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  1. 40 CFR Table 10 to Subpart IIIii... - Applicability of General Provisions to Subpart IIIII

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 10 Table 10 to Subpart IIIII of Part... monitoring plan in lieu of a promulgated performance specification for a mercury concentration CMS. § 63.8(a...

  2. 40 CFR Table 10 to Subpart IIIii... - Applicability of General Provisions to Subpart IIIII

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 10 Table 10 to Subpart IIIII of Part... monitoring plan in lieu of a promulgated performance specification for a mercury concentration CMS. § 63.8(a...

  3. 40 CFR Table 10 to Subpart IIIii... - Applicability of General Provisions to Subpart IIIII

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 10 Table 10 to Subpart IIIII of Part... monitoring plan in lieu of a promulgated performance specification for a mercury concentration CMS. § 63.8(a...

  4. 40 CFR Table 10 to Subpart IIIii... - Applicability of General Provisions to Subpart IIIII

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 10 Table 10 to Subpart IIIII of Part... monitoring plan in lieu of a promulgated performance specification for a mercury concentration CMS. §...

  5. 40 CFR Table 10 to Subpart IIIii... - Applicability of General Provisions to Subpart IIIII

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 10 Table 10 to Subpart IIIII of Part... monitoring plan in lieu of a promulgated performance specification for a mercury concentration CMS. §...

  6. 40 CFR Table 8 to Subpart IIIii of... - Requirements for Cell Room Monitoring Program

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 13 2011-07-01 2011-07-01 false Requirements for Cell Room Monitoring... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 8 Table 8 to Subpart IIIII of Part 63—Requirements for Cell Room Monitoring Program As stated in § 63.8192(g)(1), your mercury monitoring system...

  7. 40 CFR Table 8 to Subpart IIIii of... - Requirements for Cell Room Monitoring Program

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 13 2010-07-01 2010-07-01 false Requirements for Cell Room Monitoring... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 8 Table 8 to Subpart IIIII of Part 63—Requirements for Cell Room Monitoring Program As stated in § 63.8192(g)(1), your mercury monitoring system...

  8. 40 CFR Table 9 to Subpart IIIii of... - Required Records for Work Practice Standards

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 9 Table 9 to Subpart IIIII of Part 63... other deficiency in a cell room floor, pillar, or beam that could cause liquid mercury to become trapped.... f. If you take a cell off line or isolate the leaking equipment, the date and time you take the...

  9. 40 CFR Table 2 to Subpart IIIii of... - Work Practice Standards-Required Inspections

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 2 Table 2 to Subpart IIIII of Part 63—Work... must . . . 1. Each vent hose on each mercury cell Half day A leaking vent hose Take action immediately... mercury seal pot stopper securely in place. 6. Cell room floors Month Cracks, spalling, or...

  10. 40 CFR Table 7 to Subpart IIIii of... - Required Elements of Washdown Plans

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 7 Table 7 to Subpart IIIII of Part 63... following as part of your plan . . . 1. Center aisles of cell rooms A description of the manner of washdown... baskets 6. Hydrogen system piping 7. Basement floor of cell rooms 8. Tanks 9. Pillars and beams in...

  11. 40 CFR Table 7 to Subpart IIIii of... - Required Elements of Washdown Plans

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 7 Table 7 to Subpart IIIII of Part 63... following as part of your plan . . . 1. Center aisles of cell rooms A description of the manner of washdown... baskets 6. Hydrogen system piping 7. Basement floor of cell rooms 8. Tanks 9. Pillars and beams in...

  12. 40 CFR Table 7 to Subpart IIIii of... - Required Elements of Washdown Plans

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 7 Table 7 to Subpart IIIII of Part 63... following as part of your plan . . . 1. Center aisles of cell rooms A description of the manner of washdown... baskets 6. Hydrogen system piping 7. Basement floor of cell rooms 8. Tanks 9. Pillars and beams in...

  13. 40 CFR Table 9 to Subpart IIIii of... - Required Records for Work Practice Standards

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 9 Table 9 to Subpart IIIII of Part 63... other deficiency in a cell room floor, pillar, or beam that could cause liquid mercury to become trapped.... f. If you take a cell off line or isolate the leaking equipment, the date and time you take the...

  14. 40 CFR Table 9 to Subpart IIIii of... - Required Records for Work Practice Standards

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 9 Table 9 to Subpart IIIII of Part 63... other deficiency in a cell room floor, pillar, or beam that could cause liquid mercury to become trapped.... f. If you take a cell off line or isolate the leaking equipment, the date and time you take the...

  15. 40 CFR Table 7 to Subpart IIIii of... - Required Elements of Washdown Plans

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 7 Table 7 to Subpart IIIII of Part 63... following as part of your plan . . . 1. Center aisles of cell rooms A description of the manner of washdown... baskets 6. Hydrogen system piping 7. Basement floor of cell rooms 8. Tanks 9. Pillars and beams in...

  16. 40 CFR Table 9 to Subpart IIIii of... - Required Records for Work Practice Standards

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 9 Table 9 to Subpart IIIII of Part 63... other deficiency in a cell room floor, pillar, or beam that could cause liquid mercury to become trapped.... f. If you take a cell off line or isolate the leaking equipment, the date and time you take the...

  17. 40 CFR Table 2 to Subpart IIIii of... - Work Practice Standards-Required Inspections

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 2 Table 2 to Subpart IIIII of Part 63—Work... must . . . 1. Each vent hose on each mercury cell Half day A leaking vent hose Take action immediately... mercury seal pot stopper securely in place. 6. Cell room floors Month Cracks, spalling, or...

  18. 40 CFR Table 2 to Subpart IIIii of... - Work Practice Standards-Required Inspections

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 2 Table 2 to Subpart IIIII of Part 63—Work... must . . . 1. Each vent hose on each mercury cell Half day A leaking vent hose Take action immediately... mercury seal pot stopper securely in place. 6. Cell room floors Month Cracks, spalling, or...

  19. 40 CFR Table 2 to Subpart IIIii of... - Work Practice Standards-Required Inspections

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 2 Table 2 to Subpart IIIII of Part 63—Work... must . . . 1. Each vent hose on each mercury cell Half day A leaking vent hose Take action immediately... mercury seal pot stopper securely in place. 6. Cell room floors Month Cracks, spalling, or...

  20. 40 CFR Table 2 to Subpart IIIii of... - Work Practice Standards-Required Inspections

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 2 Table 2 to Subpart IIIII of Part 63—Work... must . . . 1. Each vent hose on each mercury cell Half day A leaking vent hose Take action immediately... mercury seal pot stopper securely in place. 6. Cell room floors Month Cracks, spalling, or...

  1. 40 CFR Table 7 to Subpart IIIii of... - Required Elements of Washdown Plans

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 7 Table 7 to Subpart IIIII of Part 63... following as part of your plan . . . 1. Center aisles of cell rooms A description of the manner of washdown... baskets 6. Hydrogen system piping 7. Basement floor of cell rooms 8. Tanks 9. Pillars and beams in...

  2. 40 CFR Table 9 to Subpart IIIii of... - Required Records for Work Practice Standards

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 9 Table 9 to Subpart IIIII of Part 63... other deficiency in a cell room floor, pillar, or beam that could cause liquid mercury to become trapped.... f. If you take a cell off line or isolate the leaking equipment, the date and time you take the...

  3. 40 CFR Table 4 to Subpart IIIii of... - Work Practice Standards-Requirements for Mercury Liquid Collection

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... for Mercury Liquid Collection 4 Table 4 to Subpart IIIII of Part 63 Protection of Environment... Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 4 Table 4 to Subpart IIIII of Part 63—Work Practice Standards—Requirements for Mercury Liquid Collection As stated in...

  4. 40 CFR Table 4 to Subpart IIIii of... - Work Practice Standards-Requirements for Mercury Liquid Collection

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... for Mercury Liquid Collection 4 Table 4 to Subpart IIIII of Part 63 Protection of Environment... Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 4 Table 4 to Subpart IIIII of Part 63—Work Practice Standards—Requirements for Mercury Liquid Collection As stated in...

  5. 40 CFR Table 4 to Subpart IIIii of... - Work Practice Standards-Requirements for Mercury Liquid Collection

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... for Mercury Liquid Collection 4 Table 4 to Subpart IIIII of Part 63 Protection of Environment... Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 4 Table 4 to Subpart IIIII of Part 63—Work Practice Standards—Requirements for Mercury Liquid Collection As stated in...

  6. 40 CFR Table 4 to Subpart IIIii of... - Work Practice Standards-Requirements for Mercury Liquid Collection

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... for Mercury Liquid Collection 4 Table 4 to Subpart IIIII of Part 63 Protection of Environment... Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 4 Table 4 to Subpart IIIII of Part 63—Work Practice Standards—Requirements for Mercury Liquid Collection As stated...

  7. 40 CFR Table 4 to Subpart IIIii of... - Work Practice Standards-Requirements for Mercury Liquid Collection

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... for Mercury Liquid Collection 4 Table 4 to Subpart IIIII of Part 63 Protection of Environment... Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 4 Table 4 to Subpart IIIII of Part 63—Work Practice Standards—Requirements for Mercury Liquid Collection As stated...

  8. Renal Tubular Mitochondrial Abnormalities in Complex II/III Respiratory Chain Deficiency.

    PubMed

    France, Joel; Ashoor, Isa; Craver, Randall

    2017-06-01

    Defects in the respiratory chain may present with a wide spectrum of clinical signs and symptoms. In this "Images in Pathology" discussion we correlate the clinical, histologic, and ultrastructural findings in a 12-year-old male with a complex II/III respiratory chain deficiency and kidney dysfunction.

  9. Multicenter prospective validation of the Baveno IV and Baveno II/III criteria in cirrhosis patients with variceal bleeding.

    PubMed

    Thabut, Dominique; Rudler, Marika; Dib, Nina; Carbonell, Nicolas; Mathurin, Philippe; Saliba, Faouzi; Mallet, Alain; Massard, Julien; Bernard-Chabert, Brigitte; Oberti, Frederic; Cales, Paul; Golmard, Jean-Louis; Bureau, Christophe

    2015-03-01

    The criteria for defining failure to control bleeding in cirrhosis patients were introduced at the Baveno II/III meetings and were widely used as endpoints in clinical trials. Because they lacked specificity, the Baveno IV criteria were proposed in 2005 and slightly modified in 2010 (Baveno V). These criteria included a new index for patients undergoing transfusion, called adjusted-blood-requirement-index (ABRI=number of blood units/(final-initial hematocrit+0.01)), with a cutoff value of 0.75. In this multicenter prospective study, we sought to 1) validate the Baveno IV/V criteria; 2) compare them to the Baveno II/III criteria; 3) assess ABRI performance using a standardized calculation. The key inclusion criteria were: 1) variceal bleeding; 2) cirrhosis; 3) no need to modify the transfusion policy. The patients were classified according to the Baveno IV, V, and II/III criteria. The gold standard for failure during a 5-day period was the clinical judgment of three independent experts, blinded to the Baveno assessments. A total of 249 patients were included. The experts' agreement in clinical judgment of the failure was 80%. Failure occurred in 20.5% of patients; the c-statistics were 0.72 versus 0.64 and 0.65 for Baveno IV versus Baveno II/III and Baveno V criteria (P=0.001 for both). ABRI did not improve the diagnostic performance of the Baveno IV criteria. The Baveno IV, but not Baveno II/III, criteria independently predicted survival. The Baveno IV criteria demonstrated a higher accuracy than the Baveno II/III and Baveno V criteria for assessing failure to control bleeding and predicted survival independently. Together, our results show that ABRI is not a useful metric, and the Baveno IV criteria should replace the Baveno II/III criteria. © 2014 by the American Association for the Study of Liver Diseases.

  10. Cholinergic suppression of excitatory synaptic transmission in layers II/III of the parasubiculum.

    PubMed

    Glasgow, S D; Glovaci, I; Karpowicz, L S; Chapman, C A

    2012-01-10

    Layer II of the parasubiculum (PaS) receives excitatory synaptic input from the CA1 region of the hippocampus and sends a major output to layer II of the medial and lateral entorhinal cortex. The PaS also receives heavy cholinergic innervation from the medial septum, which contributes to the generation of theta-frequency (4-12 Hz) electroencephalographic (EEG) activity. Cholinergic receptor activation exerts a wide range of effects in other areas of the hippocampal formation, including membrane depolarization, changes in neuronal excitability, and suppression of excitatory synaptic responses. The present study was aimed at determining how cholinergic receptor activation modulates excitatory synaptic input to the layer II/III neurons of the PaS in acute brain slices. Field excitatory postsynaptic potentials (fEPSPs) in layer II/III of the PaS were evoked by stimulation of either layer I afferents, or ascending inputs from layer V. Bath-application of the cholinergic agonist carbachol (0.5-10 μM) suppressed the amplitude of fEPSPs evoked by both superficial- and deep layer stimulation, and also enhanced paired-pulse facilitation. Constant bath-application of the GABA(A) antagonist bicuculline (10 μM) failed to eliminate the suppression, indicating that the cholinergic suppression of fEPSPs is not due to increased inhibitory tone. The muscarinic receptor antagonist atropine (1 μM) blocked the suppression of fEPSPs, and the selective M(1)-preferring receptor antagonist pirenzepine (1 μM), but not the M(2)-preferring antagonist methoctramine (1-5 μM), also significantly attenuated the suppression. Therefore, cholinergic receptor activation suppresses excitatory synaptic input to layer II/III neurons of the PaS, and this suppression is mediated in part by M(1) receptor activation.

  11. Esophagus or stomach? The seventh TNM classification for Siewert type II/III junctional adenocarcinoma.

    PubMed

    Hasegawa, Shinichi; Yoshikawa, Takaki; Aoyama, Toru; Hayashi, Tsutomu; Yamada, Takanobu; Tsuchida, Kazuhito; Cho, Haruhiko; Oshima, Takashi; Yukawa, Norio; Rino, Yasushi; Masuda, Munetaka; Tsuburaya, Akira

    2013-03-01

    The aim of this study is to clarify whether TNM-EC or TNM-GC is better for classifying patients with AEG types II/III. The patients who had AEG types II/III and received D1 or more radical lymphadenectomy were selected. The patients were staged both by seventh edition of TNM-EC and TNM-GC. The distribution of the patients, the hazard ratio (HR) of each stage, and the separation of the survival were compared. A total of 163 patients were enrolled in this study. TNM-EC and TNM-GC classified 25 (20 and 5) and 32 (20 and 12) patients to stage I (IA and IB), 15 (4 and 11), and 33 (11 and 22) to stage II (IIA and IIB), 88 (24, 3, and 61) and 63 (14, 26, and 23) to stage III (IIIA, IIIB, and IIIC), and 35 and 35 to stage IV, respectively. The distribution of the patients was substantially deviated to stage IIIC in TNM-EC but was almost even in TNM-GC. A stepwise increase of HR was observed in TNM-GC, but not in TNM-EC. The survival curves between stages II and III were significantly separated in TNM-GC (P = 0.019), but not in TNM-EC (P = 0.204). The 5-year survival rates of stages IIIA, IIIB, and IIIC were 69.0, 100, and 38.9% in TNM-EC and were 52.0, 43.4, and 33.9% in TNM-GC, respectively. TNM-GC is better for classifying patients with AEG types II/III than TNM-EC is. These results could impact the next TNM revision for AEG.

  12. A modified varying-stage adaptive phase II/III clinical trial design.

    PubMed

    Dong, Gaohong; Vandemeulebroecke, Marc

    2016-07-01

    Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  13. 40 CFR Table 5 to Subpart IIIii of... - Required Elements of Floor-Level Mercury Vapor Measurement and Cell Room Monitoring Plans

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Mercury Vapor Measurement and Cell Room Monitoring Plans 5 Table 5 to Subpart IIIII of Part 63 Protection... Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII... and Cell Room Monitoring Plans Your Floor-Level Mercury Vapor Measurement Plan required by §...

  14. 40 CFR Table 5 to Subpart IIIii of... - Required Elements of Floor-Level Mercury Vapor Measurement and Cell Room Monitoring Plans

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Mercury Vapor Measurement and Cell Room Monitoring Plans 5 Table 5 to Subpart IIIII of Part 63 Protection... Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII... and Cell Room Monitoring Plans Your Floor-Level Mercury Vapor Measurement Plan required by §...

  15. 40 CFR Table 3 to Subpart IIIii of... - Work Practice Standards-Required Actions for Liquid Mercury Spills and Accumulations and Hydrogen...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) National Emission Standards for Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 3 Table 3 to Subpart IIIII of Part 63—Work Practice... that you cannot repair the leaking equipment without taking the cell off line, provided that...

  16. 40 CFR Table 5 to Subpart IIIii of... - Required Elements of Floor-Level Mercury Vapor Measurement and Cell Room Monitoring Plans

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII... Mercury Vapor Measurement and Cell Room Monitoring Plans 5 Table 5 to Subpart IIIII of Part 63 Protection... and Cell Room Monitoring Plans Your Floor-Level Mercury Vapor Measurement Plan required by §...

  17. 40 CFR Table 5 to Subpart IIIii of... - Required Elements of Floor-Level Mercury Vapor Measurement and Cell Room Monitoring Plans

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII... Mercury Vapor Measurement and Cell Room Monitoring Plans 5 Table 5 to Subpart IIIII of Part 63 Protection... and Cell Room Monitoring Plans Your Floor-Level Mercury Vapor Measurement Plan required by §...

  18. 40 CFR Table 3 to Subpart IIIii of... - Work Practice Standards-Required Actions for Liquid Mercury Spills and Accumulations and Hydrogen...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (CONTINUED) National Emission Standards for Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 3 Table 3 to Subpart IIIII of Part 63—Work Practice... that you cannot repair the leaking equipment without taking the cell off line, provided that...

  19. 40 CFR Table 3 to Subpart IIIii of... - Work Practice Standards-Required Actions for Liquid Mercury Spills and Accumulations and Hydrogen...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) National Emission Standards for Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 3 Table 3 to Subpart IIIII of Part 63—Work Practice... that you cannot repair the leaking equipment without taking the cell off line, provided that...

  20. 40 CFR Table 3 to Subpart IIIii of... - Work Practice Standards-Required Actions for Liquid Mercury Spills and Accumulations and Hydrogen...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) National Emission Standards for Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 3 Table 3 to Subpart IIIII of Part 63—Work Practice... that you cannot repair the leaking equipment without taking the cell off line, provided that...

  1. 40 CFR Table 5 to Subpart IIIii of... - Required Elements of Floor-Level Mercury Vapor Measurement and Cell Room Monitoring Plans

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII... Mercury Vapor Measurement and Cell Room Monitoring Plans 5 Table 5 to Subpart IIIII of Part 63 Protection... and Cell Room Monitoring Plans Your Floor-Level Mercury Vapor Measurement Plan required by §...

  2. Risk of node metastasis of sentinel lymph nodes detected in level II/III of the axilla by single-photon emission computed tomography/computed tomography

    PubMed Central

    SHIMA, HIROAKI; KUTOMI, GORO; SATOMI, FUKINO; MAEDA, HIDEKI; TAKAMARU, TOMOKO; KAMESHIMA, HIDEKAZU; OMURA, TOSEI; MORI, MITSURU; HATAKENAKA, MASAMITSU; HASEGAWA, TADASHI; HIRATA, KOICHI

    2014-01-01

    In breast cancer, single-photon emission computed tomography/computed tomography (SPECT/CT) shows the exact anatomical location of sentinel nodes (SN). SPECT/CT mainly exposes axilla and partly exposes atypical sites of extra-axillary lymphatic drainage. The mechanism of how the atypical hot nodes are involved in lymphatic metastasis was retrospectively investigated in the present study, particularly at the level II/III region. SPECT/CT was performed in 92 clinical stage 0-IIA breast cancer patients. Sentinel lymph nodes are depicted as hot nodes in SPECT/CT. Patients were divided into two groups: With or without hot node in level II/III on SPECT/CT. The existence of metastasis in level II/III was investigated and the risk factors were identified. A total of 12 patients were sentinel lymph node biopsy metastasis positive and axillary lymph node dissection (ALND) was performed. These patients were divided into two groups: With and without SN in level II/III, and nodes in level II/III were pathologically proven. In 11 of the 92 patients, hot nodes were detected in level II/III. There was a significant difference in node metastasis depending on whether there were hot nodes in level II/III (P=0.0319). Multivariate analysis indicated that the hot nodes in level II/III and lymphatic invasion were independent factors associated with node metastasis. There were 12 SN-positive patients followed by ALND. In four of the 12 patients, hot nodes were observed in level II/III. Two of the four patients with hot nodes depicted by SPECT/CT and metastatic nodes were pathologically evident in the same lesion. Therefore, the present study indicated that the hot node in level II/III as depicted by SPECT/CT may be a risk of SN metastasis, including deeper nodes. PMID:25289038

  3. Risk of node metastasis of sentinel lymph nodes detected in level II/III of the axilla by single-photon emission computed tomography/computed tomography.

