group, the Electric Power Research Institute, and Babcock and Wilcox. The unique features of the Babcock and Wilcox design, specifically the hot leg U-bends and steam generators, prevented the use of existing integral system data or existing integral facilities to address the thermal-hydraulic SBLOCA questions. MIST was specifically designed and constructed for this program, and an existing facility --more » the Once Through Integral System (OTIS) -- was also used. Data from MIST and OTIS are used to benchmark the adequacy of system codes, such as RELAP5 and TRAC, for predicting abnormal plant transients. The MIST program is reported in 11 volumes. Volumes 2 through 8 pertain to groups of Phase 3 tests by type; Volume 9 presents inter-group comparisons; Volume 10 provides comparisons between the RELAP5/MOD2 calculations and MIST observations, and Volume 11 (with addendum) presents the later Phase 4 tests. This is Volume 1 of the MIST final report, a summary of the entire MIST program. Major topics include, Test Advisory Group (TAG) issues, facility scaling and design, test matrix, observations, comparison of RELAP5 calculations to MIST observations, and MIST versus the TAG issues. MIST generated consistent integral-system data covering a wide range of transient interactions. MIST provided insight into integral system behavior and assisted the code effort. The MIST observations addressed each of the TAG issues. 11 refs., 29 figs., 9 tabs.« less
Specific membrane lipid composition is important for plasmodesmata function in Arabidopsis.
Grison, Magali S; Brocard, Lysiane; Fouillen, Laetitia; Nicolas, William; Wewer, Vera; Dörmann, Peter; Nacir, Houda; Benitez-Alfonso, Yoselin; Claverol, Stéphane; Germain, Véronique; Boutté, Yohann; Mongrand, Sébastien; Bayer, Emmanuelle M
2015-04-01
Plasmodesmata (PD) are nano-sized membrane-lined channels controlling intercellular communication in plants. Although progress has been made in identifying PD proteins, the role played by major membrane constituents, such as the lipids, in defining specialized membrane domains in PD remains unknown. Through a rigorous isolation of "native" PD membrane fractions and comparative mass spectrometry-based analysis, we demonstrate that lipids are laterally segregated along the plasma membrane (PM) at the PD cell-to-cell junction in Arabidopsis thaliana. Remarkably, our results show that PD membranes display enrichment in sterols and sphingolipids with very long chain saturated fatty acids when compared with the bulk of the PM. Intriguingly, this lipid profile is reminiscent of detergent-insoluble membrane microdomains, although our approach is valuably detergent-free. Modulation of the overall sterol composition of young dividing cells reversibly impaired the PD localization of the glycosylphosphatidylinositol-anchored proteins Plasmodesmata Callose Binding 1 and the β-1,3-glucanase PdBG2 and altered callose-mediated PD permeability. Altogether, this study not only provides a comprehensive analysis of the lipid constituents of PD but also identifies a role for sterols in modulating cell-to-cell connectivity, possibly by establishing and maintaining the positional specificity of callose-modifying glycosylphosphatidylinositol proteins at PD. Our work emphasizes the importance of lipids in defining PD membranes. © 2015 American Society of Plant Biologists. All rights reserved.
Specific Membrane Lipid Composition Is Important for Plasmodesmata Function in Arabidopsis
Grison, Magali S.; Brocard, Lysiane; Fouillen, Laetitia; Nicolas, William; Wewer, Vera; Dörmann, Peter; Nacir, Houda; Benitez-Alfonso, Yoselin; Claverol, Stéphane; Germain, Véronique; Boutté, Yohann; Mongrand, Sébastien; Bayer, Emmanuelle M.
2015-01-01
Plasmodesmata (PD) are nano-sized membrane-lined channels controlling intercellular communication in plants. Although progress has been made in identifying PD proteins, the role played by major membrane constituents, such as the lipids, in defining specialized membrane domains in PD remains unknown. Through a rigorous isolation of “native” PD membrane fractions and comparative mass spectrometry-based analysis, we demonstrate that lipids are laterally segregated along the plasma membrane (PM) at the PD cell-to-cell junction in Arabidopsis thaliana. Remarkably, our results show that PD membranes display enrichment in sterols and sphingolipids with very long chain saturated fatty acids when compared with the bulk of the PM. Intriguingly, this lipid profile is reminiscent of detergent-insoluble membrane microdomains, although our approach is valuably detergent-free. Modulation of the overall sterol composition of young dividing cells reversibly impaired the PD localization of the glycosylphosphatidylinositol-anchored proteins Plasmodesmata Callose Binding 1 and the β-1,3-glucanase PdBG2 and altered callose-mediated PD permeability. Altogether, this study not only provides a comprehensive analysis of the lipid constituents of PD but also identifies a role for sterols in modulating cell-to-cell connectivity, possibly by establishing and maintaining the positional specificity of callose-modifying glycosylphosphatidylinositol proteins at PD. Our work emphasizes the importance of lipids in defining PD membranes. PMID:25818623
Ryterska, Agata; Jahanshahi, Marjan; Osman, Magda
2014-01-01
Studies examining decision-making in people with Parkinson's disease (PD) show impaired performance on a variety of tasks. However, there are also demonstrations that patients with PD can make optimal decisions just like healthy age-matched controls. We propose that the reason for these mixed findings is that PD does not produce a generalized impairment of decision-making, but rather affects sub-components of this process. In this review we evaluate this hypothesis by considering the empirical evidence examining decision-making in PD. We suggest that of the various stages of the decision-making process, the most affected in PD are (1) the cost-benefit analysis stage and (2) the outcome evaluation stage. We consider the implications of this proposal for research in this area.
Quantitative Analysis of Voice in Parkinson Disease Compared to Motor Performance: A Pilot Study.
Silbergleit, Alice K; LeWitt, Peter A; Peterson, Edward L; Gardner, Glendon M
2015-01-01
Characteristic features of hypokinetic dysarthria develop in Parkinson disease (PD). We hypothesized that quantified acoustic changes of voice might provide a correlate of disease severity. To determine if there are significant differences in acoustic measures of voice between mild and moderate PD; 2) To evaluate correlations between acoustic parameters of voice and subtests of the UPDRS in mild and moderate PD. Twenty six participants with PD underwent vocal acoustic testing while off PD medication, for comparison to 22 healthy controls. Participants with PD were divided into two groups based upon UPDRS activities of daily living (ADL) ratings: summed scores were used to define mild and moderate PD. Participants voiced /i/ ("ee") at comfort, high, and low pitch (3 trials/pitch). The CSpeech Waveform Analysis Program was used to analyze cycle-to-cycle frequency ("jitter") and amplitude ("shimmer") irregularities of the vocal signal, signal-to-noise ratio, and maximum phonation frequency range converted to semitones. Sections of UPDRS scores were correlated to acoustic variables of voice. Key findings included a significant difference between the semitone range of the control subjects and the moderate PD group (p = 0.036). Further analyses revealed significant differences in semitone range for males between the controls vs. mild PD (p = 0.014), and controls vs. moderate PD (p = 0.005). Significant correlations were also found between acoustic findings and both the ADL and motor portions of the UPDRS. Acoustic analysis of voice, particularly frequency range, may provide a quantifiable correlate of disease progression in PD.
Parallel Demand-Withdraw Processes in Family Therapy for Adolescent Drug Abuse
Rynes, Kristina N.; Rohrbaugh, Michael J.; Lebensohn-Chialvo, Florencia; Shoham, Varda
2013-01-01
Isomorphism, or parallel process, occurs in family therapy when patterns of therapist-client interaction replicate problematic interaction patterns within the family. This study investigated parallel demand-withdraw processes in Brief Strategic Family Therapy (BSFT) for adolescent drug abuse, hypothesizing that therapist-demand/adolescent-withdraw interaction (TD/AW) cycles observed early in treatment would predict poor adolescent outcomes at follow-up for families who exhibited entrenched parent-demand/adolescent-withdraw interaction (PD/AW) before treatment began. Participants were 91 families who received at least 4 sessions of BSFT in a multi-site clinical trial on adolescent drug abuse (Robbins et al., 2011). Prior to receiving therapy, families completed videotaped family interaction tasks from which trained observers coded PD/AW. Another team of raters coded TD/AW during two early BSFT sessions. The main dependent variable was the number of drug use days that adolescents reported in Timeline Follow-Back interviews 7 to 12 months after family therapy began. Zero-inflated Poisson (ZIP) regression analyses supported the main hypothesis, showing that PD/AW and TD/AW interacted to predict adolescent drug use at follow-up. For adolescents in high PD/AW families, higher levels of TD/AW predicted significant increases in drug use at follow-up, whereas for low PD/AW families, TD/AW and follow-up drug use were unrelated. Results suggest that attending to parallel demand-withdraw processes in parent/adolescent and therapist/adolescent dyads may be useful in family therapy for substance-using adolescents. PMID:23438248
Dialysis Modality and Readmission Following Hospital Discharge: A Population-Based Cohort Study.
Perl, Jeffrey; McArthur, Eric; Bell, Chaim; Garg, Amit X; Bargman, Joanne M; Chan, Christopher T; Harel, Shai; Li, Lihua; Jain, Arsh K; Nash, Danielle M; Harel, Ziv
2017-07-01
Readmissions following hospital discharge among maintenance dialysis patients are common, potentially modifiable, and costly. Compared with patients receiving in-center hemodialysis (HD), patients receiving peritoneal dialysis (PD) have fewer routine dialysis clinic encounters and as a result may be more susceptible to a hospital readmission following discharge. Population-based retrospective-cohort observational study. Patients treated with maintenance dialysis who were discharged following an acute-care hospitalization during January 1, 2003, to December 31, 2013, across 164 acute-care hospitals in Ontario, Canada. For those with multiple hospitalizations, we randomly selected a single hospitalization as the index hospitalization. Dialysis modality PD or in-center HD. Propensity scores were used to match each patient on PD therapy to 2 patients on in-center HD therapy to ensure that baseline indicators of health were similar between the 2 groups. All-cause 30-day readmission following the index hospital discharge. 28,026 dialysis patients were included in the study. 4,013 PD patients were matched to 8,026 in-center HD patients. Among the matched cohort, 30-day readmission rates were 7.1 (95% CI, 6.6-7.6) per 1,000 person-days for patients on PD therapy and 6.0 (95% CI, 5.7-6.3) per 1,000 person-days for patients on in-center HD therapy. The risk for a 30-day readmission among patients on PD therapy was higher compared with those on in-center HD therapy (adjusted HR, 1.19; 95% CI, 1.08-1.31). The primary results were consistent across several key prespecified subgroups. Lack of information for the frequency of nephrology physician encounters following discharge from the hospital in both the PD and in-center HD cohorts. Limited validation of International Classification of Diseases, Tenth Revision codes. The risk for 30-day readmission is higher for patients on home-based PD compared to in-center HD therapy. Interventions to improve transitions in care between the inpatient and outpatient settings are needed, particularly for patients on PD therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Nishijima, Tomohiro F; Shachar, Shlomit S; Nyrop, Kirsten A; Muss, Hyman B
2017-04-01
Compared with chemotherapy, significant improvement in survival outcomes with the programmed death receptor-1 (PD-1) inhibitors nivolumab and pembrolizumab and the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has been shown in several types of advanced solid tumors. We conducted a systematic review and meta-analysis to compare safety and tolerability between PD-1/PD-L1 inhibitors and chemotherapy. PubMed and American Society of Clinical Oncology (ASCO) databases were searched 1966 to September 2016. Eligible studies included randomized controlled trials (RCTs) comparing single-agent U.S. Food and Drug Administration-approved PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) with chemotherapy in cancer patients reporting any all-grade (1-4) or high-grade (3-4) adverse events (AEs), all- or high-grade treatment-related symptoms, hematologic toxicities and immune-related AEs, treatment discontinuation due to toxicities, or treatment-related deaths. The summary incidence, relative risk, and 95% confidence intervals were calculated. A total of 3,450 patients from 7 RCTs were included in the meta-analysis: 4 nivolumab, 2 pembrolizumab, and 1 atezolizumab trials. The underlying malignancies included were non-small cell lung cancer (4 trials) and melanoma (3 trials). Compared with chemotherapy, the PD-1/PD-L1 inhibitors had a significantly lower risk of all- and high-grade fatigue, sensory neuropathy, diarrhea and hematologic toxicities, all-grade anorexia, nausea, and constipation, any all- and high-grade AEs, and treatment discontinuation. There was an increased risk of all-grade rash, pruritus, colitis, aminotransferase elevations, hypothyroidism, and hyperthyroidism, and all- and high-grade pneumonitis with PD1/PD-L1 inhibitors. PD-1/PD-L1 inhibitors are overall better tolerated than chemotherapy. Our results provide further evidence supporting the favorable risk/benefit ratio for PD-1/PD-L1 inhibitors. The Oncologist 2017;22:470-479 IMPLICATIONS FOR PRACTICE: We conducted a systematic review and meta-analysis to compare summary toxicity endpoints and clinically relevant adverse events between programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy. PD1/PD-L1 inhibitors were associated with a lower risk of treatment-related symptoms (fatigue, anorexia, nausea, diarrhea, constipation, and sensory neuropathy) but a higher risk of immune-related adverse events (AEs). Summary toxicity endpoints favor PD1/PD-L1 inhibitors (any all- and high-grade AEs and treatment discontinuation). PD1/PD-L1 inhibitors are overall better tolerated than chemotherapy. In addition to efficacy data from trials, our findings provide useful information for clinicians for well-balanced discussions with their patients on the risks and benefits of treatment options for advanced cancer. © AlphaMed Press 2017.
Rocky Mountain Arsenal Ecological Chemical Data (1984-1985)
1986-03-01
Type Wet Areas Code Area LK Lake MT Marshy Type PD Pond C-1 APPENDIX D TISSUE CODES Code Tissue BRA Brain FIL Filet EDP Edible Portion LIV Liver MUS...ctus 472 Craton texcisis Crotoni 473 Cryptantha fcndleri Fcnder’s Cryptantha 474 Cucurbita foctidissinma Wild Gourd 475 Cytroptcrus montanus Pink Cym...adcrnocaulon Nlorthern wilIlow- herb 484 Eragrostis cilianensis Stinkgrass 485 Erfcgonum annuum Tall Erlogonum 486 Erigercn divergcns Spreading Fleabine 487
Khodadadi, Bahar; Bordbar, Maryam; Nasrollahzadeh, Mahmoud
2017-03-15
For the first time the extract of the plant of Salvia hydrangea was used to green synthesis of Pd nanoparticles (NPs) supported on Apricot kernel shell as an environmentally benign support. The Pd NPs/Apricot kernel shell as an effective catalyst was prepared through reduction of Pd 2+ ions using Salvia hydrangea extract as the reducing and capping agent and Pd NPs immobilization on Apricot kernel shell surface in the absence of any stabilizer or surfactant. According to FT-IR analysis, the hydroxyl groups of phenolics in Salvia hydrangea extract as bioreductant agents are directly responsible for the reduction of Pd 2+ ions and formation of Pd NPs. The as-prepared catalyst was characterized by Fourier transform infrared (FT-IR) and UV-Vis spectroscopy, field emission scanning electron microscopy (FESEM) equipped with an energy dispersive X-ray spectroscopy (EDS), Elemental mapping, X-ray diffraction analysis (XRD) and transmittance electron microscopy (TEM). The synthesized catalyst was used in the reduction of 4-nitrophenol (4-NP), Methyl Orange (MO), Methylene Blue (MB), Rhodamine B (RhB), and Congo Red (CR) at room temperature. The Pd NPs/Apricot kernel shell showed excellent catalytic activity in the reduction of these organic dyes. In addition, it was found that Pd NPs/Apricot kernel shell can be recovered and reused several times without significant loss of catalytic activity. Copyright © 2016 Elsevier Inc. All rights reserved.
Risk factors of severe peritoneal sclerosis in chronic peritoneal dialysis patients.
Alatab, Sudabeh; Najafi, Iraj; Pourmand, Gholamreza; Hosseini, Mostafa; Shekarchian, Soroosh
2017-11-01
Peritoneal dialysis (PD) offers the healthiest way for starting renal replacement therapy (RRT) in End Stage Renal Disease patients, however exposes long-term PD patients to a dangerous complication named encapsulating peritoneal sclerosis (EPS). In this study, we searched for possible risk factors of EPS. Data were collected from two PD centers covering period 1995-2012 and comprised 464 patients. Control group defined as PD patients stayed on PD >42 month (n = 122), and case group was 12 confirmed EPS patients. Associations were analyzed using linear regression analysis. Prevalence and incidence of EPS were 2.59% and 8.9% with an incidence of 0.7% patient-years, respectively. The age at start of PD in EPS patients (32.75 ± 10.8 year) was significantly lower compared with control group (49.61 ± 16.18 year, p = .0001). The mean duration of PD in EPS and control group were 2494.4 ± 940.9 and 1890.2 ± 598.8 days (p = .002). Control group had 145 episodes of peritonitis during total duration of 7686 patient months (peritonitis rate of 1/53). This was 1/26 with a total 38 episodes of peritonitis during the total duration of 997 patient months (p = .01) for EPS group. In regression analysis, PD duration, age at PD start and duration of Ultrafiltration failure (UFF) were associated with EPS. Longer time being on PD, younger age, and higher UFF duration were the risk factors for EPS development.
Mesbah-Namin, Seyed A; Sanati, Mohammad H; Mowjoodi, Alireza; Mason, Philip J; Vulliamy, Tom J; Noori-Daloii, Mohammad R
2002-06-01
We report the first investigation of glucose- 6-phosphate dehydrogenase (G6PD) deficiency among the Mazandaranians in the north of Iran. We analysed the G6PD gene in 74 unrelated G6PD-deficient men with a history of favism. Molecular analysis revealed three major different polymorphic variants: G6PD Mediterranean 66.2% (49 out of 74), G6PD Chatham 27% (20 out of 74), G6PD Cosenza 6.75% (5 out of 74). These findings indicated a higher prevalence of G6PD Chatham in this Iranian population than anywhere else in the world. In addition, the distribution of these G6PD variants is more similar to that found in an Italian population than in other Middle Eastern countries.
Maekawa, Naoya; Konnai, Satoru; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Takagi, Satoshi; Kagawa, Yumiko; Nakajima, Chie; Suzuki, Yasuhiko; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko
2016-01-01
Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1) is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1) or PD-L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs. PMID:27276060
Assaud, Loïc; Monyoncho, Evans; Pitzschel, Kristina; Allagui, Anis; Petit, Matthieu; Hanbücken, Margrit
2014-01-01
Summary Three-dimensionally (3D) nanoarchitectured palladium/nickel (Pd/Ni) catalysts, which were prepared by atomic layer deposition (ALD) on high-aspect-ratio nanoporous alumina templates are investigated with regard to the electrooxidation of formic acid in an acidic medium (0.5 M H2SO4). Both deposition processes, Ni and Pd, with various mass content ratios have been continuously monitored by using a quartz crystal microbalance. The morphology of the Pd/Ni systems has been studied by electron microscopy and shows a homogeneous deposition of granularly structured Pd onto the Ni substrate. X-ray diffraction analysis performed on Ni and NiO substrates revealed an amorphous structure, while the Pd coating crystallized into a fcc lattice with a preferential orientation along the [220]-direction. Surface chemistry analysis by X-ray photoelectron spectroscopy showed both metallic and oxide contributions for the Ni and Pd deposits. Cyclic voltammetry of the Pd/Ni nanocatalysts revealed that the electrooxidation of HCOOH proceeds through the direct dehydrogenation mechanism with the formation of active intermediates. High catalytic activities are measured for low masses of Pd coatings that were generated by a low number of ALD cycles, probably because of the cluster size effect, electronic interactions between Pd and Ni, or diffusion effects. PMID:24605281
Molde, Helge; Moussavi, Yasaman; Kopperud, Stine Therese; Erga, Aleksander Hagen; Hansen, Anita Lill; Pallesen, Ståle
2018-01-01
Although several case-control studies on the prevalence of Impulse-Control Disorders (ICDs) in Parkinson's Disease (PD) have been conducted, no meta-analytic study on this topic has previously been published. Thus, knowledge about the overall prevalence rate of ICD in PD and factors that might moderate this relationship is lacking. Prevalence studies of ICDs in PD were identified by computer searches in the MEDLINE, PsycINFO, and Web of Science databases, covering the period from January 2000 to February 2017. Data for N = 4,539, consisting of 2,371 PD patients and 2,168 healthy controls, representing 14 case-control studies were included. Estimation of the odds ratio ( OR ) of ICDs in PD compared to healthy controls was conducted using random-effects models. Mixed-effects models were applied in the moderator analysis of heterogeneity. Publication bias was estimated using a contour-enhanced funnel plot, the Rüker's test, and fail-safe N test for estimating the number of potential missing studies. Overall, the results showed significantly higher ratios for several ICDs in PD compared to healthy controls with the estimated overall OR s ranging between 2.07, 95% CI [1.26, 3.48], for having any ICDs, and 4.26, 95% CI [2.17, 8.36], for hypersexuality. However, the random-effects results for shopping were non-significant, though the fixed-effects model was significant ( OR = 1.66, 95%CI [1.21, 2.27]). The testing of potential moderator variables of heterogeneity identified the following two variables that were both associated with increased risk: being medically treated for PD and disease duration. The results must be interpreted with some caution due to possible small-studies effect or publication bias. Individuals with PD seem to have a significantly greater risk of suffering from ICDs compared to healthy controls. Gambling, hypersexuality, eating, punding, and hobbying are all ICDs significantly associated with PDs being medically treated for PD.
Yonemori, Kim M; Ennis, Tui; Novotny, Rachel; Fialkowski, Marie K; Ettienne, Reynolette; Wilkens, Lynne R; Leon Guerrero, Rachael T; Bersamin, Andrea; Coleman, Patricia; Li, Fenfang; Boushey, Carol J
2017-12-01
The aim was to describe differences in dietary outcomes based on the provision of food wrappers, labels or packages (WLP) to complement data from dietary records (DR) among children from the US Affiliated Pacific. The WLP were intended to aid food coding. Since WLP can be associated with ultra-processed foods, one might expect differences in sodium, sugar, and other added ingredients to emerge. Dietary intakes of children (2-8 y) in Alaska, Hawai'i, Commonwealth of the Northern Mariana Islands, and Guam were collected using parent/caregiver completed 2-day DR. Parents were encouraged to collect WLP associated with the child's intake. Trained staff entered data from the DRs including the WLP when available using PacTrac3, a web application. Of the 1,868 DRs collected and entered at the time of this report, 498 (27%) included WLP. After adjusting for confounders (sex, age, location, education, food assistance), the DRs with WLP had significantly higher amounts of energy (kcal), total fat, saturated fat, added sugar, and sodium. These results suggest the inclusion of WLP enhanced the dietary intake data. The intake of energy, fat, added sugar and sodium derived from processed foods and foods consumed outside the home was better captured in children who had WLP.
Convergent Genetic and Expression Datasets Highlight TREM2 in Parkinson's Disease Susceptibility.
Liu, Guiyou; Liu, Yongquan; Jiang, Qinghua; Jiang, Yongshuai; Feng, Rennan; Zhang, Liangcai; Chen, Zugen; Li, Keshen; Liu, Jiafeng
2016-09-01
A rare TREM2 missense mutation (rs75932628-T) was reported to confer a significant Alzheimer's disease (AD) risk. A recent study indicated no evidence of the involvement of this variant in Parkinson's disease (PD). Here, we used the genetic and expression data to reinvestigate the potential association between TREM2 and PD susceptibility. In stage 1, using 10 independent studies (N = 89,157; 8787 cases and 80,370 controls), we conducted a subgroup meta-analysis. We identified a significant association between rs75932628 and PD (P = 3.10E-03, odds ratio (OR) = 3.88, 95 % confidence interval (CI) 1.58-9.54) in No-Northern Europe subgroup, and significantly increased PD risks (P = 0.01 for Mann-Whitney test) in No-Northern Europe subgroup than in Northern Europe subgroup. In stage 2, we used the summary results from a large-scale PD genome-wide association study (GWAS; N = 108,990; 13,708 cases and 95,282 controls) to search for other TREM2 variants contributing to PD susceptibility. We identified 14 single-nucleotide polymorphisms (SNPs) associated with PD within 50-kb upstream and downstream range of TREM2. In stage 3, using two brain expression GWAS datasets (N = 773), we identified 6 of the 14 SNPs regulating increased expression of TREM2. In stage 4, using the whole human genome microarray data (N = 50), we further identified significantly increased expression of TREM2 in PD cases compared with controls in human prefrontal cortex. In summary, convergent genetic and expression datasets demonstrate that TREM2 is a potent risk factor for PD and may be a therapeutic target in PD and other neurodegenerative diseases.
TREM2 is associated with increased risk for Alzheimer's disease in African Americans.