    PubMed

    Shima, Hiroaki; Kutomi, Goro; Satomi, Fukino; Maeda, Hideki; Takamaru, Tomoko; Kameshima, Hidekazu; Omura, Tosei; Mori, Mitsuru; Hatakenaka, Masamitsu; Hasegawa, Tadashi; Hirata, Koichi

    2014-11-01

    In breast cancer, single-photon emission computed tomography/computed tomography (SPECT/CT) shows the exact anatomical location of sentinel nodes (SN). SPECT/CT mainly exposes axilla and partly exposes atypical sites of extra-axillary lymphatic drainage. The mechanism of how the atypical hot nodes are involved in lymphatic metastasis was retrospectively investigated in the present study, particularly at the level II/III region. SPECT/CT was performed in 92 clinical stage 0-IIA breast cancer patients. Sentinel lymph nodes are depicted as hot nodes in SPECT/CT. Patients were divided into two groups: With or without hot node in level II/III on SPECT/CT. The existence of metastasis in level II/III was investigated and the risk factors were identified. A total of 12 patients were sentinel lymph node biopsy metastasis positive and axillary lymph node dissection (ALND) was performed. These patients were divided into two groups: With and without SN in level II/III, and nodes in level II/III were pathologically proven. In 11 of the 92 patients, hot nodes were detected in level II/III. There was a significant difference in node metastasis depending on whether there were hot nodes in level II/III (P=0.0319). Multivariate analysis indicated that the hot nodes in level II/III and lymphatic invasion were independent factors associated with node metastasis. There were 12 SN-positive patients followed by ALND. In four of the 12 patients, hot nodes were observed in level II/III. Two of the four patients with hot nodes depicted by SPECT/CT and metastatic nodes were pathologically evident in the same lesion. Therefore, the present study indicated that the hot node in level II/III as depicted by SPECT/CT may be a risk of SN metastasis, including deeper nodes.

  4. 40 CFR Table 6 to Subpart IIIii of... - Examples of Techniques for Equipment Problem Identification, Leak Detection and Mercury Vapor

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII...; cracks or spalling in cell room floors, pillars, or beams; caustic leaks; liquid mercury accumulations or... through a detection cell where ultraviolet light at 253.7 nanometers (nm) is directed...

  5. 40 CFR Table 1 to Subpart IIIii of... - Work Practice Standards-Design, Operation, and Maintenance Requirements

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 1 Table 1 to... . . . 1. Cell rooms a. For new or modified cell rooms, construct each cell room interior using materials... mercury spills or accumulations, and are easy to clean. b. Limit access around and beneath mercury...

  6. 40 CFR Table 6 to Subpart IIIii of... - Examples of Techniques for Equipment Problem Identification, Leak Detection and Mercury Vapor

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII...; cracks or spalling in cell room floors, pillars, or beams; caustic leaks; liquid mercury accumulations or... through a detection cell where ultraviolet light at 253.7 nanometers (nm) is directed...

  7. 40 CFR Table 6 to Subpart IIIii of... - Examples of Techniques for Equipment Problem Identification, Leak Detection and Mercury Vapor

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII...; cracks or spalling in cell room floors, pillars, or beams; caustic leaks; liquid mercury accumulations or... through a detection cell where ultraviolet light at 253.7 nanometers (nm) is directed...

  8. 40 CFR Table 6 to Subpart IIIii of... - Examples of Techniques for Equipment Problem Identification, Leak Detection and Mercury Vapor

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Hazardous Air Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII...; cracks or spalling in cell room floors, pillars, or beams; caustic leaks; liquid mercury accumulations or... through a detection cell where ultraviolet light at 253.7 nanometers (nm) is directed...

  9. 40 CFR Table 1 to Subpart IIIii of... - Work Practice Standards-Design, Operation, and Maintenance Requirements

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 1 Table 1 to... . . . 1. Cell rooms a. For new or modified cell rooms, construct each cell room interior using materials... mercury spills or accumulations, and are easy to clean. b. Limit access around and beneath mercury cells...

  10. 40 CFR Table 1 to Subpart IIIii of... - Work Practice Standards-Design, Operation, and Maintenance Requirements

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 1 Table 1 to... . . . 1. Cell rooms a. For new or modified cell rooms, construct each cell room interior using materials... mercury spills or accumulations, and are easy to clean. b. Limit access around and beneath mercury cells...

  11. 40 CFR Table 1 to Subpart IIIii of... - Work Practice Standards-Design, Operation, and Maintenance Requirements

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 1 Table 1 to... . . . 1. Cell rooms a. For new or modified cell rooms, construct each cell room interior using materials... mercury spills or accumulations, and are easy to clean. b. Limit access around and beneath mercury cells...

  12. 40 CFR Table 1 to Subpart IIIii of... - Work Practice Standards-Design, Operation, and Maintenance Requirements

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Pollutants: Mercury Emissions From Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 1 Table 1 to... . . . 1. Cell rooms a. For new or modified cell rooms, construct each cell room interior using materials... mercury spills or accumulations, and are easy to clean. b. Limit access around and beneath mercury cells...

  13. Resonant L{sub II,III} x-ray Raman scattering from HCl

    SciTech Connect

    Saathe, C.; Rubensson, J.-E.; Nordgren, J.; Guimaraes, F. F.; Agui, A.; Guo, J.; Ekstroem, U.; Norman, P.; Gel'mukhanov, F.; Aagren, H.

    2006-12-15

    We have studied the spectral features of Cl L{sub II,III} resonant x-ray Raman scattering of HCl molecules in gas phase both experimentally and theoretically. The theory, formulated in the intermediate-coupling scheme, takes into account the spin-orbital and molecular-field splittings in the Cl 2p shells, as well as the Coulomb interaction of the core hole with unoccupied molecular orbitals. Experiment and theory display nondispersive dissociative peaks formed by decay transitions in both molecular and dissociative regions. The molecular and atomic peaks collapse in a single narrow resonance because the dissociative potentials of core-excited and final states are parallel to each other along the whole pathway of the nuclear wave packet.

  14. A varying-stage adaptive phase II/III clinical trial design.

    PubMed

    Dong, Gaohong

    2014-04-15

    Currently, adaptive phase II/III clinical trials are typically carried out with a strict two-stage design. The first stage is a learning stage called phase II, and the second stage is a confirmatory stage called phase III. Following phase II analysis, inefficacious or harmful dose arms are dropped, then one or two promising dose arms are selected for the second stage. However, there are often situations in which researchers are in dilemma to make 'go or no-go' decision and/or to select 'best' dose arm(s), as data from the first stage may not provide sufficient information for their decision making. In this case, it is challenging to follow a strict two-stage plan. Therefore, we propose a varying-stage adaptive phase II/III clinical trial design, in which we consider whether there is a need to have an intermediate stage to obtain more data, so that a more informative decision could be made. Hence, the number of further investigational stages in our design is determined on the basis of data accumulated to the interim analysis. With respect to adaptations, we consider dropping dose arm(s), switching another plausible endpoint as the primary study endpoint, re-estimating sample size, and early stopping for futility. We use an adaptive combination test to perform final analyses. By applying closed testing procedure, we control family-wise type I error rate at the nominal level of α in the strong sense. We delineate other essential design considerations including the threshold parameters and the proportion of alpha allocated in the two-stage versus three-stage setting.

  15. Soft recovery of polytetrafluoroethylene shocked through the crystalline phase II-III transition

    NASA Astrophysics Data System (ADS)

    Brown, E. N.; Trujillo, C. P.; Gray, G. T.; Rae, P. J.; Bourne, N. K.

    2007-01-01

    Polymers are increasingly being utilized as monolithic materials and composite matrices for structural applications historically reserved for metals. High strain-rate applications in aerospace, defense, and the automotive industries have lead to interest in the shock response of polytetrafluoroethylene (PTFE) and the ensuing changes in polymer structure due to shock prestraining. We present an experimental study of crystalline structure evolution due to pressure-induced phase transitions in a semicrystalline polymer using soft-recovery, shock loading techniques coupled with mechanical and chemical postshock analyses. Gas-launched, plate impact experiments have been performed on pedigreed PTFE 7C, mounted in momentum trapped, shock assemblies, with impact pressures above and below the phase II to phase III crystalline transition. Below the phase transition only subtle changes were observed in the crystallinity, microstructure, and mechanical response of PTFE. Shock loading of PTFE 7C above the phase II-III transition was seen to cause both an increase in crystallinity from 38% to ˜53% (by differential scanning calorimetry) and a finer crystalline microstructure, and changed the yield and flow stress behavior.

  16. ROTATION OF THE K3 II-III GIANT STAR {alpha} HYDRA

    SciTech Connect

    Gray, David F.

    2013-08-01

    Fundamental spectroscopic determination of projected rotation rates of slowly rotating stars is challenging because the rotational broadening of the spectral lines is often comparable to, or smaller than, the broadening from other sources, most notably macroturbulence. Fourier techniques have the advantage over direct profile matching when the observed profiles are complete, but when the profiles are severely blended, the Fourier analysis is compromised. A process of modeling partial profiles for determining the rotation rate for stars having blended spectral lines is investigated and applied to the evolved star {alpha} Hya (K3 II-III). Projected rotation higher than 5 km s{sup -1} can be definitively ruled out for this star. Not all lines are equally good, depending on the amount of blending and also depending on the strength of the line, as the balance between the thermal and non-thermal components changes. A modest ambiguity arises between macroturbulence and rotational broadening, but a careful look at the differences between the observations and the models allows one to measure the rotation with acceptable precision. The result for {alpha} Hya is v sin i = 2.6 {+-} 0.3 km s{sup -1}.

  17. Group II/III metabotropic glutamate receptors exert endogenous activity-dependent modulation of TRPV1 receptors on peripheral nociceptors

    PubMed Central

    Carlton, Susan M.; Zhou, Shengtai; Govea, Rosann; Du, Junhui

    2011-01-01

    There is pharmacological evidence Group II and III metabotropic glutamate receptors (mGluRs) function as activity-dependent autoreceptors, inhibiting transmission in supraspinal sites. These receptors are expressed by peripheral nociceptors. We investigated whether mGluRs function as activity-dependent autoreceptors inhibiting pain transmission to the rat CNS, particularly TRPV1-induced activity. Blocking peripheral mGluR activity by intraplantar injection of antagonists LY341495 (LY, 20, 100 μM, Group II/III ), APICA (100 μM, Group II) or UBP1112 (30 μM, Group III) increased capsaicin (CAP)-induced nociceptive behaviors and nociceptor activity. In contrast, Group II agonist APDC (0.1 μM) or Group III agonist L-AP4 (10 μM) blocked the LY-induced increase. Ca2+ imaging in dorsal root ganglion (DRG) cells confirmed LY enhanced CAP-induced Ca2+ mobilization which was blocked by APDC and L-AP4. We hypothesized that excess glutamate (GLU), released by high intensity and/or prolonged stimulation endogenously activated Group II/III, dampening nociceptor activation. In support of this, intraplantar GLU+LY produced heat hyperalgesia and exogenous GLU+LY applied to nociceptors produced enhanced nociceptor activity and thermal sensitization. Intraplantar formalin known to elevate extracellular GLU, enhanced pain behaviors in the presence of LY. LY alone produced no pain behaviors, no change in nociceptor discharge rate or heat-evoked responses and no change in cytosolic Ca2+ in DRG cells, demonstrating a lack of tonic inhibitory control. Group II/III mGluRs maintain an activity-dependent autoinhibition, capable of significantly reducing TRPV1-induced activity. They are endogenously activated following high frequency and/or prolonged nociceptor stimulation, acting as built-in negative modulators of TRPV1 and nociceptor function, reducing pain transmission to the CNS. PMID:21900552

  18. Evidence of active tectonics on a Roman aqueduct system (II-III century A.D.) near Rome, Italy

    NASA Astrophysics Data System (ADS)

    Marra, Fabrizio; Montone, Paola; Pirro, Mario; Boschi, Enzo

    2004-04-01

    In this paper we describe evidence of strong tectonic deformation affecting two aqueducts of Roman age (II-III century A.D.). The channels are located approximately 20 km northeast of Rome along the ancient Via Tiburtina. Brittle and ductile deformation affects these two structures, including extensional joint systems, NE-oriented faults, and horizontal distortion. This deformation is consistent with right-lateral movement on major N-striking faults, and represents the first evidence that tectonic deformation took place in historical times in the vicinity of Rome, with local strike-slip movement superimposed on a regional extensional fault system.

  19. Detection of methicillin-resistant Staphylococcus pseudintermedius ST169 and novel ST354 SCCmec II-III isolates related to the worldwide ST71 clone.

    PubMed

    Ishihara, K; Koizumi, A; Saito, M; Muramatsu, Y; Tamura, Y

    2016-01-01

    The recent appearance of methicillin-resistant Staphylococcus pseudintermedius (MRSP) is a concern for both veterinary and human healthcare. MRSP clonal lineages with sequence type (ST) 71-spa t02-staphylococcal cassette chromosome mec (SCCmec) II-III and ST68-spa t06-SCCmec V have spread throughout Europe and North America, respectively. The current study compared the molecular characteristics of 43 MRSP isolates from dogs in Japan with those of MRSP from previous reports using multilocus sequence typing based on seven housekeeping genes, SCCmec typing, and detection of antimicrobial resistance genes. Three related clonal lineages, ST71, ST169, and the newly registered ST354, were observed in SCCmec II-III isolates from Japan, despite MRSP SCCmec II-III isolates being thought to belong to a single clonal lineage. The majority of SCCmec II-III isolates belonging to ST169 (9/11) and ST354 (3/3), but not ST71 (0/11), harboured tetM. Four STs were observed for the SCCmec V isolates; however, neither ST68 nor related STs were found in the Japanese MRSP isolates. In conclusion, MRSP SCCmec II-III isolates from Japan belonged to ST71 and related STs (ST169 and ST354). A variety of MRSP SCCmec V clones, including some novel clones, were identified.

  20. [Characteristic of inflammatory infiltrate of gastric mucosa in patients with grade II-III gastric dysplasia and of stomach cancer].

    PubMed

    Evtushenko, V A; Vusik, M V; Karakeshisheva, M B; Pleshko, R I; Ermolaeva, L A

    2008-01-01

    The study included 85 inpatients and outpatients in whom composition of inflammatory infiltrate from gastric mucosa (GM) was determined at the Oncological Research Institute, Tomsk Research Centre of the Siberian Division, Russian Academy of Medical Sciences. The patients were allocated to 4 groups depending on nosological form of the disease. Group 1 comprised 21 patients with grade II-III GM epithelial dysplasia, group 2 - 24 patients having stomach cancer (histologically confirmed adenocarcinoma), group 3 - 19 patients with stage II-III mucinous gastric carcinoma, group 4 - 20 allegedly healthy subjects without signs of gastrointestinal pathology. It was shown that dysplastic processes in GM are associated with an increase of neutrophil, eosinophil, macrophage, and mast cell count along with a drop in the number of lymphocytes and plasmocytes. Stroma of invasive stomach cancer underwent intense inflammatory infiltration accompanied by a rise in the number of lymphocytes, plasmocytes, and neutrophils. Mucinous gastric carcinoma was characterized by an increase of the number of neutrophils and macrophages. Patients having adenocarcinoma of the stomach showed enhanced plasmocytic infiltration by plasmocytes with a low number of eosinophils and mast cells. It is concluded that characteristics of inflammatory GM infiltrate may be useful for the objective assessment of stomach cancer risk in patients with GM dysplasia, formation of a high oncological risk group, adequate dynamic monitoring and treatment of these patients.

  1. Prognostic value of tumor infiltrating NK cells and macrophages in stage II+III esophageal cancer patients

    PubMed Central

    Zheng, Xiao; Shi, Liangrong; Wu, Changping; Jiang, Jingting

    2016-01-01

    The detailed understanding of the immunobiology of tumor microenvironment has recently translated into new therapeutic approach against human cancers. Besides the role of immune cells mediating adaptive immune responses, the tumor infiltrating components of the innate immune system including, neutrophils, mast cells, NK cells, and macrophages, also role importantly in anti-tumor immunity. In our present study, we retrospectively analyzed the prognostic value of the densities of tumor infiltrating NK cells and macrophages in esophageal cancer tissues derived from stage II+III patients. Our results showed that the density of the infiltrating NK cells in tumor stroma was significantly associated with nodal status. In addition, the densities of the infiltrating NK cells in tumor nest, and the infiltrating macrophages in tumor nest as well as in tumor stroma, were significantly associated with patients' postoperative prognoses. Furthermore, the combination of infiltrating NK cells in tumor nest and stroma, or the combination of infiltrating macrophages in tumor nest and stroma, could also be used as important prognostic tool in predicting the survival of the stage II+III esophageal cancer patients. PMID:27736796

  2. Structural determinants for activation or inhibition of ryanodine receptors by basic residues in the dihydropyridine receptor II-III loop.

    PubMed Central

    Casarotto, M G; Green, D; Pace, S M; Curtis, S M; Dulhunty, A F

    2001-01-01

    The structures of peptide A, and six other 7-20 amino acid peptides corresponding to sequences in the A region (Thr671- Leu690) of the skeletal muscle dihydropyridine receptor II-III loop have been examined, and are correlated with the ability of the peptides to activate or inhibit skeletal ryanodine receptor calcium release channels. The peptides adopted either random coil or nascent helix-like structures, which depended upon the polarity of the terminal residues as well as the presence and ionisation state of two glutamate residues. Enhanced activation of Ca2+ release from sarcoplasmic reticulum, and activation of current flow through single ryanodine receptor channels (at -40 mV), was seen with peptides containing the basic residues 681Arg Lys Arg Arg Lys685, and was strongest when the residues were a part of an alpha-helix. Inhibition of channels (at +40 mV) was also seen with peptides containing the five positively charged residues, but was not enhanced in helical peptides. These results confirm the hypothesis that activation of ryanodine receptor channels by the II-III loop peptides requires both the basic residues and their participation in helical structure, and show for the first time that inhibition requires the basic residues, but is not structure-dependent. These findings imply that activation and inhibition result from peptide binding to separate sites on the ryanodine receptor. PMID:11371447

  3. Motor Training Promotes Both Synaptic and Intrinsic Plasticity of Layer II/III Pyramidal Neurons in the Primary Motor Cortex

    PubMed Central

    Kida, Hiroyuki; Tsuda, Yasumasa; Ito, Nana; Yamamoto, Yui; Owada, Yuji; Kamiya, Yoshinori; Mitsushima, Dai

    2016-01-01

    Motor skill training induces structural plasticity at dendritic spines in the primary motor cortex (M1). To further analyze both synaptic and intrinsic plasticity in the layer II/III area of M1, we subjected rats to a rotor rod test and then prepared acute brain slices. Motor skill consistently improved within 2 days of training. Voltage clamp analysis showed significantly higher α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate (AMPA/NMDA) ratios and miniature EPSC amplitudes in 1-day trained rats compared with untrained rats, suggesting increased postsynaptic AMPA receptors in the early phase of motor learning. Compared with untrained controls, 2-days trained rats showed significantly higher miniature EPSC amplitude and frequency. Paired-pulse analysis further demonstrated lower rates in 2-days trained rats, suggesting increased presynaptic glutamate release during the late phase of learning. One-day trained rats showed decreased miniature IPSC frequency and increased paired-pulse analysis of evoked IPSC, suggesting a transient decrease in presynaptic γ-aminobutyric acid (GABA) release. Moreover, current clamp analysis revealed lower resting membrane potential, higher spike threshold, and deeper afterhyperpolarization in 1-day trained rats—while 2-days trained rats showed higher membrane potential, suggesting dynamic changes in intrinsic properties. Our present results indicate dynamic changes in glutamatergic, GABAergic, and intrinsic plasticity in M1 layer II/III neurons after the motor training. PMID:27193420

  4. Racial and Socioeconomic Treatment Disparities in Adolescents and Young Adults with Stage II-III Rectal Cancer.

    PubMed

    Lee, David Y; Teng, Annabelle; Pedersen, Rose C; Tavangari, Farees R; Attaluri, Vikram; McLemore, Elisabeth C; Stern, Stacey L; Bilchik, Anton J; Goldfarb, Melanie R

    2017-02-01

    Stage II-III rectal cancer requires multidisciplinary cancer care, and adolescents and young adults (AYA, ages 15-39 years) often do not receive optimal cancer therapy. Overall, 3295 AYAs with clinical stage II-III rectal cancer were identified in the National Cancer Database. Factors associated with the receipt of adjuvant and surgical therapies, as well as overall survival (OS), were examined. The majority of patients were non-Hispanic White (72.0 %), male (57.5 %), and without comorbidities (93.8 %). A greater proportion of Black and Hispanic patients did not receive radiation (24.5 and 27.1 %, respectively, vs. 16.5 % for non-Hispanic White patients), surgery (22.4 % and 21.6 vs. 12.3 %), or chemotherapy (21.5 % and 24.1 vs. 14.7 %) compared with non-Hispanic White patients (all p < 0.05). After controlling for competing factors, Black (odds ratio [OR] 0.7, 95 % confidence interval [CI] 0.5-0.9) and Hispanic patients (OR 0.6, 95 % CI 0.4-0.9) were less likely to receive neoadjuvant chemoradiation compared with non-Hispanic White patients. Females, the uninsured, and those treated at a community cancer center were also less likely to receive neoadjuvant therapy. Having government insurance (OR 0.22, 95 % CI 010-0.49) was a predictor for not receiving surgery. Although 5-year OS was lower (p < 0.05) in Black (59.8 %) and Hispanic patients (65.9 %) compared with non-Hispanic White patients (74.9 %), on multivariate analysis race did not impact mortality. Not having surgery (hazard ratio [HR] 7.1, 95 % CI 2.8-18.2) had the greatest influence on mortality, followed by poorly differentiated histology (HR 3.0, 95 % CI 1.3-6.5), nodal positivity (HR 2.6, 95 % CI 1.9-3.6), no chemotherapy (HR 1.9, 95 % CI 1.03-3.6), no insurance (HR 1.7, 95 % CI 1.1-2.7), and male sex (HR 1.5, 95 % CI 1.1-2.0). There are racial and socioeconomic disparities in the treatment of stage II-III rectal cancer in AYAs, many of which impact OS. Interventions that can

  5. Oxidation modes and thermodynamics of Fe II-III oxyhydroxycarbonate green rust: Dissolution-precipitation versus in situ deprotonation

    NASA Astrophysics Data System (ADS)

    Ruby, Christian; Abdelmoula, Mustapha; Naille, Sébastien; Renard, Aurélien; Khare, Varsha; Ona-Nguema, Georges; Morin, Guillaume; Génin, Jean-Marie R.

    2010-02-01

    Fe II-III hydroxycarbonate green rust GR(CO 32-), Fe II4 Fe III2 (OH) 12 CO 3·3H 2O, is oxidized in aqueous solutions with varying reaction kinetics. Rapid oxidation with either H 2O 2 or dissolved oxygen under neutral and alkaline conditions leads to the formation of ferric oxyhydroxycarbonate GR(CO 32-)∗, Fe III6 O 12 H 8 CO 3·3H 2O, via a solid-state reaction. By decreasing the flow of oxygen bubbled in the solution, goethite α-FeOOH forms by dissolution-precipitation mechanism whereas a mixture of non-stoichiometric magnetite Fe (3-x)O 4 and goethite is observed for lower oxidation rates. The intermediate Fe II-III oxyhydroxycarbonate of formula Fe II6(1-x) Fe III6x O 12 H 2(7-3x) CO 3·3H 2O, i.e. GR( x)∗ for which x ɛ [1/3, 1], is the synthetic compound that is homologous to the fougerite mineral present in hydromorphic gleysol; in situ oxidation accounts for the variation of ferric molar fraction x = [Fe III]/{[Fe II]+[Fe III]} observed in the field as a function of depth and season but limited to the range [1/3, 2/3]. The domain of stability for partially oxidized green rust is observed in the Eh-pH Pourbaix diagrams if thermodynamic properties of GR( x)∗ is compared with those of lepidocrocite, γ-FeOOH, and goethite, α-FeOOH. Electrochemical equilibrium between GR( x)∗ and Fe II in solution corresponds to Eh-pH conditions close to those measured in the field. Therefore, the reductive dissolution of GR( x)∗ can explain the relatively large concentration of Fe II measured in aqueous medium of hydromorphic soils containing fougerite.

  6. Composition and anion ordering in some Fe II-III hydroxysalt green rusts (carbonate, oxalate, methanoate): The fougerite mineral

    NASA Astrophysics Data System (ADS)

    Génin, Jean-Marie R.; Ruby, Christian

    2008-03-01

    Main features of Fe II-III hydroxysalts (green rusts) are obtained from XRD. Moreover, Mössbauer spectroscopy revealed that several Fe II sites exist. The structure is classified in green rusts one and two (GR1 and GR2) according to the stacking sequence of Fe(OH) 2 brucite-like layers depending on the shape and type of anions inserted within interlayers. Long range order as determined for hydroxysulphate GR2(SO 42-) is extended to distributions of cations and anions within GR1s even though these are not observed by XRD. Abundances of Fe II and Fe III environments within GR1s that intercalate carbonate, oxalate and methanoate (formate) are found for compositions [Fe 6IIFe 2III(OH) 16] 2+·[CO 32-·5H 2O] 2-, [Fe 4IIFe 2III(OH) 12] 2+·[CO 32-·3H 2O] 2-, [Fe 6IIFe 2III(OH) 16] 2+·[C 2O 42-·4H 2O] 2- and [Fe 5IIFe 2III(OH) 14] 2+·[2HCOO -·3H 2O] 2-, which correspond to orders α, β and γ where the cation distances are (2 × a0), (√3 × a0) or a mixture of both, with a ferric molar ratio x = {[Fe III]/[Fe total]} = 1/4, 1/3 and 2/7, respectively. Anion distributions within interlayers are devised and long range orders in other layered double hydroxides could questionably be extended from these models. The formula [Fe 6II(1- x) Fe 6 xIIIO 12H 2(7-3 x) ] 2+·[CO 32-·3H 2O] 2- for the fougerite mineral, which is the oxyhydroxycarbonate obtained by deprotonation of Fe II-III hydroxycarbonate [Fe 4IIFe 2III(OH) 12] 2+·[CO 32-·3H 2O] 2- where x ∈ [1/3,2/3] is confirmed.

  7. Reducing the Time From Diagnosis to Treatment of Patients With Stage II/III Rectal Cancer at a Large Public Hospital

    PubMed Central

    Leslie, Lori A.; Jacobs, Ryan W.; Millas, Stefanos; Surabhi, Venkateswar; Mok, Henry; Jhaveri, Pavan; Kott, Marylee M.; Jackson, Lymesia; Rieber, Alyssa; Bhadkamkar, Nishin A.

    2016-01-01

    Curative-intent therapy for stage II/III rectal cancer is necessarily complex. Current guidelines by the National Comprehensive Cancer Network recommend preoperative concurrent chemoradiation followed by resection and additional adjuvant chemotherapy. We used standard quality improvement methodology to implement a cost-effective intervention that reduced the time from diagnosis to treatment of patients with stage II/III rectal cancer by approximately 30% in a large public hospital in Houston, Texas. Implementation of the program resulted in a reduction in time from pathologic diagnosis to treatment of 29% overall, from 62 to 44 days. These gains were cost neutral and resulted from improvements in scheduling and coordination of care alone. Our results suggest that: (1) quality improvement methodology can be successfully applied to multidisciplinary cancer care, (2) effective interventions can be cost neutral, and (3) effective strategies can overcome complexities such as having multiple sites of care, high staff turnover, and resource limitations. PMID:26869658

  8. Changes in the BDNF-immunopositive cell population of neocortical layers I and II/III after focal cerebral ischemia in rats.

    PubMed

    Choi, Yongwon; Kang, Sung Goo; Kam, Kyung-Yoon

    2015-04-24

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and is widely distributed in the central nervous system, including the cerebral cortex. BDNF plays an important role in normal neural development, survival of existing neurons, and activity-dependent neuroplasticity. BDNF can also be neuroprotective and evoke neurogenesis in certain pathological conditions, such as cerebral ischemia. Neocortical layer I is an important region that can integrate feedforward and feedback information from other cortical areas and subcortical regions. In addition, it has recently been proposed as a possible source of neuronal progenitor cells after ischemia. Therefore, we investigated changes in the BDNF-immunoreactive cell population of neocortical layers I and II/III after middle cerebral artery occlusion (MCAO)-induced cerebral ischemia in rats. In unaffected condition, the number of BDNF(+) cells in layer I was significantly less than in layer II/III in the cingulate cortex and in the motor and sensory areas. The increase in the number of BDNF(+) cells in layer I 8 days after MCAO was more remarkable than layer II/III, in all regions except the area of cingulate cortex farthest from the infarct core. Only BDNF(+)-Ox-42(+) cells showed a tendency to increase consistently toward the infarct core in both layers I and II/III, implying a major source of BDNF for response to ischemic injury. The present study suggests that some beneficial effects during recovery from ischemic injury, such as increased supportive microglia/macrophages, occur owing to a sensitive response of BDNF in layer I.

  9. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas

    PubMed Central

    Hatanpaa, Kimmo J.; Foong, Chan; Raisanen, Jack M.; Oliver, Dwight; Hiemenz, Matthew C.; Burns, Dennis K.; White, Charles L.; Whitworth, L. Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A.; Fink, Karen; Maher, Elizabeth A.; Bachoo, Robert M.

    2015-01-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n=50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p=0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III). PMID:24519516

  10. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas.

    PubMed

    Hatanpaa, Kimmo J; Hu, Tianshen; Vemireddy, Vamsidhara; Foong, Chan; Raisanen, Jack M; Oliver, Dwight; Hiemenz, Matthew C; Burns, Dennis K; White, Charles L; Whitworth, L Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A; Fink, Karen; Maher, Elizabeth A; Bachoo, Robert M

    2014-03-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n = 50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p = 0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III).

  11. Equatorial π-stacking interactions in diruthenium (II,III) tetracarboxylate complexes containing extended π-systems

    NASA Astrophysics Data System (ADS)

    O'Rourke, Natasha F.; Ronaldson, Michael; Stanley Cameron, T.; Wang, Ruiyao; Aquino, Manuel A. S.

    2013-11-01

    The synthesis of three new valent-averaged tetracarboxylatodiruthenium (II,III) complexes, [Ru2(1-naphthylacetate)4(H2O)2](PF6)ṡ4THF, 1ṡ4THF, [Ru2(2-naphthoate)4(THF)2](PF6)ṡ3THF, 2ṡ3THF, and [Ru2(coumarin-3-carboxylate)4(MeOH)2](PF6)ṡMeOHṡH2O, 3ṡMeOHṡH2O, was accomplished using a well documented carboxylate exchange reaction. All three complexes were thoroughly characterized using infrared and UV-Vis spectroscopies, elemental analysis and X-ray diffraction. Due to the extended π-systems present, two of the complexes, 2ṡ3THF and 3ṡMeOHṡH2O, display extensive π-stacking in two dimensions, with similar interactions notably absent in 1ṡ4THF due to the perpendicular orientation of the naphthyl rings. Modest H-bonding is seen in complexes 1ṡ4THF and 3ṡMeOHṡH2O. As these types of complexes are noted secondary building units (SBU's) in the construction of metal-organic frameworks (MOF's), the significance of these interactions in stabilizing even larger, supramolecular structures, are noted.

  12. Image analysis-derived metrics of histomorphological complexity predicts prognosis and treatment response in stage II-III colon cancer

    PubMed Central

    Mezheyeuski, Artur; Hrynchyk, Ina; Karlberg, Mia; Portyanko, Anna; Egevad, Lars; Ragnhammar, Peter; Edler, David; Glimelius, Bengt; Östman, Arne

    2016-01-01

    The complexity of tumor histomorphology reflects underlying tumor biology impacting on natural course and response to treatment. This study presents a method of computer-aided analysis of tissue sections, relying on multifractal (MF) analyses, of cytokeratin-stained tumor sections which quantitatively evaluates of the morphological complexity of the tumor-stroma interface. This approach was applied to colon cancer collection, from an adjuvant treatment randomized study. Metrics obtained with the method acted as independent markers for natural course of the disease, and for benefit of adjuvant treatment. Comparative analyses demonstrated that MF metrics out-performed standard histomorphological features such as tumor grade, budding and configuration of invasive front. Notably, the MF analyses-derived “αmax” –metric constitutes the first response-predictive biomarker in stage II-III colon cancer showing significant interactions with treatment in analyses using a randomized trial-derived study population. Based on these results the method appears as an attractive and easy-to-implement tool for biomarker identification. PMID:27805003

  13. Flexible selection of a single treatment incorporating short-term endpoint information in a phase II/III clinical trial.

    PubMed

    Stallard, Nigel; Kunz, Cornelia Ursula; Todd, Susan; Parsons, Nicholas; Friede, Tim

    2015-10-15

    Seamless phase II/III clinical trials in which an experimental treatment is selected at an interim analysis have been the focus of much recent research interest. Many of the methods proposed are based on the group sequential approach. This paper considers designs of this type in which the treatment selection can be based on short-term endpoint information for more patients than have primary endpoint data available. We show that in such a case, the familywise type I error rate may be inflated if previously proposed group sequential methods are used and the treatment selection rule is not specified in advance. A method is proposed to avoid this inflation by considering the treatment selection that maximises the conditional error given the data available at the interim analysis. A simulation study is reported that illustrates the type I error rate inflation and compares the power of the new approach with two other methods: a combination testing approach and a group sequential method that does not use the short-term endpoint data, both of which also strongly control the type I error rate. The new method is also illustrated through application to a study in Alzheimer's disease. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  14. Methodological quality of animal studies of neuroprotective agents currently in phase II/III acute ischemic stroke trials.

    PubMed

    Philip, Maria; Benatar, Michael; Fisher, Marc; Savitz, Sean I

    2009-02-01

    Numerous neuroprotective agents have proven effective in animal stroke studies, but every drug has failed to achieve its primary outcome when brought forward to clinical trials. We analyzed the quality and adequacy of animal studies supporting the efficacy of NXY-059 and other neuroprotective agents that are currently being investigated in phase II/III trials. We conducted a systematic search of all neuroprotective drugs in Phase II or III trials and collected data from animal studies of focal cerebral ischemia testing agents systemically administered within 24 hours of occlusion. The methodological rigor of each individual study was evaluated using 5 criteria derived from the STAIR guidelines. The adequacy of the preclinical "package" for each drug was then evaluated by combining the results of all studies for each drug to determine which of a further 5 STAIR criteria were met before moving forward from animal to human studies. Our search yielded 13 agents of which 10 had published data in peer-reviewed journals. There is substantial within-drug variability in the quality of preclinical studies as well as substantial variation in the completeness of the collective preclinical literature for different drugs. There has been little or no improvement in the quality of animal studies since NXY-059, and current agents have not been subjected to a more complete preclinical evaluation. There is significant heterogeneity in the quality of animal testing for neuroprotective agents in stroke. Drugs in the post-SAINT era have not been subjected to more thorough preclinical evaluation.

  15. Cux1 Enables Interhemispheric Connections of Layer II/III Neurons by Regulating Kv1-Dependent Firing.

    PubMed

    Rodríguez-Tornos, Fernanda M; Briz, Carlos G; Weiss, Linnea A; Sebastián-Serrano, Alvaro; Ares, Saúl; Navarrete, Marta; Frangeul, Laura; Galazo, Maria; Jabaudon, Denis; Esteban, José A; Nieto, Marta

    2016-02-03

    Neuronal subtype-specific transcription factors (TFs) instruct key features of neuronal function and connectivity. Activity-dependent mechanisms also contribute to wiring and circuit assembly, but whether and how they relate to TF-directed neuronal differentiation is poorly investigated. Here we demonstrate that the TF Cux1 controls the formation of the layer II/III corpus callosum (CC) projections through the developmental transcriptional regulation of Kv1 voltage-dependent potassium channels and the resulting postnatal switch to a Kv1-dependent firing mode. Loss of Cux1 function led to a decrease in the expression of Kv1 transcripts, aberrant firing responses, and selective loss of CC contralateral innervation. Firing and innervation were rescued by re-expression of Kv1 or postnatal reactivation of Cux1. Knocking down Kv1 mimicked Cux1-mediated CC axonal loss. These findings reveal that activity-dependent processes are central bona fide components of neuronal TF-differentiation programs and establish the importance of intrinsic firing modes in circuit assembly within the neocortex.

  16. Adverse Effects of Intraoperative Blood Loss on Long-Term Outcomes after Curative Gastrectomy of Patients with Stage II/III Gastric Cancer.

    PubMed

    Mizuno, Akira; Kanda, Mitsuro; Kobayashi, Daisuke; Tanaka, Chie; Iwata, Naoki; Yamada, Suguru; Fujii, Tsutomu; Nakayama, Goro; Sugimoto, Hiroyuki; Koike, Masahiko; Fujiwara, Michitaka; Kodera, Yasuhiro

    2016-01-01

    Gastrectomy with systemic lymphadenectomy sometimes causes excessive bleeding even by experienced surgeons. The aim of this study was to evaluate how intraoperative estimated blood loss (EBL) affected the long-term outcomes after curative surgery of patients with stage II/III gastric cancer (GC). This study included 203 patients with stage II/III GC who did not receive perioperative blood transfusion between 1999 and 2015. The optimal cutoff and the prognostic significance of EBL were determined retrospectively. The median EBL was 285 ml. Receiver operating characteristic curve analysis identified 400 ml as an optimal cutoff. Patients with EBL ≥400 ml were more likely to have hepatic relapse and worse prognosis compared to those with EBL <400 ml. EBL ≥400 ml was identified as an independent prognostic factor for mortality by multivariable analysis. When patients were subdivided according to administration of adjuvant chemotherapy, there was a significant difference between the EBL ≥400 and <400 ml groups in patients who underwent surgery alone, whereas the prognosis was similar for patients of both groups who received adjuvant chemotherapy. EBL serves as a useful predictor for risk stratification after curative gastrectomy in patients with stage II/III GC. © 2016 S. Karger AG, Basel.

  17. Clinical significance of platelet-derived growth factor receptor-β gene expression in stage II/III gastric cancer with S-1 adjuvant chemotherapy

    PubMed Central

    Higuchi, Akio; Oshima, Takashi; Yoshihara, Kazue; Sakamaki, Kentaro; Aoyama, Toru; Suganuma, Nobuyasu; Yamamoto, Naoto; Sato, Tsutomu; Cho, Haruhiko; Shiozawa, Manabu; Yoshikawa, Takaki; Rino, Yasushi; Kunisaki, Chikara; Imada, Toshio; Masuda, Munetaka

    2017-01-01

    Overall survival remains unsatisfactory in stage II/III gastric cancer, even after curative surgery and adjuvant chemotherapy. Platelet-derived growth factor receptor-β (PDGFR-β) is associated with the proliferation of cancer cells. The present study therefore investigated the association of PDGFR-β gene expression with patient outcome in 134 stage II/III gastric cancer patients who received adjuvant chemotherapy with S-1. Relative PDGFR-β gene expression was measured in surgical cancer tissue and adjacent normal mucosa specimens by reverse transcription-quantitative polymerase chain reaction. The PDGFR-β gene expression levels were found to be significantly higher in the cancer tissues compared with the adjacent normal mucosa. A high level of PDGFR-β gene expression was associated with a significantly poorer 5-year overall survival rate compared with a low level of PDGFR-β expression. Upon multivariate analysis, PDGFR-β gene expression was found to be an independent predictor of survival. Overall, the study indicates that PDGFR-β overexpression in gastric cancer tissues is a useful independent predictor of outcome in patients with stage II/III gastric cancer who receive adjuvant chemotherapy with S-1.

  18. Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS-PC Study.

    PubMed

    Yamaue, Hiroki; Tsunoda, Takuya; Tani, Masaji; Miyazawa, Motoki; Yamao, Kenji; Mizuno, Nobumasa; Okusaka, Takuji; Ueno, Hideki; Boku, Narikazu; Fukutomi, Akira; Ishii, Hiroshi; Ohkawa, Shinichi; Furukawa, Masayuki; Maguchi, Hiroyuki; Ikeda, Masafumi; Togashi, Yosuke; Nishio, Kazuto; Ohashi, Yasuo

    2015-07-01

    Gemcitabine is a key drug for the treatment of pancreatic cancer; however, with its limitation in clinical benefits, the development of another potent therapeutic is necessary. Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis, and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide (elpamotide). Based on the promising results of this phase I trial, a multicenter, randomized, placebo-controlled, double-blind phase II/III clinical trial has been carried out for pancreatic cancer. The eligibility criteria included locally advanced or metastatic pancreatic cancer. Patients were assigned to either the Active group (elpamotide + gemcitabine) or Placebo group (placebo + gemcitabine) in a 2:1 ratio by the dynamic allocation method. The primary endpoint was overall survival. The Harrington-Fleming test was applied to the statistical analysis in this study to evaluate the time-lagged effect of immunotherapy appropriately. A total of 153 patients (Active group, n = 100; Placebo group, n = 53) were included in the analysis. No statistically significant differences were found between the two groups in the prolongation of overall survival (Harrington-Fleming P-value, 0.918; log-rank P-value, 0.897; hazard ratio, 0.87, 95% confidence interval [CI], 0.486-1.557). Median survival time was 8.36 months (95% CI, 7.46-10.18) for the Active group and 8.54 months (95% CI, 7.33-10.84) for the Placebo group. The toxicity observed in both groups was manageable. Combination therapy of elpamotide with gemcitabine was well tolerated. Despite the lack of benefit in overall survival, subgroup analysis suggested that the patients who experienced severe injection site reaction, such as ulceration and erosion, might have better survival.