Jin, Sheng Chih; Carrasquillo, Minerva M; Benitez, Bruno A; Skorupa, Tara; Carrell, David; Patel, Dwani; Lincoln, Sarah; Krishnan, Siddharth; Kachadoorian, Michaela; Reitz, Christiane; Mayeux, Richard; Wingo, Thomas S; Lah, James J; Levey, Allan I; Murrell, Jill; Hendrie, Hugh; Foroud, Tatiana; Graff-Radford, Neill R; Goate, Alison M; Cruchaga, Carlos; Ertekin-Taner, Nilüfer
2015-04-10
TREM2 encodes for triggering receptor expressed on myeloid cells 2 and has rare, coding variants that associate with risk for late-onset Alzheimer's disease (LOAD) in Caucasians of European and North-American origin. This study evaluated the role of TREM2 in LOAD risk in African-American (AA) subjects. We performed exonic sequencing and validation in two independent cohorts of >800 subjects. We selected six coding variants (p.R47H, p.R62H, p.D87N, p.E151K, p.W191X, and p.L211P) for case-control analyses in a total of 906 LOAD cases vs. 2,487 controls. We identified significant LOAD risk association with p.L211P (p=0.01, OR=1.27, 95%CI=1.05-1.54) and suggestive association with p.W191X (p=0.08, OR=1.35, 95%CI=0.97-1.87). Conditional analysis suggests that p.L211P, which is in linkage disequilibrium with p.W191X, may be the stronger variant of the two, but does not rule out independent contribution of the latter. TREM2 p.L211P resides within the cytoplasmic domain and p.W191X is a stop-gain mutation within the shorter TREM-2V transcript. The coding variants within the extracellular domain of TREM2 previously shown to confer LOAD risk in Caucasians were extremely rare in our AA cohort and did not associate with LOAD risk. Our findings suggest that TREM2 coding variants also confer LOAD risk in AA, but implicate variants within different regions of the gene than those identified for Caucasian subjects. These results underscore the importance of investigating different ethnic populations for disease risk variant discovery, which may uncover allelic heterogeneity with potentially diverse mechanisms of action.
Association between PD-L1 expression and driven gene status in NSCLC: A meta-analysis.
Li, D; Zhu, X; Wang, H; Li, N
2017-07-01
We explored the potential clinical association between programmed death-ligand 1 (PD-L1) expression and driven gene status in non-small cell lung cancer (NSCLC). We systemically searched through October 2015. Odd ratios (ORs) with 95% CIs were calculated to examine the association of PD-L1 expression with driven gene status. A random- or fixed-effects model was used. Nine studies were identified. KRAS-mutant tumors were more likely to be PD-L1 positive than KRAS-wild type tumors (51% vs 36%; OR 1.69; 95% CI 1.01-2.84; p = 0.045). In contrast, PD-L1 expression did not differ by EGFR (OR 0.86; 95% CI 0.43-1.73; p = 0.675) or ALK (OR 1.02; 95% CI 0.44-2.37; p = 0.954) status. In subgroup analysis, there was also no significant association between PD-L1 expression and EGFR status in term of the cut-offs or ethnicity. In conclusion, NSCLC with KRAS mutations showed a trend for higher frequency of positive PD-L1 expression. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
Haptoglobin Phenotype Modifies Serum Iron Levels and the Effect of Smoking on Parkinson Disease Risk
Costa-Mallen, Paola; Zabetian, Cyrus P.; Agarwal, Pinky; Hu, Shu-Ching; Yearout, Dora; Samii, Ali; Leverenz, James B.; Roberts, John W.; Checkoway, Harvey
2015-01-01
Introduction Haptoglobin is a hemoglobin-binding protein that exists in three functionally different phenotypes, and haptoglobin phenotype 2-1 has previously been associated with Parkinson disease (PD) risk, with mechanisms not elucidated. Some evidence is emerging that low levels of serum iron may increase PD risk. In this study we investigated whether PD patients have lower serum iron and ferritin than controls, and whether this is dependent on haptoglobin phenotype. We also investigated the effect of Hp phenotype as a modifier of the effect of smoking on PD risk. Methods The study population consisted of 128 PD patients and 226 controls. Serum iron, ferritin, and haptoglobin phenotype were determined, and compared between PD cases and controls. Stratified analysis by haptoglobin phenotype was performed to determine effect of haptoglobin phenotype on serum iron parameter differences between PD cases and controls and to investigate its role in the protective effect of smoking on PD risk. Results PD cases had lower serum iron than controls (83.28 ug/100ml vs 94.00 ug/100 ml, p 0.006), and in particular among subjects with phenotype 2-1. The protective effect of smoking on PD risk resulted stronger in subjects with phenotype 1-1 and 2-2, and weakest among subjects with phenotype 2-1. Ferritin levels were higher in PD cases than controls among subjects of White ethnicity. Conclusions Our results report for the first time that the haptoglobin phenotype may be a contributor of iron levels abnormalities in PD patients. The mechanisms for these haptoglobin-phenotype specific effects will have to be further elucidated. PMID:26228081
Pattern destabilization and emotional processing in cognitive therapy for personality disorders
Hayes, Adele M.; Yasinski, Carly
2015-01-01
Clinical trials of treatments for personality disorders can provide a medium for studying the process of therapeutic change with particularly entrenched and self-perpetuating systems and might reveal important principles of system transition. We examined the extent to which maladaptive personality patterns were destabilized in a trial of cognitive therapy personality disorders (CT-PD) and how destabilization was associated with emotional processing and treatment outcomes. Dynamic systems theory was used as a theoretical framework for studying change. Method: Participants were 27 patients diagnosed with Avoidant or Obsessive Compulsive Personality Disorder (AVPD or OCPD), who completed an open trial of CT-PD. Raters coded treatment sessions using a coding system that operationalizes emotional processing, as well as cognitive, affective, behavioral, and somatic components of pathological (negative) and more adaptive (positive) patterns of functioning. Pattern destabilization (dispersion) scores during the early phase of treatment (phase 1: session 1–10) and the schema-focused phase (phase 2: session 11–34) were calculated using a program called GridWare. Results: More pattern destabilization and emotional processing in the schema-focused phase of CT-PD predicted more improvement in personality disorder symptoms and positive pattern strength at the end of treatment, whereas these variables in phase 1 did not predict outcome. Conclusion: In addition to illustrating a quantitative method for studying destabilization and change of patterns of psychopathology, we present findings that are consistent with recent updates of emotional processing theory and with principles from dynamic systems theory. PMID:25755647
Pattern destabilization and emotional processing in cognitive therapy for personality disorders.
Hayes, Adele M; Yasinski, Carly
2015-01-01
Clinical trials of treatments for personality disorders can provide a medium for studying the process of therapeutic change with particularly entrenched and self-perpetuating systems and might reveal important principles of system transition. We examined the extent to which maladaptive personality patterns were destabilized in a trial of cognitive therapy personality disorders (CT-PD) and how destabilization was associated with emotional processing and treatment outcomes. Dynamic systems theory was used as a theoretical framework for studying change. Participants were 27 patients diagnosed with Avoidant or Obsessive Compulsive Personality Disorder (AVPD or OCPD), who completed an open trial of CT-PD. Raters coded treatment sessions using a coding system that operationalizes emotional processing, as well as cognitive, affective, behavioral, and somatic components of pathological (negative) and more adaptive (positive) patterns of functioning. Pattern destabilization (dispersion) scores during the early phase of treatment (phase 1: session 1-10) and the schema-focused phase (phase 2: session 11-34) were calculated using a program called GridWare. More pattern destabilization and emotional processing in the schema-focused phase of CT-PD predicted more improvement in personality disorder symptoms and positive pattern strength at the end of treatment, whereas these variables in phase 1 did not predict outcome. In addition to illustrating a quantitative method for studying destabilization and change of patterns of psychopathology, we present findings that are consistent with recent updates of emotional processing theory and with principles from dynamic systems theory.
High-resolution EPMA X-ray images of mother liquid inclusions in a Pd2Ga single crystal
NASA Astrophysics Data System (ADS)
Müller, D.; Schwerin, J.; Gille, P.; Fehr, K. T.
2014-03-01
During crystal growth from solution inclusions of different compositions were trapped at the rim of a Pd2Ga single crystal. Their fine-grained (< 5 μm) internal structure demands special requirements for electron microprobe analysis, realized by low-voltage (5 keV) element mapping applying a step size of 0.138 μm for each pixel. It can be shown, that these inclusions represent an isolated chemical system, and that crystallisation upon cooling follows the expected thermodynamic phase relations. Thus the final composition in the centre of the inclusion consists of a small-scale mixture of PdGa and Pd5Ga3 evolved out of a solid-solid decomposition of Pd5Ga4.
Miyoshi, Hiroaki; Kiyasu, Junichi; Kato, Takeharu; Yoshida, Noriaki; Shimono, Joji; Yokoyama, Shintaro; Taniguchi, Hiroaki; Sasaki, Yuya; Kurita, Daisuke; Kawamoto, Keisuke; Kato, Koji; Imaizumi, Yoshitaka; Seto, Masao; Ohshima, Koichi
2016-09-08
Programmed cell death ligand 1 (PD-L1) is expressed on both tumor and tumor-infiltrating nonmalignant cells in lymphoid malignancies. The programmed cell death 1 (PD-1)/PD-L1 pathway suppresses host antitumor responses, although little is known about the significance of PD-1/PD-L1 expression in the tumor microenvironment. To investigate the clinicopathological impact of PD-L1 expression in adult T-cell leukemia/lymphoma (ATLL), we performed PD-L1 immunostaining in 135 ATLL biopsy samples. We observed 2 main groups: 1 had clear PD-L1 expression in lymphoma cells (nPD-L1(+), 7.4% of patients), and the other showed minimal expression in lymphoma cells (nPD-L1(-), 92.6%). Within the nPD-L1(-) group, 2 subsets emerged: the first displayed abundant PD-L1 expression in nonmalignant stromal cells of the tumor microenvironment (miPD-L1(+), 58.5%) and the second group did not express PD-L1 in any cell (PD-L1(-), 34.1%). nPD-L1(+) ATLL (median survival time [MST] 7.5 months, 95% CI [0.4-22.3]) had inferior overall survival (OS) compared with nPD-L1(-) ATLL (MST 14.5 months, 95% CI [10.1-20.0]) (P = .0085). Among nPD-L1(-) ATLL, miPD-L1(+) ATLL (MST 18.6 months, 95% CI [11.0-38.5]) showed superior OS compared with PD-L1(-) ATLL (MST 10.2 months, 95% CI [8.0-14.7]) (P = .0029). The expression of nPD-L1 and miPD-L1 maintained prognostic value for OS in multivariate analysis (P = .0322 and P = .0014, respectively). This is the first report describing the clinicopathological features and outcomes of PD-L1 expression in ATLL. More detailed studies will disclose clinical and biological significance of PD-L1 expression in ATLL. © 2016 by The American Society of Hematology.
Balsis, Steve; Gleason, Marci E. J.; Woods, Carol M.; Oltmanns, Thomas F.
2015-01-01
Many of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM–IV; American Psychiatric Association, 1994) personality disorder (PD) diagnostic criteria focus on a younger social and occupational context. The absence of age-appropriate criteria for older adults forces researchers and clinicians to draw conclusions based on existing criteria, which are likely inadequate. To explore which DSM–IV PD criteria contain age group measurement bias, the authors report 2 analyses of data on nearly 37,000 participants, ages 18–98 years, taken from a public data set that includes 7 of the 10 PDs (antisocial, avoidant, dependent, histrionic, obsessive–compulsive, paranoid, and schizoid). The 1st analysis revealed that older age groups tend to endorse fewer PD criteria than younger age groups. The 2nd analysis revealed that 29% of the criteria contain measurement bias. Although the latent variable structure for each PD was quite similar across younger and older age groups, some individual criteria were differentially endorsed by younger and older adults with equivalent PD pathology. The presence of measurement bias for these criteria raises questions concerning the assessment of PDs in older adults and the interpretation of existing data. PMID:17385993
Meta-Analysis of Early Nonmotor Features and Risk Factors for Parkinson Disease
Noyce, Alastair J; Bestwick, Jonathan P; Silveira-Moriyama, Laura; Hawkes, Christopher H; Giovannoni, Gavin; Lees, Andrew J; Schrag, Anette
2012-01-01
Objective To evaluate the association between diagnosis of Parkinson disease (PD) and risk factors or early symptoms amenable to population-based screening. Methods A systematic review and meta-analysis of risk factors for PD. Results The strongest associations with later diagnosis of PD were found for having a first-degree or any relative with PD (odds ratio [OR], 3.23; 95% confidence interval [CI], 2.65–3.93 and OR, 4.45; 95% CI, 3.39–5.83) or any relative with tremor (OR, 2.74; 95% CI, 2.10–3.57), constipation (relative risk [RR], 2.34; 95% CI, 1.55–3.53), or lack of smoking history (current vs never: RR, 0.44; 95% CI, 0.39–0.50), each at least doubling the risk of PD. Further positive significant associations were found for history of anxiety or depression, pesticide exposure, head injury, rural living, beta-blockers, farming occupation, and well-water drinking, and negative significant associations were found for coffee drinking, hypertension, nonsteroidal anti-inflammatory drugs, calcium channel blockers, and alcohol, but not for diabetes mellitus, cancer, oral contraceptive pill use, surgical menopause, hormone replacement therapy, statins, acetaminophen/paracetamol, aspirin, tea drinking, history of general anesthesia, or gastric ulcers. In the systematic review, additional associations included negative associations with raised serum urate, and single studies or studies with conflicting results. Interpretation The strongest risk factors associated with later PD diagnosis are having a family history of PD or tremor, a history of constipation, and lack of smoking history. Further factors also but less strongly contribute to risk of PD diagnosis or, as some premotor symptoms, require further standardized studies to demonstrate the magnitude of risk associated with them. ANN NEUROL 2012 PMID:23071076
Genome-wide association study of Parkinson's disease in East Asians.
Foo, Jia Nee; Tan, Louis C; Irwan, Ishak D; Au, Wing-Lok; Low, Hui Qi; Prakash, Kumar-M; Ahmad-Annuar, Azlina; Bei, Jinxin; Chan, Anne Yy; Chen, Chiung Mei; Chen, Yi-Chun; Chung, Sun Ju; Deng, Hao; Lim, Shen-Yang; Mok, Vincent; Pang, Hao; Pei, Zhong; Peng, Rong; Shang, Hui-Fang; Song, Kyuyoung; Tan, Ai Huey; Wu, Yih-Ru; Aung, Tin; Cheng, Ching-Yu; Chew, Fook Tim; Chew, Soo-Hong; Chong, Siow-Ann; Ebstein, Richard P; Lee, Jimmy; Saw, Seang-Mei; Seow, Adeline; Subramaniam, Mythily; Tai, E-Shyong; Vithana, Eranga N; Wong, Tien-Yin; Heng, Khai Koon; Meah, Wee-Yang; Khor, Chiea Chuen; Liu, Hong; Zhang, Furen; Liu, Jianjun; Tan, Eng-King
2017-01-01
Genome-wide association studies (GWAS) on Parkinson's disease (PD) have mostly been done in Europeans and Japanese. No study has been done in Han Chinese, which make up nearly a fifth of the world population. We conducted the first Han Chinese GWAS analysing a total of 22,729 subjects (5,125 PD cases and 17,604 controls) from Singapore, Hong Kong, Malaysia, Korea, mainland China and Taiwan. We performed imputation, merging and logistic regression analyses of 2,402,394 SNPs passing quality control filters in 779 PD cases, 13,227 controls, adjusted for the first three principal components. 90 SNPs with association P < 10-4 were validated in 9 additional sample collections and the results were combined using fixed-effects inverse-variance meta-analysis. We observed strong associations reaching genome-wide significance at SNCA, LRRK2 and MCCC1, confirming their important roles in both European and Asian PD. We also identified significant (P < 0.05) associations at 5 loci (DLG2, SIPA1L2, STK39, VPS13C and RIT2), and observed the same direction of associations at 9 other loci including BST1 and PARK16. Allelic heterogeneity was observed at LRRK2 while European risk SNPs at 6 other loci including MAPT and GBA-SYT11 were non-polymorphic or very rare in our cohort. Overall, we replicate associations at SNCA, LRRK2, MCCC1 and 14 other European PD loci but did not identify Asian-specific loci with large effects (OR > 1.45) on PD risk. Our results also demonstrate some differences in the genetic contribution to PD between Europeans and Asians. Further pan-ethnic meta-analysis with European GWAS cohorts may unravel new PD loci. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Wang, Cuihua; Yu, Xuetao; Wang, Wei
2016-01-01
Abstract Background: Nonsmall cell lung cancer (NSCLC)-patients treated with standard chemotherapy experienced progression rapidly. A novel therapy based on programed death 1 (PD-1)/programed death ligand 1 (PD-L1) inhibitors showed an increasing potential in several malignancies including advanced NSCLC. Objectives: This article is a meta-analysis aiming to systematically evaluate the efficacy and safety profiles of PD-1/PD-L1 agents in patients with NSCLC. Data sources: Data were collected from eligible studies searched from PubMed, ScienceDirect, and Web of Science. Synthesis methods: Pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) was estimated to assess the efficacy of PD-1/PD-L1 inhibitors versus docetaxel, pooled odds ratio (OR) was calculated for objective response rate (ORR). The overall frequency was estimated for 1-year OS, 1-year progression-free survival, and ORR. A subgroup analysis among NSCLC patients tested with different epidermal growth factor receptor (EGFR) status was also performed to figure out the relationship between EGFR status and efficacy of PD-1/PD-L1 therapies. OR for occurrence of any grade and grade 3 to 5 treatment-related adverse effect was calculated for evaluating the safety of PD-1/PD-L1 therapies. Results: Nine studies were included in this analysis. The pooled HRs for OS and PFS were 0.68 (95% confidence interval [CI] 0.61–0.75) and 0.83 (95% CI 0.75–0.91), respectively, the pooled OR for ORR was 1.83 (95% CI 1.41–2.36), indicating a significant improvement in OS, PFS, and ORR. In the results of subgroup analysis, the HR for OS in NSCLC patients was 1.05 (95% CI 0.69–1.59) in patients with mutant EGFR and 0.66 (95% CI 0.57–0.77) in patients with wild-type EGFR status. OR for occurrence was 0.36 (95% CI 0.28–0.46) in any grade treatment-related adverse effect and 0.18 (95% CI 0.14–0.22) in grade 3 to 5 treatment-related adverse effect, suggesting a superior safety profile of PD-1/PD-L1 inhibitors. Conclusion: The PD-1/PD-L1 therapy significantly prolonged the OS and improved the ORR, simultaneously lowering the treatment-related adverse effect events versus docetaxel. PMID:28033249
Human X-Linked genes regionally mapped utilizing X-autosome translocations and somatic cell hybrids.
Shows, T B; Brown, J A
1975-01-01
Human genes coding for hypoxanthine phosphoribosyltransferase (HPRT, EC 2.4.2.8; IMP:pyrophosphate phosphoribosyltransferase), glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49; D-glucose-6-phosphate:NADP+ 1-oxidoreductase), and phosphoglycerate kinase (PGK, EC 2.7.2.3; ATP:3-phospho-D-glycerate 1-phosphotransferase) have been assigned to specific regions on the long arm of the X chromosome by somatic cell gentic techniques. Gene assignment and linear order were determined by employing human somatic cells possessing an X/9 translocation or an X/22 translocation in man-mouse cell hybridization studies. The X/9 translocation involved the majority of the X long arm translocated to chromosome 9 and the X/22 translocation involved the distal half of the X long arm translocated to 22. In each case these rearrangements appeared to be reciprocal. Concordant segregation of X-linked enzymes and segments of the X chromosome generated by the translocations indicated assignment of the PGK gene to a proximal long arm region (q12-q22) and the HPRT and G6PD genes to the distal half (q22-qter) of the X long arm. Further evidence suggests a gene order on the X long arm of centromere-PGK-HPRT-G6PD. Images PMID:1056018
Giladi, Nir; Nicholas, Anthony P; Asgharnejad, Mahnaz; Dohin, Elisabeth; Woltering, Franz; Bauer, Lars; Poewe, Werner
2016-10-19
The efficacy of rotigotine has been demonstrated in studies of patients with early (i.e. not receiving levodopa) and advanced (i.e. not adequately controlled on levodopa; average 2.5 h/day in 'off' state) Parkinson's disease (PD). To further investigate the efficacy of rotigotine transdermal patch across different stages of PD symptom severity and functional disability, according to baseline Hoehn and Yahr (HY) staging. Post hoc analysis of six placebo-controlled studies of rotigotine in patients with early PD (SP506, SP512, SP513; rotigotine ≤8 mg/24 h) or advanced-PD (CLEOPATRA-PD, PREFER, SP921; rotigotine ≤16 mg/24 h). Data were pooled and analyzed according to baseline HY stage (1, 2, 3 or 4) for change from baseline to end of maintenance in Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living), UPDRS III (motor) and UPDRS II+III; statistical tests are exploratory. Data were available for 2057 patients (HY 1 : 262; HY 2 : 1230; HY 3 : 524; HY 4 : 41). Patients at higher HY stages were older, had a longer time since PD diagnosis and higher baseline UPDRS II+III scores vs patients at lower HY stages. Rotigotine improved UPDRS II+III versus placebo for each individual HY stage (p < 0.05 for each HY stage), with treatment differences increasing with increasing HY stages. Similar results were observed for UPDRS II and UPDRS III. This post hoc analysis suggests that rotigotine may be efficacious across a broad range of progressive stages of PD symptom severity and functional disability (HY stages 1-4).
Kolter, Marlene; Koszinowski, Konrad
2016-10-24
The reduction of Pd II precatalysts to catalytically active Pd 0 species is a key step in many palladium-mediated cross-coupling reactions. Besides phosphines, the stoichiometrically used organometallic reagents can afford this reduction, but do so in a poorly understood way. To elucidate the mechanism of this reaction, we have treated solutions of Pd(OAc) 2 and a phosphine ligand L in tetrahydrofuran with RMgCl (R=Ph, Bn, Bu) as well as other organometallic reagents. Analysis of these model systems by electrospray- ionization mass spectrometry found palladate(II) complexes [L n PdR 3 ] - (n=0 and 1), thus pointing to the occurrence of transmetallation reactions. Upon gas-phase fragmentation, the [L n PdR 3 ] - anions preferentially underwent a reductive elimination to yield Pd 0 species. The sequence of the transmetallation and reductive elimination, thus, constitutes a feasible mechanism for the reduction of the Pd(OAc) 2 precatalyst. Other species of interest observed include the Pd IV complex [PdBn 5 ] - , which did not fragment via a reductive elimination but lost BnH instead. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease
Fernández, Maria Victoria; Kim, Jong Hun; Budde, John P.; Black, Kathleen; Medvedeva, Alexandra; Saef, Ben; Del-Aguila, Jorge; Ibañez, Laura; Dube, Umber; Harari, Oscar; Norton, Joanne; Chasse, Rachel; Morris, John C.; Goate, Alison
2017-01-01
Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations. PMID:29091718
Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.
Fernández, Maria Victoria; Kim, Jong Hun; Budde, John P; Black, Kathleen; Medvedeva, Alexandra; Saef, Ben; Deming, Yuetiva; Del-Aguila, Jorge; Ibañez, Laura; Dube, Umber; Harari, Oscar; Norton, Joanne; Chasse, Rachel; Morris, John C; Goate, Alison; Cruchaga, Carlos
2017-11-01
Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.
Shibahara, Daisuke; Tanaka, Kentaro; Iwama, Eiji; Kubo, Naoki; Ota, Keiichi; Azuma, Koichi; Harada, Taishi; Fujita, Jiro; Nakanishi, Yoichi; Okamoto, Isamu
2018-03-27
The interaction of programmed cell death ligand 2 (PD-L2) with programmed cell death 1 is implicated in tumor immune escape. The regulation of PD-L2 expression in tumor cells has remained unclear, however. We here examined intrinsic and extrinsic regulation of PD-L2 expression in NSCLC. PD-L2 expression was evaluated by reverse transcription and real-time polymerase chain reaction analysis and by flow cytometry. BEAS-2B cells stably expressing an activated mutant form of EGFR or the echinoderm microtubule associated protein like 4 (EML4)-ALK receptor tyrosine kinase fusion oncoprotein manifested increased expression of PD-L2 at both the mRNA and protein levels. Furthermore, treatment of NSCLC cell lines that harbor such driver oncogenes with corresponding EGFR or ALK tyrosine kinase inhibitors or depletion of EGFR or ALK by small interfering RNA transfection suppressed expression of PD-L2, demonstrating that activating EGFR mutations or echinoderm microtubule associated protein like 4 gene (EML4)-ALK receptor tyrosine kinase gene (ALK) fusion intrinsically induce PD-L2 expression. We also found that interferon gamma (IFN-γ) extrinsically induced expression of PD-L2 through signal transducer and activator of transcription 1 signaling in NSCLC cells. Oncogene-driven expression of PD-L2 in NSCLC cells was inhibited by knockdown of the transcription factors signal transducer and activator of transcription 3 (STAT3) or c-FOS. IFN-γ also activated STAT3 and c-FOS, suggesting that these proteins may also contribute to the extrinsic induction of PD-L2 expression. Expression of PD-L2 is induced intrinsically by activating EGFR mutations or EML4-ALK fusion and extrinsically by IFN-γ, with STAT3 and c-FOS possibly contributing to both intrinsic and extrinsic pathways. Our results thus provide insight into the complexity of tumor immune escape in NSCLC. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Radio frequency tags systems to initiate system processing
NASA Astrophysics Data System (ADS)
Madsen, Harold O.; Madsen, David W.
1994-09-01
This paper describes the automatic identification technology which has been installed at Applied Magnetic Corp. MR fab. World class manufacturing requires technology exploitation. This system combines (1) FluoroTrac cassette and operator tracking, (2) CELLworks cell controller software tools, and (3) Auto-Soft Inc. software integration services. The combined system eliminates operator keystrokes and errors during normal processing within a semiconductor fab. The methods and benefits of this system are described.
Scalable, Flexible and Active Learning on Distributions
2016-09-01
enthusiasm about widely varying research ideas was inspiring. Junier Oliva always knew the right way to think about something when I got stuck. Tzu -Kuo...109 Bibliography 113 iii iv Chapter 1 Introduction Traditional machine learning approaches focus on learning problems defined on...with Tzu -Kuo (TK) Huang. 2 et al. 2012; Ntampaka, Trac, Sutherland, Battaglia, et al. 2015; Jin 2016; Jin et al. 2016; Sutherland, J. B. Oliva, et al
La Porta, F; Giordano, A; Caselli, S; Foti, C; Franchignoni, F
2015-12-01
It is unclear whether the BBS is an effective tool for the measurement of early postural control impairments in patients with Parkinson's disease (PD). The aim of this paper was to evaluate BBS' content validity, internal construct validity, reliability and targeting in patients with PD within the Rasch analysis framework. Observational, cross-sectional study. Outpatient Rehabilitation Unit. A sample of 285 outpatients with PD. The content validity of the BBS was assessed using standard linking techniques. The BBS was administered by trained physiotherapists. The data collected then underwent Rasch analysis. Content validity analysis showed a lack of items assessing postural responses to tripping and slips and stability during walking. On Rasch analysis, the BBS failed the requirements of monotonicity, local independence, unidimensionality and invariance. After rescoring 7 items, grouping of locally dependent items into testlets, and deletion of the static sitting balance item because mistargeted and underdiscriminating, the Rasch-modified BBS for PD (BBS-PD) showed adequate internal construct validity (χ(2)24=39.693; P=0.023), including absence of differential item functioning (DIF) across gender and age, and was, as a whole, sufficiently precise for individual person measurement (PSI=0.894). However, the scale was not well targeted to the sample in view of the prevalence of higher scores. This study demonstrated the internal construct validity and reliability of the BBS-PD as a measurement tool for patients with PD within the Rasch analysis framework. However, the lack of items critical to the assessment of postural control impairments typical of PD, affected negatively the targeting, so that a significant percentage of patients was located in the higher ability range of the measurement continuum, where precision of measurement is reduced. These findings suggest that the BBS, even if modified, may not be an effective tool for the measurement of early postural control in patients with PD.
Hengartner, Michael P; Ajdacic-Gross, Vladeta; Rodgers, Stephanie; Müller, Mario; Haker, Helene; Rössler, Wulf
2014-08-01
There is some evidence that fluid intelligence as well as empathy may be significantly related to personality disorders (PDs). To our knowledge, no study has addressed those issues simultaneously in all 10 DSM PDs in a sample of the general population. We analysed data from 196 participants aged 20–41 from the Epidemiology Survey of the Zurich Programme for Sustainable Development of Mental Health Services (ZInEP), a comprehensive psychiatric survey in the general population of Zurich, Switzerland. We assessed the digit symbol-coding test (DSCT), the “reading the mind in the eyes” test (RMET) and the interpersonal reactivity index (IRI). Both measures of cognitive empathy (i.e. RMET and IRI perspective taking) were not related to any PD trait-score. The total PD trait-score was significantly associated with low scores on DSCT and IRI empathic concern and high scores on IRI personal distress, which indicates a dose–response relationship in those measures. DSCT was particularly related to borderline PD, IRI empathic concern to schizoid and narcissistic PDs, and IRI personal distress to avoidant PD. The proportion of variance explained in the total PD trait-score accounted for by DSCT, IRI empathic concern and IRI personal distress was 2.6, 2.3 and 13.3 %, respectively. Symptomatology and severity of PDs are related to low fluid intelligence and reduced emotional empathy as characterized by low empathic concern and high personal distress towards emotional expressions of others. Further research is needed that examines the association between cognitive empathy and personality pathology as well as potential clinical applications.
Body mass index in Parkinson's disease: a meta-analysis.
van der Marck, Marjolein A; Dicke, Heleen C; Uc, Ergun Y; Kentin, Zippora H A; Borm, George F; Bloem, Bastiaan R; Overeem, Sebastiaan; Munneke, Marten
2012-03-01
Prior work suggested that patients with Parkinson's disease (PD) have a lower Body Mass Index (BMI) than controls, but evidence is inconclusive. We therefore conducted a meta-analysis on BMI in PD. We searched MEDLINE, EMBASE, Cinahl and Scopus to identify cohort studies on BMI in PD, published before February 2011. Studies that reported mean BMI for PD patients and healthy controls were eligible. Twelve studies were included, with a total of 871 patients and 736 controls (in three studies controls consisted of subjects from other published studies). Our primary aim was to assess differences in BMI between patients and controls; this was analyzed with random effects meta-analysis. Our secondary aim was to evaluate the relation with disease severity (Hoehn and Yahr stage) and disease duration, using random effects meta-regression. PD patients had a significantly lower BMI than controls (overall effect 1.73, 95% CI 1.11-2.35, P<0.001). Pooled data of seven studies showed that patients with Hoehn and Yahr stage 3 had a lower BMI than patients with stage 2 (3.9, 95% CI 0.1-7.7, P<0.05). Disease duration was not associated with BMI. Because a low body weight is associated with negative health effects and a poorer prognosis, monitoring weight and nutritional status should be part of PD management. Copyright © 2011. Published by Elsevier Ltd.
Lai, Yin Key; Lai, Nai Ming; Lee, Shaun Wen Huey
2017-05-01
Emerging epidemiological evidence suggests that patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may have a higher risk of developing diabetes. The aim of the review was to synthesise the evidence on the association between G6PD deficiency and diabetes. A systematic search on Medline, EMBASE, AMED and CENTRAL databases for studies published between January 1966 and September 2016 that assessed the association between G6PD deficiency and diabetes was conducted. This was supplemented by a review of the reference list of retrieved articles. We extracted data on study characteristics, outcomes and performed an assessment on the methodological quality of the studies. A random-effects model was used to compute the summary risk estimates. Fifteen relevant publications involving 949,260 participants were identified, from which seven studies contributed to the meta-analysis. G6PD deficiency was associated with a higher odd of diabetes (odds ratio 2.37, 95% confidence interval 1.50-3.73). The odds ratio of diabetes among men was higher (2.22, 1.31-3.75) compared to women (1.87, 1.12-3.12). This association was broadly consistent in the sensitivity analysis. Current evidence suggests that G6PD deficiency may be a risk factor for diabetes, with higher odds among men compared to women. Further research is needed to determine how G6PD deficiency moderates diabetes.
NASA Astrophysics Data System (ADS)
Zhang, Xiuying; Li, Shuyan; Yang, Lin; Fan, Changqing
2007-11-01
Ag(I), Pd(II) and Pt(II) complexes of 5-methoxy-5,6-diphenyl-4,5-dihydro-2H-[1,2,4]triazine-3-thione (LH 2OCH 3) have been synthesized and characterized by elemental analysis, molar conductance, 1H NMR, IR spectra, UV spectra and thermal analysis (TG-DTA). The components of the three complexes are [Ag(C 15H 10N 3S)] 6, Pd(C 15H 10N 3S) 2 and Pt(C 15H 10N 3S) 2·C 3H 6O·2H 2O, respectively. All the complexes are nonelectrolyte and have high thermodynamic stability. The ligand may act as bidentate NS donor for Pd(II) and Pt(II) complexes, while it seems to be bidentate NS bridging via sulphur atom for Ag(I) complex. A planar quadrangular structure is proposed for Pd(II) and Pt(II) complexes and Ag(I) complex may be a hexanuclear cluster. Their interactions with bovine serum albumin (BSA) are investigated using steady state fluorescence technology. It is observed that all of them can quench the intrinsic fluorescence of BSA through static quenching procedure. The binding constants ( KA) at different temperatures, thermodynamic parameters enthalpy changes (Δ H) and entropy changes (Δ S) between BSA and the compounds are calculated. Based on the values of Δ H and Δ S, it is judged that the main acting force of PtL 2·C 3H 6O·2H 2O with BSA may be electrostatic interaction, and for the LH 2OCH 3, Ag 6L 6 and PdL 2, hydrophobic and electrostatic interactions may be involved in their binding processes.
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Parkinson's disease and pesticides: A meta-analysis of disease connection and genetic alterations.
Ahmed, Hussien; Abushouk, Abdelrahman Ibrahim; Gabr, Mohamed; Negida, Ahmed; Abdel-Daim, Mohamed M
2017-06-01
Parkinson's disease (PD) is a globally prevalent, multifactorial disorder that occurs due to interactions between genetic and environmental factors. Observational studies have shown a link between exposure to pesticides and the risk of PD. We performed this study to systemically review published case-control studies and estimate quantitatively the association between pesticide exposure and PD. We searched Medline (through PubMed) for eligible case-control studies. The association between pesticide exposure and PD risk or occurrence of certain genetic alterations, related to the pathogenesis of PD was presented as odds ratios (OR) and pooled under the random effects model, using the statistical add-in (MetaXL, version 5.0). The pooled result showed that exposure to pesticides is linked to PD (OR 1.46, 95% CI [1.21, 1.77]), but there was a significant heterogeneity among included studies. Exposure to pesticides increased the risk of alterations in different PD pathogenesis-related genes, such as GST (OR 1.97, 95% CI [1.41, 2.76]), PON-1 (OR 1.32, 95% CI [1.09, 1.6]), MDR1 (OR 2.06, 95% CI [1.58, 2.68]), and SNCA genes (OR 1.28, 95% CI [1.02, 1.37]). There was no statistically significant association between exposure to pesticides and alteration of CYP2D6 (OR 1.19, 95% CI [0.91, 1.54]), SLC6A3 (OR 0.74, 95% CI [0.55, 1]), MnSOD (OR 1.45, 95% CI [0.97, 2.16]), NQO1 (OR 1.35, 95% CI [0.91, 2.01]), and PON-2 genes (OR 0.88, 95% CI [0.53, 1.45]). In conclusion, this meta-analysis provides evidence that pesticide exposure is significantly associated with the risk of PD and alterations in genes involved in PD pathogenesis. However, the underlying mechanism of this association and the effect of the duration of exposure or the type of pesticides should be addressed by future research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Gavrish, Sergey P; Lampeka, Yaroslaw D; Pritzkow, Hans; Lightfoot, Philip
2010-09-07
The crystal structures of the palladium(II) complexes of the open-chain and macrocyclic ligands PdL(1).3H(2)O, PdL(2).6H(2)O and PdL(3).5H(2)O have been determined (H(2)L(1) = 1,4,8,11-tetraazaundecane-5,7-dione, H(2)L(2) = 1,4,8,11-tetraazacyclotetradecane-5,7-dione, H(2)L(3) = 1,4,8,11-tetraazacyclotridecane-5,7-dione). The coordination polyhedra of the palladium(II) ions in all complexes are formed by two deprotonated amide and two amine donors with Pd-N distances being similar in PdL(1) and PdL(2) and substantially shorter in PdL(3). A detailed analysis of the (1)H NMR spectra of the macrocyclic complexes supports the formation in aqueous solution of only N-meso isomers of both compounds in agreement with the X-ray data. The spectra of the palladium(II) macrocyclic complexes are shifted downfield as a whole as compared to those of the nickel(II) analogues with the shifts being essentially non-uniform. The latter feature can be related to the differences in magnetic anisotropy of the M-N bonds. The maxima of d-d absorption bands of the palladium(II) complexes demonstrate weaker dependence on the macrocycle size as compared to those of the nickel(II) analogues. Both macrocyclic compounds PdL(2).6H(2)O and PdL(3).5H(2)O are characterized by lamellar crystal structures consisting of interleaved layers formed by macrocyclic units and by water molecules with similar metal complex layers and different 2D water sheets. A columnar crystal structure is inherent for PdL(1).3H(2)O with the water molecules present as discrete (H(2)O)(3) clusters.
Wang, Bing; Chen, Li-Hua
2016-01-01
In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain. PMID:27747105
Taşaltın, Nevin; Oztürk, Sadullah; Kılınç, Necmettin; Yüzer, Hayrettin; Oztürk, Zaferziya
2010-05-01
A vertically aligned Pd nanowire array was successfully fabricated on an Au/Ti substrate using an anodic aluminum oxide (AAO) template by a direct voltage electrodeposition method at room temperature using diluted neutral electrolyte. The fabrication of Pd nanowires was controlled by analyzing the current-time transient during electrodeposition using potentiostat. The AAO template and the Pd nanowires were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) methods and X-Ray diffraction (XRD). It was observed that the Pd nanowire array was standing freely on an Au-coated Ti substrate after removing the AAO template in a relatively large area of about 5 cm2, approximately 50 nm in diameter and 2.5 μm in length with a high aspect ratio. The nucleation rate and the number of atoms in the critical nucleus were determined from the analysis of current transients. Pd nuclei density was calculated as 3.55 × 108 cm-2. Usage of diluted neutral electrolyte enables slower growing of Pd nanowires owing to increase in the electrodeposition potential and thus obtained Pd nanowires have higher crystallinity with lower dislocations. In fact, this high crystallinity of Pd nanowires provides them positive effect for sensor performances especially.
2010-01-01
A vertically aligned Pd nanowire array was successfully fabricated on an Au/Ti substrate using an anodic aluminum oxide (AAO) template by a direct voltage electrodeposition method at room temperature using diluted neutral electrolyte. The fabrication of Pd nanowires was controlled by analyzing the current–time transient during electrodeposition using potentiostat. The AAO template and the Pd nanowires were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) methods and X-Ray diffraction (XRD). It was observed that the Pd nanowire array was standing freely on an Au-coated Ti substrate after removing the AAO template in a relatively large area of about 5 cm2, approximately 50 nm in diameter and 2.5 μm in length with a high aspect ratio. The nucleation rate and the number of atoms in the critical nucleus were determined from the analysis of current transients. Pd nuclei density was calculated as 3.55 × 108 cm−2. Usage of diluted neutral electrolyte enables slower growing of Pd nanowires owing to increase in the electrodeposition potential and thus obtained Pd nanowires have higher crystallinity with lower dislocations. In fact, this high crystallinity of Pd nanowires provides them positive effect for sensor performances especially. PMID:20596417
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ruttanapun, Chesta, E-mail: chesta.ruttanapun@gmail.com
Cu{sub (1−x)}Pd{sub (x)}FeO{sub 2} (x=0.01, 0.03 and 005) delafossite was prepared by solid state reactions and was calcined/sintered at 1050 °C. The effect of Pd{sup 2+} substitution for the Cu{sup 1+} sites on the thermoelectric and electronic properties of Cu{sub (1−x)}Pd{sub (x)}FeO{sub 2} were investigated. The crystal structure, oxygen decomposition, thermoelectric and electronic properties were characterized by X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy (XPS), Seebeck coefficient, electrical conductivity and thermal conductivity measurements. The characterization showed that Cu{sub (1−x)}Pd{sub (x)}FeO{sub 2} formed a hexagonal delafossite structure with R3−m symmetry. The existence of Pd{sup 2+}, Cu{sup 1+}, Cu{sup 2+}, Fe{sup 3+},more » Fe{sup 4+} and O was revealed from the XPS results. Confirmation of Pd{sup 2+} substitution for the Cu{sup 1+} sites occurred by increasing the c-axis in the lattice parameter with a Pd content. The O content intercalated at the center of the triangular Cu acted as a support to produce Cu{sup 2+} ions and was reduced with an increasing Pd content. The mixed valencies of Cu{sup 1+}/Cu{sup 2+} and Cu{sup 1+}/Pd{sup 2+} in the Cu layer changed the electrical conductivity and the Fe{sup 3+}/Fe{sup 4+} mixed valencies in the FeO{sub 6} layer caused the Seebeck coefficient to increase. Both the electrical conductivity and Seebeck coefficient for Pd contents of x=0.01 and 0.03 were higher than that of non-doped CuFeO{sub 2}. The low thermal conductivity of Cu{sub (1−x)}Pd{sub (x)}FeO{sub 2} resulted from the substitution of Pd, which has a large atomic mass, into structure. The Jonker plot indicated that the electronic properties displayed a degenerate density of states and that Cu{sub (1−x)}Pd{sub (x)}FeO{sub 2} was a semiconductor. A high ZT value of 0.055 was obtained for a Pd content of 0.03 at 950 K. The Pd{sup 2+} substitution for the Cu{sup 1+} sites influenced the thermoelectric and electronic properties of the delafossite Cu{sub (1−x)}Pd{sub (x)}FeO{sub 2} samples. - Graphical abstract: Cu{sub (1−x)}Pd{sub (x)}FeO{sub 2} (x=0.01, 0.03 and 005) delafossite was prepared by solid state reactions. The characterization showed that Cu{sub (1−x)}Pd{sub (x)}FeO{sub 2} formed a hexagonal delafossite structure with R3−m symmetry. The existence of Pd{sup 2+}, Cu{sup 1+}, Cu{sup 2+}, Fe{sup 3+}, Fe{sup 4+} and O was revealed from the XPS results. The O content intercalated at the center of the triangular Cu acted as a support to produce Cu{sup 2+} ions and was reduced with an increasing Pd content. The mixed valencies of Cu{sup 1+}/Cu{sup 2+} and Cu{sup 1+}/Pd{sup 2+} in the Cu layer changed the electrical conductivity and the Fe{sup 3+}/Fe{sup 4+} mixed valencies in the FeO{sub 6} layer caused the Seebeck coefficient to increase. Both the electrical conductivity and Seebeck coefficient for Pd contents of x=0.01 and 0.03 were higher than that of non-doped CuFeO{sub 2}. The low thermal conductivity of Cu{sub (1−x)}Pd{sub (x)}FeO{sub 2} resulted from the substitution of Pd, which has a large atomic mass, into structure. A high ZT value of 0.055 was obtained for a Pd content of 0.03 at 950 K. The Pd{sup 2+} substitution for the Cu{sup 1+} sites influenced the thermoelectric and electronic properties of the delafossite Cu{sub (1−x)}Pd{sub (x)}FeO{sub 2} samples. - Highlights: • New compound of Cu{sub 1−x}Pd{sub x}FeO{sub 2} (x=0.01, 0.03 and 0.05) forms phase of delafossite. • The compound displays p-type thermoelectric materials. • The Pd-substituted for Cu{sup 1+} sites forms Pd{sup 2+}. • Mixed valencies of Cu{sup +}/Cu{sup 2+}, Cu{sup +}/Pd{sup 2+} and Fe{sup 3+}/Fe{sup 4+} appear in the compound. • Large atomic mass of Pd-substituted causes low thermal conductivity.« less
NASA Astrophysics Data System (ADS)
Yang, Yonggang; Li, Donglin; Li, Chaozheng; Liu, YuFang; Jiang, Kai
2017-12-01
Researchers have proposed different effective mechanisms of hydrogen bonding (HB) on the fluorescence of 6-propionyl-2-dimethylaminonaphthalene (PRODAN) and its derivatives. Herein, excited state transition and dynamics analysis confirm that the fluorescence of PD (a derivative of PRODAN with ethyl replaced by 3-hydroxy-2,2-dimethylpropan) emits from the planar intramolecular charge transfer (PICT) state rather than twist ICT (TICT) state, because the fluorescence emission and surface hopping from the TICT state to the twist ground (T-S0) state is energy forbidden. Nevertheless, the strengthening of intramolecular-HB (intra-HB) and intermolecular-HB (inter-HB) of PD-(methanol)2 smooth the pathway of surface hopping from TICT to T-S0 state and the external conversion going to planar ground state by decreasing the energy difference of the two states. This smoothing changes the fluorescence state of PD-(methanol)2 to the TICT state in which fluorescence emission does not occur but surface hopping, leading to the partial fluorescence quenching of PD in methanol solvent. This conclusion is different from previous related reports. Moreover, the inter-HB strengthening of PD-methanol in PICT state induces the cleavage of intra-HB and a fluorescence red-shift of 54 nm compared to PD. This red-shift increases to 66 nm for PD-(methanol)2 for the strengthening of the one intra-HB and two inter-HBs. The dipole moments of PD-methanol and PD-(methanol)2 respectively increase about 10.3D and 8.1D in PICT state compared to PD. The synergistic effect of intra-HB and inter-HB induces partial quenching of PD in methanol solvent by turning on the TICT state and fluorescence red-shift. This work gives a reasonable description on the fluorescence red-shift and partial quenching of PD in methanol solvent, which will bring insight into the study of spectroscopic properties of molecules owning better spectral characteristics.
Yang, Yonggang; Li, Donglin; Li, Chaozheng; Liu, YuFang; Jiang, Kai
2017-12-05
Researchers have proposed different effective mechanisms of hydrogen bonding (HB) on the fluorescence of 6-propionyl-2-dimethylaminonaphthalene (PRODAN) and its derivatives. Herein, excited state transition and dynamics analysis confirm that the fluorescence of PD (a derivative of PRODAN with ethyl replaced by 3-hydroxy-2,2-dimethylpropan) emits from the planar intramolecular charge transfer (PICT) state rather than twist ICT (TICT) state, because the fluorescence emission and surface hopping from the TICT state to the twist ground (T-S 0 ) state is energy forbidden. Nevertheless, the strengthening of intramolecular-HB (intra-HB) and intermolecular-HB (inter-HB) of PD-(methanol) 2 smooth the pathway of surface hopping from TICT to T-S 0 state and the external conversion going to planar ground state by decreasing the energy difference of the two states. This smoothing changes the fluorescence state of PD-(methanol) 2 to the TICT state in which fluorescence emission does not occur but surface hopping, leading to the partial fluorescence quenching of PD in methanol solvent. This conclusion is different from previous related reports. Moreover, the inter-HB strengthening of PD-methanol in PICT state induces the cleavage of intra-HB and a fluorescence red-shift of 54nm compared to PD. This red-shift increases to 66nm for PD-(methanol) 2 for the strengthening of the one intra-HB and two inter-HBs. The dipole moments of PD-methanol and PD-(methanol) 2 respectively increase about 10.3D and 8.1D in PICT state compared to PD. The synergistic effect of intra-HB and inter-HB induces partial quenching of PD in methanol solvent by turning on the TICT state and fluorescence red-shift. This work gives a reasonable description on the fluorescence red-shift and partial quenching of PD in methanol solvent, which will bring insight into the study of spectroscopic properties of molecules owning better spectral characteristics. Copyright © 2017 Elsevier B.V. All rights reserved.
Oral microbiome in HIV-associated periodontitis.
Noguera-Julian, Marc; Guillén, Yolanda; Peterson, Jessica; Reznik, David; Harris, Erica V; Joseph, Sandeep J; Rivera, Javier; Kannanganat, Sunil; Amara, Rama; Nguyen, Minh Ly; Mutembo, Simon; Paredes, Roger; Read, Timothy D; Marconi, Vincent C
2017-03-01
HIV-associated periodontal diseases (PD) could serve as a source of chronic inflammation. Here, we sought to characterize the oral microbial signatures of HIV+ and HIV- individuals at different levels of PD severity.This cross-sectional study included both HIV+ and HIV- patients with varying degrees of PD. Two tooth, 2 cheek, and 1 saliva samples were obtained for microbiome analysis. Mothur/SILVADB were used to classify sequences. R/Bioconductor (Vegan, PhyloSeq, and DESeq2) was employed to assess overall microbiome structure differences and differential abundance of bacterial genera between groups. Polychromatic flow cytometry was used to assess immune activation in CD4 and CD8 cell populations.Around 250 cheek, tooth, and saliva samples from 50 participants (40 HIV+ and 10 HIV-) were included. Severity of PD was classified clinically as None/Mild (N), Moderate (M), and Severe (S) with 18 (36%), 16 (32%), and 16 (32%) participants in each category, respectively. Globally, ordination analysis demonstrated clustering by anatomic site (R2 = 0.25, P < 0.001). HIV status and PD severity showed a statistically significant impact on microbiome composition but only accounted for a combined 2% of variation. HIV+ samples were enriched in genera Abiotrophia, Neisseria, Kingella, and unclassified Neisseriaceae and depleted in Leptotrichia and Selenomonas. The Neisseria genus was consistently enriched in HIV+ participants regardless of sampling site and PD level. Immune markers were altered in HIV+ participants but did not show association with the oral microbiome.HIV-associated changes in oral microbiome result in subtle microbial signatures along different stages of PD that are common in independent oral anatomic sites.
Oral microbiome in HIV-associated periodontitis
Noguera-Julian, Marc; Guillén, Yolanda; Peterson, Jessica; Reznik, David; Harris, Erica V.; Joseph, Sandeep J.; Rivera, Javier; Kannanganat, Sunil; Amara, Rama; Nguyen, Minh Ly; Mutembo, Simon; Paredes, Roger; Read, Timothy D.; Marconi, Vincent C.