  19. Cytokine serum levels in patients with cervical intraepithelial neoplasia grade II-III treated with intralesional interferon-α 2b.

    PubMed

    Misson, Daniela Ribeiro; Abdalla, Douglas Reis; Borges, Ariana Melo; Shimba, Denis Sakamoto; Adad, Sheila Jorge; Michelin, Márcia Antoniazi; Murta, Eddie Fernando Candido

    2011-01-01

    Cervical intraepithelial neoplasia (CIN) grade II-III is being diagnosed in younger women and, because of the reproductive age range for women and the habits associated with a modern lifestyle, is now affecting a broad age range. Surgical treatment for CIN has been associated with premature amenorrhea, low birth weight, and premature labor and birth. It is therefore imperative to develop clinical treatments for CIN, such as conservative treatment with interferons. The object of the present study was to evaluate the behavior of cytokines (IFN- g, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF β) in the serum of patients with an initial diagnosis of CIN II-III. Ten patients with CIN-CIN II (60%, n = 6) and CIN III (40%, n = 4), 23 to 51 years of age and who had not received any prior treatments, were evaluated. The patients were given 3 million/UI (per cm2 of colposcopic lesion) of human recombinant IFN-α 2b by intralesional administration (18 applications on alternate days). Before treatment, in the 6th, 12th, and 18th applications, blood was collected from the patients for cytokine analysis using ELISA. Half of the patients had a good pathologic response; the other half, all of whom were smokers, had therapeutic failure. The average concentration of IL-12 (pg/ml) in the serum of patients who responded well to therapy was elevated from the 12th and 18th application of IFN-α 2b compared to patients who experienced therapeutic failure: 1804.0 ± 1020 vs 391.2 ± 722.3 and 1738.0 ± 2426.0 vs 448.5 ± 407.2, respectively, P <0.05. CIN II-III treated with intralesional IFN-α 2b achieved a good response in non-smoking patients and was associated with an increase in IL-12 serum levels.

  20. Phase II Study of Chemoradiotherapy With 5-Fluorouracil and Cisplatin for Stage II-III Esophageal Squamous Cell Carcinoma: JCOG Trial (JCOG 9906)

    SciTech Connect

    Kato, Ken; Muro, Kei; Minashi, Keiko; Ohtsu, Atsushi; Ishikura, Satoshi; Boku, Narikazu; Takiuchi, Hiroya; Komatsu, Yoshito; Miyata, Yoshinori; Fukuda, Haruhiko

    2011-11-01

    Purpose: In this Phase II study, we evaluated the efficacy and toxicity of chemoradiotherapy (CRT) with cisplatin (CDDP) and 5-fluorouracil (5-FU) for Stage II-III esophageal squamous cell carcinoma (ESCC). Patients and Methods: Patients with clinical Stage II-III (T1N1M0 or T2-3N0-1M0) thoracic ESCC were enrolled between April 2000 and March 2002. Chemotherapy comprised two courses of protracted infusion of 5-FU (400 mg/m{sup 2}/day) on Days 1-5 and 8-12, and 2-h infusion of CDDP (40 mg/m{sup 2}) on Days 1 and 8; this regimen was repeated every 5 weeks. Concurrent radiotherapy involved 60-Gy irradiation (30 fractions) for 8 weeks with a 2-week break. Responders received two courses of 5-FU (800 mg/m{sup 2}/day) on Days 1-5 and CDDP (80 mg/m{sup 2}) on Day 1. Final analysis was conducted in March 2007. Survival and late toxicities were monitored for 5 years. Results: The characteristics of the 76 patients enrolled were as follows: median age, 61 years; male/female, 68/8; performance status 0/1, 59/17 patients; Stage IIA/IIB/III, 26/12/38 patients. Of the 74 eligible patients, 46 (62.2%) achieved complete response. Median survival time was 29 months, with 3- and 5-year survival rates of 44.7% and 36.8%, respectively. Acute toxicities included Grade 3/4 esophagitis (17%), nausea (17%), hyponatremia (16%), and infection without neutropenia (12%). Late toxicities comprised Grade 3/4 esophagitis (13%), pericardial (16%) and pleural (9%) effusion, and radiation pneumonitis (4%), causing 4 deaths. Conclusions: CRT is effective for Stage II-III ESCC with manageable acute toxicities and can provide a nonsurgical treatment option. However, further improvement is required for reduction in late toxicity.

  1. Dose-Response Relationship between Radiation Dose and Loco-regional Control in Patients with Stage II-III Esophageal Cancer Treated with Definitive Chemoradiotherapy.

    PubMed

    Kim, Hyun Ju; Suh, Yang-Gun; Lee, Yong Chan; Lee, Sang Kil; Shin, Sung Kwan; Cho, Byung Chul; Lee, Chang Geol

    2017-07-01

    The correlation between radiation dose and loco-regional control (LRC) was evaluated in patients with stage II-III esophageal cancer treated with definitive concurrent chemoradiotherapy (CRT). Medical records of 236 stage II-III esophageal cancer patients treated with definitive CRT at Yonsei Cancer Center between 1994 and 2013 were retrospectively reviewed. Among these, 120 received a radiation dose of < 60 Gy (standard-dose group), while 116 received ≥ 60 Gy (high-dose group). The median doses of radiation in the standard- and high-dose groups were 50.4 and 63 Gy, respectively. Concurrent 5-fluorouracil/cisplatin chemotherapy was administered to most patients. There were no differences in patient characteristics between the two groups except for high Karnofsky performance status and lower-thoracic lesions being more prevalent in the standard-dose group. The median progression-free survival (PFS) and overall survival (OS) times were 13.2 months and 26.2 months, respectively. Patients in the high-dose group had significantly better 2-year LRC (69.1% vs. 50.3%, p=0.002), median PFS (16.7 months vs. 11.7 months, p=0.029), and median OS (35.1 months vs. 22.3 months, p=0.043). Additionally, LRC exhibited a dose-response relationship and the complete response rate was significantly higher in the high-dose group (p=0.006). There were no significant differences in treatment-related toxicities between the groups. A higher radiation dose (> 60 Gy) is associated with increased LRC, PFS, and OS in patients with stage II-III esophageal cancer treated with definitive CRT.

  2. Voluntary exercise partially reverses neonatal alcohol-induced deficits in mPFC layer II/III dendritic morphology of male adolescent rats.

    PubMed

    Hamilton, G F; Criss, K J; Klintsova, A Y

    2015-08-01

    Developmental alcohol exposure in humans can produce a wide range of deficits collectively referred to as fetal alcohol spectrum disorders (FASD). FASD-related impairments in executive functioning later in life suggest long-term damage to the prefrontal cortex (PFC). In rodent neonates, moderate to high levels of alcohol exposure decreased frontal lobe brain size and altered medial PFC pyramidal neuron dendritic morphology. Previous research in our lab demonstrated that neonatal alcohol exposure decreased basilar dendritic complexity but did not affect spine density in Layer II/III pyramidal neurons in 26- to 30-day-old rats. The current study adds to the literature by evaluating the effect of neonatal alcohol exposure on mPFC Layer II/III basilar dendritic morphology in adolescent male rats. Additionally, it examines the potential for voluntary exercise to mitigate alcohol-induced deficits on mPFC dendritic complexity. An animal model of binge drinking during the third trimester of pregnancy was used. Rats were intubated with alcohol (alcohol-exposed, AE; 5.25 g kg(-1) day(-1)) on postnatal days (PD) 4-9; two control groups were included (suckle control and sham-intubated). Rats were anesthetized and perfused with heparinized saline solution on PD 42, and brains were processed for Golgi-Cox staining. Developmental alcohol exposure decreased spine density and dendritic complexity of basilar dendrites of Layer II/III neurons in the medial PFC (mPFC) compared to dendrites of control animals. Voluntary exercise increased spine density and dendritic length in AE animals resulting in elimination of the differences between AE and SH rats. Thus, voluntary exercise during early adolescence selectively rescued alcohol-induced morphological deficits in the mPFC.

  3. Strychnine-sensitive glycine receptors on pyramidal neurons in layers II/III of the mouse prefrontal cortex are tonically activated.

    PubMed

    Salling, Michael C; Harrison, Neil L

    2014-09-01

    Processing of signals within the cerebral cortex requires integration of synaptic inputs and a coordination between excitatory and inhibitory neurotransmission. In addition to the classic form of synaptic inhibition, another important mechanism that can regulate neuronal excitability is tonic inhibition via sustained activation of receptors by ambient levels of inhibitory neurotransmitter, usually GABA. The purpose of this study was to determine whether this occurs in layer II/III pyramidal neurons (PNs) in the prelimbic region of the mouse medial prefrontal cortex (mPFC). We found that these neurons respond to exogenous GABA and to the α4δ-containing GABAA receptor (GABA(A)R)-selective agonist gaboxadol, consistent with the presence of extrasynaptic GABA(A)R populations. Spontaneous and miniature synaptic currents were blocked by the GABA(A)R antagonist gabazine and had fast decay kinetics, consistent with typical synaptic GABA(A)Rs. Very few layer II/III neurons showed a baseline current shift in response to gabazine, but almost all showed a current shift (15-25 pA) in response to picrotoxin. In addition to being a noncompetitive antagonist at GABA(A)Rs, picrotoxin also blocks homomeric glycine receptors (GlyRs). Application of the GlyR antagonist strychnine caused a modest but consistent shift (∼15 pA) in membrane current, without affecting spontaneous synaptic events, consistent with the tonic activation of GlyRs. Further investigation showed that these neurons respond in a concentration-dependent manner to glycine and taurine. Inhibition of glycine transporter 1 (GlyT1) with sarcosine resulted in an inward current and an increase of the strychnine-sensitive current. Our data demonstrate the existence of functional GlyRs in layer II/III of the mPFC and a role for these receptors in tonic inhibition that can have an important influence on mPFC excitability and signal processing. Copyright © 2014 the American Physiological Society.

  4. The impact of local control in the treatment of type II/III pleuropulmonary blastoma. Experience of the Cooperative Weichteilsarkom Studiengruppe (CWS).

    PubMed

    Sparber-Sauer, Monika; Seitz, Guido; Kirsch, Sylvia; Vokuhl, Christian; Leuschner, Ivo; Dantonello, Tobias M; Scheer, Monika; von Kalle, Thekla; Ljungman, Gustaf; Bielack, Stefan S; Klingebiel, Thomas; Fuchs, Joerg; Koscielniak, Ewa

    2017-02-01

    This study aims at examining the potential survival benefits of primary versus secondary surgery in the management of children diagnosed with pleuropulmonary blastoma (PPB) type II/III. Disease characteristics, treatment, and survival of 29 children with localized PPB type II/III, treated in six prospective Cooperative Weichteilsarkom Studiengruppe (CWS) trials, were reviewed retrospectively. Five year event free survival (EFS) and overall survival (OS) of children treated according to CWS protocols was 72%. Patients with tumors ≤10 cm had a 5 year OS of 91% versus 57% in patients with tumors >10 cm (P = 0.025). Five year OS of patients with macroscopically incomplete upfront resections was 44% as opposed to 68% in patients with delayed/secondary microscopically or macroscopically complete resection after an initial biopsy (P = 0.476). Ten patients died of disease, one patient died of second malignancy. Tumor size and complete tumor resection at any time were significant prognostic factors (P = 0.025/0.003) for EFS. EFS for microscopically complete, microscopically incomplete, and macroscopically incomplete resection at any time was 91%, 90%, and 25%, respectively (P = 0.01). Primary or secondary microscopically/macroscopically complete tumor resections in combination with chemotherapy correlates with long term survival in children with PPB. J. Surg. Oncol. 2017;115:164-172. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Caffeine sensitivity of native RyR channels from normal and malignant hyperthermic pigs: effects of a DHPR II-III loop peptide.

    PubMed

    Gallant, Esther M; Hart, James; Eager, Kevin; Curtis, Suzanne; Dulhunty, Angela F

    2004-04-01

    Enhanced sensitivity to caffeine is part of the standard tests for susceptibility to malignant hyperthermia (MH) in humans and pigs. The caffeine sensitivity of skeletal muscle contraction and Ca(2+) release from the sarcoplasmic reticulum is enhanced, but surprisingly, the caffeine sensitivity of purified porcine ryanodine receptor Ca(2+)-release channels (RyRs) is not affected by the MH mutation (Arg(615)Cys). In contrast, we show here that native malignant hyperthermic pig RyRs (incorporated into lipid bilayers with RyR-associated lipids and proteins) were activated by caffeine at 100- to 1000-fold lower concentrations than native normal pig RyRs. In addition, the results show that the mutant ryanodine receptor channels were less sensitive to high-affinity activation by a peptide (C(S)) that corresponds to a part of the II-III loop of the skeletal dihydropyridine receptor (DHPR). Furthermore, subactivating concentrations of peptide C(S) enhanced the response of normal pig and rabbit RyRs to caffeine. In contrast, the caffeine sensitivity of MH RyRs was not enhanced by the peptide. These novel results showed that in MH-susceptible pig muscles 1). the caffeine sensitivity of native RyRs was enhanced, 2). the sensitivity of RyRs to a skeletal II-III loop peptide was depressed, and 3). an interaction between the caffeine and peptide C(S) activation mechanisms seen in normal RyRs was lost.

  6. Insertion of alpha1S II-III loop and C terminal sequences into alpha1H fails to restore excitation-contraction coupling in dysgenic myotubes.

    PubMed

    Wilkens, Christina M; Beam, Kurt G

    2003-01-01

    The L-type Ca2+ channel in skeletal muscle (alpha1S) is essential for excitation-contraction (EC) coupling. Previous studies using chimeras composed of alpha1S together with alpha1C or alpha1M demonstrated the importance of the alpha1S II-III loop and of a smaller subdomain (residues 720-764; 'ECC') in skeletal EC coupling. However, these chimeras failed to test the significance of regions outside the II-III loop, which are highly conserved between alpha1S and alpha1C. Therefore, we have injected dysgenic (alpha1S-lacking) myotubes with cDNAs encoding chimeras between alpha1S and the highly divergent T-type Ca2+ channel, alpha1H. The chimeras consisted of GFP-tagged alpha1H with one or more of the following substitutions: alpha1S II-III loop residues 720-764 ('ECC'), a putative targeting domain of the alpha1S C terminus ('target'; residues 1543-1662) or the entire alpha1S C terminus ('Cterm'; residues 1382-1873). The presence of either target or Cterm affected the expression and/or kinetics of whole-cell currents recorded from both dysgenic muscle cells and tsa-201 cells. Importantly, substitution of ECC alone into GFP-alpha1H (GFP-alpha1H + ECC), or together with either target (GFP-alpha1H + ECC + target) or Cterm (GFP-alpha1H + ECC + Cterm), was insufficient to restore electrically evoked contractions. Depolarization-induced fluorescence transients for GFP-alpha1H + ECC, GFP-alpha1H + ECC + target or GFP-alpha1H + ECC + Cterm had a bell shaped dependence upon membrane voltage (inconsistent with skeletal EC coupling) and were also exceedingly small (unlike cardiac EC coupling). The absence of EC coupling for these chimeras raises the possibility that regions of alpha1S outside of ECC and target are necessary for providing the context that allows these two domains to function in EC coupling and targeting, respectively. Additionally, an inadequate membrane density of the chimeras may have contributed to the lack of coupling.

  7. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas.

    PubMed

    Olar, Adriana; Wani, Khalida M; Alfaro-Munoz, Kristin D; Heathcock, Lindsey E; van Thuijl, Hinke F; Gilbert, Mark R; Armstrong, Terri S; Sulman, Erik P; Cahill, Daniel P; Vera-Bolanos, Elizabeth; Yuan, Ying; Reijneveld, Jaap C; Ylstra, Bauke; Wesseling, Pieter; Aldape, Kenneth D

    2015-04-01

    Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade II-III diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and IDH-wild type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR) = 1.21, 95 % confidence interval (CI) = 0.91-1.61] compared to IDH-wild type tumors (HR = 1.74, 95 % CI = 0.95-3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank p < 0.0001, HR = 4.41, 95 % CI = 2.55-7.63), it was not associated with outcome in IDH-mutant tumors (log-rank p = 0.5157, HR = 1.10, 95 % CI = 0.80-1.51), and could demonstrate a statistical interaction (p < 0.0001) between IDH mutation and mitotic index (i.e., suggesting that the effect of mitotic index on patient outcome is dependent on IDH mutation status). Patient age, an established prognostic factor in diffuse glioma, was significantly associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade II-III gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade II-III gliomas as independent entities.

  8. The random-coil 'C' fragment of the dihydropyridine receptor II-III loop can activate or inhibit native skeletal ryanodine receptors.

    PubMed Central

    Haarmann, Claudia S; Green, Daniel; Casarotto, Marco G; Laver, Derek R; Dulhunty, Angela F

    2003-01-01

    The actions of peptide C, corresponding to (724)Glu-Pro(760) of the II-III loop of the skeletal dihydropyridine receptor, on ryanodine receptor (RyR) channels incorporated into lipid bilayers with the native sarcoplasmic reticulum membrane show that the peptide is a high-affinity activator of native skeletal RyRs at cytoplasmic concentrations of 100 nM-10 microM. In addition, we found that peptide C inhibits RyRs in a voltage-independent manner when added for longer times or at higher concentrations (up to 150 microM). Peptide C had a random-coil structure indicating that it briefly assumes a variety of structures, some of which might activate and others which might inhibit RyRs. The results suggest that RyR activation and inhibition by peptide C arise from independent stochastic processes. A rate constant of 7.5 x 10(5) s(-1).M(-1) was obtained for activation and a lower estimate for the rate constant for inhibition of 5.9 x 10(3) s(-1).M(-1). The combined actions of peptide C and peptide A (II-III loop sequence (671)Thr-Leu(690)) showed that peptide C prevented activation but not blockage of RyRs by peptide A. We suggest that the effects of peptide C indicate functional interactions between a part of the dihydropyridine receptor and the RyR. These interactions could reflect either dynamic changes that occur during excitation-contraction coupling or interactions between the proteins at rest. PMID:12620094

  9. FKBP12 modulation of the binding of the skeletal ryanodine receptor onto the II-III loop of the dihydropyridine receptor.

    PubMed Central

    O'Reilly, Fiona M; Robert, Mylène; Jona, Istvan; Szegedi, Csaba; Albrieux, Mireille; Geib, Sandrine; De Waard, Michel; Villaz, Michel; Ronjat, Michel

    2002-01-01

    In skeletal muscle, excitation-contraction coupling involves a functional interaction between the ryanodine receptor (RyR) and the dihydropyridine receptor (DHPR). The domain corresponding to Thr(671)-Leu(690) of the II-III loop of the skeletal DHPR alpha(1)-subunit is able to regulate RyR properties and calcium release from sarcoplasmic reticulum, whereas the domain corresponding to Glu(724)-Pro(760) antagonizes this effect. Two peptides, covering these sequences (peptide A(Sk) and C(Sk), respectively) were immobilized on polystyrene beads. We demonstrate that peptide A(Sk) binds to the skeletal isoform of RyR (RyR1) whereas peptide C(Sk) does not. Using surface plasmon resonance detection, we show that 1) domain Thr(671)-Leu(690) is the only sequence of the II-III loop binding with RyR1 and 2) the interaction of peptide A(Sk) with RyR1 is not modulated by Ca(2+) (pCa 9-2) nor by Mg(2+) (up to 10 mM). In contrast, this interaction is strongly potentiated by the immunophilin FKBP12 (EC(50) = 10 nM) and inhibited by both rapamycin (IC(50) = 5 nM) and FK506. Peptide A(Sk) induces a 300% increase of the opening probability of the RyR1 incorporated in lipid bilayer. Removal of FKBP12 from RyR1 completely abolishes this effect of domain A(Sk) on RyR1 channel behavior. These results demonstrate a direct interaction of the RyR1 with the discrete domain of skeletal DHPR alpha(1)-subunit corresponding to Thr(671)-Leu(690) and show that the association of FKBP12 with RyR1 specifically modulates this interaction. PMID:11751303

  10. Thyroid Function in Women after Multimodal Treatment for Breast Cancer Stage II/III: Comparison With Controls From a Population Sample

    SciTech Connect

    Reinertsen, Kristin Valborg; Cvancarova, Milada; Wist, Erik; Bjoro, Trine; Dahl, Alv A.; Danielsen, Turi; Fossa, Sophie D.