2017-01-01
Abstract HIV-associated periodontal diseases (PD) could serve as a source of chronic inflammation. Here, we sought to characterize the oral microbial signatures of HIV+ and HIV– individuals at different levels of PD severity. This cross-sectional study included both HIV+ and HIV– patients with varying degrees of PD. Two tooth, 2 cheek, and 1 saliva samples were obtained for microbiome analysis. Mothur/SILVADB were used to classify sequences. R/Bioconductor (Vegan, PhyloSeq, and DESeq2) was employed to assess overall microbiome structure differences and differential abundance of bacterial genera between groups. Polychromatic flow cytometry was used to assess immune activation in CD4 and CD8 cell populations. Around 250 cheek, tooth, and saliva samples from 50 participants (40 HIV+ and 10 HIV–) were included. Severity of PD was classified clinically as None/Mild (N), Moderate (M), and Severe (S) with 18 (36%), 16 (32%), and 16 (32%) participants in each category, respectively. Globally, ordination analysis demonstrated clustering by anatomic site (R2 = 0.25, P < 0.001). HIV status and PD severity showed a statistically significant impact on microbiome composition but only accounted for a combined 2% of variation. HIV+ samples were enriched in genera Abiotrophia, Neisseria, Kingella, and unclassified Neisseriaceae and depleted in Leptotrichia and Selenomonas. The Neisseria genus was consistently enriched in HIV+ participants regardless of sampling site and PD level. Immune markers were altered in HIV+ participants but did not show association with the oral microbiome. HIV-associated changes in oral microbiome result in subtle microbial signatures along different stages of PD that are common in independent oral anatomic sites. PMID:28328799
Shin, Su-Jin; Jeon, Yoon Kyung; Cho, Yong Mee; Lee, Jae-Lyun; Chung, Doo Hyun; Park, Ji Young
2015-01-01
Background. Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are used as the first-line treatment for patients with metastatic clear cell renal cell carcinoma (mCCRCC). Recently, programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) blockade emerged as promising therapy for renal cell carcinoma. However, the expression pattern and prognostic implication of programmed death-ligands (PD-Ls) in mCCRCC patients receiving VEGF-TKI remain unclear. Patients and Methods. PD-L1 and PD-L2 expression in tumor cells and the quantities of PD-1+ tumor-infiltrating lymphocytes were immunohistochemically evaluated in 91 mCCRCC patients treated with VEGF-TKI, and their associations with VEGF-TKI responsiveness and clinical outcome were analyzed. Results. PD-L1 immunopositivity was observed in 17.6% and significantly associated with a high International Society of Urological Pathology grade (p = .031) and sarcomatoid features (p = .014). PD-L2 immunopositivity was observed in 39.6% and was not associated with any of the assessed clinicopathological variables. PD-L1-positive cases showed poor VEGF-TKI responsiveness (p = .012) compared with PD-L1-negative cases. In univariate survival analysis, PD-L1 immunopositivity was significantly associated with shorter overall survival (OS) (p = .037) and progression-free survival (PFS) (p = .043). Multivariate survival analysis revealed that PD-L1 expression was independently associated with poor OS (p = .038) and PFS (p = .013) in addition to tumor necrosis (p = .006; p = .029, respectively) and Memorial Sloan Kettering Cancer Center score (p = .018; p = .032, respectively). PD-L2 expression was neither associated with VEGF-TKI responsiveness nor patients’ outcome. Conclusion. PD-L1 expression was significantly related to lack of VEGF-TKI responsiveness and independently associated with shorter survival in mCCRCC patients after VEGF-TKI treatment. PD-L1 may have a predictive and prognostic value for determining the value of VEGF-TKI treatment in patients with mCCRCC. Implications for Practice: Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are essential for the treatment of metastatic renal cell carcinoma patients, but the treatment suffers from a lack of predictive markers. This study demonstrates that PD-L1 expression is a predictor for unfavorable response to VEGF-TKI and a prognostic indicator for poor overall survival and progression-free survival in patients with metastatic clear cell renal cell carcinoma receiving VEGF-TKI. PMID:26424759
NASA Astrophysics Data System (ADS)
Härter Vaniel, Ana Paula; Mauro, Antonio Eduardo; de Godoy Netto, Adelino Vieira; de Almeida, Eduardo Tonon; Piquini, Paulo Cesar; Zambiazi, Priscilla; Back, Davi Fernando; Hörner, Manfredo
2015-03-01
The reaction of [Pd{dmba}(μ-N3)]2 (dmba = N,N-dimethylbenzylamine) with 1-(2-fluorophenyl)-3-(4-nitrophenyl)triazenido (L1) or 1,3-bis(4-nitrophenyl)triazenido (L2) anions, in methanol, and subsequent treatment with pyridine (py) allows the preparation of the corresponding cyclopalladated compounds [Pd(dmba)(L1)(py)] (1) and [Pd(dmba)(L2)(py)]ṡpy (2). The acentric mononuclear entities of (1) and (2) are connected by weak intermolecular non-classical Csbnd H⋯C hydrogen bonds, which results in 2-D arrangements by translation, along the [1 0 0] and [0 0 1] crystallographic directions, respectively.
Shi, Danfeng; Zhou, Shuangyan; Liu, Xuewei; Zhao, Chenxi; Liu, Huanxiang; Yao, Xiaojun
2018-03-01
The inhibitors blocking the interaction between programmed cell death protein 1(PD-1) and programmed death-ligand 1(PD-L1) can activate the immune response of T cell and eliminate cancer cells. The crystallographic studies have provided structural insights of the interactive interfaces between PD-L1 and its protein ligands. However, the hotspot residues on PD-L1 as well as structural and energetic basis for different protein ligands still need to be further investigated. Molecular modeling methods including molecular dynamics simulation, per-residue free energy decomposition, virtual alanine scanning mutagenesis and residue-residue contact analysis were used to qualitatively and quantitatively analyze the interactions between PD-L1 and different protein ligands. The results of virtual alanine scanning mutagenesis suggest that Y56, Q66, M115, D122, Y123, R125 are the hotspot residues on PD-L1. The residue-residue contact analysis further shows that PD-1 interacts with PD-L1 mainly by F and G strands while monoclonal antibodies like avelumab and BMS-936559 mainly interact with PD-L1 by CDR2 and CDR3 loops of the heavy chain. A structurally similar β-hairpin peptide with 13 or 14 residues was extracted from each protein ligand and these β-hairpin peptides were found tightly binding to the putative hotspot residues on PD-L1. This study recognizes the hotspot residues on PD-L1 and uncovers the common structural and energetic basis of different protein ligands binding to PD-L1. These results will be valuable for the design of small molecule or peptide inhibitors targeting on PD-L1. Copyright © 2017 Elsevier B.V. All rights reserved.
An alternative to hydrogenation processes. Electrocatalytic hydrogenation of benzophenone.
Mozo Mulero, Cristina; Sáez, Alfonso; Iniesta, Jesús; Montiel, Vicente
2018-01-01
The electrocatalytic hydrogenation of benzophenone was performed at room temperature and atmospheric pressure using a polymer electrolyte membrane electrochemical reactor (PEMER). Palladium (Pd) nanoparticles were synthesised and supported on a carbonaceous matrix (Pd/C) with a 28 wt % of Pd with respect to carbon material. Pd/C was characterised by transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). Cathodes were prepared using Pd electrocatalytic loadings (L Pd ) of 0.2 and 0.02 mg cm -2 . The anode consisted of hydrogen gas diffusion for the electrooxidation of hydrogen gas, and a 117 Nafion exchange membrane acted as a cationic polymer electrolyte membrane. Benzophenone solution was electrochemically hydrogenated in EtOH/water (90/10 v/v) plus 0.1 M H 2 SO 4 . Current densities of 10, 15 and 20 mA cm -2 were analysed for the preparative electrochemical hydrogenation of benzophenone and such results led to the highest fractional conversion (X R ) of around 30% and a selectivity over 90% for the synthesis of diphenylmethanol upon the lowest current density. With regards to an increase by ten times the Pd electrocatalytic loading the electrocatalytic hydrogenation led neither to an increase in fractional conversion nor to a change in selectivity.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thakur, Gautam
A data-driven realistic design and evalua- tion of vehicular mobility has been particularly chal- lenging due to a lack of large-scale real-world mea- surements in the research community. Current research methodologies rely on articial scenarios, random con- nectivity, and use small and biased samples. In this pa- per, we perform a combined study to learn the struc- ture and connectivity of urban streets and modeling and characterization of vehicular trac densities on them. Our dataset is a collection of more than 222 thousand routes and 25 million vehicular mobility images from 1091 online web cameras located in six dierent re-more » gions of the world. Our results centered around four major observations: i. study shows that driving routes and visiting locations of regions demonstrate power-law distribution, indicating a planned or recently designed road infrastructure; ii. we represent regions by network graphs in which nodes are camera locations and edges are urban streets that connect the nodes. Such represen- tation exhibits small world properties with short path lengths and large clustering coecient; iii. trac densi- ties show 80% temporal correlation during several hours of a day; iv. modeling trac densities against known theoretical distributions show less than 5% deviation for heavy-trailed models such as log-logistic and log- gamma distributions. We believe this work will provide a much-needed contribution to the research community for design and evaluation of future vehicular networks and smart cities.« less
Effect of PdO on TiO(sub2) Loading on Chemochromic Detection of Hydrogen
NASA Technical Reports Server (NTRS)
Mohajeri, Nahid; T-Rassisi, Ali; Bokerman, Gary; Captain, Janine E.; Peterson, Barbara V.; Whitten, Mary; Berger, Cristina
2007-01-01
Safety is always a concern in all applications that utilize hydrogen (H(sub2)) in one form or the other. Hydrogen leaks are invisible and odorless. In addition, blending odorants or additives into hydrogen in a manner similar to natural gas is generally undesirable for certain applications including proton exchange membrane fuel cells. To facilitate detection of the location of hydrogen leaks, a special chemochromic H(sub2) sensing material that employs titania (Ti0(sub2)) supported palladium oxide (PdO) pigments encapsulated within a special silicone matrix has been developed at the Florida Solar Energy Center (FSEC). Several batches of PdO H(sub2) sensing pigments were synthesized using various Ti0(sub2) supports and their hydrogen detection activity determined. TEM and Particle size distribution analysis showed that smaller particles with hemispherical crystalline structure produced faster coloration kinetics when exposed to H(sub2) gas. However, uniformly distributed PdO particles on the Ti0(sub2) surface displayed greater color contrast, quantified by delta epsilon measurements. XRD analysis indicated that the crystalline phase of Ti0(sub2) had no effect on the chemochromic performance of the pigments in laboratory environment.
ATP13A2 variability in Parkinson disease
Vilariño-Güell, Carles; Soto, Alexandra I.; Lincoln, Sarah J.; Yahmed, Samia Ben; Kefi, Mounir; Heckman, Michael G.; Hulihan, Mary M.; Chai, Hua; Diehl, Nancy N.; Amouri, Rim; Rajput, Alex; Mash, Deborah C.; Dickson, Dennis W.; Middleton, Lefkos T.; Gibson, Rachel A.; Hentati, Faycal; Farrer, Matthew J.
2008-01-01
Recessively inherited mutations in ATP13A2 result in Kufor-Rakeb syndrome, whereas genetic variability and elevated ATP13A2 expression have been implicated in Parkinson disease (PD). Given this background, ATP13A2 was comprehensively assessed to support or refute its contribution to PD. Sequencing of ATP13A2 exons and intron-exon boundaries was performed in 89 probands with familial parkinsonism from Tunisia. The segregation of mutations with parkinsonism was subsequently assessed within pedigrees. The frequency of genetic variants and evidence for association was also examined in 240 patients with non-familial PD and 372 healthy controls. ATP13A2 mRNA expression was also quantified in brain tissues from 38 patients with non-familial PD and 38 healthy subjects from the US. Sequencing analysis revealed 37 new variants; seven missense, six silent and 24 that were noncoding. However, no single ATP13A2 mutation segregated with familial parkinsonism in either a dominant or recessive manner. Four markers showed marginal association with non-familial PD, prior to correction for multiple testing. ATP13A2 mRNA expression was marginally decreased in PD brains compared with tissue from control subjects. In conclusion, neither ATP13A2 genetic variability nor quantitative gene expression in brain appears to contribute to familial parkinsonism or non-familial PD. PMID:19085912
DOE Office of Scientific and Technical Information (OSTI.GOV)
Luan, Xin; Gao, Yun-Ge; Guan, Ying-Yun
2014-11-15
Platycodin D (PD) is an active component mainly isolated from the root of Platycodon grandiflorum. Recent studies proved that PD exhibited inhibitory effect on proliferation, migration, invasion and xenograft growth of diverse cancer cell lines. However, whether PD is suppressive for angiogenesis, an important hallmark in cancer development, remains unknown. Here, we found that PD could dose-dependently inhibit human umbilical vein endothelial cell (HUVEC) proliferation, motility, migration and tube formation. PD also significantly inhibited angiogenesis in the chick embryo chorioallantoic membrane (CAM). Moreover, the antiangiogenic activity of PD contributed to its in vivo anticancer potency shown in the decreased microvesselmore » density and delayed growth of HCT-15 xenograft in mice with no overt toxicity. Western blot analysis indicated that PD inhibited the phosphorylation of VEGFR2 and its downstream protein kinase including PLCγ1, JAK2, FAK, Src, and Akt in endothelial cells. Molecular docking simulation showed that PD formed hydrogen bonds and hydrophobic interactions within the ATP binding pocket of VEGFR2 kinase domain. The present study firstly revealed the high antiangiogenic activity and the underlying molecular basis of PD, suggesting that PD may be a potential antiangiogenic agent for angiogenesis-related diseases. - Highlights: • Platycodin D inhibits HUVEC proliferation, motility, migration and tube formation. • Platycodin D inhibits the angiogenesis in chick embryo chorioallantoic membrane. • Platycodin D suppresses the angiogenesis and growth of HCT-15 xenograft in mice. • Platycodin D inhibits the phosphorylation of VEGFR2 and downstream kinases in HUVEC.« less
Skinner, James E; Meyer, Michael; Dalsey, William C; Nester, Brian A; Ramalanjaona, George; O’Neil, Brian J; Mangione, Antoinette; Terregino, Carol; Moreyra, Abel; Weiss, Daniel N; Anchin, Jerry M; Geary, Una; Taggart, Pamela
2008-01-01
Heart rate variability (HRV) reflects both cardiac autonomic function and risk of sudden arrhythmic death (AD). Indices of HRV based on linear stochastic models are independent risk factors for AD in postmyocardial infarction (MI) cohorts. Indices based on nonlinear deterministic models have a higher sensitivity and specificity for predicting AD in retrospective data. A new nonlinear deterministic model, the automated Point Correlation Dimension (PD2i), was prospectively evaluated for prediction of AD. Patients were enrolled (N = 918) in 6 emergency departments (EDs) upon presentation with chest pain and being determined to be at risk of acute MI (AMI) >7%. Brief digital ECGs (>1000 heartbeats, ∼15 min) were recorded and automated PD2i results obtained. Out-of-hospital AD was determined by modified Hinkle-Thaler criteria. All-cause mortality at 1 year was 6.2%, with 3.5% being ADs. Of the AD fatalities, 34% were without previous history of MI or diagnosis of AMI. The PD2i prediction of AD had sensitivity = 96%, specificity = 85%, negative predictive value = 99%, and relative risk >24.2 (p ≤ 0.001). HRV analysis by the time-dependent nonlinear PD2i algorithm can accurately predict risk of AD in an ED cohort and may have both life-saving and resource-saving implications for individual risk assessment. PMID:19209249
TU-AB-BRC-08: Egs-brachy, a Fast and Versatile Monte Carlo Code for Brachytherapy Applications
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chamberland, M; Taylor, R; Rogers, D
2016-06-15
Purpose: To introduce egs-brachy, a new, fast, and versatile Monte Carlo code for brachytherapy applications. Methods: egs-brachy is an EGSnrc user-code based on the EGSnrc C++ class library (egs++). Complex phantom, applicator, and source model geometries are built using the egs++ geometry module. egs-brachy uses a tracklength estimator to score collision kerma in voxels. Interaction, spectrum, energy fluence, and phase space scoring are also implemented. Phase space sources and particle recycling may be used to improve simulation efficiency. HDR treatments (e.g. stepping source through dwell positions) can be simulated. Standard brachytherapy seeds, as well as electron and miniature x-ray tubemore » sources are fully modelled. Variance reduction techniques for electron source simulations are implemented (Bremsstrahlung cross section enhancement, uniform Bremsstrahlung splitting, and Russian Roulette). TG-43 parameters of seeds are computed and compared to published values. Example simulations of various treatments are carried out on a single 2.5 GHz Intel Xeon E5-2680 v3 processor core. Results: TG-43 parameters calculated with egs-brachy show excellent agreement with published values. Using a phase space source, 2% average statistical uncertainty in the PTV ((2mm){sup 3} voxels) can be achieved in 10 s for 100 {sup 125}I or {sup 103}Pd seeds in a 36.2 cm{sup 3} prostate PTV, 31 s for 64 {sup 103}Pd seeds in a 64 cm{sup 3} breast PTV, and 56 s for a miniature x-ray tube in a 27 cm{sup 3} breast PTV. Comparable uncertainty is reached in 12 s in a (1 mm){sup 3} water voxel 5 mm away from a COMS 16mm eye plaque with 13 {sup 103}Pd seeds. Conclusion: The accuracy of egs-brachy has been demonstrated through benchmarking calculations. Calculation times are sufficiently fast to allow full MC simulations for routine treatment planning for diverse brachytherapy treatments (LDR, HDR, miniature x-ray tube). egs-brachy will be available as free and open-source software to the medical physics research community. This work is partially funded by the Canada Research Chairs program, the Natural Sciences and Engineering Research Council of Canada, and the Ontario Ministry of Research and Innovation (Ontario Early Researcher Award).« less
NASA Astrophysics Data System (ADS)
Rajegowda, H. R.; Kumar, P. Raghavendra; Hosamani, Amar; Butcher, R. J.; Naveen, S.; Lokanath, N. K.
2018-03-01
A new chiral Schiff base ligand 2-{N-[(2S)-(1-hydroxy-3-phenylpropan-2-yl]ethanimidoyl} phenol ((S)sbnd H2L) was obtained by acid catalyzed condensation of (2S)-(-)-2-amino-3-phenyl-1-propanol with 2‧-hydroxyacetophenone. The palladium complex was prepared by treating a solution of (S)sbnd H2L in acetone with a solution of Na2PdCl4 in water in 1:1 M ratio. The new ligand and its complex were characterized by FT-IR, 1H, 13C{1H} NMR spectroscopy, polarimetry and elemental analysis and their molecular structures were determined by single crystal X-ray diffraction. Both the compounds crystallizes in monoclinic system in the space group P21. There exists an intra [Osbnd H ⋯N (1.62(5) Å)] and intermolecular [Osbnd H ⋯O (1.53(5) Å) and Csbnd H ⋯O (2.59 Å)] hydrogen bonding and secondary interactions in the crystal of (S)sbnd H2L. The structure of the palladium complex was found very interesting wherein the ligand coordinated to metal center as tridentate dianionic (O-, N, O-) fashion, (S)-L, resulting in a tetranuclear palladium cluster, [Pd4((S)-L)4]. In these supramolecular structures phenolate oxygen coordinated to Pd(II) ion as Pdsbnd O terminal bonds [1.934(12) - 1.977(11) Å] and the alkoxide oxygen coordinated as Pdsbnd Osbnd Pd bridging bonds [1.993(11) - 2.012(12) Å]. The Pdsbnd N bond lengths found were in the range of 1.949(13) to 1.919(12) Å. There exists two asymmetric tetranuclear complex molecules in its crystal lattice. There exists very strong metal-metal bond interaction, Pd(2)sbnd Pd(3) [3.0410(18) Å] and Pd(6)sbnd Pd(7) [3.0517(19) Å] respectively in the two asymmetric units.
Partial discharge detection and analysis in low pressure environments
NASA Astrophysics Data System (ADS)
Liu, Xin
Typical aerospace vehicles (aircraft and spacecraft) experience a wide range of operating pressures during ascending and returning to earth. Compared to the sea-level atmospheric pressure (760 Torr), the pressure at about 60 km altitude is 2 Torr. The performance of the electric power system components of the aerospace vehicles must remain reliable even under such sub-atmospheric operating conditions. It is well known that the dielectric strength of gaseous insulators, while the electrode arrangement remains unchanged, is pressure dependent. Therefore, characterization of the performance and behavior of the electrical insulation in flight vehicles in low-pressure environments is extremely important. Partial discharge testing is one of the practical methods for evaluating the integrity of electrical insulation in aerospace vehicles. This dissertation describes partial discharge (PD) measurements performed mainly with 60 Hz ac energization in air, argon and helium, for pressures between 2 and 760 Torr. Two main electrode arrangements were used. One was a needle-plane electrode arrangement with a Teflon insulating barrier. The other one was a twisted pair of insulated conductors taken from a standard aircraft wiring harness. The measurement results are presented in terms of typical PD current pulse waveforms and waveform analysis for both main electrode arrangements. The evaluation criteria are the waveform polarity, magnitude, shape, rise time, and phase angle (temporal location) relative to the source voltage. Two-variable histograms and statistical averages of the PD parameters are presented. The PD physical mechanisms are analyzed. For PD pattern recognition, both statistical methods (such as discharge parameter dot pattern representation, discharge parameter phase distribution, statistical operator calculations, and PD fingerprint development) and wavelet transform applications are investigated. The main conclusions of the dissertation include: (1) The PD current pulse waveforms are dependent on the pressure. (2) The rise time of the waveform is another effective PD current pulse characteristic indicator. (3) PD fingerprint patterns that are already available for atmospheric pressure (760 Torr) conditions are inadequate for the evaluation of PD pulses at low pressures. (4) Various wavelet transform techniques can be used effectively for PD pulse signal denoising purposes, and for PD pulse waveform transient feature recognition.
COX-2 expression positively correlates with PD-L1 expression in human melanoma cells.
Botti, Gerardo; Fratangelo, Federica; Cerrone, Margherita; Liguori, Giuseppina; Cantile, Monica; Anniciello, Anna Maria; Scala, Stefania; D'Alterio, Crescenzo; Trimarco, Chiara; Ianaro, Angela; Cirino, Giuseppe; Caracò, Corrado; Colombino, Maria; Palmieri, Giuseppe; Pepe, Stefano; Ascierto, Paolo Antonio; Sabbatino, Francesco; Scognamiglio, Giosuè
2017-02-23
The resistance to PD-1/PD-L1 inhibitors for the treatment of melanoma have prompted investigators to implement novel clinical trials which combine immunotherapy with different treatment modalities. Moreover is also important to investigate the mechanisms which regulate the dynamic expression of PD-L1 on tumor cells and PD-1 on T cells in order to identify predictive biomarkers of response. COX-2 is currently investigated as a major player of tumor progression in several type of malignancies including melanoma. In the present study we investigated the potential relationship between COX-2 and PD-L1 expression in melanoma. Tumor samples obtained from primary melanoma lesions and not matched lymph node metastases were analyzed for both PD-L1 and COX-2 expression by IHC analysis. Status of BRAF and NRAS mutations was analyzed by sequencing and PCR. Co-localization of PD-L1 and COX-2 expression was analyzed by double fluorescence staining. Lastly the BRAF V600E A375 and NRAS Q61R SK-MEL-2 melanoma cell lines were used to evaluate the effect of COX-2 inhibition by celecoxib on expression of PD-L1 in vitro. BRAF V600E/V600K and NRAS Q61R/Q61L were detected in 57.8 and 8.9% of the metastatic lesions, and in 65.9 and 6.8% of the primary tumors, respectively. PD-L1 and COX-2 expression were heterogeneously expressed in both primary melanoma lesions and not matched lymph node metastases. A significantly lower number of PD-L1 negative lesions was found in primary tumors as compared to not matched metastatic lesions (P = 0.002). COX-2 expression significantly correlated with PD-L1 expression in both primary (P = 0.001) and not matched metastatic (P = 0.048) lesions. Furthermore, in melanoma tumors, cancer cells expressing a higher levels of COX-2 also co-expressed a higher level of PD-L1. Lastly, inhibition of COX-2 activity by celecoxib down-regulated the expression of PD-L1 in both BRAF V600E A375 and NRAS Q61R SK-MEL-2 melanoma cell lines. COX-2 expression correlates with and modulates PD-L1 expression in melanoma cells. These findings have clinical relevance since they provide a rationale to implement novel clinical trials to test COX-2 inhibition as a potential treatment to prevent melanoma progression and immune evasion as well as to enhance the anti-tumor activity of PD-1/PD-L1 based immunotherapy for the treatment of melanoma patients with or without BRAF/NRAS mutations.
Pizarro, Carolina; García-Díaz, Diego F; Codner, Ethel; Salas-Pérez, Francisca; Carrasco, Elena; Pérez-Bravo, Francisco
2014-11-01
Type 1 diabetes (T1D) has a complex etiology in which genetic and environmental factors are involved, whose interactions have not yet been completely clarified. In this context, the role in PD-1 pathway and its ligands 1 and 2 (PD-L1 and PD-L2) have been proposed as candidates in several autoimmune diseases. The aim of this work was to determine the allele and haplotype frequency of six gene polymorphisms of PD-ligands (PD-L1 and PD-L2) in Chilean T1D patients and their effect on serum levels of PD-L1 and autoantibody profile (GAD65 and IA2). This study cohort comprised 205 T1D patients and 205 normal children. We performed genotypic analysis of PD-L1 and PD-L2 genes by TaqMan method. Determination of anti-GAD65 and anti-IA-2 autoantibodies was performed by ELISA. The PD-L1 serum levels were measured. The allelic distribution of PD-L1 variants (rs2297137 and rs4143815) showed differences between T1D patients and controls (p = 0.035 and p = 0.022, respectively). No differences were detected among the PD-L2 polymorphisms, and only the rs16923189 showed genetic variation. T1D patients showed decreased serum levels of PD-L1 compared to controls: 1.42 [0.23-7.45] ng/mL versus 3.35 [0.49-5.89] ng/mL (p < 0.025). In addition, the CGG haplotype in PD-L1 associated with T1D (constructed from rs822342, rs2297137 and rs4143815 polymorphisms) showed an OR = 1.44 [1.08 to 1.93]. Finally, no association of these genetic variants was observed with serum concentrations of PD ligands or auto-antibody profile, although a correlation between PD-L1 ligand serum concentration and the age at disease onset was detected. Two polymorphism of PD-L1 are presented in different allelic variants between T1D and healthy subjects, also PDL-1 serum levels are significantly lowered in diabetics patients. Moreover, the age of onset of the disease determine differences between serum ligand levels in diabetics, being lower in younger. These results points to a possible establishment of PDL-1 as a genetic and biochemical marker for T1D onset, at least in Chilean population. Copyright © 2014 John Wiley & Sons, Ltd.
Dane, Andrew B; Teh, Elaine; Reckelhoff, Kenneth E; Ying, Pee Kui
2017-09-01
The aim of this study was to investigate if there were differences in the two-point discrimination (2-PD) of fingers among students at different stages of a chiropractic program. This study measured 2-PD thresholds for the dominant and nondominant index finger and dominant and nondominant forearm in groups of students in a 4-year chiropractic program at the International Medical University in Kuala Lumpur, Malaysia. Measurements were made using digital calipers mounted on a modified weighing scale. Group comparisons were made among students for each year of the program (years 1, 2, 3, and 4). Analysis of the 2-PD threshold for differences among the year groups was performed with analysis of variance. The mean 2-PD threshold of the index finger was higher in the students who were in the higher year groups. Dominant-hand mean values for year 1 were 2.93 ± 0.04 mm and 1.69 ± 0.02 mm in year 4. There were significant differences at finger sites (P < .05) among all year groups compared with year 1. There were no significant differences measured at the dominant forearm between any year groups (P = .08). The nondominant fingers of the year groups 1, 2, and 4 showed better 2-PD compared with the dominant finger. There was a significant difference (P = .005) between the nondominant (1.93 ± 1.15) and dominant (2.27 ± 1.14) fingers when all groups were combined (n = 104). The results of this study demonstrated that the finger 2-PD of the chiropractic students later in the program was more precise than that of students in the earlier program. Copyright © 2017. Published by Elsevier Inc.
Sui, Jiang-Dong; Wang, Ying; Wan, Yue; Wu, Yong-Zhong
2018-01-01
Programmed cell death-1 (PD-1) inhibitor-related hematologic toxicities are a category of rare but clinically serious and potentially life-threatening adverse events; however, little is known about their risks across different treatment regimens and tumor types. The objective of this study was to compare the incidences of PD-1 inhibitor-related hematologic toxicities among different therapeutic regimens and tumor types. Twenty-six original articles on PD-1 inhibitor trials were identified based on a PubMed search completed on September 26, 2017. The incidences of hematologic toxicities were collected. A total of 26 studies containing 5,088 patients were included in the meta-analysis. PD-1 inhibitor monotherapy was associated with an increased risk of all-grade anemia in cancer patients (5%, 95% CI 4%-6%), particularly in patients with renal cell carcinoma (RCC) (8%, 95% CI 6%-12%), compared with all-grade thrombocytopenia (2%, 95% CI 1%-5%), leukopenia (2%, 95% CI 1%-3%), and neutropenia (1%, 95% CI 0-1%). However, low incidences of high-grade hematologic toxicities were observed in cancer patients treated with PD-1 inhibitor monotherapy. The use of PD-1 inhibitors in combination with ipilimumab, peptide vaccines, or chemotherapy had significantly higher risks than PD-1 inhibitor monotherapy for all-grade anemia (13%, 95% CI 5%-31%), thrombocytopenia (6%, 95% CI 2%-18%), leukopenia (5%, 95% CI 1%-35%), neutropenia (4%, 95% CI 1%-26%), and only high-grade thrombocytopenia (4%, 95% CI 1%-15%). In addition, all-grade and high-grade hematologic toxicities in chemotherapy and everolimus treatment arms were more frequent than in PD-1 inhibitor monotherapy arms. The risks of PD-1 inhibitor-related hematologic toxicities were higher in RCC than in other cancers, and during combination therapy. These results may contribute toward enhancing awareness among clinicians about frequent clinical monitoring when managing PD-1 inhibitors.
NASA Astrophysics Data System (ADS)
Celani, Francesco; Spallone, A.; Righi, E.; Trenta, G.; Catena, C.; D'Agostaro, G.; Quercia, P.; Andreassi, V.; Marini, P.; di Stefano, V.; Nakamura, M.; Mancini, A.; Sona, P. G.; Fontana, F.; Gamberale, L.; Garbelli, D.; Celia, E.; Falcioni, F.; Marchesini, M.; Novaro, E.; Mastromatteo, U.
2006-02-01
In the framework of cold fusion studies one of the most important parameters is the deuterium (D) to palladium (Pd) ratio, D/Pd. It is well known that the value of this parameter is related to the normalised resistivity (R/R0) of the D-Pd system. When at high D/Pd ratios (i.e. at low R/R0 values) some excess heat occurs, the Pd wire temperature increase and, as a consequence, the apparent R/R0 value also increases. This effect might give raise to ambiguous data interpretation: similar results are in fact expected in case of a Pd wire degassing (i.e. decreasing of D/Pd ratio). To solve this problem, we developed an innovative procedure and a suitable experimental set-up for the in situ measurement of the Resistive Temperature Coefficient (which is affected only by the real D/Pd ratio) during electrolysis. We will report the results on the hydrogen and deuterium loading of thin (50 μm), and long (60cm) Pd wires, immersed in a solution of C2H5OD (or C2H5OH) and D2O (or H2O), with addition of thorium (Th) and mercury (Hg) salts at micromolar concentrations. Evidence of "transmutations" of some elements occasionally present on the Pd surface, and sometimes also in the electrolytic solution, have often been claimed in cold fusion experiments. In the present work, unexpected elements have been detected by high-resolution ICP-MS analysis. Some of these elements have also an isotopic composition different from the natural one.
NASA Astrophysics Data System (ADS)
Ahmad, Saeed; Nadeem, Shafqat; Anwar, Aneela; Hameed, Abdul; Tirmizi, Syed Ahmed; Zierkiewicz, Wiktor; Abbas, Azhar; Isab, Anvarhusein A.; Alotaibi, Mshari A.
2017-08-01
Palladium(II) cyanide complexes of thioamides (or thiones) having the general formula PdL2(CN)2, where L = Thiourea (Tu), Methylthiourea (Metu), N,N‧-Dimethylthiourea (Dmtu), Tetramethylthiourea (Tmtu), 2-Mercaptopyridine (Mpy) and 2-Mercaptopyrimidine (Mpm) were prepared by reacting K2[PdCl4] with potassium cyanide and thioamides in the molar ratio of 1:2:2. The complexes were characterized by elemental analysis, thermal and spectroscopic methods (IR, 1H and 13C NMR). The structures of three of the complexes were predicted by DFT calculations. The appearance of a band around 2100 cm-1 in IR and resonances around 120-130 ppm in the 13C NMR spectra indicated the coordination of cyanide to palladium(II). More than one resonances were observed for CN- carbon atoms in 13C NMR indicating the existence of equilibrium between different species in solution. DFT calculations revealed that in the case of the palladium(II) complex of Tmtu, the ionic dinuclear [Pd(Tmtu)4][Pd(CN)4] form was more stable than the dimer of mononuclear complex [Pd(Tmtu)2(CN)2] by 0.91 kcal mol-1, while for the complexes of Tu or Mpy ligands, the nonionic [Pd(L)2(CN)2] forms were more stable than the corresponding [Pd(L)4][Pd(CN)4] complexes by 1.26 and 6.49 kcal mol-1 for L = Tu and Mpy, respectively. The complexes were screened for antibacterial effects and some of them showed significant activities against both gram positive as well as gram negative bacteria.
NASA Astrophysics Data System (ADS)
Dutta, Abhijit; Mondal, Achintya; Broekmann, Peter; Datta, Jayati
2017-09-01
The designing and fabrication of economically viable electro-catalysts for ethanol oxidation reaction (EOR) in direct ethanol fuel cell (DEFC) has been one of the challenging issues over the decades. The present work deals with controlled synthesis of Pd coupled Au nano structure, as the non Pt group of catalysts for DEFC. The catalytic proficiency of bimetallic NPs (2-10 nm) are found to be strongly dependent on the Pd:Au ratio. The over voltage of EOR is considerably reduced by ∼260 mV with 33% of Au content in PdAu composition compared to Pd alone, demonstrating the beneficial role of Au and/or its surface oxides providing oxygen species at much lower potentials compared to Pd. The catalysts are further subjected to electrochemical analysis through voltammetry along with the temperature study on activation parameters. The quantitative determination of EOR products during the electrolysis is carried out by ion chromatographic analysis; vis-a-vis the coulombic efficiency of the product yield were derived from each of the compositions. Furthermore, a strong correlation among catalytic performances and bimetallic composition is established by screening the catalysts in an in-house fabricated direct ethanol anion exchange membrane fuel cell, DE(AEM)FC. The performance testing demonstrates outstanding increase of peak power density (∼40 mWcm-2, 93%) for the best accomplishment Au (33%) covered Pd (67%) catalyst in comparison with the monometallic Pd.
Takashima, Yasuo; Kawaguchi, Atsushi; Kanayama, Tomohiko; Hayano, Azusa; Yamanaka, Ryuya
2018-04-10
Common cancer treatments include radiation therapy, chemotherapy including molecular targeted drugs and anticancer drugs, and surgical treatment. Recent studies have focused on investigating the mechanisms by which immune cells attack cancer cells and produce immune tolerance-suppressing cytokines, as well as on their potential application in cancer immunotherapy. We conducted expression profiling of CD274 ( PD-L1 ), GATA3, IFNG, IL12R, IL12RB2, IL4, PDCD1 ( PD-1 ), PDCD1LG2 ( PD-L2 ), and TBX21 ( T-bet ) using data of 158 glioblastoma multiforme (GBM) patients with clinical information available at The Cancer Genome Atlas. Principal component analysis of the expression profiling data was used to derive an equation for evaluating the status of Th1 and Th2 cells. GBM specimens were divided based on the median of the Th scores. The results revealed that Th1 High Th2 Low and Th1 Low Th2 Low statuses indicated better prognosis than Th1 High Th2 High , and were evaluated based on the downregulation of PD-L1, PD-L2, and PD-1. Furthermore, Th2 Low divided based on the threshold, as well as CD274 Low and PDCD1 Low , were associated with good prognosis. In the Th2 Low subgroup, 14 genes were identified as potential prognostic markers. Of these, SLC11A1 Low , TNFRSF1B Low , and LTBR Low also indicated good prognosis. These results suggest that low Th2 balance and low activity of the PD-L1/PD-1 axis predict good prognosis in GBM. The set of genes identified in the present study could reliably predict survival in GBM patients and serve as useful molecular markers. Furthermore, this set of genes could prove to be novel targets for cancer immunotherapy.
Wang, Peng-Fei; Chen, Yang; Song, Si-Ying; Wang, Ting-Jian; Ji, Wen-Jun; Li, Shou-Wei; Liu, Ning; Yan, Chang-Xiang
2017-01-01
Background: Treatment of cancers with programmed cell death protein 1 (PD-1) pathway inhibitors can lead to immune-related adverse events (irAEs), which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs. Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence. Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis. The anti-PD-1/PD-L1 agents included nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and BMS-936559. The tumor types were melanomas, Hodgkin lymphomas, urothelial carcinomas, breast cancers, non-small cell lung cancers, renal cell carcinomas (RCC), colorectal cancers, and others. We described irAEs according to organ systems, namely, the skin (pruritus, rash, maculopapular rash, vitiligo, and dermatitis), endocrine system (hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, and adrenal insufficiency), digestive system (colitis, diarrhea, pancreatitis, and increased AST/ALT/bilirubin), respiratory system (pneumonitis, lung infiltration, and interstitial lung disease), and urinary system (increased creatinine, nephritis, and renal failure). In patients treated with the PD-1 signaling inhibitors, the overall incidence of irAEs was 26.82% (95% CI, 21.73–32.61; I2, 92.80) in any grade and 6.10% (95% CI, 4.85–7.64; I2, 52.00) in severe grade, respectively. The development of irAEs was unrelated to the dose of anti-PD-1/PD-L1 agents. The incidence of particular irAEs varied when different cancers were treated with different drugs. The incidence of death due to irAEs was around 0.17%. Conclusion: The occurrence of irAEs was organ-specific and related to drug and tumor types. PMID:29093678
NASA Astrophysics Data System (ADS)
Sharmila, G.; Farzana Fathima, M.; Haries, S.; Geetha, S.; Manoj Kumar, N.; Muthukumaran, C.
2017-06-01
Synthesis of metal nanoparticles through green chemistry route is an emerging eco-friendly approach in the present days. An eco-friendly, biogenic synthesis of palladium nanoparticles (PdNPs) using Filicium decipiens leaf extract was reported in the present study. The synthesized PdNPs were characterized by UV-visible spectroscopy, Transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The PdNPs formation was confirmed by UV-visible spectrophotometer and spherical shaped PdNPs with size range of 2-22 nm was observed in TEM analysis. Energy dispersive X-ray spectroscopy (EDS) analysis confirmed the presence of palladium in the synthesized nanoparticles. The crystalline nature of PdNPs was confirmed by XRD pattern and compared with the standard. The phytochemicals and proteins were identified by their functional groups in FT-IR spectrum and revealed the amide, amine groups present in F. decipiens may have involved in the bio-reduction reaction for PdNPs synthesis. Prepared PdNPs showed potential antibacterial activity against both Gram-positive and Gram-negative bacteria. F. decipiens leaf extract based PdNPs showed high bactericidal activity against Escherichia coli, Pseudomonas aeruginosa as compared to Staphylococcus aureus and Bacillus subtilis Results showed that phytochemicals rich F. decipiens leaf extract may be utilized as an effective non-toxic reducing agent for PdNPs synthesis and prepared PdNPs may useful in biomedical applications.
Microbial synthesis of core/shell gold/palladium nanoparticles for applications in green chemistry
Deplanche, Kevin; Merroun, Mohamed L.; Casadesus, Merixtell; Tran, Dung T.; Mikheenko, Iryna P.; Bennett, James A.; Zhu, Ju; Jones, Ian P.; Attard, Gary A.; Wood, J.; Selenska-Pobell, Sonja; Macaskie, Lynne E.
2012-01-01
We report a novel biochemical method based on the sacrificial hydrogen strategy to synthesize bimetallic gold (Au)–palladium (Pd) nanoparticles (NPs) with a core/shell configuration. The ability of Escherichia coli cells supplied with H2 as electron donor to rapidly precipitate Pd(II) ions from solution is used to promote the reduction of soluble Au(III). Pre-coating cells with Pd(0) (bioPd) dramatically accelerated Au(III) reduction, with the Au(III) reduction rate being dependent upon the initial Pd loading by mass on the cells. Following Au(III) addition, the bioPd–Au(III) mixture rapidly turned purple, indicating the formation of colloidal gold. Mapping of bio-NPs by energy dispersive X-ray microanalysis suggested Au-dense core regions and peripheral Pd but only Au was detected by X-ray diffraction (XRD) analysis. However, surface analysis of cleaned NPs by cyclic voltammetry revealed large Pd surface sites, suggesting, since XRD shows no crystalline Pd component, that layers of Pd atoms surround Au NPs. Characterization of the bimetallic particles using X-ray absorption spectroscopy confirmed the existence of Au-rich core and Pd-rich shell type bimetallic biogenic NPs. These showed comparable catalytic activity to chemical counterparts with respect to the oxidation of benzyl alcohol, in air, and at a low temperature (90°C). PMID:22399790
Bancalari, Elena; Bernini, Valentina; Bottari, Benedetta; Neviani, Erasmo; Gatti, Monica
2016-01-01
Impedance microbiology is a method that enables tracing microbial growth by measuring the change in the electrical conductivity. Different systems, able to perform this measurement, are available in commerce and are commonly used for food control analysis by mean of measuring a point of the impedance curve, defined "time of detection." With this work we wanted to find an objective way to interpret the metabolic significance of impedance curves and propose it as a valid approach to evaluate the potential acidifying performances of starter lactic acid bacteria to be employed in milk transformation. To do this it was firstly investigated the possibility to use the Gompertz equation to describe the data coming from the impedance curve obtained by mean of BacTrac 4300®. Lag time (λ), maximum specific M% rate (μmax), and maximum value of M% (Yend) have been calculated and, given the similarity of the impedance fitted curve to the bacterial growth curve, their meaning has been interpreted. Potential acidifying performances of eighty strains belonging to Lactobacillus helveticus, Lactobacillus delbrueckii subsp. bulgaricus, Lactococcus lactis , and Streptococcus thermophilus species have been evaluated by using the kinetics parameters, obtained from Excel add-in DMFit version 2.1. The novelty and importance of our findings, obtained by means of BacTrac 4300®, is that they can also be applied to data obtained from other devices. Moreover, the meaning of λ, μmax, and Yend that we have extrapolated from Modified Gompertz equation and discussed for lactic acid bacteria in milk, can be exploited also to other food environment or other bacteria, assuming that they can give a curve and that curve is properly fitted with Gompertz equation.
Bancalari, Elena; Bernini, Valentina; Bottari, Benedetta; Neviani, Erasmo; Gatti, Monica
2016-01-01
Impedance microbiology is a method that enables tracing microbial growth by measuring the change in the electrical conductivity. Different systems, able to perform this measurement, are available in commerce and are commonly used for food control analysis by mean of measuring a point of the impedance curve, defined “time of detection.” With this work we wanted to find an objective way to interpret the metabolic significance of impedance curves and propose it as a valid approach to evaluate the potential acidifying performances of starter lactic acid bacteria to be employed in milk transformation. To do this it was firstly investigated the possibility to use the Gompertz equation to describe the data coming from the impedance curve obtained by mean of BacTrac 4300®. Lag time (λ), maximum specific M% rate (μmax), and maximum value of M% (Yend) have been calculated and, given the similarity of the impedance fitted curve to the bacterial growth curve, their meaning has been interpreted. Potential acidifying performances of eighty strains belonging to Lactobacillus helveticus, Lactobacillus delbrueckii subsp. bulgaricus, Lactococcus lactis, and Streptococcus thermophilus species have been evaluated by using the kinetics parameters, obtained from Excel add-in DMFit version 2.1. The novelty and importance of our findings, obtained by means of BacTrac 4300®, is that they can also be applied to data obtained from other devices. Moreover, the meaning of λ, μmax, and Yend that we have extrapolated from Modified Gompertz equation and discussed for lactic acid bacteria in milk, can be exploited also to other food environment or other bacteria, assuming that they can give a curve and that curve is properly fitted with Gompertz equation. PMID:27799925
Son, M-Y; Sim, H; Son, Y S; Jung, K B; Lee, M-O; Oh, J-H; Chung, S-K; Jung, C-R; Kim, J
2017-12-01
The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic cause of Parkinson's disease (PD). There is compelling evidence that PD is not only a brain disease but also a gastrointestinal disorder; nonetheless, its pathogenesis remains unclear. We aimed to develop human neural and intestinal tissue models of PD patients harbouring an LRRK2 mutation to understand the link between LRRK2 and PD pathology by investigating the gene expression signature. We generated PD patient-specific induced pluripotent stem cells (iPSCs) carrying an LRRK2 G2019S mutation (LK2GS) and then differentiated into three-dimensional (3D) human neuroectodermal spheres (hNESs) and human intestinal organoids (hIOs). To unravel the gene and signalling networks associated with LK2GS, we analysed differentially expressed genes in the microarray data by functional clustering, gene ontology (GO) and pathway analyses. The expression profiles of LK2GS were distinct from those of wild-type controls in hNESs and hIOs. The most represented GO biological process in hNESs and hIOs was synaptic transmission, specifically synaptic vesicle trafficking, some defects of which are known to be related to PD. The results were further validated in four independent PD-specific hNESs and hIOs by microarray and qRT-PCR analysis. We provide the first evidence that LK2GS also causes significant changes in gene expression in the intestinal cells. These hNES and hIO models from the same genetic background of PD patients could be invaluable resources for understanding PD pathophysiology and for advancing the complexity of in vitro models with 3D expandable organoids. © 2017 British Neuropathological Society.
Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat
Bruder, Eric D.; Taylor, Jennifer K.; Kamer, Kimberli J.; Raff, Hershel
2008-01-01
Acute episodes of severe hypoxia are among the most common stressors in neonates. An understanding of the development of the physiological response to acute hypoxia will help improve clinical interventions. The present study measured ACTH and corticosterone responses to acute, severe hypoxia (8% inspired O2 for 4 h) in neonatal rats at postnatal days (PD) 2, 5, and 8. Expression of specific hypothalamic, anterior pituitary, and adrenocortical mRNAs was assessed by real-time PCR, and expression of specific proteins in isolated adrenal mitochondria from adrenal zona fascisulata/reticularis was assessed by immunoblot analyses. Oxygen saturation, heart rate, and body temperature were also measured. Exposure to 8% O2 for as little as 1 h elicited an increase in plasma corticosterone in all age groups studied, with PD2 pups showing the greatest response (∼3 times greater than PD8 pups). Interestingly, the ACTH response to hypoxia was absent in PD2 pups, while plasma ACTH nearly tripled in PD8 pups. Analysis of adrenal mRNA expression revealed a hypoxia-induced increase in Ldlr mRNA at PD2, while both Ldlr and Star mRNA were increased at PD8. Acute hypoxia decreased arterial O2 saturation (SPo2) to ∼80% and also decreased body temperature by 5–6°C. The hypoxic thermal response may contribute to the ACTH and corticosterone response to decreases in oxygen. The present data describe a developmentally regulated, differential corticosterone response to acute hypoxia, shifting from ACTH independence in early life (PD2) to ACTH dependence less than 1 wk later (PD8). PMID:18703410
Smoller, Jordan W.; Gallagher, Patience J.; Duncan, Laramie E.; McGrath, Lauren M.; Haddad, Stephen A.; Holmes, Avram.; Wolf, Aaron B.; Hilker, Sidney; Block, Stefanie R.; Weill, Sydney; Young, Sarah; Choi, Eun Young; Rosenbaum, Jerrold F.; Biederman, Joseph; Faraone, Stephen V.; Roffman, Joshua; Manfro, Gisele G.; Blaya, Carolina; Hirshfeld-Becker, Dina R.; Stein, Murray B.; Van Ameringen, Michael; Tolin, David F.; Otto, Michael W.; Pollack, Mark H.; Simon, Naomi M.; Buckner, Randy L.; Ongur, Dost; Cohen, Bruce M.
2014-01-01
Background Individuals with panic disorder (PD) exhibit a hypersensitivity to inhaled carbon dioxide (CO2), possibly reflecting a lowered threshold for sensing signals of suffocation. Animal studies have shown that CO2-mediated fear behavior depends on chemosensing of acidosis in the amygdala via the acid sensing ion channel ASIC1a. We examined whether the human ortholog of the ASIC1a gene, ACCN2, is associated with the presence of PD and with amygdala structure and function. Methods We conducted a case-control analysis (N=414 PD cases, 846 healthy controls) of ACCN2single nucleotide polymorphisms (SNPs) and PD. We then tested whether variants showing significant association with PD are also associated with amygdala volume (n=1,048) and/or task-evoked reactivity to emotional stimuli (n=103) in healthy individuals. Results Two SNPs at the ACCN2 locus showed evidence of association with PD: rs685012 (OR=1.32, gene-wise corrected p=0.011) and rs10875995 (OR=1.26, gene-wise corrected p=0.046). The association appeared to be stronger when early-onset (age ≤ 20) PD cases and when cases with prominent respiratory symptoms were compared to controls. The PD risk allele at rs10875995 was associated with increased amygdala volume (p=0.035), as well as task-evoked amygdala reactivity to fearful and angry faces (p=0.0048). Conclusions Genetic variation at ACCN2 appears to be associated with PD and with amygdala phenotypes that have been linked to anxiety proneness. These results support the possibility that modulation of acid-sensing ion channels may have therapeutic potential for PD. PMID:24529281
Scheen, Gilles; Bassu, Margherita; Douchamps, Antoine; Zhang, Chao; Debliquy, Marc; Francis, Laurent A
2014-01-01
We present an original two-step method for the deposition via precipitation of Pd nanoparticles into macroporous silicon. The method consists in immersing a macroporous silicon sample in a PdCl2/DMSO solution and then in annealing the sample at a high temperature. The impact of composition and concentration of the solution and annealing time on the nanoparticle characteristics is investigated. This method is compared to electroless plating, which is a standard method for the deposition of Pd nanoparticles. Scanning electron microscopy and computerized image processing are used to evaluate size, shape, surface density and deposition homogeneity of the Pd nanoparticles on the pore walls. Energy-dispersive x-ray spectroscopy (EDX) and x-ray photoelectron spectroscopy (XPS) analyses are used to evaluate the composition of the deposited nanoparticles. In contrast to electroless plating, the proposed method leads to homogeneously distributed Pd nanoparticles along the macropores depth with a surface density that increases proportionally with the PdCl2 concentration. Moreover EDX and XPS analysis showed that the nanoparticles are composed of Pd in its metallic state, while nanoparticles deposited by electroless plating are composed of both metallic Pd and PdOx. PMID:27877732
Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2.