    2009-11-01

    Purpose: A possible association between thyroid diseases (TD) and breast cancer (BC) has been debated. We examined prevalence and development of TD in women after multimodal treatment for Stage II/III BC compared with women from a general population. Secondarily, we explored the impact of two different radiotherapy (RT) techniques (standardized field arrangements vs. computed tomography [CT]-based dose planning) on TD in BC patients examined 35-120 months after primary BC treatment. Methods and Materials: A total of 403 BC patients completed a questionnaire about TD and had blood samples taken for analyses of thyroid function. All had undergone postoperative RT with or without (2%) adjuvant systemic treatment. The results in the BC patients were compared with a cancer-free, age-matched control group from a general population (CGr). Results: There was higher prevalence of self-reported hypothyroidism in the BC patients as compared with the CGr (18% vs. 6%, p < 0.001). The raised prevalence was predominantly due to a substantial increase in the development of hypothyroidism after BC diagnosis, whereas the prevalence of hypothyroidism before BC diagnosis was similar to that observed in the CGr. Patients treated with CT-based RT showed a trend for increased post-BC development of hypothyroidism as compared with those treated with standardized field arrangements (p = 0.08). Conclusions: Hypothyroidism is significantly increased in women after multimodal treatment for Stage II/III BC. Radiation to the thyroid gland may be a contributing factor. BC patients should be routinely screened for hypothyroidism.

  11. Predictors of Long-Term Quality of Life for Survivors of Stage II/III Rectal Cancer in the Cancer Care Outcomes Research and Surveillance Consortium

    PubMed Central

    Charlton, Mary E.; Stitzenberg, Karyn B.; Lin, Chi; Schlichting, Jennifer A.; Halfdanarson, Thorvardur R.; Juarez, Grelda Yazmin; Pendergast, Jane F.; Chrischilles, Elizabeth A.; Wallace, Robert B.

    2015-01-01

    Purpose: Many patients do not receive guideline-recommended neoadjuvant chemoradiotherapy for resectable rectal cancer. Little is known regarding long-term quality of life (QOL) associated with various treatment approaches. Our objective was to determine patient characteristics and subsequent QOL associated with treatment approach. Methods: Our study was a geographically diverse population- and health system–based cohort study that included adults age 21 years or older with newly diagnosed stage II/III rectal cancer who were recruited from 2003 to 2005. Eligible patients were contacted 1 to 4 months after diagnosis and asked to participate in a telephone survey and to consent to medical record review, with separate follow-up QOL surveys conducted 1 and 7 years after diagnosis. Results: Two hundred thirty-nine patients with stage II/III rectal cancer were included in this analysis. Younger age (< 65 v ≥ 65 years: odds ratio, 2.49; 95% CI, 1.33 to 4.65) was significantly associated with increased odds of receiving neoadjuvant or adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy group had significantly worse mean EuroQol-5D (range, 0 to 1) and Short Form-12 physical health component scores (standardized mean, 50) at 1-year follow-up than the neoadjuvant chemoradiotherapy group (0.75 v 0.85; P = .002; 37.2 v 43.3; P = .01, respectively) and the group that received only one or neither form of treatment (0.75 v 0.85; P = .02; 37.2 v 45.1; P = .008, respectively). Conclusion: Neoadjuvant treatment may result in better QOL and functional status 1 year after diagnosis. Further evaluation of patient and provider reasons for not pursuing neoadjuvant therapy is necessary to determine how and where to target process improvement and/or education efforts to ensure that patients have access to recommended treatment options. PMID:26080831

  12. Effect of CXCR4 and CD133 co-expression on the prognosis of patients with stage II~III colon cancer.

    PubMed

    Li, Xiao-Feng; Guo, Xiao-Guang; Yang, Yong-Yan; Liu, Ai-Yong

    2015-01-01

    To explore the relationship between CXCR4, CD133 co-expression and clinicopathological features as well as prognosis of patients with phase II~III colon cancer. Forty-nine paraffin-embedded samples of tumor tissue and epithelial tissue adjacent to cancer were collected from patients with colon cancer undergoing radical surgery in Baotou Cancer Hospital from January, 2010 to June, 2011. CXCR4 and CD133 expression was detected using immunohistochemistry and its relationship with clinicopathological features and the 3-year survival rate was analyzed. In the tumor tissue and colonic epithelial tissue adjacent to cancer, the positive expression rates of CXCR4 were respectively 61.2% (30/49) and 8.16% (4/49), while those of CD133 being 36.7% (18/49) and 6.12% (3/49). CXCR4 and CD133 expression in tumor tissue was not related to patient age, gender, primary focal sites, tumor size, TNM staging, histological type, tumor infiltration depth and presence or absence of lymphatic metastasis, but CXCR4 and CD133 co-expression was associated with TNM staging and lymphatic metastasis. The 3-year survival rate of patients with CXCR4 and CD133 co-expression was 27.3% (3/11), and that of the remainderwas 76.3% (29/38), the difference being significant (χ2=7.0206, p=0.0081). CXCR4 and CD133 co-expression may be a risk factor for poor prognosis of patients with stage II~III colon cancer.

  13. Adjuvant regional chemotherapy and systemic chemotherapy versus systemic chemotherapy alone in patients with stage II-III colorectal cancer: a multicentre randomised controlled phase III trial.

    PubMed

    Nordlinger, Bernard; Rougier, Philippe; Arnaud, Jean-Pierre; Debois, Muriel; Wils, Jaques; Ollier, Jean-Claude; Grobost, Olivier; Lasser, Philippe; Wals, Jacob; Lacourt, Jerome; Seitz, Jean-François; Guimares dos Santos, Jose; Bleiberg, Harry; Mackiewickz, Rémy; Conroy, Thierry; Bouché, Olivier; Morin, Thierry; Baila, Liliana; van Cutsem, Eric; Bedenne, Laurent

    2005-07-01

    Systemic adjuvant chemotherapy can improve overall survival and reduce the incidence of distant metastases for patients with advanced colon cancer. This study aimed to investigate whether regional chemotherapy (given by intraperitoneal or intraportal methods) combined with systemic chemotherapy was more effective than was systemic chemotherapy alone in terms of survival and recurrence for patients with stage II-III colorectal cancer. The study also compared systemic chemotherapy with fluorouracil and folinic acid with that of fluorouracil and levamisole. During surgery, 753 patients with stage II-III colorectal cancer were randomly assigned to systemic chemotherapy alone (379 with fluorouracil and folinic acid, and 374 with fluorouracil and levamisole), and 748 to postoperative regional chemotherapy with fluorouracil followed by systemic chemotherapy with fluorouracil and folinic acid (n=368) or with fluorouracil and levamisole (n=380). Regional chemotherapy was given intraperitoneally (n=415) or intraportally (n=235) according to institution. The primary endpoint was 5-year overall survival. Secondary endpoints were 5-year disease-free survival and toxic effects. Analyses were by intention to treat. Median follow-up was 6.8 years (range 0.0-10.1). 5-year overall survival was 72.3% (95% CI 69.0-75.6) for patients assigned regional and systemic chemotherapy, compared with 72.0% (68.7-75.3) for those assigned systemic chemotherapy alone (hazard ratio [HR] 0.97 [0.81-1.15], p=0.69). 5-year overall survival for all patients assigned fluorouracil and levamisole was 72.0% (68.7-75.2) compared with 72.3% (69.0-75.6) for all those assigned fluorouracil and folinic acid (HR 0.98 [0.82-1.17], p=0.81). The hazard ratios for 5-year disease-free survival were 0.94 (0.80-1.10) for regional versus non-regional treatment, and 0.92 (0.79-1.08) for all fluorouracil and levamisole versus fluorouracil and folinic acid. Grade 3-4 toxic effects were low in all groups. Fluorouracil

  14. The role of postmastectomy radiotherapy in clinically node-positive, stage II-III breast cancer patients with pathological negative nodes after neoadjuvant chemotherapy: an analysis from the NCDB

    PubMed Central

    Jiang, Shuai; Jiang, Wen; Chen, Kai; Kim, Betty Y.S.; Liu, Qiang; Jacobs, Lisa K.

    2016-01-01

    Purpose The role of postmastectomy radiotherapy (PMRT) in clinically node-positive, stage II-III breast cancer patients with pathological negative nodes (ypN0) after neoadjuvant chemotherapy (NAC) remains controversial. Methods A total of 1560 clinically node-positive, stage II-III breast cancer patients treated with NAC and mastectomy who achieved ypN0 between 1998 and 2009 in the National Cancer Database were analyzed. The effects of PMRT on overall survival (OS) for the entire cohort and multiple subgroups were evaluated. Imputation and propensity score matching were used as sensitivity analyses to minimize biases. Results Of the entire 1560 eligible patients, 903 (57.9%) received PMRT and 657 (42.1%) didn’t. At a median follow-up of 56.0 months, no statistical difference was observed for OS between two groups by univariate and multivariate analyses (P = 0.120; HR 1.571, 95% CI 0.839-2.943). On subgroup analyses, PMRT significantly improved OS in patients with clinical stage IIIB/IIIC disease, T3/T4 tumor, or residual invasive breast cancer after NAC (P < 0.05). This improvement in OS remained significant after sensitivity analyses for the propensity score-matched patients. Conclusions This study demonstrated that PMRT showed a heterogeneous effect in clinically node-positive, stage II-III breast cancer patients with ypN0 following NAC. PMRT improved OS for patients with clinical stage IIIB/IIIC disease, T3/T4 tumor, or residual invasive breast tumor after NAC. In the absence of definitive conclusions from prospective studies, including the ongoing NSABP B-51 trial, our findings may help identify specific groups of women with clinically node-positive, stage II-III breast cancers who could benefit from PMRT after NAC. PMID:26709538

  15. Effect of Postmastectomy Radiotherapy in Patients <35 Years Old With Stage II-III Breast Cancer Treated With Doxorubicin-Based Neoadjuvant Chemotherapy and Mastectomy

    SciTech Connect

    Garg, Amit K.; Oh, Julia L. Oswald, Mary Jane; Huang, Eugene; Strom, Eric A.; Perkins, George H.; Woodward, Wendy A.; Yu, T. Kuan; Tereffe, Welela; Meric-Bernstam, Funda; Hahn, Karin; Buchholz, Thomas A.

    2007-12-01

    Purpose: Postmastectomy radiotherapy (PMRT) improves locoregional control (LRC) in patients with high-risk features after mastectomy. Young age continues to evolve as a potentially important risk factor. The objective of this study was to assess the benefits of PMRT in patients <35 years old treated with doxorubicin-based neoadjuvant chemotherapy for Stage II-III breast cancer. Patients and Methods: We retrospectively analyzed 107 consecutive breast cancer patients <35 years old with Stage IIA-IIIC disease treated at our institution with doxorubicin-based neoadjuvant chemotherapy and mastectomy, with or without PMRT. The treatment groups were compared in terms of LRC and overall survival. Results: Despite more advanced disease stages, the patients who received PMRT (n = 80) had greater rates of LRC (5-year rate, 88% vs. 63%, p = 0.001) and better overall survival (5-year rate, 67% vs. 48%, p = 0.03) than patients who did not receive PMRT (n = 27). Conclusion: Among breast cancer patients <35 years old at diagnosis, the use of PMRT after doxorubicin-based neoadjuvant chemotherapy and mastectomy led to a statistically greater rate of LRC and overall survival compared with patients without PMRT. The benefit seen for PMRT in young patients provides valuable data to better tailor adjuvant, age-specific treatment decisions after mastectomy.

  16. Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial

    PubMed Central

    Pugliese, Mariateresa; Gallo, Marco; Brignardello, Enrico; Milla, Paola; Orlandi, Fabio; Limone, Paolo Piero; Arvat, Emanuela; Boccuzzi, Giuseppe; Piovesan, Alessandro

    2016-01-01

    Anaplastic thyroid cancer (ATC) has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxel in vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly) and valproic acid (1,000 mg/day); the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered with EudraCT 2008-005221-11. PMID:27766105

  17. Beating the Odds: Successful Establishment of a Phase II/III Clinical Research Trial in Resource-Poor Liberia during the Largest-Ever Ebola Outbreak

    PubMed Central

    Doe-Anderson, J; Baseler, B; Driscoll, P; Johnson, M; Lysander, J; McNay, L; Njoh, WS; Smolskis, M; Wehrlen, L; Zuckerman, J

    2016-01-01

    It has been argued that a country such as Liberia, not fully recovered from the devastation of decades of civil unrest, lacked the appropriate ethical and regulatory framework, basic human and health care services, and infrastructure to carry out clinical trials according to international standards of quality during a public health emergency. However, as Liberia, Sierra Leone, and Guinea were being ravaged by the largest and most devastating Ebola Virus Disease (EVD) outbreak ever recorded, the topic of conducting clinical trials of experimental vaccine and treatment candidates in these resource-poor countries generated the keen interest and concern of scientists, researchers, physicians, bioethicists, philanthropists, and even politicians. Decisive action on behalf of the Liberian government, and a timely positive and supportive response from the United States (U.S.) government, led to the formation of PREVAIL (Partnership for Research on Ebola Vaccines in Liberia) – a clinical research partnership between the two governments. Within a span of 12 weeks, this partnership accomplished the unimaginable: the successful initiation of a Phase II/III vaccine clinical trial for EVD in Liberia. This paper will discuss the dynamics of the research collaboration, barriers encountered, breakthroughs realized, key elements of success, and lessons learned in the process. PMID:28042619

  18. Functional outcome after Mason II-III radial head and neck fractures: study protocol for a systematic review in accordance with the PRISMA statement.

    PubMed

    Hagelberg, Mårten; Thune, Alexandra; Krupic, Ferid; Salomonsson, Björn; Sköldenberg, Olof

    2017-01-27

    Fractures of the radial head and neck are the most common fractures of the elbow, and account for approximately one-third of all elbow fractures. Depending on the fracture type the treatment is either conservative or surgical. There is no absolute consensus regarding optimal treatment for different fracture types. The aim of this protocol is to present the method that will be used to collect, describe and analyse the current evidence regarding the treatment of Mason II-III radial head and neck fractures. We will conduct a systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines statement. We will search a number of databases with a predefined search strategy to collect both randomised and non-randomised studies. The articles will be summarised with descriptive statistics. If applicable a meta-analysis will be conducted. Ethical approval is not required since this is a protocol for a systematic review and no primary data will be collected. The authors will publish findings from this review in a peer-reviewed scientific journal. CRD42016037627. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. Ion paired chromatography of iron (II,III), nickel (II) and copper (II) as their 4,7-Diphenyl-1,10-phenanthroline chelates.

    PubMed

    Mudasir; Yoshioka, N; Inoue, H

    1997-07-01

    A reversed phase ion-paired chromatographic method that can be used to determine trace amounts of iron (II,III), nickel (II) and copper (II) was developed and applied to the determination of iron (II) and iron (III) levels in natural water. The separation of these metal ions as their 4,7-diphenyl-1,10-phenanthroline (bathophenanthroline) chelates on an Inertsil ODS column was investigated by using acetonitrile-water (80/20, v/v) containing 0.06 M perchloric acid as mobile phase and diode array spectrophotometric detection at 250-650 nm. Chromatographic parameters such as composition of mobile phase and concentration of perchloric acid in mobile phase were optimized. The calibration graphs of iron (II), nickel (II) and copper (II) ions were linear (r > 0.991) in the concentration range 0-0.5, 0-2.0 and 0-4.0 mug ml(-1), respectively. The detection limit of iron (II), nickel (II) and copper (II) were 2.67, 5.42 and 18.2 ng ml(-1) with relative standard deviation (n = 5) of 3.11, 5.81 and 7.16% at a concentration level of 10 ng ml(-1) for iron (II) and nickel (II) and 25 ng ml(-1) for copper (II), respectively. The proposed method was applied to the determination of iron(II) and iron(III) in tap water and sea water samples without any interference from other common metal ions.

  20. Three-Dimensional Localization of the α and β Subunits and of the II-III Loop in the Skeletal Muscle L-type Ca2+ Channel*

    PubMed Central

    Szpyt, John; Lorenzon, Nancy; Perez, Claudio F.; Norris, Ethan; Allen, Paul D.; Beam, Kurt G.; Samsó, Montserrat

    2012-01-01

    The L-type Ca2+ channel (dihydropyridine receptor (DHPR) in skeletal muscle acts as the voltage sensor for excitation-contraction coupling. To better resolve the spatial organization of the DHPR subunits (α1s or CaV1.1, α2, β1a, δ1, and γ), we created transgenic mice expressing a recombinant β1a subunit with YFP and a biotin acceptor domain attached to its N- and C- termini, respectively. DHPR complexes were purified from skeletal muscle, negatively stained, imaged by electron microscopy, and subjected to single-particle image analysis. The resulting 19.1-Å resolution, three-dimensional reconstruction shows a main body of 17 × 11 × 8 nm with five corners along its perimeter. Two protrusions emerge from either face of the main body: the larger one attributed to the α2-δ1 subunit that forms a flexible hook-shaped feature and a smaller protrusion on the opposite side that corresponds to the II-III loop of CaV1.1 as revealed by antibody labeling. Novel features discernible in the electron density accommodate the atomic coordinates of a voltage-gated sodium channel and of the β subunit in a single docking possibility that defines the α1-β interaction. The β subunit appears more closely associated to the membrane than expected, which may better account for both its role in localizing the α1s subunit to the membrane and its suggested role in excitation-contraction coupling. PMID:23118233

  1. Fibroblast Growth Factor 2-A Predictor of Outcome for Patients Irradiated for Stage II-III Non-Small-Cell Lung Cancer

    SciTech Connect

    Rades, Dirk; Setter, Cornelia; Dahl, Olav; Schild, Steven E.; Noack, Frank

    2012-01-01

    Purpose: The prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients with non-small-cell lung cancer (NSCLC) is unclear. The present study investigated the effect of tumor cell expression of FGF-2 on the outcome of 60 patients irradiated for Stage II-III NSCLC. Methods and Materials: The effect of FGF-2 expression and 13 additional factors on locoregional control (LRC), metastasis-free survival (MFS), and overall survival (OS) were retrospectively evaluated. These additional factors included age, gender, Karnofsky performance status, histologic type, histologic grade, T and N category, American Joint Committee on Cancer stage, surgery, chemotherapy, pack-years, smoking during radiotherapy, and hemoglobin during radiotherapy. Locoregional failure was identified by endoscopy or computed tomography. Univariate analyses were performed with the Kaplan-Meier method and the Wilcoxon test and multivariate analyses with the Cox proportional hazard model. Results: On univariate analysis, improved LRC was associated with surgery (p = .017), greater hemoglobin levels (p = .036), and FGF-2 negativity (p <.001). On multivariate analysis of LRC, surgery (relative risk [RR], 2.44; p = .037), and FGF-2 expression (RR, 5.06; p <.001) maintained significance. On univariate analysis, improved MFS was associated with squamous cell carcinoma (p = .020), greater hemoglobin levels (p = .007), and FGF-2 negativity (p = .001). On multivariate analysis of MFS, the hemoglobin levels (RR, 2.65; p = .019) and FGF-2 expression (RR, 3.05; p = .004) were significant. On univariate analysis, improved OS was associated with a lower N category (p = .048), greater hemoglobin levels (p <.001), and FGF-2 negativity (p <.001). On multivariate analysis of OS, greater hemoglobin levels (RR, 4.62; p = .002) and FGF-2 expression (RR, 3.25; p = .002) maintained significance. Conclusions: Tumor cell expression of FGF-2 appeared to be an independent negative predictor

  2. Does internal mammary node irradiation affect treatment outcome in clinical stage II-III breast cancer patients receiving neoadjuv ant chemotherapy?

    PubMed

    Kim, Kyung Hwan; Noh, Jae Myoung; Kim, Yong Bae; Chang, Jee Suk; Keum, Ki Chang; Huh, Seung Jae; Choi, Doo Ho; Park, Won; Suh, Chang-Ok

    2015-08-01

    The purpose of this study is to assess the value of internal mammary node irradiation (IMNI) in patients receiving postoperative radiotherapy after neoadjuvant chemotherapy (NAC) using modern systemic therapy. Between 2001 and 2009, 521 consecutive patients with clinical stage II-III breast cancer received NAC and postoperative radiotherapy. With a consistent policy, the treating radiation oncologist either included (N = 284) or excluded (N = 237) the internal mammary node in the treatment volume. Anthracycline- and taxane-based chemotherapy was provided to 482 (92.5 %) patients. To account for the unbalanced characteristics between the two groups, we performed propensity score matching and covariate adjustment using the propensity score. The median follow-up duration was 71 months (range 31-153 months). The 5-year disease-free survival (DFS) with and without IMNI was 81.8 and 72.7 %, respectively (p = 0.019). The benefit of IMNI varied according to patient characteristics such that it was more apparent in patients with N1-2 disease, inner/central location, and triple-negative subtype. After adjusting for all potential confounding variables, IMNI was independently associated with improved DFS (p = 0.049). The significant effect of IMNI on DFS was sustained after propensity score matching (p = 0.040) and covariate adjustment using the propensity score (p = 0.048). Symptomatic radiation pneumonitis developed in 9 (3.2 %) patients receiving IMNI. Our results indicated that IMNI was associated with a significant improvement in DFS with low toxicity rate for breast cancer patients receiving NAC. Further prospective studies are warranted to confirm the effect of IMNI in the NAC setting.