Chuang, Yu-Hsuan; Lill, Christina M; Lee, Pei-Chen; Hansen, Johnni; Lassen, Christina F; Bertram, Lars; Greene, Naomi; Sinsheimer, Janet S; Ritz, Beate
2016-01-01
Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2) metabolizes caffeine; thus, gene polymorphisms in ADORA2A and CYP1A2 may influence the effect coffee consumption has on PD risk. In a population-based case-control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and gender-matched controls), we assessed interactions between lifetime coffee consumption and 3 polymorphisms in ADORA2A and CYP1A2 for all subjects, and incident and prevalent PD cases separately using logistic regression models. We also conducted a meta-analysis combining our results with those from previous studies. We estimated statistically significant interactions for ADORA2A rs5760423 and heavy vs. light coffee consumption in incident (OR interaction = 0.66 [95% CI 0.46-0.94], p = 0.02) but not prevalent PD. We did not observe interactions for CYP1A2 rs762551 and rs2472304 in incident or prevalent PD. In meta-analyses, PD associations with daily coffee consumption were strongest among carriers of variant alleles in both ADORA2A and CYP1A2. We corroborated results from a previous report that described interactions between ADORA2A and CYP1A2 polymorphisms and coffee consumption. Our results also suggest that survivor bias may affect results of studies that enroll prevalent PD cases. © 2017 S. Karger AG, Basel.
Hsiao, Ing-Tsung; Weng, Yi-Hsin; Lin, Wey-Yil; Hsieh, Chia-Ju; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Kung, Mei-Ping; Lu, Chin-Song; Lin, Kun-Ju
2014-04-01
(99m)Tc-TRODAT-1 is the first clinical routine (99m)Tc radiopharmaceutical to evaluate dopamine neurons loss in Parkinson's disease (PD). (18)F-AV-133 is a novel PET radiotracer targeting the vesicular monoamine transporter type 2 (VMAT2) to detect monoaminergic terminal reduction in PD patients. The aim of this study is to compare both images in the same health control (HC) and PD subjects. Eighteen subjects (8 HC and 10 PD) were recruited for (99m)Tc-TRODAT-1 SPECT, (18)F-AV-133 PET and MRI scans within two weeks. The SPECT images were performed at 4-h post-injection for 45 min, and the PET images were performed at 90 min post-injection for 10 min. Each PET and SPECT image was normalized into Montreal Neurological Institute template aided from individual MRI for comparison. For regional analysis, volume of interest (VOIs) of bilateral caudate nuclei, anterior, posterior putamen and occipital cortex (as reference region) were delineated from the normalized MRI. The specific uptake ratio (SUR) was calculated as (regional mean counts/reference mean counts-1). The nonparametric Mann-Whitney U test was used to evaluate the power of differentiating control from PD subjects for both image modalities. The correlations of the SURs to the clinical parameters were examined. For voxelwise analysis, two-sample t-test for group comparison between HC and PD was computed in both image modalities. The SURs of caudate nucleus and putamen correlated well between two image modalities (r = 0.81, p<0.001), and showed significant different between HC and PD subjects. Of note, the (18)F-AV-133 SUR displayed a better correlation to PD clinical laterality index as compared to (99m)Tc-TRODAT-1 (r = 0.73 vs. r = 0.33). Voxelwise analysis showed more lesions for PD subjects from (18)F-AV-133 image as compared to (99m)Tc-TRODAT-1 especially at the substantia nigra region. (18)F-AV-133 PET demonstrated similar performance in differentiation PD from control, and a better correlation to clinical characteristics than that of (99m)Tc-TRODAT-1 SPECT. (18)F-AV-133 PET also showed additional information in substantia nigra integrity in PD subjects by voxelwise analysis. Collectively, (18)F-AV-133 could be a promising and better tracer for clinical use to detect monoaminergic terminal reduction in PD patients. Copyright © 2014 Elsevier Inc. All rights reserved.
Mikherdov, Alexander S; Novikov, Alexander S; Kinzhalov, Mikhail A; Boyarskiy, Vadim P; Starova, Galina L; Ivanov, Alexander Yu; Kukushkin, Vadim Yu
2018-03-19
The reaction of cis-[PdCl 2 (CNCy) 2 ] (1) with thiazol-2-amines (2-10) leads to the C,N-chelated diaminocarbene-like complexes [PdCl{ C(N(H)4,5-R 2 -thiazol-2-yl)NHCy}(CNCy)] (11-14; 82-91%) in the case of 4,5-R 2 -thiazol-2-amines (R, R = H, H (2), Me, Me (3), -(CH 2 ) 4 - (4)) and benzothiazol-2-amine (5) or gives the diaminocarbene species cis-[PdCl 2 {C(N(H)Cy)N(H)4-R-thiazol-2-yl}(CNCy)] (15-19; 73-93%) for the reaction with 4-aryl-substituted thiazol-2-amines (R = Ph (6), 4-MeC 6 H 4 (7), 4-FC 6 H 4 (8), 4-ClC 6 H 4 (9), 3,4-F 2 C 6 H 3 (10)). Inspection of the single-crystal X-ray diffraction data for 15-17 and 19 suggests that the structures of all these species exhibit previously unrecognized bifurcated chalcogen-hydrogen bonding μ (S,N-H) Cl and also Pd II ···Pd II metallophilic interactions. These noncovalent interactions collectively connect two symmetrically located molecules of 15-17 and 19, resulting in their solid-state dimerization. The existence of the μ (S,N-H) Cl system and its strength (6-9 kcal/mol) were additionally verified/estimated by a Hirshfeld surface analysis and DFT calculations combined with a topological analysis of the electron density distribution within the formalism of Bader's theory (AIM method) and NBO analysis. The observed noncovalent interactions are jointly responsible for the dimerization of 15-19 not only in the solid phase but also in CHCl 3 solutions, as predicted theoretically by DFT calculations and confirmed experimentally by FTIR, HRESI-MS, 1 H NMR, and diffusion coefficient NMR measurements. Available CCDC data were processed under the new moiety angle, and the observed μ (S,E-H) Cl systems were classified accordingly to E (E = N, O, C) type atoms.
Pd/RGO modified carbon felt cathode for electro-Fenton removing of EDTA-Ni.
Zhang, Zhen; Zhang, Junya; Ye, Xiaokun; Hu, Yongyou; Chen, Yuancai
Ethylenediaminetetraacetic acid (EDTA) forms stable complexes with toxic metals such as nickel due to its strong chelation. The electro-Fenton (EF) process using a cathode made from palladium (Pd), reduced graphene oxide (RGO) and carbon felt, fed with air, exhibited high activities and stability for the removal of 10 mg L(-1) EDTA-Ni solution. Pd/RGO catalyst was prepared by one-pot synthesis; the scanning electron microscopy and X-ray diffraction analysis indicated nanoparticles and RGO were well distributed on carbon felt, forming three dimensional architecture with both large macropores and a mesoporous structure. The cyclic voltammetric results showed that the presence of RGO in Pd/RGO/carbon felt significantly increased the current response of two-electron reduction of O2 (0.45 V). The key factors influencing the removal efficiency of EDTA-Ni, such as pH, current and Fe(2+) concentration, were investigated. Under the optimum conditions, the removal efficiency of EDTA-Ni reached 83.8% after 100 min EF treatment. Mechanism analysis indicated that the introduction of RGO in Pd/RGO/carbon felt significantly enhanced the electrocatalytic activities by inducing •OH in the EF process; direct H2O2 oxidation still accounted for a large amount of EDTA-Ni removal efficiency.
Motor automaticity in Parkinson’s disease
Wu, Tao; Hallett, Mark; Chan, Piu
2017-01-01
Bradykinesia is the most important feature contributing to motor difficulties in Parkinson’s disease (PD). However, the pathophysiology underlying bradykinesia is not fully understood. One important aspect is that PD patients have difficulty in performing learned motor skills automatically, but this problem has been generally overlooked. Here we review motor automaticity associated motor deficits in PD, such as reduced arm swing, decreased stride length, freezing of gait, micrographia and reduced facial expression. Recent neuroimaging studies have revealed some neural mechanisms underlying impaired motor automaticity in PD, including less efficient neural coding of movement, failure to shift automated motor skills to the sensorimotor striatum, instability of the automatic mode within the striatum, and use of attentional control and/or compensatory efforts to execute movements usually performed automatically in healthy people. PD patients lose previously acquired automatic skills due to their impaired sensorimotor striatum, and have difficulty in acquiring new automatic skills or restoring lost motor skills. More investigations on the pathophysiology of motor automaticity, the effect of L-dopa or surgical treatments on automaticity, and the potential role of using measures of automaticity in early diagnosis of PD would be valuable. PMID:26102020
Carriere, N; Verloop, D; Dupont, C; Fontaine, V; Tir, M; Krystkowiak, P; Blanchard, A; Defebvre, M-M; Defebvre, L
2017-06-01
The "neurodegenerative diseases plan" under elaboration for the Hauts-de-France region requires better knowledge of the patient population and care pathways. In France, the prevalence of Parkinson's disease (PD) has been estimated from cohorts to be about 1-3 per 1000 inhabitants, but exhaustive data are scarce for the general population. The purpose of this study was to evaluate the prevalence of PD in the Hauts-de-France region and to assess PD-related healthcare consumption. A descriptive study was conducted to identify the parkinsonian population in the Hauts-de-France region (including the administrative districts of Pas-de-Calais and Picardie) for the year 2014. Parkinsonian patients were identified from health insurance fund reimbursement data using the following criteria: (i) reimbursement for a PD-specific medication; (ii) attribution of long-duration disease status coded as PD; (iii) hospital stay with PD diagnosis in the standard discharge report contained in the French medico-economic database on hospital activity (PMSI). The raw prevalence of PD in the region was 5.03 per 1000 inhabitants aged 20 years and older. The standardized prevalence by health territory ranged from 4.0 to 9.0 per 1000 inhabitants aged 20 years and older. During the 1-year study period, 33.5% of patients had a neurology consultation, 57.1% attended a physiotherapy session, and 7.7% received speech therapy. Most of patients (79.6%) were treated with levodopa, sometimes in combination with a catechol-O-methyl transferase inhibitor (14.4%). Dopaminergic agonists were prescribed in 33.5% of cases. A neuroleptic was prescribed for 6.9% of the population (clozapine for 25.9%). The prevalence of PD is high in the Hauts-de-France region with a heterogeneous distribution by health territory. Neurology consultations were attended by a minority of patients in 2014. This work provides perspectives for necessary improvement in specialized care for this disease, both in terms of follow-up consultations and home care. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Kristensen, Steffan K; Eikeland, Espen Z; Taarning, Esben; Lindhardt, Anders T; Skrydstrup, Troels
2017-12-01
A protocol for the Pd-catalysed cyanation of aryl bromides using near stoichiometric and gaseous hydrogen cyanide is reported for the first time. A two-chamber reactor was adopted for the safe liberation of ex situ generated HCN in a closed environment, which proved highly efficient in the Ni-catalysed hydrocyanation as the test reaction. Subsequently, this setup was exploited for converting a range of aryl and heteroaryl bromides (28 examples) directly into the corresponding benzonitriles in high yields, without the need for cyanide salts. Cyanation was achieved employing the Pd(0) precatalyst, P( t Bu) 3 -Pd-G3 and a weak base, potassium acetate, in a dioxane-water solvent mixture. The methodology was also suitable for the synthesis of 13 C-labelled benzonitriles with ex situ generated 13 C-hydrogen cyanide. Stoichiometric studies with the metal complexes were undertaken to delineate the mechanism for this catalytic transformation. Treatment of Pd(P( t Bu) 3 ) 2 with H 13 CN in THF provided two Pd-hydride complexes, (P( t Bu) 3 ) 2 Pd(H)( 13 CN), and [(P( t Bu) 3 )Pd(H)] 2 Pd( 13 CN) 4 , both of which were isolated and characterised by NMR spectroscopy and X-ray crystal structure analysis. When the same reaction was performed in a THF : water mixture in the presence of KOAc, only (P( t Bu) 3 ) 2 Pd(H)( 13 CN) was formed. Subjection of this cyano hydride metal complex with the oxidative addition complex (P( t Bu) 3 )Pd(Ph)(Br) in a 1 : 1 ratio in THF led to a transmetallation step with the formation of (P( t Bu) 3 ) 2 Pd(H)(Br) and 13 C-benzonitrile from a reductive elimination step. These experiments suggest the possibility of a catalytic cycle involving initially the formation of two Pd(ii)-species from the oxidative addition of L n Pd(0) into HCN and an aryl bromide followed by a transmetallation step to L n Pd(Ar)(CN) and L n Pd(H)(Br), which both reductively eliminate, the latter in the presence of KOAc, to generate the benzonitrile and L n Pd(0).
OpenElectrophy: An Electrophysiological Data- and Analysis-Sharing Framework
Garcia, Samuel; Fourcaud-Trocmé, Nicolas
2008-01-01
Progress in experimental tools and design is allowing the acquisition of increasingly large datasets. Storage, manipulation and efficient analyses of such large amounts of data is now a primary issue. We present OpenElectrophy, an electrophysiological data- and analysis-sharing framework developed to fill this niche. It stores all experiment data and meta-data in a single central MySQL database, and provides a graphic user interface to visualize and explore the data, and a library of functions for user analysis scripting in Python. It implements multiple spike-sorting methods, and oscillation detection based on the ridge extraction methods due to Roux et al. (2007). OpenElectrophy is open source and is freely available for download at http://neuralensemble.org/trac/OpenElectrophy. PMID:19521545
Chirality in distorted square planar Pd(O,N)2 compounds.
Brunner, Henri; Bodensteiner, Michael; Tsuno, Takashi
2013-10-01
Salicylidenimine palladium(II) complexes trans-Pd(O,N)2 adopt step and bowl arrangements. A stereochemical analysis subdivides 52 compounds into 41 step and 11 bowl types. Step complexes with chiral N-substituents and all the bowl complexes induce chiral distortions in the square planar system, resulting in Δ/Λ configuration of the Pd(O,N)2 unit. In complexes with enantiomerically pure N-substituents ligand chirality entails a specific square chirality and only one diastereomer assembles in the lattice. Dimeric Pd(O,N)2 complexes with bridging N-substituents in trans-arrangement are inherently chiral. For dimers different chirality patterns for the Pd(O,N)2 square are observed. The crystals contain racemates of enantiomers. In complex two independent molecules form a tight pair. The (RC) configuration of the ligand induces the same Δ chirality in the Pd(O,N)2 units of both molecules with varying square chirality due to the different crystallographic location of the independent molecules. In complexes and atrop isomerism induces specific configurations in the Pd(O,N)2 bowl systems. The square chirality is largest for complex [(Diop)Rh(PPh3 )Cl)], a catalyst for enantioselective hydrogenation. In the lattice of two diastereomers with the same (RC ,RC) configuration in the ligand Diop but opposite Δ and Λ square configurations co-crystallize, a rare phenomenon in stereochemistry. © 2013 Wiley Periodicals, Inc.
Shen, Liang; Ji, Hong-Fang
2015-06-15
The present study aimed to quantitatively assess the associations between vitamin D and Parkinson's Disease (PD) risks, which include: (i) risk of PD in subjects with deficient and insufficient vitamin D levels; (ii) association between vitamin D supplementation and risk of PD; and (iii) association between outdoor work and PD risk, through meta-analyzing available data. An electronic literature search supplemented by hand searching up to March 2015 identified seven eligible studies comprising 5690 PD patients and 21251 matched controls. Odds ratio (OR) and 95% confidence interval (CI) of PD risk were assessed through pooling the collected data from eligible studies using Stata software. Pooled data showed that subjects with deficient and insufficient vitamin D levels had increased PD risks compared with matched-controls according to the corresponding OR: 2.08, 95% CI: 1.63 to 2.65, and 1.29, 95% CI: 1.10 to 1.51. Vitamin D supplementation was associated with significantly reduced risk of PD (OR: 0.62, 95% CI: 0.35 to 0.90). Outdoor work was also related to reduced risk of PD (OR: 0.72, 95% CI: 0.63 to 0.81). The findings may stimulate larger, well-designed studies to further verify the associations between vitamin D and PD risk.
Borghammer, Per; Chakravarty, Mallar; Jonsdottir, Kristjana Yr; Sato, Noriko; Matsuda, Hiroshi; Ito, Kengo; Arahata, Yutaka; Kato, Takashi; Gjedde, Albert
2010-05-01
Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 early-stage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 late-stage PD patients with that of 13 controls. Three different normalization methods were compared: (1) GM normalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxel-based analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD.
NASA Astrophysics Data System (ADS)
Anku, William Wilson; Oppong, Samuel Osei-Bonsu; Shukla, Sudheesh Kumar; Agorku, Eric Selorm; Govender, Poomani Penny
2016-06-01
The photocatalytic degradation of organic pollutants from water using palladium-doped-zirconium oxide-multiwalled carbon nanotubes (Pd-ZrO2-MWCNTs) nanocomposites is presented. A series of Pd doped-ZrO2-MWCNTs nanocomposites with varying percentage compositions of Pd were prepared by the homogenous co-precipitation method. The photocatalytic applicability of the materials was investigated by the degradation of acid blue 40 dye in water under simulated solar light. The optical, morphological and structural properties of the nanocomposites were evaluated using X-ray powder diffraction, Fourier transformer infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, BET surface area analysis and (UV-Vis) spectroscopy. The Pd-ZrO2-MWCNTs nanocomposites showed enhanced photocatalytic activity toward the degradation of the acid blue 40 dye under visible light compared with bare ZrO2 and ZrO2-MWCNTs alone. The remarkable photocatalytic activity of Pd-ZrO2-MWCNTs nanocomposites in the visible light makes it an ideal photocatalyst for the removal of organic pollutants in water. The 0.5 % Pd-ZrO2-MWCNT was the most efficient photocatalyst with 98 % degradation after 3 h with corresponding K a and band gap values of 16.8 × 10-3 m-1 and 2.79 eV, respectively.
Force 2025 and Beyond Strategic Force Design Analytic Model
2017-01-12
depiction of the core ideas of our force design model. Figure 1: Description of Force Design Model Figure 2 shows an overview of our methodology ...the F2025B Force Design Analytic Model research conducted by TRAC- MTRY and the Naval Postgraduate School. Our research develops a methodology for...designs. We describe a data development methodology that characterizes the data required to construct a force design model using our approach. We
NASA Astrophysics Data System (ADS)
Tao, Hu-Chun; Gu, Yi-Han; Liu, Wei; Huang, Shuai-Bin; Cheng, Ling; Zhang, Li-Juan; Zhu, Li-Li; Wang, Yong
2017-11-01
Three kinds of functional monomers, 4-vinylpridine(4-VP), 2-(allylthio)nicotinic acid(ANA), and 2-Acetamidoacrylic acid(AAA), were used to synthetize palladium(II) ion-imprinted polymeric nanospheres (Pd(II) IIPs) via precipitation-polymerization method in order to study the effects of different functional monomers on the adsorption properties of ion-imprinted materials. The results of UV spectra in order to study the interaction between template ion PdCl4 2- and functional monomers showed that there were great differences in structure after the template reacted with three functional monomers, 4-VP and ANA caused a large structural change, while AAA basically did not change. Further results on the adsorption performance of Pd(II) IIPs on Pd(II) confirmed 4-VP was the most promising candidate for the synthesis of Pd(II) IIPs with an adsorption capacity of 5.042 mg/g as compared with ANA and AAA. The influence of operating parameters on Pd(II) IIP's performance on Pd(II) adsorption was investigated. There was an increase in the adsorption capacity of Pd(II) IIPs at higher pH, temperature, and initial concentration of Pd(II). The results of multi-metal competitive adsorption experiments showed that Pd(II) IIPs had selectivity for Pd(II). An adsorption equilibrium could be reached at 180 min. Kinetic analysis showed that the adsorption test data fitted best to the pseudo-second order kinetic model, and the theoretical equilibrium adsorption capacity was about 5.085 mg/g. The adsorption isotherms of Pd(II) by Pd(II) IIPs agreed well with the Freundlich equation, suggesting a favorable adsorption reaction under optimal conditions. These results showed that Pd(II) IIPs have potential application in the removal of Pd(II) from aqueous solutions and may provide some information for the selection of functional monomers in the preparation of Pd(II) IIPs.
Lahner, D; Kabon, B; Marschalek, C; Chiari, A; Pestel, G; Kaider, A; Fleischmann, E; Hetz, H
2009-09-01
Fluid management guided by oesophageal Doppler monitor has been reported to improve perioperative outcome. Stroke volume variation (SVV) is considered a reliable clinical predictor of fluid responsiveness. Consequently, the aim of the present trial was to evaluate the accuracy of SVV determined by arterial pulse contour (APCO) analysis, using the FloTrac/Vigileo system, to predict fluid responsiveness as measured by the oesophageal Doppler. Patients undergoing major abdominal surgery received intraoperative fluid management guided by oesophageal Doppler monitoring. Fluid boluses of 250 ml each were administered in case of a decrease in corrected flow time (FTc) to <350 ms. Patients were connected to a monitoring device, obtaining SVV by APCO. Haemodynamic variables were recorded before and after fluid bolus application. Fluid responsiveness was defined as an increase in stroke volume index >10%. The ability of SVV to predict fluid responsiveness was assessed by calculation of the area under the receiver operating characteristic (ROC) curve. Twenty patients received 67 fluid boluses. Fifty-two of the 67 fluid boluses administered resulted in fluid responsiveness. SVV achieved an area under the ROC curve of 0.512 [confidence interval (CI) 0.32-0.70]. A cut-off point for fluid responsiveness was found for SVV > or =8.5% (sensitivity: 77%; specificity: 43%; positive predictive value: 84%; and negative predictive value: 33%). This prospective, interventional observer-blinded study demonstrates that SVV obtained by APCO, using the FloTrac/Vigileo system, is not a reliable predictor of fluid responsiveness in the setting of major abdominal surgery.
Fu, Chunyun; Luo, Shiyu; Li, Qifei; Xie, Bobo; Yang, Qi; Geng, Guoxing; Lin, Caijuan; Su, Jiasun; Zhang, Yue; Wang, Jin; Qin, Zailong; Luo, Jingsi; Chen, Shaoke; Fan, Xin
2018-01-16
The aim of this study is to assess the disease incidence and mutation spectrum of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangxi, China, and to determine an optimal cutoff value to identify heterozygous female neonates. A total of 130, 635 neonates were screened from the year of 2013 to 2017. Neonates suspected for G6PD deficiency were further analyzed by quantitatively enzymatic assay and G6PD mutation analysis. The overall incidence of G6PD deficiency was 7.28%. A total of 14 G6PD mutations were identified, and different mutations lead to varying levels of G6PD enzymatic activities. The best cut-off value of G6PD activity in male subjects is 2.2 U/g Hb, same as conventional setting. In female population, however, the cut-off value is found to be 2.8 U/g Hb (sensitivity: 97.5%, specificity: 87.7%, AUC: 0.964) to best discriminate between normal and heterozygotes, and 1.6 U/g Hb (sensitivity: 82.2%, specificity: 85.9%, AUC: 0.871) between heterozygotes and deficient subjects. In conclusion, we have conducted a comprehensive newborn screening of G6PD deficiency in a large cohort of population from Guangxi, China, and first established a reliable cut-off value of G6PD activity to distinguish heterozygous females from either normal or deficient subjects.
Nantakomol, Duangdao; Paul, Rick; Palasuwan, Attakorn; Day, Nicholas P J; White, Nicholas J; Imwong, Mallika
2013-08-21
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is particularly prevalent in historically malaria-endemic countries. Although most individuals with G6PD deficiency are asymptomatic, deficiency can result in acute haemolytic anaemia after exposure to oxidative agents. A reliable test is necessary for diagnosing the deficiency to prevent an acute haemolytic crisis following, for example, anti-malarial treatment. The aim of this study was to investigate which method was the best predictor of this disorder. The present study investigated four G6PD activity detections (fluorescence spot (FS), methaemoglobin reduction (MR), biochemical and cytochemical test). These methods accompanied with mutation analysis of blood samples were taken from 295 apparently healthy individuals with unknown G6PD deficiency status. Molecular characterization of 295 Thai adults revealed an overall prevalence of 14.2%. The G6PD Viangchan (871 G>A) was the most common (83.3%), followed by G6PD Mahidol (487G>A) (11.9%), and G6PD Union (1360 C>T) (4.8%). There were two cases of G6PD deficiency carrying the double mutations of Viangchan (871G > A)-Mahidol (487G > A) and Viangchan (871G > A)-Union (1360C > T). In comparison, the prevalence of G6PD deficiency was 6.1% by FS test and 7.1% by MR test. G6PD activity was 11 ± 2.5 IU/gHb in non-deficient females (mean ± SD), and 10.9 ± 0.6 IU/gHb in non-deficient males. The upper and lower limit cut-off points for partial and severe deficiency in adults were 5.7 IU/gHb (60% of the normal mean) and 0.95 IU/gHb (10% of the normal mean), respectively. All hemizygote, homozygote and double mutations were associated with severe enzyme deficiency (the residual enzyme activity <10% of the normal mean), whereas only 14.3% of the heterozygote mutations showed severe enzyme deficiency. Based on the cut-off value <5.7 IU/gHb, the quantitative G6PD assay diagnosed 83% of cases as G6PD-deficient. Using a cut-off number of negative cell >20% in the cytochemical assay to define G6PD deficiency, the prevalence of G6PD deficiency was closest to the molecular analysis (12.9% G6PD-deficient) compared to the others methods. The cytochemical method is a significant predictor of this disease, while FS and MR test are recommended for the detection of severe G6PD deficiency in developing countries.
Loftus, Andrea M; Bucks, Romola S; Thomas, Meghan; Kane, Robert; Timms, Caitlin; Barker, Roger A; Gasson, Natalie
2015-02-01
A Movement Disorder Society (MDS) taskforce recently proposed diagnostic criteria for Parkinson's disease with features of mild cognitive impairment (PD-MCI). This study first examined the prevalence and nature of PD-MCI in a non-demented cohort using the MDS criteria. Using the generic Monte Carlo simulation method developed by Crawford and colleagues (2007), this study then estimated the base rate of the representative population who would demonstrate PD-MCI due to chance alone. A total of 104 participants with idiopathic PD underwent extensive motor and neuropsychological testing at baseline and 2 years later. The Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess motor symptoms of PD and a range of established neuropsychological tests was used to assess PD-MCI in accord with MDS criteria. In accord with MDS criteria, 38% of this cohort demonstrated PD-MCI at baseline and 48% at follow-up. Of the 36 participants in the multiple-domain PD-MCI subtype at time-1, 9 (25%) demonstrated no PD-MCI at follow up. Analysis revealed that approximately 13% of the representative population would demonstrate abnormally low scores for 2 of the 9 tests used, thereby meeting MDS criteria for PD-MCI. Clinicians and researchers need to approach a single diagnosis (i.e., based on one assessment) of PD-MCI with considerable caution.
Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A Pilot Study.
Arrigo, Alessandro; Rania, Laura; Calamuneri, Alessandro; Postorino, Elisa Imelde; Mormina, Enricomaria; Gaeta, Michele; Marino, Silvia; Di Lorenzo, Giuseppe; Quartarone, Angelo; Anastasi, Giuseppe; Puzzolo, Domenico; Aragona, Pasquale
2018-04-01
To describe corneal innervation and trigeminal alterations in drug-naive patients with Parkinson disease (PD). A case series study was conducted by recruiting 3 early drug-naive patients with PD, 2 men and 1 woman (age: 72, 68, and 66, respectively). Ophthalmologic assessment included Ocular Surface Disease Index questionnaire, visual acuity by the logarithm of the minimum angle of resolution score, pupillary light reflexes, extrinsic ocular movements, corneal sensitivity, and slit-lamp examination. Corneal innervation parameter changes were evaluated in vivo using the Confoscan 4 confocal microscope, and they were compared with a control data set. The Heidelberg Retina Tomograph 3 (HRT3) has been used to assess retinal alterations in our patients, if compared with normal range values provided by the HRT3. Moreover, 3T magnetic resonance imaging (MRI) analysis of water diffusion property changes of trigeminal nerves was performed. All data were analyzed and compared with 2 control data sets made by 14 age-matched controls. Patients with PD showed profound alterations of corneal innervation and of trigeminal diffusion MRI parameters, compared with controls. Strong differences (PD vs. controls) were found for deep nerve tortuosity (Kallinikos mean 19.94 vs. 2.13) and the number of beadings (mean 34.2 vs. 15.5). HRT3 retinal evaluation revealed less structural changes compared with the normal range. Diffusion MRI showed profound changes of white matter diffusion properties (PD vs. controls), with fractional anisotropy decrement (mean 0.3029 vs. 0.3329) and mean diffusivity increment (mean 0.00127 vs. 0.00106). Corneal innervation changes might occur earlier in patients with PD than in retinal ones. Confocal corneal innervation analysis might provide possible early biomarkers for a better PD evaluation and for its earlier diagnosis.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gloudemans, J.R.
1991-08-01
The multiloop integral system test (MIST) was part of a multiphase program started in 1983 to address small-break loss-of-coolant accidents (SBLOCAs) specific to Babcock Wilcox-designed plants. MIST was sponsored by the US Nuclear Regulatory Commission, the Babcock Wilcox Owners Group, the Electric Power Research Institute, and Babcock Wilcox. The unique features of the Babcock Wilcox design, specifically the hot leg U-bends and steam generators, prevented the use of existing integral system data or existing integral system facilities to addresss the thermal-hydraulic SBLOCA questions. MIST was specifically designed and constructed for this program, and an existing facility -- the once-through integralmore » system (OTIS) -- was also used. Data from MIST and OTIS are used to benchmark the adequacy of system codes, such as RELAP5 and TRAC, for predicting abnormal plant transients. The MIST program is reported in eleven volumes; Volumes 2 through 8 pertain to groups of Phase 3 tests by type, Volume 9 presents inter-group comparisons. Volume 10 provides comparisons between the RELAP5 MOD2 calculations and MIST observations, and Volume 11 (with addendum) presents the later, Phase 4 tests. This is Volume 1 of the MIST final report, a summary of the entire MIST program. Major topics include: test advisory grop (TAG) issues; facility scaling and design; test matrix; observations; comparisons of RELAP5 calculations to MIST observations; and MIST versus the TAG issues. 11 refs., 29 figs., 9 tabs.« less
Point Defects in Quenched and Mechanically-Milled Intermetallic Compounds
NASA Astrophysics Data System (ADS)
Sinha, Praveen
Investigations were made of structural and thermal point defects in the highly-ordered B2 compound PdIn and deformation-induced defects in PdIn and NiAl. The defects were detected through the quadrupole interactions they induce at nearby ^{111}In/Cd probe atoms using the technique of perturbed gamma-gamma angular correlations (PAC). Measurements on annealed PdIn on both sides of stoichiometry show structural defects that are the Pd vacancies on the Pd-poor side of the stoichiometry and Pd antisite atoms on the Pd-rich side. Signals were attributed to various defect configurations near the In/Cd probes. In addition to the first-shell Pd vacancy and second-shell Pd antisite atom configurations previously observed by Hahn and Muller, we observed two Pd-divacancy configurations in the first shell, a fourth-shell Pd vacancy, a second-shell In vacancy and the combination of a first -shell Pd vacancy and fourth-shell Pd vacancy. Vacancies on both the Pd and In sublattices were detected after quenching. Fractions of probe atoms having each type of neighboring vacancy defect were observed to increase monotonically with quenching temperature over the range 825-1500 K. For compositions very close to 50.15 at.% Pd, nearly equal site fractions were observed for Pd and In vacancies, indicating that the Schottky vacancy-pair defect is the thermal defect at high temperature. The formation enthalpy of the Schottky defect was determined from measurements of the Pd-vacancy site fraction to be 1.30(18) eV from analysis of quenching data in the range 825-1200 K, using the law of mass action and assuming a random distribution. Above 1200 K, the Pd-vacancy concentration was observed to be saturated at a value of 1.3(2) atomic percent. For more Pd-rich compositions, evidence was also obtained for a defect reaction in which a Pd antisite atom and Pd vacancy react to form an In vacancy, thereby increasing the In vacancy concentration and decreasing the Pd vacancy concentration. Analysis of defect concentrations allowed the conclusion that the In vacancy signal was due to second-shell and not third-shell defects. PAC spectroscopy was applied to study deformation -induced defects in PdIn and NiAl after mechanically milling in a SPEX 8000 vibrator mill for periods of up to four hours. For PdIn, the Pd vacancy concentration increased rapidly for short milling times and was observed to saturate at a value of 3.5(5) at.% after 10 minutes of milling when milling was carried out using a WC vial to avoid sample contamination. Such a large vacancy concentration accounts for 4.41(63) kJ mol-1 excess-stored energy in milled PdIn and implies a high density of "broken bonds" which may lead to mechanical instability of the lattice. Milling also produced In antisite atoms on the Pd sublattice. The antisite-atom concentration increased linearly with milling time, reaching a value of 4.0(7) at.% after 2 hours of milling. The Ni vacancy concentration in NiAl was also observed to increase with milling and to saturate after two hours of milling. Here, the "local" Ni vacancy concentration in the first-neighbor shell of the probe, deduced from the vacancy site fraction, was in excess of values that should occur if defects were located at random. This is attributed to binding between the Ni vacancy and the In/Cd probe, which is known from other work to be 0.22 eV.
Survival analysis: comparing peritoneal dialysis and hemodialysis in Taiwan.
Huang, Chiu-Ching; Cheng, Kuang-Fu; Wu, Hong-Dar Isaac
2008-06-01
Comparisons of survival in patients on peritoneal dialysis (PD) and on hemodialysis (HD) have been conducted in many Western countries, but publications on this subject in Asian populations are scarce. The present study estimated the survival and the relative mortality hazard for HD and PD patients in Taiwan. Incident end-stage renal disease patients reported to the Taiwan Renal Registry during 1995 - 2002 were included in the study. Patients had to be 20 years of age or older and had to have survived for the first 90 days on dialysis. A total of 45,820 incident HD and 2,809 incident PD patients formed the study population. Patients on PD were treated mainly with traditional glucose-based solutions. Using an intent-to-treat analysis, the Cox proportional hazards (CPH) model was applied to identify the factors that predict survival by treatment modality. Subgroup analyses were conducted by stratifying patients according to sex, comorbidity, age, and diabetes status. Kaplan-Meier estimates were used to explore the survival of HD and PD patients. Adjustments were implemented using the CPH model. The overall 1-year, 2-year, 3-year, 5-year and 10-year survival rates for PD patients were 89.8%, 77.6%, 67.6%, 55.5%, and 35% respectively. The equivalent survival rates for HD patients were 87.5%, 76.6%, 68.1%, 54.3%, and 33.8%. The differences were not statistically significant (p = 0.125). The CPH analysis stratified by diabetes status and age revealed that PD patients 55 years of age or younger and nondiabetic had a lower mortality ratio (MR) of 0.94. But the MR increased to 1.31 for nondiabetic patients older than 55. The MR for PD versus HD further increased to 1.72 for diabetic patients 55 years of age or younger, and to 1.99 for diabetic patients older than 55. After adjusting for both demographic and clinical case-mix differences, PD and HD patients were observed to have similar long-term survival. Subgroup analyses revealed that, among diabetic patients and patients older than 55, those on HD experienced better survival than did those on PD.
NASA Astrophysics Data System (ADS)
Li, Lingzhi; Chen, Mingxi; Huang, Guanbo; Yang, Nian; Zhang, Li; Wang, Huan; Liu, Yu; Wang, Wei; Gao, Jianping
2014-10-01
Bimetallic palladium-silver nanoparticles (NPs) supported on reduced oxide graphene (RGO) with different Pd/Ag ratios (Pd-Ag/RGO) were prepared by an easy green method which did not use any additional reducing agents or a dispersing agent. During the process, simultaneous redox reactions between AgNO3, K2PdCl4 and graphene oxide (GO) led to bimetallic Pd-Ag NPs. The morphology and composition of the Pd-Ag/RGO were characterized by transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, thermogravimetric analysis and Raman spectroscopy. Cyclic voltammetry and chronoamperometry were used to investigate the electrochemical activities and stabilities of these Pd-Ag/RGO catalysts for the electro-oxidation of methanol and ethanol in alkaline media. Among the different Pd/Ag ratios, the Pd-Ag (1:1)/RGO had the best catalytic activities and stability. So it is a promising catalyst for direct alcohol fuel cell applications.
Catalytic and electrocatalytic oxidation of ethanol over palladium-based nanoalloy catalysts.
Yin, Jun; Shan, Shiyao; Ng, Mei Shan; Yang, Lefu; Mott, Derrick; Fang, Weiqin; Kang, Ning; Luo, Jin; Zhong, Chuan-Jian
2013-07-23
The control of the nanoscale composition and structure of alloy catalysts plays an important role in heterogeneous catalysis. This paper describes novel findings of an investigation for Pd-based nanoalloy catalysts (PdCo and PdCu) for ethanol oxidation reaction (EOR) in gas phase and alkaline electrolyte. Although the PdCo catalyst exhibits a mass activity similar to Pd, the PdCu catalyst is shown to display a much higher mass activity than Pd for the electrocatalytic EOR in alkaline electrolyte. This finding is consistent with the finding on the surface enrichment of Pd on the alloyed PdCu surface, in contrast to the surface enrichment of Co in the alloyed PdCo surface. The viability of C-C bond cleavage was also probed for the PdCu catalysts in both gas-phase and electrolyte-phase EOR. In the gas-phase reaction, although the catalytic conversion rate for CO2 product is higher over Pd than PdCu, the nanoalloy PdCu catalyst appears to suppress the formation of acetic acid, which is a significant portion of the product in the case of pure Pd catalyst. In the alkaline electrolyte, CO2 was detected from the gas phase above the electrolyte upon acid treatment following the electrolysis, along with traces of aldehyde and acetic acid. An analysis of the electrochemical properties indicates that the oxophilicity of the base metal alloyed with Pd, in addition to the surface enrichment of metals, may have played an important role in the observed difference of the catalytic and electrocatalytic activities. In comparison with Pd alloyed with Co, the results for Pd alloyed with Cu showed a more significant positive shift of the reduction potential of the oxygenated Pd species on the surface. These findings have important implications for further fine-tuning of the Pd nanoalloys in terms of base metal composition toward highly active and selective catalysts for EOR.
PD-L1 expression and presence of TILs in small intestinal neuroendocrine tumours
Lamarca, Angela; Nonaka, Daisuke; Breitwieser, Wolfgang; Ashton, Garry; Barriuso, Jorge; McNamara, Mairéad G.; Moghadam, Sharzad; Rogan, Jane; Mansoor, Wasat; Hubner, Richard A.; Clark, Christopher; Chakrabarty, Bipasha; Valle, Juan W.
2018-01-01
Background The extent of resistance to immune surveillance in patients with well-differentiated (Wd) (grade 1/2) small-intestinal neuroendocrine tumours (Si-NETs) is unknown. Methods Patients diagnosed with Wd Si-NETs (excluding appendix, which are considered to have a different biology to other midgut NETs) were eligible. Tumoural programmed death (PD)-ligand(L) 1 (PD-L1)/PD-L2/PD-1 and tumour infiltrating lymphocytes (TILs) [presence and phenotype] were analysed in archival tissue by immunohistochemistry (IHC); reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used for confirmation of IHC results. Results Of 109 patients screened, 62 were eligible: 54.8% were male; median age was 63.7 years (95%-CI 59.7-67.2); disease stage II: 4.8%, III: 40.3% and IV: 54.8%; 41.9% were functional. Analysed samples (67.1% from primary tumours, 32.9% from metastases) were of grade 1 (67.1%) or 2 (32.86%) with a median Ki-67 of 2%. From the total of 62 eligible patients, 70 and 63 samples were suitable for IHC and RT-qPCR analysis, respectively. PD-L1 expression within tumour cells and TILs were identified in 12.8% and 24.3% of samples respectively; 30% of samples showed PD-L1 expression within tumour cells and/or TILs. PD-1 was present in TILs in 22.8% of samples. Majority of samples showed significant presence of CD4+ (focal 42.86%; moderate 2.86%) and CD8+ (focal 92.86%; moderate 4.29%) TILs. IHC findings were confirmed with RT-qPCR; which showed higher expression levels of PD-L1 (p-value 0.007) and PD-1 (p-value 0.001) in samples positive for IHC compared to negative-IHC. Conclusions Thirty-percent of patients express PD-L1 within tumour cells and/or TILs. Identification of presence of TILs was also significant and warrant the investigation of immunotherapy in this setting. PMID:29599916
Palgi, Mari; Greco, Dario; Lindström, Riitta; Auvinen, Petri; Heino, Tapio I
2012-04-11
MANF and CDNF are evolutionarily conserved neurotrophic factors that specifically support dopaminergic neurons. To date, the receptors and signalling pathways of this novel MANF/CDNF family have remained unknown. Independent studies have showed upregulation of MANF by unfolded protein response (UPR). To enlighten the role of MANF in multicellular organism development we carried out a microarray-based analysis of the transcriptional changes induced by the loss and overexpression of Drosophila Manf. The most dramatic change of expression was observed with genes coding membrane transport proteins and genes related to metabolism. When evaluating in parallel the ultrastructural data and transcriptome changes of maternal/zygotic and only zygotic Manf mutants, the endoplasmic reticulum (ER) stress and membrane traffic alterations were evident. In Drosophila Manf mutants the expression of several genes involved in Parkinson's disease (PD) was altered as well. We conclude that besides a neurotrophic factor, Manf is an important cellular survival factor needed to overcome the UPR especially in tissues with high secretory function. In the absence of Manf, the expression of genes involved in membrane transport, particularly exocytosis and endosomal recycling pathway was altered. In neurodegenerative diseases, such as PD, correct protein folding and proteasome function as well as neurotransmitter synthesis and uptake are crucial for the survival of neurons. The degeneration of dopaminergic neurons is the hallmark for PD and our work provides a clue on the mechanisms by which the novel neurotrophic factor MANF protects these neurons.
Glucose-6-phosphate dehydrogenase deficiency in northern Mexico and description of a novel mutation.
García-Magallanes, N; Luque-Ortega, F; Aguilar-Medina, E M; Ramos-Payán, R; Galaviz-Hernández, C; Romero-Quintana, J G; Del Pozo-Yauner, L; Rangel-Villalobos, H; Arámbula-Meraz, E
2014-08-01
Glucose-6-phosphate dehydrogenase deficiency (G6PD) is the most common enzyme pathology in humans; it is X-linked inherited and causes neonatal hyperbilirubinaemia, chronic nonspherocytic haemolytic anaemia and drug-induced acute haemolytic anaemia. G6PD deficiency has scarcely been studied in the northern region of Mexico, which is important because of the genetic heterogeneity described in Mexican population. Therefore, samples from the northern Mexico were biochemically screened for G6PD deficiency, and PCR-RFLPs, and DNA sequencing used to identify mutations in positive samples. The frequency of G6PD deficiency in the population was 0.95% (n = 1993); the mutations in 86% of these samples were G6PD A(-202A/376G), G6PDA(-376G/968C) and G6PD Santamaria(376G/542T). Contrary to previous reports, we demonstrated that G6PD deficiency distribution is relatively homogenous throughout the country (P = 0.48336), and the unique exception with high frequency of G6PD deficiency does not involve a coastal population (Chihuahua: 2.4%). Analysis of eight polymorphic sites showed only 10 haplotypes. In one individual we identified a new G6PD mutation named Mexico DF(193A>G) (rs199474830), which probably results in a damaging functional effect, according to PolyPhen analysis. Proteomic impact of the mutation is also described.
Carter, Nick; Pamba, Allan; Duparc, Stephan; Waitumbi, John N
2011-08-17
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in populations living in malaria endemic areas. G6PD genotype and phenotype were determined for malaria patients enrolled in the chlorproguanil-dapsone-artesunate (CDA) phase III clinical trial programme. Study participants, aged > 1 year, with microscopically confirmed uncomplicated Plasmodium falciparum malaria, and haemoglobin ≥ 70 g/L or haematocrit ≥ 25%, were recruited into two clinical trials conducted in six African countries (Burkina Faso, Ghana, Kenya, Nigeria, Tanzania, Mali). G6PD genotype of the three most common African forms, G6PD*B, G6PD*A (A376G), and G6PD*A- (G202A, A542T, G680T and T968C), were determined and used for frequency estimation. G6PD phenotype was assessed qualitatively using the NADPH fluorescence test. Exploratory analyses investigated the effect of G6PD status on baseline haemoglobin concentration, temperature, asexual parasitaemia and anti-malarial efficacy after treatment with CDA 2/2.5/4 mg/kg or chlorproguanil-dapsone 2/2.5 mg/kg (both given once daily for three days) or six-dose artemether-lumefantrine. Of 2264 malaria patients enrolled, 2045 had G6PD genotype available and comprised the primary analysis population (1018 males, 1027 females). G6PD deficiency prevalence was 9.0% (184/2045; 7.2% [N = 147] male hemizygous plus 1.8% [N = 37] female homozygous), 13.3% (273/2045) of patients were heterozygous females, 77.7% (1588/2045) were G6PD normal. All deficient G6PD*A- genotypes were A376G/G202A. G6PD phenotype was available for 64.5% (1319/2045) of patients: 10.2% (134/1319) were G6PD deficient, 9.6% (127/1319) intermediate, and 80.2% (1058/1319) normal. Phenotype test specificity in detecting hemizygous males was 70.7% (70/99) and 48.0% (12/25) for homozygous females. Logistic regression found no significant effect of G6PD genotype on adjusted mean baseline haemoglobin (p = 0.154), adjusted mean baseline temperature (p = 0.9617), or adjusted log mean baseline parasitaemia (p = 0.365). There was no effect of G6PD genotype (p = 0.490) or phenotype (p = 0.391) on the rate of malaria recrudescence, or reinfection (p = 0.134 and p = 0.354, respectively). G6PD deficiency is common in African patients with malaria and until a reliable and simple G6PD test is available, the use of 8-aminoquinolines will remain problematic. G6PD status did not impact baseline haemoglobin, parasitaemia or temperature or the outcomes of anti-malarial therapy. Clinicaltrials.gov: NCT00344006 and NCT00371735.
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-23
...: Tip Reporting Alternative Commitment (TRAC) for Use in the Food and Beverage Industry. Abstract...., Room 6129, Washington, DC 20224; (202) 622-3634. OMB Reviewer: Shagufta Ahmed, Office of Management and...
Jo, Wan-Kuen; Eun, Sung-Soo; Shin, Seung-Ho
2011-01-01
Limited environmental pollutants have only been investigated for the feasibility of light-emitting diodes (LED) uses in photocatalytic decomposition (PD). The present study investigated the applicability of LEDs for annular photocatalytic reactors by comparing PD efficiencies of dimethyl sulfide (DMS), which has not been investigated with any LED-PD system, between photocatalytic systems utilizing conventional and various LED lamps with different wavelengths. A conventional 8 W UV/TiO(2) system exhibited a higher DMS PD efficiency as compared with UV-LED/TiO(2) system. Similarly, a conventional 8 W visible-lamp/N-enhanced TiO(2) (NET) system exhibited a higher PD efficiency as compared with six visible-LED/NET systems. However, the ratios of PD efficiency to the electric power consumption were rather high for the photocatalytic systems using UV- or visible-LED lamps, except for two LED lamps (yellow- and red-LED lamps), compared to the photocatalytic systems using conventional lamps. For the photocatalytic systems using LEDs, lower flow rates and input concentrations and shorter hydraulic diameters exhibited higher DMS PD efficiencies. An Fourier-transformation infrared analysis suggested no significant absorption of byproducts on the catalyst surface. Consequently, it was suggested that LEDs can still be energy-efficiently utilized as alternative light sources for the PD of DMS, under the operational conditions used in this study. © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.
Barrantes, Sergi; Sánchez Egea, Antonio J; González Rojas, Hernán A; Martí, Maria J; Compta, Yaroslau; Valldeoriola, Francesc; Simo Mezquita, Ester; Tolosa, Eduard; Valls-Solè, Josep
2017-01-01
The differential diagnosis between patients with essential tremor (ET) and those with Parkinson's disease (PD) whose main manifestation is tremor may be difficult unless using complex neuroimaging techniques such as 123I-FP-CIT SPECT. We considered that using smartphone's accelerometer to stablish a diagnostic test based on time-frequency differences between PD an ET could support the clinical diagnosis. The study was carried out in 17 patients with PD, 16 patients with ET, 12 healthy volunteers and 7 patients with tremor of undecided diagnosis (TUD), who were re-evaluated one year after the first visit to reach the definite diagnosis. The smartphone was placed over the hand dorsum to record epochs of 30 s at rest and 30 s during arm stretching. We generated frequency power spectra and calculated receiver operating characteristics curves (ROC) curves of total spectral power, to establish a threshold to separate subjects with and without tremor. In patients with PD and ET, we found that the ROC curve of relative energy was the feature discriminating better between the two groups. This threshold was then used to classify the TUD patients. We could correctly classify 49 out of 52 subjects in the category with/without tremor (97.96% sensitivity and 83.3% specificity) and 27 out of 32 patients in the category PD/ET (84.38% discrimination accuracy). Among TUD patients, 2 of 2 PD and 2 of 4 ET were correctly classified, and one patient having PD plus ET was classified as PD. Based on the analysis of smartphone accelerometer recordings, we found several kinematic features in the analysis of tremor that distinguished first between healthy subjects and patients and, ultimately, between PD and ET patients. The proposed method can give immediate results for the clinician to gain valuable information for the diagnosis of tremor. This can be useful in environments where more sophisticated diagnostic techniques are unavailable.
Increased Risk of Dementia in Patients With Chronic Obstructive Pulmonary Disease.
Liao, Kuang-Ming; Ho, Chung-Han; Ko, Shian-Chin; Li, Chung-Yi
2015-06-01
Neurodegenerative disease in patients with chronic obstructive pulmonary disease (COPD) was observed. We aim to clarify the risk of dementia in patients with COPD. The study used claims data from Taiwan's National Health Insurance Research Database. Subjects were those who received a discharge diagnosis of COPD between January 1, 2002 and December 31, 2011. Only the first hospitalization was enrolled, and the index date was the first day of admission. Patients younger than 40 years or those with a history of Alzheimer disease (AD) or Parkinson disease (PD) before the index date were excluded. The patients with COPD were then followed until receiving a diagnosis of AD or PD, death, or the end of the study. Control subjects were selected from hospitalized patients without a history of COPD, AD, or PD and were matched according to age (±3 years), gender, and the year of admission at a 2:1 ratio. The comorbidities were measured from 1 year before the index date based on the ICD-9-CM codes. The study included 8640 patients with COPD and a mean age of 68.76 (±10.74) years. The adjusted hazard ratio of developing dementia (AD or PD) was 1.74 (95% confidence interval = 1.55-1.96) in patients with COPD compared with patients without COPD after adjusting for age, gender, and comorbidities. This nationwide cohort study demonstrates that the risk of dementia, including AD and PD, is significantly increased in patients with COPD compared with individuals in the general population.