  3. Hospital Characteristics Associated with Stage II/III Rectal Cancer Guideline Concordant Care: Analysis of Surveillance, Epidemiology and End Results-Medicare Data.

    PubMed

    Charlton, Mary E; Hrabe, Jennifer E; Wright, Kara B; Schlichting, Jennifer A; McDowell, Bradley D; Halfdanarson, Thorvardur R; Lin, Chi; Stitzenberg, Karyn B; Cromwell, John W

    2016-05-01

    Evidence suggests that high-volume facilities achieve better rectal cancer outcomes. Logistic regression was used to evaluate association of facility type with treatment after adjusting for patient demographics, stage, and comorbidities. SEER-Medicare beneficiaries who were diagnosed with stage II/III rectal adenocarcinoma at age ≥66 years from 2005 to 2009 and had Parts A/B Medicare coverage for ≥1 year prediagnosis and postdiagnosis plus a claim for cancer-directed surgery were included. Institutions were classified according to National Cancer Institute (NCI) designation, presence of residency program, or medical school affiliation. Two thousand three hundred subjects (average age = 75) met the criteria. Greater proportions of those treated at NCI-designated facilities received transrectal ultrasound (TRUS) or magnetic resonance imaging (MRI)-pelvis (62.1 vs. 29.9 %), neoadjuvant chemotherapy (63.9 vs. 41.8 %), and neoadjuvant radiation (70.8 vs. 46.3 %), all p < 0.0001. On multivariate analysis, odds ratios (95 % confidence intervals) for receiving TRUS or MRI, neoadjuvant chemotherapy, or neoadjuvant radiation among beneficiaries treated at NCI-designated facilities were 3.51 (2.60-4.73), 2.32 (1.71-3.16), and 2.66 (1.93-3.67), respectively. Results by residency and medical school affiliation were similar in direction to NCI designation. Those treated at hospitals with an NCI designation, residency program, or medical school affiliation received more guideline-concordant care. Initiatives involving provider education and virtual tumor boards may improve care.

  4. Oral 5-aminolevulinic acid mediated photodynamic diagnosis using fluorescence cystoscopy for non-muscle-invasive bladder cancer: A randomized, double-blind, multicentre phase II/III study.

    PubMed

    Inoue, Keiji; Anai, Satoshi; Fujimoto, Kiyohide; Hirao, Yoshihiko; Furuse, Hiroshi; Kai, Fumitake; Ozono, Seiichiro; Hara, Takahiko; Matsuyama, Hideyasu; Oyama, Masafumi; Ueno, Munehisa; Fukuhara, Hideo; Narukawa, Mamoru; Shuin, Taro

    2015-06-01

    Photodynamic diagnosis (PDD) of non-muscle-invasive bladder cancer (NMIBC) following transurethral administration of a hexalated form of 5-aminolevulinic acid (5-ALA), 5-ALA hexyl ester, is widely performed in Western countries. In this study, effectiveness and safety of the oral administration of 5-ALA is assessed in a phase II/III study of PDD for NMIBC in comparison to those of conventional white-light endoscopic diagnosis. Patients with NMIBC were allocated to two groups that were orally administered 10 and 20 mg/kg of 5-ALA under the double-blind condition. Effectiveness was evaluated by setting the primary endpoint to sensitivity. Safety was also analyzed. Moreover, clinically recommended doses of 5-ALA was also investigated as an investigator-initiated multicenter cooperative clinical trial in which five medical institutions participated. All 62 enrolled patients completed the clinical trial. The sensitivities of PDD were higher (84.4 and 75.8% in the 10 and 20 m g/kg-groups, respectively) than those of conventional endoscopic diagnosis (67.5 and 47.6%, respectively) (p = 0.014 and p < 0.001, respectively). Five episodes of serious adverse events developed in four patients; whereas a causal relationship with the investigational agent was ruled out in all episodes. This investigator-initiated clinical trial confirmed the effectiveness and safety of PDD for NMIBC following oral administration of 5-ALA. Both doses of 5-ALA may be clinically applicable; however, the rate of detecting tumors only by PDD was higher in the 20 mg/kg-group suggesting that this dose would be more useful. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Clinical Effectiveness of Intravenous Exenatide Infusion in Perioperative Glycemic Control after Coronary Artery Bypass Graft Surgery: A Phase II/III Randomized Trial.

    PubMed

    Besch, Guillaume; Perrotti, Andrea; Mauny, Frederic; Puyraveau, Marc; Baltres, Maude; Flicoteaux, Guillaume; Salomon du Mont, Lucie; Barrucand, Benoit; Samain, Emmanuel; Chocron, Sidney; Pili-Floury, Sebastien

    2017-08-18

    We aimed to assess the clinical effectiveness of intravenous exenatide compared to insulin in perioperative blood glucose control in coronary artery bypass grafting surgery patients. Patients more than 18 yr old admitted for elective coronary artery bypass grafting were included in a phase II/III nonblinded randomized superiority trial. Current insulin use and creatinine clearance of less than 60 ml/min were exclusion criteria. Two groups were compared: the exenatide group, receiving exenatide (1-h bolus of 0.05 µg/min followed by a constant infusion of 0.025 µg/min), and the control group, receiving insulin therapy. The blood glucose target range was 100 to 139 mg/dl. The primary outcome was the proportion of patients who spent at least 50% of the study period within the target range. The consumption of insulin (Cinsulin) and the time to start insulin (Tinsulin) were compared between the two groups. In total, 53 and 51 patients were included and analyzed in the exenatide and control groups, respectively (age: 70 ± 9 vs. 68 ± 11 yr; diabetes mellitus: 12 [23%] vs. 10 [20%]). The primary outcome was observed in 38 (72%) patients in the exenatide group and in 41 (80%) patients in the control group (odds ratio [95% CI] = 0.85 [0.34 to 2.11]; P = 0.30). Cinsulin was significantly lower (60 [40 to 80] vs. 92 [63 to 121] U, P < 0.001), and Tinsulin was significantly longer (12 [7 to 16] vs. 7 [5 to 10] h, P = 0.02) in the exenatide group. Exenatide alone at the dose used was not enough to achieve adequate blood glucose control in coronary artery bypass grafting patients, but it reduces overall consumption of insulin and increases the time to initiation of insulin.

  6. Rab27a GTPase modulates L-type Ca2+ channel function via interaction with the II-III linker of CaV1.3 subunit.

    PubMed

    Reichhart, Nadine; Markowski, Magdalena; Ishiyama, Shimpei; Wagner, Andrea; Crespo-Garcia, Sergio; Schorb, Talitha; Ramalho, José S; Milenkovic, Vladimir M; Föckler, Renate; Seabra, Miguel C; Strauß, Olaf

    2015-11-01

    In a variety of cells, secretory processes require the activation of both Rab27a and L-type channels of the Ca(V)1.3 subtype. In the retinal pigment epithelium (RPE), Rab27a and Ca(V)1.3 channels regulate growth-factor secretion towards its basolateral side. Analysis of murine retina sections revealed a co-localization of both Rab27a and Ca(V)1.3 at the basolateral membrane of the RPE. Heterologously expressed Ca(V)1.3/β3/α2δ1 channels showed negatively shifted voltage-dependence and decreased current density of about 70% when co-expressed with Rab27a. However, co-localization analysis using α(5)β(1) integrin as a membrane marker revealed that Rab27a co-expression reduced the surface expression of Ca(V)1.3 only about 10%. Physical binding of heterologously expressed Rab27a with Ca(V)1.3 channels was shown by co-localization in immunocytochemistry as well as co-immunoprecipitation which was abolished after deletion of a MyRIP-homologous amino acid sequence at the II-III linker of the Ca(V)1.3 subunit. Rab27a over-expression in ARPE-19 cells positively shifted the voltage dependence, decreased current density of endogenous Ca(V)1.3 channels and reduced VEGF-A secretion. We show the first evidence of a direct functional modulation of an ion channel by Rab27a suggesting a new mechanism of Rab and ion channel interaction in the control of VEGF-A secretion in the RPE.

  7. Safety and immunogenicity of Bio Pox™, a live varicella vaccine (Oka strain) in Indian children: A comparative multicentric, randomized phase II/III clinical trial.

    PubMed

    Dubey, Anand Prakash; Faridi, Mohammad Moonis Akbar; Mitra, Monjori; Kaur, Iqbal Rajinder; Dabas, Aashima; Choudhury, Jaydeep; Mukherjee, Mallar; Mishra, Devendra

    2017-09-02

    Varicella or chickenpox is a highly contagious disease with a high secondary attack rate. Almost 30% of Indian adolescents lack protective antibodies against varicella, emphasizing the need of routine varicella immunization. The Oka VZV is a well-established, safe and efficacious vaccine strain that is highly immunogenic and produces lifelong protective immunity. The present multicentric, open label, randomized, controlled Phase II/III study, compared the Bio Pox™ (indigenous investigational vaccine) with a licensed vaccine, Varivax™ ([a])([a]) Please note that this article refers to the product named VARIVAX as manufactured by Changchun Keygen Biological Products Ltd., China and marketed in India by VHB Life Sciences Limited, Mumbai, and not the product VARIVAX® owned by Merck Sharp & Dohme Corp., Rahway, New Jersey, USA. Merck Sharp & Dohme Corp. have asked us to make clear that the product manufactured by Changchun Keygen Biological Products Ltd. is unrelated to and is not sponsored, endorsed or otherwise authorised by Merck Sharp & Dohme Corp. , for its safety and immunogenicity profile in 252 healthy subjects in the age group of 1-12 y (cohort I: 6-12 years, II:1-6 years) in 3 tertiary medical institutions. Antibodies were measured by VZV Glycoprotein Enzyme Linked Immunoassay (IgG ELISA) kit. Seroconversion percentage in children having pre-vaccination anti VZV IgG titer <10 mIU/mL (< 5 gp ELISA units/mL) were 80% for Bio Pox™ and 77% for Varivax™ (p = 0.692). The seroconversion rate in the group receiving Bio Pox™ was non-inferior to the group that received Varivax™. There were mild local reactions for both the vaccines; none of the patient had fever or required hospitalization or medication. The Bio Pox™ was found to be safe and immunogenic in children against VZV infection.

  8. [Emergency closed reduction and percutaneous Kirschner wire fixation for treatment of Gartland type II-III supracondylar fractures of the humerus in children].

    PubMed

    Fan, Jiang-rong; Xu, Yi-wen; Zheng, Yong; You, Jing-yang

    2015-05-01

    To analyze the clinical effect and related risk factors of Gartland type II-III supracondylar fractures of humerus in children in the emergency closed reduction and percutaneous Kirschner wire fixation. From January 2008 to June 2013,112 children of Gartland type II to III supracondylar humeral fractures were treated in children in emergency closed reduction and percutaneous K-wire fixation, including 72 males and 40 females with an average age of 6.2 years old ranging from 2 to 11 years old. Among them,74 cases were in Gartland type II fractures,38 cases were in type III; The duration from injury to surgery time was 2.5 to 8 hours (averaged 4.6 hours). Elbow cast was applied after operation with the elbow extended of 100 degrees for 4 to 6 weeks, then the gypsum and Kirschner wires were removed. All patients were follow-up from 6 to 60 months (averaged 12 months). All fractures reached clinical healing. The final follow-up was assessed by Flynn criteria, the result was excellent in 86 cases, good in 23 cases, general in 3 cases, excellent and good rate was 97.3%. Three patients had mild cubitus varus deformity without orthopedic treatment. No pin tract infections, iatrogenic ulnar nerve injury, compartment syndrome, and complications such as Volkmann ischemic contracture occurred. Closed reduction and percutaneous Kirschner wire fixation had advantages of exact reduction, firm fixation, fewer complications ,less pain in children undergoing emergency surgery, and.high success rate, so it is a safe and efficient treatment for humeral supracondylar fracture in children.

  9. Mastectomy With Immediate Expander-Implant Reconstruction, Adjuvant Chemotherapy, and Radiation for Stage II-III Breast Cancer: Treatment Intervals and Clinical Outcomes

    SciTech Connect

    Wright, Jean L.; Cordeiro, Peter G.; Ben-Porat, Leah; Van Zee, Kimberly J.; Hudis, Clifford; Beal, Kathryn; McCormick, Beryl

    2008-01-01

    Purpose: To determine intervals between surgery and adjuvant chemotherapy and radiation in patients treated with mastectomy with immediate expander-implant reconstruction, and to evaluate locoregional and distant control and overall survival in these patients. Methods and Materials: Between May 1996 and March 2004, 104 patients with Stage II-III breast cancer were routinely treated at our institution under the following algorithm: (1) definitive mastectomy with axillary lymph node dissection and immediate tissue expander placement, (2) tissue expansion during chemotherapy, (3) exchange of tissue expander for permanent implant, (4) radiation. Patient, disease, and treatment characteristics and clinical outcomes were retrospectively evaluated. Results: Median age was 45 years. Twenty-six percent of patients were Stage II and 74% Stage III. All received adjuvant chemotherapy. Estrogen receptor staining was positive in 77%, and 78% received hormone therapy. Radiation was delivered to the chest wall with daily 0.5-cm bolus and to the supraclavicular fossa. Median dose was 5040 cGy. Median interval from surgery to chemotherapy was 5 weeks, from completion of chemotherapy to exchange 4 weeks, and from exchange to radiation 4 weeks. Median interval from completion of chemotherapy to start of radiation was 8 weeks. Median follow-up was 64 months from date of mastectomy. The 5-year rate for locoregional disease control was 100%, for distant metastasis-free survival 90%, and for overall survival 96%. Conclusions: Mastectomy with immediate expander-implant reconstruction, adjuvant chemotherapy, and radiation results in a median interval of 8 weeks from completion of chemotherapy to initiation of radiation and seems to be associated with acceptable 5-year locoregional control, distant metastasis-free survival, and overall survival.

  10. Three-dimensional localization of the α and β subunits and of the II-III loop in the skeletal muscle L-type Ca2+ channel.

    PubMed

    Szpyt, John; Lorenzon, Nancy; Perez, Claudio F; Norris, Ethan; Allen, Paul D; Beam, Kurt G; Samsó, Montserrat

    2012-12-21

    The L-type Ca(2+) channel (dihydropyridine receptor (DHPR) in skeletal muscle acts as the voltage sensor for excitation-contraction coupling. To better resolve the spatial organization of the DHPR subunits (α(1s) or Ca(V)1.1, α(2), β(1a), δ1, and γ), we created transgenic mice expressing a recombinant β(1a) subunit with YFP and a biotin acceptor domain attached to its N- and C- termini, respectively. DHPR complexes were purified from skeletal muscle, negatively stained, imaged by electron microscopy, and subjected to single-particle image analysis. The resulting 19.1-Å resolution, three-dimensional reconstruction shows a main body of 17 × 11 × 8 nm with five corners along its perimeter. Two protrusions emerge from either face of the main body: the larger one attributed to the α(2)-δ1 subunit that forms a flexible hook-shaped feature and a smaller protrusion on the opposite side that corresponds to the II-III loop of Ca(V)1.1 as revealed by antibody labeling. Novel features discernible in the electron density accommodate the atomic coordinates of a voltage-gated sodium channel and of the β subunit in a single docking possibility that defines the α1-β interaction. The β subunit appears more closely associated to the membrane than expected, which may better account for both its role in localizing the α(1s) subunit to the membrane and its suggested role in excitation-contraction coupling.

  11. Molecular basis of multiple sulfatase deficiency, mucolipidosis II/III and Niemann-Pick C1 disease - Lysosomal storage disorders caused by defects of non-lysosomal proteins.

    PubMed

    Dierks, Thomas; Schlotawa, Lars; Frese, Marc-André; Radhakrishnan, Karthikeyan; von Figura, Kurt; Schmidt, Bernhard

    2009-04-01

    Multiple sulfatase deficiency (MSD), mucolipidosis (ML) II/III and Niemann-Pick type C1 (NPC1) disease are rare but fatal lysosomal storage disorders caused by the genetic defect of non-lysosomal proteins. The NPC1 protein mainly localizes to late endosomes and is essential for cholesterol redistribution from endocytosed LDL to cellular membranes. NPC1 deficiency leads to lysosomal accumulation of a broad range of lipids. The precise functional mechanism of this membrane protein, however, remains puzzling. ML II, also termed I cell disease, and the less severe ML III result from deficiencies of the Golgi enzyme N-acetylglucosamine 1-phosphotransferase leading to a global defect of lysosome biogenesis. In patient cells, newly synthesized lysosomal proteins are not equipped with the critical lysosomal trafficking marker mannose 6-phosphate, thus escaping from lysosomal sorting at the trans Golgi network. MSD affects the entire sulfatase family, at least seven members of which are lysosomal enzymes that are specifically involved in the degradation of sulfated glycosaminoglycans, sulfolipids or other sulfated molecules. The combined deficiencies of all sulfatases result from a defective post-translational modification by the ER-localized formylglycine-generating enzyme (FGE), which oxidizes a specific cysteine residue to formylglycine, the catalytic residue enabling a unique mechanism of sulfate ester hydrolysis. This review gives an update on the molecular bases of these enigmatic diseases, which have been challenging researchers since many decades and so far led to a number of surprising findings that give deeper insight into both the cell biology and the pathobiochemistry underlying these complex disorders. In case of MSD, considerable progress has been made in recent years towards an understanding of disease-causing FGE mutations. First approaches to link molecular parameters with clinical manifestation have been described and even therapeutical options have been

  12. Systemic, postsymptomatic antisense oligonucleotide rescues motor unit maturation delay in a new mouse model for type II/III spinal muscular atrophy

    PubMed Central

    Bogdanik, Laurent P.; Osborne, Melissa A.; Davis, Crystal; Martin, Whitney P.; Austin, Andrew; Rigo, Frank; Bennett, C. Frank; Lutz, Cathleen M.

    2015-01-01

    Clinical presentation of spinal muscular atrophy (SMA) ranges from a neonatal-onset, very severe disease to an adult-onset, milder form. SMA is caused by the mutation of the Survival Motor Neuron 1 (SMN1) gene, and prognosis inversely correlates with the number of copies of the SMN2 gene, a human-specific homolog of SMN1. Despite progress in identifying potential therapies for the treatment of SMA, many questions remain including how late after onset treatments can still be effective and what the target tissues should be. These questions can be addressed in part with preclinical animal models; however, modeling the array of SMA severities in the mouse, which lacks SMN2, has proven challenging. We created a new mouse model for the intermediate forms of SMA presenting with a delay in neuromuscular junction maturation and a decrease in the number of functional motor units, all relevant to the clinical presentation of the disease. Using this new model, in combination with clinical electrophysiology methods, we found that administering systemically SMN-restoring antisense oligonucleotides (ASOs) at the age of onset can extend survival and rescue the neurological phenotypes. Furthermore, these effects were also achieved by administration of the ASOs late after onset, independent of the restoration of SMN in the spinal cord. Thus, by adding to the limited repertoire of existing mouse models for type II/III SMA, we demonstrate that ASO therapy can be effective even when administered after onset of the neurological symptoms, in young adult mice, and without being delivered into the central nervous system. PMID:26460027

  13. Contributions of Kv7-mediated potassium current to sub- and suprathreshold responses of rat layer II/III neocortical pyramidal neurons

    PubMed Central

    Guan, D.; Higgs, M. H.; Horton, L. R.; Spain, W. J.

    2011-01-01

    After block of Kv1- and Kv2-mediated K+ currents in acutely dissociated neocortical pyramidal neurons from layers II/III of rat somatosensory and motor cortex, the remaining current is slowly activating and persistent. We used whole cell voltage clamp to show that the Kv7 blockers linopirdine and XE-991 blocked a current with similar kinetics to the current remaining after combined block of Kv1 and Kv2 channels. This current was sensitive to low doses of linopirdine and activated more slowly and at more negative potentials than Kv1- or Kv2-mediated current. The Kv7-mediated current decreased in amplitude with time in whole cell recordings, but in most cells the current was stable for several minutes. Current in response to a traditional M-current protocol was blocked by muscarine, linopirdine, and XE-991. Whole cell slice recordings revealed that the Q10 for channel deactivation was ∼2.5. Sharp electrode current-clamp recordings from adult pyramidal cells demonstrated that block of Kv7-mediated current with XE-991 reduced rheobase, shortened the latency to firing to near rheobase current, induced more regular firing at low current intensity, and increased the rate of firing to a given current injection. XE-991 did not affect single action potentials or spike frequency adaptation. Application of XE-991 also eliminated subthreshold voltage oscillations and increased gain for low-frequency inputs (<10 Hz) without affecting gain for higher frequency inputs. These data suggest important roles for Kv7 channels in subthreshold regulation of excitability, generation of theta-frequency subthreshold oscillations, regulation of interspike intervals, and biasing selectivity toward higher frequency inputs. PMID:21697446

  14. Long-term results and recurrence patterns from SCOPE-1: a phase II/III randomised trial of definitive chemoradiotherapy +/− cetuximab in oesophageal cancer

    PubMed Central

    Crosby, T; Hurt, C N; Falk, S; Gollins, S; Staffurth, J; Ray, R; Bridgewater, J A; Geh, J I; Cunningham, D; Blazeby, J; Roy, R; Maughan, T; Griffiths, G; Mukherjee, S

    2017-01-01

    Background: The SCOPE-1 study tested the role of adding cetuximab to conventional definitive chemoradiotherapy (dCRT), and demonstrated greater toxicity and worse survival outcomes. We present the long-term outcomes and patterns of recurrence. Methods: SCOPE-1 was a phase II/III trial in which patients were randomised to cisplatin 60 mg m−2 (day 1) and capecitabine 625 mg m−2 bd (days 1–21) for four cycles +/− cetuximab 400 mg m−2 day 1 then by 250 mg m−2 weekly. Radiotherapy consisted of 50 Gy/25# given concurrently with cycles 3 and 4. Recruitment was between February 2008 and February 2012, when the IDMC recommended closure on the basis of futility. Results: About 258 patients (dCRT=129; dCRT+cetuximab (dCRT+C)=129) were recruited from 36 centres. About 72.9% (n=188) had squamous cell histology. The median follow-up (IQR) was 46.2 (35.9–48.3) months for surviving patients. The median overall survival (OS; months; 95% CI) was 34.5 (24.7–42.3) in dCRT and 24.7 (18.6–31.3) in dCRT+C (hazard ratio (HR)=1.25, 95% CIs: 0.93–1.69, P=0.137). Median progression-free survival (PFS; months; 95% CI) was 24.1 (15.3–29.9) and 15.9 (10.7–20.8) months, respectively (HR=1.28, 95% CIs: 0.94–1.75; P=0.114). On multivariable analysis only earlier stage, full-dose RT, and higher cisplatin dose intensity were associated with improved OS. Conclusions: The mature analysis demonstrates that the dCRT regimen used in the study provided useful survival outcomes despite its use in patients who were largely unfit for surgery or who had inoperable disease. Given the competing risk of systemic and local failure, future studies should continue to focus on enhancing local control as well as optimising systemic therapy. PMID:28196063

  15. Paclitaxel injection concentrate for nanodispersion versus nab-paclitaxel in women with metastatic breast cancer: a multicenter, randomized, comparative phase II/III study.

    PubMed

    Jain, Minish M; Gupte, Smita U; Patil, Shekhar G; Pathak, Anand B; Deshmukh, Chetan D; Bhatt, Niraj; Haritha, Chiramana; Govind Babu, K; Bondarde, Shailesh A; Digumarti, Raghunadharao; Bajpai, Jyoti; Kumar, Ravi; Bakshi, Ashish V; Bhattacharya, Gouri Sankar; Patil, Poonam; Subramanian, Sundaram; Vaid, Ashok K; Desai, Chirag J; Khopade, Ajay; Chimote, Geetanjali; Bapsy, Poonamalle P; Bhowmik, Shravanti

    2016-02-01

    Paclitaxel is widely used in the treatment of patients with metastatic breast cancer (MBC). Formulations of paclitaxel contain surfactants and solvents or albumin derived from human blood. The use of co-solvents such as polyoxyethylated castor oil is thought to contribute to toxicity profile and hypersensitivity reactions as well as leaching of plasticizers from polyvinyl chloride bags and infusion sets. Currently, nab-paclitaxel, an albumin-bound paclitaxel in nanometer range continues to be the preferred taxane formulation used in clinic. This study (CTRI/2010/091/001116) investigated the efficacy and tolerability of a polyoxyethylated castor oil- and albumin-free formulation of paclitaxel [paclitaxel injection concentrate for nanodispersion (PICN)] compared with nab-paclitaxel in women with refractory MBC. The current study was a multicenter, open-label, parallel-group, randomized, comparative phase II/III trial evaluating the efficacy and safety of PICN (260 mg/m(2) [n = 64] and 295 mg/m(2) [n = 58] every 3 weeks) compared with nab-paclitaxel (260 mg/m(2) every 3 weeks [n = 58]) in women 18 and 70 years old with confirmed MBC. Overall response rate (ORR) was assessed with imaging every 2 cycles. An independent analysis of radiologic data was performed for evaluable patients. Progression-free survival (PFS) was a secondary efficacy measure. Independent radiologist-assessed ORRs in the evaluable population of women aged ≥70 years were 35, 49, and 43 % in the PICN 260 mg/m(2), PICN 295 mg/m(2), and nab-paclitaxel 260 mg/m(2) arms, respectively. Median PFS in the evaluable population was 23, 35, and 34 weeks in the PICN 260 mg/m(2), PICN 295 mg/m(2), and nab-paclitaxel 260 mg/m(2) arms, respectively. Adverse events occurred in similar proportions of patients across treatment arms. Hypersensitivity reactions were not frequently observed with the clinical use of PICN across the treatment cohorts. In women with metastatic breast cancer, PICN at 260 and 295 mg/m(2

  16. Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial.

    PubMed

    Ghi, M G; Paccagnella, A; Ferrari, D; Foa, P; Alterio, D; Codecà, C; Nolè, F; Verri, E; Orecchia, R; Morelli, F; Parisi, S; Mastromauro, C; Mione, C A; Rossetto, C; Polsinelli, M; Koussis, H; Loreggian, L; Bonetti, A; Campostrini, F; Azzarello, G; D'Ambrosio, C; Bertoni, F; Casanova, C; Emiliani, E; Guaraldi, M; Bunkheila, F; Bidoli, P; Niespolo, R M; Gava, A; Massa, E; Frattegiani, A; Valduga, F; Pieri, G; Cipani, T; Da Corte, D; Chiappa, F; Rulli, E

    2017-09-01

    Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy. Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or three cycles of induction docetaxel/cisplatin/5 fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC versus no-IC (Arms B1 + B2 versus A1 + A2) required 204 deaths to detect an absolute 3-year OS difference of 12% (HR 0.675, with 80% power at two-sided 5% significance level). 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95% CI 0.56-0.97; P = 0.031). Complete Responses (P = 0.0028), Progression Free Survival (P = 0.013) and the Loco-regional Control (P = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF. IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy. NCT01086826, www.clinicaltrials.gov.

  17. Prognostic Impact of Erythropoietin Expression and Erythropoietin Receptor Expression on Locoregional Control and Survival of Patients Irradiated for Stage II/III Non-Small-Cell Lung Cancer

    SciTech Connect

    Rades, Dirk; Setter, Cornelia; Dahl, Olav; Schild, Steven E.; Noack, Frank

    2011-06-01

    Purpose: Prognostic factors can guide the physician in selecting the optimal treatment for an individual patient. This study investigates the prognostic value of erythropoietin (EPO) and EPO receptor (EPO-R) expression of tumor cells for locoregional control and survival in non-small-cell lung cancer (NSCLC) patients. Methods and Materials: Fourteen factors were investigated in 62 patients irradiated for stage II/III NSCLC, as follows: age, gender, Karnofsky performance score (KPS), histology, grading, TNM/American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, pack years (average number of packages of cigarettes smoked per day multiplied by the number of years smoked), smoking during radiotherapy, hemoglobin levels during radiotherapy, EPO expression, and EPO-R expression. Additionally, patients with tumors expressing both EPO and EPO-R were compared to those expressing either EPO or EPO-R and to those expressing neither EPO nor EPO-R. Results: On univariate analysis, improved locoregional control was associated with AJCC stage II cancer (p < 0.048), surgery (p < 0.042), no smoking during radiotherapy (p = 0.024), and no EPO expression (p = 0.001). A trend was observed for a KPS of >70 (p = 0.08), an N stage of 0 to 1 (p = 0.07), and no EPO-R expression (p = 0.10). On multivariate analysis, AJCC stage II and no EPO expression remained significant. No smoking during radiotherapy was almost significant. On univariate analysis, improved survival was associated with N stage 0 to 1 (p = 0.009), surgery (p = 0.039), hemoglobin levels of {>=}12 g/d (p = 0.016), and no EPO expression (p = 0.001). On multivariate analysis, N stage 0 to 1 and no EPO expression maintained significance. Hemoglobin levels of {>=}12 g/d were almost significant. On subgroup analyses, patients with tumors expressing both EPO and EPO-R had worse outcomes than those expressing either EPO or EPO-R and those expressing neither EPO nor RPO-R. Conclusions: EPO expression of tumor cells

  18. SU-E-J-88: Margin Reduction of Level II/III Planning Target Volume for Image-Guided Simultaneous Integrated Boost Head-And-Neck Treatment

    SciTech Connect

    Can, S; Neylon, J; Qi, S; Santhanam, A; Low, D

    2014-06-01

    Purpose: To investigate the feasibility of improved normal tissue sparing for head-and-neck (H'N) image-guided radiotherapy (IGRT) by employing tighter CTV-to-PTV margins for target level II/III though a GPU-based deformable image registration and dose accumulation framework. Methods: Ten H'N simultaneous integrated boost cases treated on TomoTherapy were retrospectively analyzed. Weekly kVCT scans in addition to daily MVCT scans were acquired for each patient. Reduced margin plans were generated with 0- mm margin for level II and III PTV (while 3-5 mm margin for PTV1) and compared with the standard margin plan using 3-5mm margin to all CTV1-3 (reference plan). An in-house developed GPU-based 3D image deformation tool was used to register and deform the weekly KVCTs with the planning CT and determine the delivered mean/minimum/maximum dose, dose volume histograms (DVHs), etc. Results: Compared with the reference plans, the averaged cord maximum, the right and left parotid doses reduced by 22.7 %, 16.5 %, and 9 % respectively in the reduced margin plans. The V95 for PTV2 and PTV3 were found within 2 and 5% between the reference and tighter margin plans. For the reduced margin plans, the averaged cumulative mean doses were consistent with the planned dose for PTV1, PTV2 and PTV3 within 1.5%, 1.7% and 1.4%. Similar dose variations of the delivered dose were seen for the reference and tighter margin plans. The delivered maximum and mean doses for the cord were 3.55 % and 2.37% higher than the planned doses; a 5 % higher cumulative mean dose for the parotids was also observed for the delivered dose than the planned doses in both plans. Conclusion: By imposing tighter CTV-to-PTV margins for level II and III targets for H'N irradiation, acceptable cumulative doses were achievable when coupled with weekly kVCT guidance while improving normal structure sparing.

  19. Neoadjuvant triweekly nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for Stage II/III HER2-negative breast cancer: evaluation of efficacy and safety.

    PubMed

    Shimada, Hiroko; Ueda, Shigeto; Saeki, Toshiaki; Shigekawa, Takashi; Takeuchi, Hideki; Hirokawa, Eiko; Sugitani, Ikuko; Sugiyama, Michiko; Takahashi, Takao; Matsuura, Kazuo; Yamane, Tomohiko; Kuji, Ichiei; Hasebe, Takahiro; Osaki, Akihiko

    2015-07-01

    Nanoparticle albumin-bound paclitaxel (nab-PTX) is a solvent-free paclitaxel coupled to human albumin without an associated increase in toxicity. The neoadjuvant study of primary breast cancer was planned to evaluate tumor response and safety of triweekly nanoparticle albumin-bound paclitaxel. Patients with Stage II/III HER2-negative primary breast cancer received four courses of nanoparticle albumin-bound paclitaxel 260 mg/m(2) every 3 weeks (q3w), followed by four courses of epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) q3w. Tumor response after nanoparticle albumin-bound paclitaxel was histologically evaluated. In addition, the clinical response, breast-conserving rate and safety of this treatment were monitored. Among 53 patients who received nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide neoadjuvant chemotherapy, pathological complete response and near-pathological complete response were confirmed in 3 (5.7%) and 7 (13.2%) patients who had surgery, respectively. The overall objective response rate was 71.7% after completion of chemotherapy. Based on Positron Emission Tomography Response Criteria in Solid Tumors using (18)F-fluorodeoxyglucose, complete metabolic response and partial metabolic response after 2-3 courses of nanoparticle albumin-bound paclitaxel were 15.1 and 52.8%, respectively. The most common significant toxicities of q3w nanoparticle albumin-bound paclitaxel were Grade 3 muscle pain, neuropathy and febrile neutropenia, each in 1 (1.9%) patient. There were no incidences of anaphylaxis or Grade 4/5 adverse events. Neoadjuvant chemotherapy using q3w nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide was feasible in breast cancer patients with acceptable clinical response and drug tolerance, but conferred a low rate of pathological complete response. Monotherapy with q3w nanoparticle albumin-bound paclitaxel could be an appropriate substitute for solvent-based taxane in

  20. Docetaxel, cisplatin and 5-fluorouracil adjuvant chemotherapy following three-field lymph node dissection for stage II/III N1, 2 esophageal cancer.

    PubMed

    Hashiguchi, Tadasuke; Nasu, Motomi; Hashimoto, Takashi; Kuniyasu, Tetsuji; Inoue, Hirohumi; Sakai, Noritaka; Ouchi, Kazutomo; Amano, Takayuki; Isayama, Fuyumi; Tomita, Natsumi; Iwanuma, Yoshimi; Tsurumaru, Masahiko; Kajiyama, Yoshiaki

    2014-09-01

    To determine the efficacy of postoperative adjuvant chemotherapy with docetaxel + cisplatin + 5-fluorouracil (DCF) in lymph node metastasis-positive esophageal cancer, we retrospectively analyzed 139 patients with stage II/III (non-T4) esophageal cancer with lymph node metastasis (1-6 nodes), who did not receive preoperative treatment and underwent three-field lymph node dissection in the Juntendo University Hospital between December, 2004 and December, 2009. The tumors were histologically diagnossed as squamous cell carcinoma. The patients were divided into two groups, a surgery alone group (S group, 88 patients) and a group that received postoperative DCF therapy (DCF group, 51 patients). The disease-free and overall survival were compared between the groups and a multivariate analysis of prognostic factors was performed. The same analysis was performed for cases classified as N1 and N2, according to the TNM classification. There were no significant differences between the S and DCF groups regarding clinicopathological factors other than intramural metastasis and main tumor location. The presence of intramural metastasis, blood vessel invasion and the number of lymph nodes were identified as prognostic factors. The 5-year disease-free and overall survival were 55.8 and 57.3%, respectively, in the S group and 52.8 and 63.0%, respectively, in the DCF group. These differences were not considered to be statistically significant (P=0.789 and 0.479 for disease-free and overall survival, respectively). Although there were no significant differences in disease-free and overall survival between the S and DCF groups in N1 cases, both disease-free and overall survival were found to be better in the DCF group (54.2 and 61.4%, respectively) compared to the S group (29.6 and 28.8%, respectively) in N2 cases (P=0.029 and 0.020 for disease-free and overall survival, respectively). Therefore, postoperative adjuvant chemotherapy with DCF was shown to improve disease-free and

  1. SCOPE1: a randomised phase II/III multicentre clinical trial of definitive chemoradiation, with or without cetuximab, in carcinoma of the oesophagus

    PubMed Central

    2011-01-01

    Background Chemoradiotherapy is the standard of care for patients with oesophageal cancer unsuitable for surgery due to the presence of co-morbidity or extent of disease, and is a standard treatment option for patients with squamous cell carcinoma of the oesophagus. Modern regimens of chemoradiotherapy can lead to significant long-term survival. However the majority of patients will die of their disease, most commonly with local progression/recurrence of their tumours. Cetuximab may overcome one of the principal mechanisms of tumour radio-resistance, namely tumour repopulation, in patients treated with chemoradiotherapy. The purpose of this research is first to determine whether the addition of cetuximab to definitive chemoradiotherapy for treatment of patients with non-metastatic carcinoma of the oesophagus is active (in terms of failure-free rate), safe, and feasible within the context of a multi-centre randomised controlled trial in the UK. If the first stage is successful then the trial will continue to accrue sufficient patients to establish whether the addition of cetuximab to the standard treatment improves overall survival. Methods/Design SCOPE1 is a two arm, open, randomised multicentre Phase II/III trial. Eligible patients will have histologically confirmed carcinoma of the oesophagus and have been chosen to receive definitive chemoradiotherapy by an accredited multidisciplinary team including a specialist Upper GI surgeon. 420 patients will be randomised to receive definitive chemoradiotherapy with or without cetuximab using a 1:1 allocation ratio. During Phase II of the study, the trial will assess safety (toxicity), activity (failure-free rate) and feasibility (recruitment rate and protocol dose modifications/delays) in 90 patients in the experimental arm. If the experimental arm is found to be active, safe, and feasible by the Independent Data Monitoring Committee then recruitment will continue into Phase III. This second stage will recruit a further

  2. MTHFR-1298 A>C (rs1801131) is a predictor of survival in two cohorts of stage II/III colorectal cancer patients treated with adjuvant fluoropyrimidine chemotherapy with or without oxaliplatin.

    PubMed

    Cecchin, E; Perrone, G; Nobili, S; Polesel, J; De Mattia, E; Zanusso, C; Petreni, P; Lonardi, S; Pella, N; D'Andrea, M; Errante, D; Rizzolio, F; Mazzei, T; Landini, I; Mini, E; Toffoli, G

    2015-06-01

    Adjuvant treatment based on fluoropyrimidines (FL) improves the prognosis of stage II/III colorectal cancer (CRC). Validated predictive/prognostic biomarkers would spare therapy-related morbidity in patients with a good prognosis. We compared the impact of a set of 22 FL-related polymorphisms with the prognosis of two cohorts of CRC patients treated with adjuvant FL with or without OXA, including a total of 262 cases. 5,10-Methylentetrahydrofolate reductase (MTHFR) MTHFR-1298 A>C (rs1801131) polymorphism had a concordant effect: MTHFR-rs1801131-1298CC genotype carriers had a worse disease free survival (DFS) in both the cohorts. In the pooled population MTHFR-rs1801131-1298CC carriers had also a worse overall survival. We computed a clinical score related to DFS including MTHFR-rs1801131, tumor stage, sex and tumor location, where rs1801131 is the most detrimental factor (hazard ratio=5.3, 95% confidence interval=2.2-12.9; P-value=0.0006). MTHFR-rs1801131 is a prognostic factor that could be used as an additional criteria for the choice of the proper adjuvant regimen in stage II/III colorectal cancer patients.

  3. PET/CT with (18)F-FDG predicts short-term outcome in stage II/III breast cancer patients upstaged to N2/3 nodal disease.