Programming of a flexible computer simulation to visualize pharmacokinetic-pharmacodynamic models.
Lötsch, J; Kobal, G; Geisslinger, G
2004-01-01
Teaching pharmacokinetic-pharmacodynamic (PK/PD) models can be made more effective using computer simulations. We propose the programming of educational PK or PK/PD computer simulations as an alternative to the use of pre-built simulation software. This approach has the advantage of adaptability to non-standard or complicated PK or PK/PD models. Simplicity of the programming procedure was achieved by selecting the LabVIEW programming environment. An intuitive user interface to visualize the time courses of drug concentrations or effects can be obtained with pre-built elements. The environment uses a wiring analogy that resembles electrical circuit diagrams rather than abstract programming code. The goal of high interactivity of the simulation was attained by allowing the program to run in continuously repeating loops. This makes the program behave flexibly to the user input. The programming is described with the aid of a 2-compartment PK simulation. Examples of more sophisticated simulation programs are also given where the PK/PD simulation shows drug input, concentrations in plasma, and at effect site and the effects themselves as a function of time. A multi-compartmental model of morphine, including metabolite kinetics and effects is also included. The programs are available for download from the World Wide Web at http:// www. klinik.uni-frankfurt.de/zpharm/klin/ PKPDsimulation/content.html. For pharmacokineticists who only program occasionally, there is the possibility of building the computer simulation, together with the flexible interactive simulation algorithm for clinical pharmacological teaching in the field of PK/PD models.
Ranganathan, Dwarakanathan; John, George T; Yeoh, Edward; Williams, Nicola; O'Loughlin, Barry; Han, Thin; Jeyaseelan, Lakshmanan; Ramanathan, Kavitha; Healy, Helen
2017-01-01
The optimal time for the commencement of peritoneal dialysis (PD) after PD catheter insertion is unclear. If dialysis is started too soon after insertion, dialysate leaks and infection could occur. However, by starting PD earlier, morbidity and costs can be reduced through lesser hemodialysis requirements. This is the first randomized controlled trial to determine the safest and shortest interval to commence PD after catheter insertion. All consecutive patients undergoing PD catheter insertion at the Royal Brisbane and Women's Hospital and Rockhampton Hospital from 1 March 2008 to 31 May 2013 who met the inclusion and exclusion criteria were invited to participate in the trial. Participants were randomized to 1 of 3 groups. Group 1 (G1) commenced PD at 1 week, group 2 (G2) at 2 weeks and group 3 (G3) at 4 weeks after PD catheter insertion. These groups were stratified by hospital and the presence of diabetes. Primary outcomes were the incidence of peritoneal fluid leaks or PD-related infection during the 4 weeks after commencement of PD. In total 122 participants were recruited, 39, 42, and 41 randomized to G1, G2, and G3, respectively. The primary outcome catheter leak was significantly higher in G1 (28.2%) compared with G3 (2.4%, p = 0.001) but not compared with G2 (9.5%, p = 0.044), based on intention to treat analysis. These differences were even more marked when analyzed with per protocol method: G1 had a significantly higher percentage (32.4 %) compared with G3 (3.3%, p = 0.003) but not compared with G2 (10.5%, p = 0.040). Event percentages of leak were statistically higher in G1 and occurred significantly earlier compared with other groups ( p = 0.002). Amongst diabetics, technique failure was significantly higher (28.6%) in G3 compared with 0% in G1 and 7.1% in G2 ( p = 0.036) and earlier in G3 at 163.2 days vs 176.8 and 175.8 ( p = 0.037) for G1 and G2, respectively. Leaks were higher in participants commencing PD at 1 week after catheter insertion compared with the other 2 groups, and technique failure was higher in diabetics starting PD at 4 weeks. Copyright © 2017 International Society for Peritoneal Dialysis.
Fang, Ling; Gu, Caiyun; Liu, Xinyu; Xie, Jiabin; Hou, Zhiguo; Tian, Meng; Yin, Jia; Li, Aizhu; Li, Yubo
2017-01-01
Primary dysmenorrhea (PD) is a common gynecological disorder which, while not life-threatening, severely affects the quality of life of women. Most patients with PD suffer ovarian hormone imbalances caused by uterine contraction, which results in dysmenorrhea. PD patients may also suffer from increases in estrogen levels caused by increased levels of prostaglandin synthesis and release during luteal regression and early menstruation. Although PD pathogenesis has been previously reported on, these studies only examined the menstrual period and neglected the importance of the luteal regression stage. Therefore, the present study used urine metabolomics to examine changes in endogenous substances and detect urine biomarkers for PD during luteal regression. Ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry was used to create metabolomic profiles for 36 patients with PD and 27 healthy controls. Principal component analysis and partial least squares discriminate analysis were used to investigate the metabolic alterations associated with PD. Ten biomarkers for PD were identified, including ornithine, dihydrocortisol, histidine, citrulline, sphinganine, phytosphingosine, progesterone, 17-hydroxyprogesterone, androstenedione, and 15-keto-prostaglandin F2α. The specificity and sensitivity of these biomarkers was assessed based on the area under the curve of receiver operator characteristic curves, which can be used to distinguish patients with PD from healthy controls. These results provide novel targets for the treatment of PD. PMID:28098892
NASA Astrophysics Data System (ADS)
Okhlopkova, Lyudmila B.; Kerzhentsev, Michail A.; Tuzikov, Fedor V.; Larichev, Yurii V.; Ismagilov, Zinfer R.
2012-09-01
Nanoparticle-doped mesoporous titania coating was synthesized by incorporation of PdZn nanoparticles into TiO2 sol followed by dip coating of the sol on inner surface of fused silica capillary. Monodispersed PdZn bimetallic colloidal particles with average particle diameters of approximately 2 nm have been prepared by an ethylene glycol reduction of ZnCl2 and Pd(CH3COO)2 in the presence of polyvinylpyrrolidone. The textural properties, surface structure, chemical composition, and morphology of the samples were investigated by means of N2 sorption measurements, TEM, and X-ray diffraction. PdZn/TiO2 coating has been further analyzed by quantitative analysis of the SAXS data in combination with the density contrast method, providing direct structural-dispersion information about the active component and support. Calcination conditions suitable for surfactant removal have been optimized to obtain PdZn/TiO2 coatings with required metal particle size and composition. The high dispersion and chemical composition of the nanoparticles embedded in mesoporous titania coating have been retained with no modification after thermal treatment in vacuum at 300 °C. Results suggest how porous structure of the PdZn coating may be fine-tuned to improve the accessibility of the pores to reactants. The control of the pore size in the range of 4.9-6.8 nm of the mesoporous titania was achieved by adding co-surfactants, such as n-butanol.
{sup 45}Sc Solid State NMR studies of the silicides ScTSi (T=Co, Ni, Cu, Ru, Rh, Pd, Ir, Pt)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Harmening, Thomas; Eckert, Hellmut, E-mail: eckerth@uni-muenster.de; Fehse, Constanze M.
The silicides ScTSi (T=Fe, Co, Ni, Cu, Ru, Rh, Pd, Ir, Pt) were synthesized by arc-melting and characterized by X-ray powder diffraction. The structures of ScCoSi, ScRuSi, ScPdSi, and ScIrSi were refined from single crystal diffractometer data. These silicides crystallize with the TiNiSi type, space group Pnma. No systematic influences of the {sup 45}Sc isotropic magnetic shift and nuclear electric quadrupolar coupling parameters on various structural distortion parameters calculated from the crystal structure data can be detected. {sup 45}Sc MAS-NMR data suggest systematic trends in the local electronic structure probed by the scandium atoms: both the electric field gradients andmore » the isotropic magnetic shifts relative to a 0.2 M aqueous Sc(NO{sub 3}){sub 3} solution decrease with increasing valence electron concentration and within each T group the isotropic magnetic shift decreases monotonically with increasing atomic number. The {sup 45}Sc nuclear electric quadrupolar coupling constants are generally well reproduced by quantum mechanical electric field gradient calculations using the WIEN2k code. Highlights: Black-Right-Pointing-Pointer Arc-melting synthesis of silicides ScTSi. Black-Right-Pointing-Pointer Single crystal X-ray data of ScCoSi, ScRuSi, ScPdSi, and ScIrSi. Black-Right-Pointing-Pointer {sup 45}Sc solid state NMR of silicides ScTSi.« less
Beger, Hans G; Poch, Bertram; Mayer, Benjamin; Siech, Marco
2018-02-01
The aim of this study was to assess the frequency and severity of new onset of diabetes mellitus (NODM) and pancreatic exocrine insufficiency (PEI) after pancreaticoduodenectomy (PD) for benign and malignant tumors. When PD is performed on patients for benign tumors, the question of long-term metabolic dysfunctions becomes of importance. Medline/PubMed, Embase, and Cochrane Library were searched for articles reporting results of measuring endocrine and exocrine pancreatic functions after PD. The methodological quality of 19 studies was assessed by means of the Newcastle-Ottawa scale and Moga-Score. The mean weighted overall percentages of NODM and PEI after PD were calculated with a 95% confidence interval (CI). Of 1295 patients, data valid-for-efficacy-analysis are based on 845 patients measuring pancreatic endocrine and on 964 patients determining exocrine functions after PD. The cumulative incidence of NODM was 40 of 275 patients (14.5%; 95% CI: 10.3-18.7) in the benign tumor group, 25 of 161 (15.5%; 95% CI: 9.9-21.2) in the malignant tumor group, and 91 of 409 patients (22.2%; 95% CI: 18.2-26.3) in the benign and malignant tumor group. Comparing the frequency of NODM after PD revealed significant differences between the groups (benign vs benign and malignant P < 0.0121; malignant vs benign and malignant P < 0.0017). Exocrine pancreatic insufficiency was found in the benign tumor group in 76 of 301 patients (25.2%; 95% CI: 20.3-30.7) and in the malignant tumor group in 80 of 163 patients (49.1%, 95% CI: 41.4-56.8) (P < 0.0001). The results of a significant increase of NODM after PD for benign and malignant tumors and a significant decrease of exocrine functions contribute to a rational weighting of metabolic long-term risks following PD.
Local structure order in Pd 78Cu 6Si 16 liquid
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yue, G. Q.; Zhang, Y.; Sun, Y.
2015-02-05
The short-range order (SRO) in Pd 78Cu 6Si 16 liquid was studied by high energy x-ray diffraction and ab initio molecular dynamics (MD) simulations. The calculated pair correlation functions at different temperatures agree well with the experimental results. The partial pair correlation functions from ab intio MD simulations indicate that Si atoms prefer to be uniformly distributed while Cu atoms tend to aggregate. By performing structure analysis using Honeycutt-Andersen index, Voronoi tessellation, and atomic cluster alignment method, we show that the icosahedron and face-centered cubic SRO increase upon cooling. The dominant SRO is the Pd-centered Pd 9Si 2 motif, namelymore » the structure of which motif is similar to the structure of Pd-centered clusters in the Pd 9Si 2 crystal. The study further confirms the existence of trigonal prism capped with three half-octahedra that is reported as a structural unit in Pd-based amorphous alloys. The majority of Cu-centered clusters are icosahedra, suggesting that the presence of Cu is benefit to promote the glass forming ability.« less
Baran, Talat; Inanan, Tülden; Menteş, Ayfer
2016-07-10
The aim of this study is to analyze the synthesis of a new chitosan supported Pd catalyst and examination of its catalytic activity in: Pd catalyst was synthesized using chitosan as a biomaterial and characterized with FTIR, TG/DTG, XRD, (1)H NMR, (13)C NMR, SEM-EDAX, ICP-OES, Uv-vis spectroscopies, and magnetic moment, along with molar conductivity analysis. Biomaterial supported Pd catalyst indicated high activity and long life time as well as excellent turnover number (TON) and turnover frequency (TOF) values in Suzuki reaction. Biomaterial supported Pd catalyst catalyzed H2O2 decomposition reaction with considerable high activity using comparatively small loading catalyst (10mg). Redox potential of biomaterial supported Pd catalyst was still high without negligible loss (13% decrease) after 10 cycles in reusability tests. As a consequence, eco-friendly biomaterial supported Pd catalyst has superior properties such as high thermal stability, long life time, easy removal from reaction mixture and durability to air, moisture and high temperature. Copyright © 2016 Elsevier Ltd. All rights reserved.
Silencing of the pentose phosphate pathway genes influences DNA replication in human fibroblasts.
Fornalewicz, Karolina; Wieczorek, Aneta; Węgrzyn, Grzegorz; Łyżeń, Robert
2017-11-30
Previous reports and our recently published data indicated that some enzymes of glycolysis and the tricarboxylic acid cycle can affect the genome replication process by changing either the efficiency or timing of DNA synthesis in human normal cells. Both these pathways are connected with the pentose phosphate pathway (PPP pathway). The PPP pathway supports cell growth by generating energy and precursors for nucleotides and amino acids. Therefore, we asked if silencing of genes coding for enzymes involved in the pentose phosphate pathway may also affect the control of DNA replication in human fibroblasts. Particular genes coding for PPP pathway enzymes were partially silenced with specific siRNAs. Such cells remained viable. We found that silencing of the H6PD, PRPS1, RPE genes caused less efficient enterance to the S phase and decrease in efficiency of DNA synthesis. On the other hand, in cells treated with siRNA against G6PD, RBKS and TALDO genes, the fraction of cells entering the S phase was increased. However, only in the case of G6PD and TALDO, the ratio of BrdU incorporation to DNA was significantly changed. The presented results together with our previously published studies illustrate the complexity of the influence of genes coding for central carbon metabolism on the control of DNA replication in human fibroblasts, and indicate which of them are especially important in this process. Copyright © 2017 Elsevier B.V. All rights reserved.
Associations of welding and manganese exposure with Parkinson disease
Borenstein, Amy R.; Nelson, Lorene M.
2012-01-01
Objective: To examine associations of welding and manganese exposure with Parkinson disease (PD) using meta-analyses of data from cohort, case-control, and mortality studies. Methods: Epidemiologic studies related to welding or manganese exposure and PD were identified in a PubMed search, article references, published reviews, and abstracts. Inclusion criteria were 1) cohort, case-control, or mortality study with relative risk (RR), odds ratio (OR), or mortality OR (MOR) and 95 confidence intervals (95% CI); 2) RR, OR, and MOR matched or adjusted for age and sex; 3) valid study design and analysis. When participants of a study were a subgroup of those in a larger study, only results of the larger study were included to assure independence of datasets. Pooled RR/OR estimates and 95% CIs were obtained using random effects models; heterogeneity of study effects were evaluated using the Q statistic and I2 index in fixed effect models. Results: Thirteen studies met inclusion criteria for the welding meta-analysis and 3 studies for the manganese exposure meta-analysis. The pooled RR for the association between welding and PD for all study designs was 0.86 (95% CI 0.80–0.92), with absence of between-study heterogeneity (I2 = 0.0). Effect measures for cohort, case-control, and mortality studies were similar (0.91, 0.82, 0.87). For the association between manganese exposure and PD, the pooled OR was 0.76 (95% CI 0.41–1.42). Conclusions: Welding and manganese exposure are not associated with increased PD risk. Possible explanations for the inverse association between welding and PD include confounding by smoking, healthy worker effect, and hormesis. PMID:22965675
Wang, Dian; Stahl, Shannon S
2017-04-26
Copper salts find widespread use in Pd-catalyzed oxidation reactions, and they are typically used as oxidants or redox-active cocatalysts. Here, we probe the origin of a dramatic acceleration effect of Cu(OTf) 2 in the C-H/C-H aerobic oxidative coupling of o-xylene. NMR spectroscopic analysis of the Pd II catalyst in the presence of Cu(OTf) 2 , together with other experimental and DFT computational studies of the catalytic reaction, show that Cu(OTf) 2 activates the Pd II catalyst for C-H activation via a non-redox pathway and has negligible impact on catalyst reoxidation. These observations led to the testing of other metal triflate salts as cocatalysts, the results of which show that Fe(OTf) 3 is even more effective than Cu(OTf) 2 .
Gu, Shaojin; Xu, Hui; Zhang, Na; Chen, Wanzhi
2010-07-05
Imidazolium salts bearing triazole groups are synthesized via a copper catalyzed click reaction, and the silver, palladium, and platinum complexes of their N-heterocyclic carbenes are studied. [Ag(4)(L1)(4)](PF(6))(4), [Pd(L1)Cl](PF(6)), [Pt(L1)Cl](PF(6)) (L1=3-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1-(pyrimidin-2-yl)-1H-imidazolylidene), [Pd(2)(L2)(2)Cl(2)](PF(6))(2), and [Pd(L2)(2)](PF(6))(2) (L2=1-butyl-3-((1-(pyridin-2-yl)-1H-1,2,3-triazol-4-yl)methyl)imidazolylidene) have been synthesized and fully characterized by NMR, elemental analysis, and X-ray crystallography. The silver complex [Ag(4)(L1)(4)](PF(6))(4) consists of a Ag(4) zigzag chain. The complexes [Pd(L1)Cl](PF(6)) and [Pt(L1)Cl](PF(6)), containing a nonsymmetrical NCN' pincer ligand, are square planar with a chloride trans to the carbene donor. [Pd(2)(L2)(2)Cl(2)](PF(6))(2) consists of two palladium centers with CN(2)Cl coordination mode, whereas the palladium in [Pd(L2)(2)](PF(6))(2) is surrounded by two carbene and two triazole groups with two uncoordinated pyridines. The palladium compounds are highly active for Suzuki-Miyaura cross coupling reactions of aryl bromides and 1,1-dibromo-1-alkenes in neat water under an air atmosphere.
Sleep abnormalities in children with Dravet syndrome.
Dhamija, Radhika; Erickson, Maia K; St Louis, Erik K; Wirrell, Elaine; Kotagal, Suresh
2014-05-01
Mutations in the voltage-gated sodium channel SCN1A gene are responsible for the majority of Dravet syndrome cases. There is evidence that the Nav1.1 channel coded by the SCN1A gene is involved in sleep regulation. We evaluated sleep abnormalities in children with Dravet syndrome using nocturnal polysomnography. We identified six children at our institution with genetically confirmed Dravet syndrome who had also undergone formal sleep consultation with nocturnal polysomnography. Indications for polysomnography were parental concern of daytime fatigue or sleepiness, hyperactivity, inattention, disruptive behavior, nighttime awakenings, or nocturnal seizures. Sleep studies were scored according to guidelines of the American Academy of Sleep Medicine and non-rapid eye movement cyclic alternating pattern was visually identified and scored according to established methods. The mean age of the subjects at the time of polysomnography was 6 years. Standard polysomnography did not show any consistent abnormalities in the obstructive or central apnea index, arousal index, sleep efficiency, or architecture. Cyclic alternating pattern analysis on five patients showed an increased mean rate of 50.3% (vs 31% to 34% in neurological normal children) with a mild increase in A1 subtype of 89.4% (vs 84.5%). A2/A3 subtype (5.3% vs 7.3%) and B phase duration (22.4 vs 24.7 seconds) were similar to previously reported findings in neurologically normal children. Despite parental concerns for sleep disturbance in patients with Dravet syndrome, we could not identify abnormalities in sleep macroarchitecture. Non-rapid eye movement sleep microarchitecture was, however, abnormal, with increased A1 subtype, somewhat resembling a tracé alternant pattern of neonates and possibly suggestive of cortical synaptic immaturity in Dravet syndrome. Larger studies are needed to replicate these results. Copyright © 2014 Elsevier Inc. All rights reserved.
Fang, Yuan; Zheng, Tao; Liu, Lanxiang; Gao, Dawei; Shi, Qinglei; Dong, Yanchao; Du, Dan
2017-11-17
Simple diffusion delivery (SDD) has attained good effects with only tiny amounts of drugs. Fractional anisotropy (FA) and relaxation time T2* that indicate the integrity of fiber tracts and iron concentration within brain tissue were used to evaluate the therapeutic effect of SDD. To evaluate therapeutic effect of SDD in the Parkinson's disease (PD) rat model with FA and T2* parameters. Prospective case-control animal study. Thirty-two male Sprague Dawley rats (eight normal, eight PD, eight SDD, and eight subcutaneous injection rats). Single-shot spin echo echo-planar imaging and fast low-angle shot T 2 WI sequences at 3.0T. Parameters of FA and T2* on the treated side of the substantia nigra were measured to evaluate the therapeutic effect of SDD in a PD rat model. The effects of time on FA and T2* values were analyzed by repeated measurement tests. A one-way analysis of variance was conducted, followed by individual comparisons of the mean FA and T2* values at different timepoints. The FA values on the treated side of the substantia nigra in the SDD treatment group and subcutaneous injection treatment group were significantly higher at week 1 and lower at week 6 than that of the PD control group (SDD vs. PD, week 1, adjusted P = 0.012; subcutaneous vs. PD, week 1, adjusted P < 0.001; SDD vs. PD, week 6, adjusted P = 0.004; subcutaneous vs. PD, week 6, adjusted P = 0.024). The T2* parameter in the SDD treatment group and subcutaneous injection treatment group was significantly higher than that in the PD control group at week 6 (SDD vs. PD, adjusted P = 0.032; subcutaneous vs. PD, adjusted P < 0.001). The combination of FA and T2* parameters can potentially serve as a new effective evaluation method of the therapeutic effect of SDD. 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2017. © 2017 International Society for Magnetic Resonance in Medicine.
Hu, Yang-Bo; Zhang, Qun; Li, Hui-Juan; Michot, Jean Maire; Liu, Hong-Bing
2017-01-01
Background Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitor therapy is showing marked efficacy in advanced non-small cell lung cancer (NSCLC). Meanwhile, it is concomitant with distinctive immune-related adverse effects. We aim to describe the incidence of pneumonitis and other rare but severe immune-related adverse effects (IRAEs), as well as treatment related deaths. In addition, we analyze the differences in incidence of pneumonitis between PD-1 and PD-L1 inhibitors and standard-of-care chemotherapy. Methods PubMed was searched up to 24 March 2017 for clinical trials of PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, avelumab and durvalumab) in treatment of NSCLC. Besides, references of relevant articles were screened. Results Finally, 22 trials were included in our study, 14 with data of pneumonitis, 19 with other severe IRAEs or treatment related deaths and 5 with control groups. Incidence of all-grade pneumonitis was 2.9% (95% CI, 2.0–4.8%) and grade 3 or higher pneumonitis 2.0% (95% CI, 1.0–2.0%). Incidence of all-grade pneumonitis in PD-1 and PD-L1 inhibitor therapy (n=1,313) was significantly higher than that in chemotherapy (n=918) (OR=2.35, 95% CI, 1.32–4.20, P=0.004), but had no significance in grade 3–5 pneumonitis. Incidence of cardiorespiratory arrest (n=537) was 1.0% (95% CI, 0–2.0%), cardiac failure (n=214) 2.0% (95% CI, 1.0–5.7%), myocardial infarction (n=402) 1.0% (95% CI, 0–3.8%), stroke (n=135) 2.0% (95% CI, 0–13.0%), disease progression (n=391) 1.0% (95% CI, 0–2.9%), pancreatitis (n=700) 1.0% (95% CI, 0–2.0%) and severe skin reactions (n=836) 2.0% (95% CI, 1.0–3.8%). Incidence of treatment related deaths was 0.7%. Conclusions Immune related adverse effects can on occasion be life-threatening even though usually rare. Incidence of pneumonitis in PD-1 and PD-L1 inhibitors was significantly higher than that in chemotherapy. More studies should be conducted to investigate the incidence of these rare but life-threatening IRAEs. PMID:29299404
Giladi, Nir; Nicholas, Anthony P.; Asgharnejad, Mahnaz; Dohin, Elisabeth; Woltering, Franz; Bauer, Lars; Poewe, Werner
2016-01-01
Background: The efficacy of rotigotine has been demonstrated in studies of patients with early (i.e. not receiving levodopa) and advanced (i.e. not adequately controlled on levodopa; average 2.5 h/day in ‘off’ state) Parkinson’s disease (PD). Objective: To further investigate the efficacy of rotigotine transdermal patch across different stages of PD symptom severity and functional disability, according to baseline Hoehn and Yahr (HY) staging. Methods: Post hoc analysis of six placebo-controlled studies of rotigotine in patients with early PD (SP506, SP512, SP513; rotigotine ≤8 mg/24 h) or advanced-PD (CLEOPATRA-PD, PREFER, SP921; rotigotine ≤16 mg/24 h). Data were pooled and analyzed according to baseline HY stage (1, 2, 3 or 4) for change from baseline to end of maintenance in Unified Parkinson’s Disease Rating Scale (UPDRS) II (activities of daily living), UPDRS III (motor) and UPDRS II+III; statistical tests are exploratory. Results: Data were available for 2057 patients (HY 1 : 262; HY 2 : 1230; HY 3 : 524; HY 4 : 41). Patients at higher HY stages were older, had a longer time since PD diagnosis and higher baseline UPDRS II+III scores vs patients at lower HY stages. Rotigotine improved UPDRS II+III versus placebo for each individual HY stage (p < 0.05 for each HY stage), with treatment differences increasing with increasing HY stages. Similar results were observed for UPDRS II and UPDRS III. Conclusions: This post hoc analysis suggests that rotigotine may be efficacious across a broad range of progressive stages of PD symptom severity and functional disability (HY stages 1–4). PMID:27567886
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