    PubMed

    Teixeira, S C; Koolen, B B; Elkhuizen, P H M; Vrancken Peeters, M-J T F D; Stokkel, M P M; Rodenhuis, S; van der Noort, V; Rutgers, E J T; Valdés Olmos, R A

    2017-04-01

    (18)F-FDG PET/CT has high positive predictive value for the detection of avid lymph node metastases in breast cancer patients. We analysed the effect of upstaging lymph nodes by PET/CT on short-term outcome in stage II/III breast cancer patients. A total of 278 stage II/III primary breast cancer patients (mean age 48.9 years, range 19-75 years) were re-staged with (18)F-FDG PET/CT before start of pre-operative systemic treatment (PST). Patients were divided in three groups based on risk for local recurrence: a low - (T2N0), intermediate - (T0-2N1 and T3N0) and a high-risk group (T0-3N2-3, T3N1 and T4). Within these groups we looked at local recurrence-free survival (LRFS), recurrence-free survival (RFS) and overall survival (OS) within the first 3 years of follow-up. With a median follow-up (FU) of 50 months the RFS, LRFS and OS were 87%, 88% and 92% respectively for the whole group. PET/CT upstaged 43 patients from the low- and intermediate risk group to the high-risk group, based on detection of ≥4 avid axillary nodes or occult N2/3-disease. Patients upstaged with PET/CT had more events for all three analyses compared to the original risk groups, which resulted in a significantly worse RFS (69.8%; p = 0.03) a nearly significantly worse LRFS (p = 0.052) and no effect in OS (p = 0.433). Additional PET/CT staging allows breast cancer patients to be treated according to the true stage, still stage II/III breast cancer patients upstaged to N2/3 by PET/CT have worse short-term outcome, despite adjustment of treatment, than patients staged high-risk with conventional imaging. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  4. The Role of Postmastectomy Radiation Therapy After Neoadjuvant Chemotherapy in Clinical Stage II-III Breast Cancer Patients With pN0: A Multicenter, Retrospective Study (KROG 12-05)

    SciTech Connect

    Shim, Su Jung; Park, Won; Huh, Seung Jae; Choi, Doo Ho; Shin, Kyung Hwan; Lee, Nam Kwon; Suh, Chang-Ok; Keum, Ki Chang; Kim, Yong Bae; Ahn, Seung Do; Kim, Su Ssan; Ha, Sung W.; Chie, Eui Kyu; Kim, Kyubo; Shin, Hyun Soo; Kim, Jin Hee; Lee, Hyung-Sik

    2014-01-01

    Purpose: The purpose of this study was to investigate the role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) in clinical stage II-III breast cancer patients with pN0. Methods and Materials: We retrospectively identified 417 clinical stage II-III breast cancer patients who achieved an ypN0 at surgery after receiving NAC between 1998 and 2009. Of these, 151 patients underwent mastectomy after NAC. The effect of PMRT on disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and overall survival (OS) was evaluated by multivariate analysis including known prognostic factors using the Kaplan-Meier method and compared using the log–rank test and Cox proportional regression analysis. Results: Of the 151 patients who underwent mastectomy, 105 (69.5%) received PMRT and 46 patients (30.5%) did not. At a median follow-up of 59 months, 5 patients (3.3%) developed LRR (8 sites of recurrence) and 14 patients (9.3%) developed distant metastasis. The 5-year DFS, LRRFS, and OS rates were 91.2, 98.1, and 93.3% with PMRT and 83.0%, 92.3%, and 89.9% without PMRT, respectively (all P values not significant). By univariate analysis, only age (≤40 vs >40 years) was significantly associated with decreased DFS (P=.027). By multivariate analysis, age (≤40 vs >40 years) and pathologic T stage (0-is vs 1 vs 2-4) were significant prognostic factors affecting DFS (hazard ratio [HR] 0.353, 95% confidence interval [CI] 0.135-0.928, P=.035; HR 2.223, 95% CI 1.074-4.604, P=.031, respectively). PMRT showed no correlation with a difference in DFS, LRRFS, or OS by multivariate analysis. Conclusions: PMRT might not be necessary for pN0 patients after NAC, regardless of clinical stage. Prospective randomized clinical trial data are needed to assess whether PMRT can be safely omitted in pN0 patients after NAC and mastectomy for clinical stage II-III breast cancer.

  5. Omission of doxorubicin from the treatment of stage II-III, intermediate-risk Wilms' tumour (SIOP WT 2001): an open-label, non-inferiority, randomised controlled trial.

    PubMed

    Pritchard-Jones, Kathy; Bergeron, Christophe; de Camargo, Beatriz; van den Heuvel-Eibrink, Marry M; Acha, Tomas; Godzinski, Jan; Oldenburger, Foppe; Boccon-Gibod, Liliane; Leuschner, Ivo; Vujanic, Gordan; Sandstedt, Bengt; de Kraker, Jan; van Tinteren, Harm; Graf, Norbert

    2015-09-19

    Before this study started, the standard postoperative chemotherapy regimen for stage II-III Wilms' tumour pretreated with chemotherapy was to include doxorubicin. However, avoidance of doxorubicin-related cardiotoxicity effects is important to improve long-term outcomes for childhood cancers that have excellent prognosis. We aimed to assess whether doxorubicin can be omitted safely from chemotherapy for stage II-III, histological intermediate-risk Wilms' tumour when a newly defined high-risk blastemal subtype was excluded from randomisation. For this international, multicentre, open-label, non-inferiority, phase 3, randomised SIOP WT 2001 trial, we recruited children aged 6 months to 18 years at the time of diagnosis of a primary renal tumour from 251 hospitals in 26 countries who had received 4 weeks of preoperative chemotherapy with vincristine and actinomycin D. Children with stage II-III intermediate-risk Wilms' tumours assessed after delayed nephrectomy were randomly assigned (1:1) by a minimisation technique to receive vincristine 1·5 mg/m(2) at weeks 1-8, 11, 12, 14, 15, 17, 18, 20, 21, 23, 24, 26, and 27, plus actinomycin D 45 μg/kg every 3 weeks from week 2, either with five doses of doxorubicin 50 mg/m(2) given every 6 weeks from week 2 (standard treatment) or without doxorubicin (experimental treatment). The primary endpoint was non-inferiority of event-free survival at 2 years, analysed by intention to treat and a margin of 10%. Assessment of safety and adverse events included systematic monitoring of hepatic toxicity and cardiotoxicity. This trial is registered with EudraCT, number 2007-004591-39, and is closed to new participants. Between Nov 1, 2001, and Dec 16, 2009, we recruited 583 patients, 341 with stage II and 242 with stage III tumours, and randomly assigned 291 children to treatment including doxorubicin, and 292 children to treatment excluding doxorubicin. Median follow-up was 60·8 months (IQR 40·8-79·8). 2 year event-free survival was

  6. Randomized phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck: Japan Clinical Oncology Group Study (JCOG1008).

    PubMed

    Kunieda, Futoshi; Kiyota, Naomi; Tahara, Makoto; Kodaira, Takeshi; Hayashi, Ryuichi; Ishikura, Satoshi; Mizusawa, Junki; Nakamura, Kenichi; Fukuda, Haruhiko; Fujii, Masato

    2014-08-01

    A randomized Phase II/III study was launched in Japan to evaluate the non-inferiority of concurrent chemoradiotherapy with weekly cisplatin (40 mg/m(2)) compared with concurrent chemoradiotherapy with 3-weekly cisplatin (100 mg/m(2)) for post-operative high-risk patients with locally advanced squamous cell carcinoma of head and neck. This study began in October 2012, and a total of 260 patients will be accrued from 18 institutions within 5 years. The primary endpoint of the Phase II part is proportion of treatment completion and that of the Phase III part is overall survival. The secondary endpoints are relapse-free survival, local relapse-free survival, nutrition-support-free survival, non-hospitalized treatment period during permissible treatment period and adverse events. This trial was registered at the UMIN Clinical Trials Registry as UMIN 000009125 [http://www.umin.ac.jp/ctr/].

  7. A Phase II/III randomized controlled trial comparing perioperative versus postoperative chemotherapy with mFOLFOX6 for lower rectal cancer with suspected lateral pelvic node metastasis: Japan Clinical Oncology Group Study JCOG1310 (PRECIOUS study).

    PubMed

    Ohue, Masayuki; Iwasa, Satoru; Kanemitsu, Yukihide; Hamaguchi, Tetsuya; Shiozawa, Manabu; Ito, Masaaki; Yasui, Masayoshi; Katayama, Hiroshi; Mizusawa, Junki; Shimada, Yasuhiro

    2017-01-01

    A randomized phase II/III trial was started in May 2015 comparing perioperative versus postoperative chemotherapy with modified infusional fluorouracil and folinic acid with oxaliplatin for lower rectal cancer patients with suspected lateral pelvic node metastasis. The standard arm is total mesorectal excision or tumor-specific mesorectal excision with lateral pelvic node dissection (LND) followed by postoperative chemotherapy (modified infusional fluorouracil and folinic acid with oxaliplatin; 12 cycles). The experimental (perioperative chemotherapy) arm is six courses of modified infusional fluorouracil and folinic acid with oxaliplatin before and six courses after total mesorectal excision with lateral pelvic node dissection. The aim of this trial is to confirm the superiority of perioperative chemotherapy. A total of 330 patients will be enrolled over 7 years. The primary endpoint in Phase II part is proportion of R0 resection and that in Phase III part is overall survival. Secondary endpoints are progression-free survival, local progression-free survival, etc. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000017603 [http://www.umin.ac.jp/ctr/index-j.htm].

  8. The effectiveness and safety of topical PhotoActif phosphatidylcholine-based anti-cellulite gel and LED (red and near-infrared) light on Grade II-III thigh cellulite: a randomized, double-blinded study.

    PubMed

    Sasaki, Gordon H; Oberg, Kerby; Tucker, Barbara; Gaston, Margaret

    2007-06-01

    Cellulite of the upper lateral and posterior thighs and lower buttocks represents a common, physiological and unwanted condition whose etiologies and effective management are subjects of continued debate. The purpose of this controlled, double-blinded study is to evaluate the efficacy and safety of a novel phosphatidylcholine-based, cosmeceutical anti-cellulite gel combined with a light-emitting diode (LED) array at the wavelengths of red (660 nm) and near-infrared (950 nm), designed to counter the possible mechanisms that purportedly accentuate the presence of thigh cellulite. Nine healthy female volunteers with Grade II-III thigh cellulite were randomly treated twice daily with an active gel on one thigh and a placebo gel on the control thigh for 3 months. Twice weekly, each thigh was exposed for a 15-minute treatment with LED light for a total of 24 treatments. At 0, 6, and 12 weeks of the study the following clinical determinants were obtained: standardized digital photography, height and weight measurements, standardized thigh circumference tape measurements, pinch testing, body mass index (kg/m2), body fat analysis (Futrex-5500/XL near-infrared analyzer), and digital high-resolution ultrasound imaging of the dermal-adiposal border. In selected patients, full-thickness biopsies of the placebo and active-treated sites were obtained. At 18 months, repeat standardized digital photography, height and weight measurements, and body mass index measurements were obtained. At the end of 3 months, eight of nine thighs treated with the phosphatidylcholine-based, anti-cellulite gel and LED treatments were downgraded to a lower cellulite grade by clinical examination, digital photography, and pinch test assessment. Digital ultrasound at the dermal-adiposal interface demonstrated not only a statistically significant reduction of immediate hypodermal depth, but also less echo-like intrusions into the dermal layer. Three of six biopsies from thighs treated for 3 months with

  9. Long-term Survival Outcomes Following Internal Mammary Node Irradiation in Stage II-III Breast Cancer: Results of a Large Retrospective Study With 12-Year Follow-up

    SciTech Connect

    Chang, Jee Suk; Park, Won; Kim, Yong Bae; Lee, Ik Jae; Keum, Ki Chang; Lee, Chang Geol; Choi, Doo Ho; Suh, Chang-Ok; Huh, Seung Jae

    2013-08-01

    Purpose: To examine the effect of internal mammary node irradiation (IMNI) on disease-free survival (DFS) and overall survival (OS) in breast cancer patients treated with modified radical mastectomy and postoperative radiation therapy. Methods and Materials: Between 1994 and 2002, 396 patients with stage II-III breast cancer were treated with postmastectomy radiation therapy with (n=197) or without (n=199) IMNI. Patients who received neoadjuvant chemotherapy were excluded. IMNI was administered at the clinical discretion of the treating physician. Median RT dose was 50.4 Gy (range, 45.0-59.4 Gy) in 28 fractions, with inclusion of the supraclavicular fossa in 96% of patients. Adjuvant chemotherapy was administered to 99.7% of the patients and endocrine therapy to 53%. Results: The median follow-up was 149 months (range, 124-202). IMNI patients had more advanced nodal stage and non-high grade tumors than those without IMNI (P<.001). Otherwise, disease and treatment characteristics were well balanced. The 10-year DFS with and without IMNI was 65% and 57%, respectively (P=.05). Multivariate analysis demonstrated that IMNI was an independent, positive predictor of DFS (hazard ratio [HR], 0.70; P=.02). Benefits of IMNI in DFS were seen most apparently in N2 patients (HR, 0.44; 95% confidence interval [CI], 0.26-0.74) and inner/central tumors (HR, 0.55; 95% CI, 0.34-0.90). The 10-year OS with and without IMNI was 72% and 66%, respectively (P=.62). The 10-year DFS and OS were 61%, and 69%, respectively. Conclusions: Internal mammary node irradiation significantly improved DFS in postmastectomy breast cancer patients. Pending long-term results from randomized trials, treatment of internal mammary nodes should be considered in postmastectomy radiation therapy.

  10. Long-term survival outcomes following internal mammary node irradiation in stage II-III breast cancer: results of a large retrospective study with 12-year follow-up.

    PubMed

    Chang, Jee Suk; Park, Won; Kim, Yong Bae; Lee, Ik Jae; Keum, Ki Chang; Lee, Chang Geol; Choi, Doo Ho; Suh, Chang-Ok; Huh, Seung Jae

    2013-08-01

    To examine the effect of internal mammary node irradiation (IMNI) on disease-free survival (DFS) and overall survival (OS) in breast cancer patients treated with modified radical mastectomy and postoperative radiation therapy. Between 1994 and 2002, 396 patients with stage II-III breast cancer were treated with postmastectomy radiation therapy with (n=197) or without (n=199) IMNI. Patients who received neoadjuvant chemotherapy were excluded. IMNI was administered at the clinical discretion of the treating physician. Median RT dose was 50.4 Gy (range, 45.0-59.4 Gy) in 28 fractions, with inclusion of the supraclavicular fossa in 96% of patients. Adjuvant chemotherapy was administered to 99.7% of the patients and endocrine therapy to 53%. The median follow-up was 149 months (range, 124-202). IMNI patients had more advanced nodal stage and non-high grade tumors than those without IMNI (P<.001). Otherwise, disease and treatment characteristics were well balanced. The 10-year DFS with and without IMNI was 65% and 57%, respectively (P=.05). Multivariate analysis demonstrated that IMNI was an independent, positive predictor of DFS (hazard ratio [HR], 0.70; P=.02). Benefits of IMNI in DFS were seen most apparently in N2 patients (HR, 0.44; 95% confidence interval [CI], 0.26-0.74) and inner/central tumors (HR, 0.55; 95% CI, 0.34-0.90). The 10-year OS with and without IMNI was 72% and 66%, respectively (P=.62). The 10-year DFS and OS were 61%, and 69%, respectively. Internal mammary node irradiation significantly improved DFS in postmastectomy breast cancer patients. Pending long-term results from randomized trials, treatment of internal mammary nodes should be considered in postmastectomy radiation therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. The effect of COX-2 inhibitor on capecitabine-induced hand-foot syndrome in patients with stage II/III colorectal cancer: a phase II randomized prospective study.

    PubMed

    Zhang, Rong-Xin; Wu, Xiao-Jun; Lu, Shi-Xun; Pan, Zhi-Zhong; Wan, De-Sen; Chen, Gong

    2011-06-01

    Hand-foot syndrome (HFS) is a common adverse event that can be induced by capecitabine. It is hypothesized that capecitabine (Hoffmann-La Roche Inc.) based chemotherapy can cause overexpression of COX-2 in tumor and healthy tissue, which finally induced HFS in hands and feet. Based on this, we believed that a selected COX-2 inhibitor (celecoxib, Pfizer Pharmaceuticals LLC) could ease HFS. We designed a prospective clinical study to test the hypothesis. From August 2008 to January 2010, 110 patients with stage II/III colorectal cancer who were eligible for adjuvant chemotherapy were enrolled in the study and divided into 4 groups by random, but 9 patients did not finish at least 4 cycles of chemotherapy. There were sixteen patients in capecitabine group, and fifteen patients in capecitabine and celecoxib group. Thirty-four patients were in XELOX (capecitabine plus oxaliplatine) group, and thirty-six patients in XELOX+ celecoxib group. All 101 patients finished chemotherapy and follow-up interviews. The group that had received capecitabine and celecoxib had a significantly reduced frequency of  >grade 1 hand-foot syndrome (29 vs. 72% P < 0.001), and >grade 2 (11.76% vs. 30% P = 0.024). Five patients experienced grade 3 HFS in capecitabine group and only 1 patient had grade 3 HFS in capecitabine and celecoxib group. There were 5 patients in capecitabine group who refused to go on chemotherapy because of HFS, but there was none in capecitabine and celecoxib group. From the result of this study, we could learn that celecoxib could reduce HFS that was induced by capecitabine. So we recommend that celecoxib can be used in capecitabine-based chemotherapy.

  12. Oral liarozole in the treatment of patients with moderate/severe lamellar ichthyosis: results of a randomized, double-blind, multinational, placebo-controlled phase II/III trial

    PubMed Central

    Vahlquist, A; Blockhuys, S; Steijlen, P; van Rossem, K; Didona, B; Blanco, D; Traupe, H

    2014-01-01

    Summary Background Oral liarozole, a retinoic acid metabolism-blocking agent, may be an alternative to systemic retinoid therapy in patients with lamellar ichthyosis. Objective To demonstrate the efficacy and safety of once-daily oral liarozole in the treatment of moderate/severe lamellar ichthyosis. Methods This was a double-blind, multinational, parallel phase II/III trial (NCT00282724). Patients aged ≥ 14 years with moderate/severe lamellar ichthyosis [Investigator's Global Assessment (IGA) score ≥ 3] were randomized 3 : 3 : 1 to receive oral liarozole (75 or 150 mg) or placebo once daily for 12 weeks. Assessments included: IGA; a five-point scale for erythema, scaling and pruritus severity; Short Form-36 health survey; Dermatology Life Quality Index (DLQI); and safety parameters. The primary efficacy variable was response rate at week 12 (responder: ≥ 2-point decrease in IGA from baseline). Results Sixty-four patients were enrolled. At week 12, 11/27 (41%; liarozole 75 mg), 14/28 (50%; liarozole 150 mg) and one out of nine (11%; placebo) patients were responders; the difference between groups (liarozole 150 mg vs. placebo) was not significant (P = 0·056). Mean IGA and scaling scores decreased from baseline in both liarozole groups at weeks 8 and 12 vs. placebo; erythema and pruritus scores were similar between treatment groups. Improvement in DLQI score was observed in both liarozole groups. Treatment with liarozole for 12 weeks was well tolerated. Conclusions The primary efficacy variable did not reach statistical significance, possibly owing to the small sample size following premature termination. However, once-daily oral liarozole, 75 and 150 mg, improved scaling and DLQI and was well tolerated in patients with moderate/severe lamellar ichthyosis. PMID:24102348

  13. Efficacy and safety of bilastine in Japanese patients with chronic spontaneous urticaria: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II/III study.

    PubMed

    Hide, Michihiro; Yagami, Akiko; Togawa, Michinori; Saito, Akihiro; Furue, Masutaka

    2017-04-01

    Bilastine, a novel non-sedating second-generation H1-antihistamine, has been widely used in the treatment of allergic rhinoconjunctivitis and urticaria with a recommended dose of 20 mg once daily in most European countries since 2010. We evaluated its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU). We conducted a multicenter, randomized, double-blind, placebo-controlled phase II/III study (trial registration No. JapicCTI-142574). Patients (age, 18-74 years) were randomly assigned to receive bilastine 20 mg, 10 mg or placebo once daily for 2 weeks. The primary efficacy endpoint was the change from baseline (Day -3 to 0) in total symptom score (TSS) at 2 weeks (Day 8-14), consisting of the itch and rash scores. A total of 304 patients were randomly allocated to bilastine 20 mg (101 patients), bilastine 10 mg (100 patients), and placebo (103 patients). The changes in TSS at 2 weeks were significantly decreased by bilastine 20 mg than did placebo (p < 0.001), demonstrating the superiority of bilastine 20 mg. Bilastine 10 mg also showed a significant difference from placebo (p < 0.001). The TSS changes for the bilastine showed significant improvement from Day 1, and were maintained during the treatment period. The Dermatology Life Quality Index scores were also improved in bilastine than in placebo. The bilastine treatments were safe and well tolerated. Two-week treatment with bilastine (20 or 10 mg) once daily was effective and tolerable in Japanese patients with CSU, demonstrating an early onset of action. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  14. Phase II Results of RTOG 0537: A Phase II/III Study Comparing Acupuncture-like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Early Radiation-Induced Xerostomia

    PubMed Central

    Wong, Raimond K. W.; James, Jennifer L.; Sagar, Stephen; Wyatt, Gwen; Nguyen-Tân, Phuc Felix; Singh, Anurag K.; Lukaszczyk, Barbara; Cardinale, Francis; Yeh, Alexander M.; Berk, Lawrence

    2011-01-01

    Purpose This phase II component of a multi-institutional phase II/III randomized trial assessed the feasibility and preliminary efficacy of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) in reducing radiation-induced xerostomia. Methods Head and neck cancer patients who were 3–24 months from completing radiotherapy ± chemotherapy (RT±C) and experiencing xerostomia symptoms with basal whole saliva production ≥0.1 ml/min and without recurrence were eligible. Patients received twice weekly ALTENS sessions (24 over 12 weeks) using a Codetron™ unit. The primary objective assessed the feasibility of ALTENS treatment. A patient was considered compliant if 19/24 ALTENS were delivered, with a targeted 85% compliance rate. Secondary objectives measured treatment-related toxicities and ALTENS effect on overall radiation-induced xerostomia burden using the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS). Results Of 48 accrued patients, 47 were evaluable. Median age was 60 years; 84% were male, 70% completed RT±C for > 12 months and 21% had received prior pilocarpine. All ALTENS sessions were completed in 34 patients, but 9 and 1 completed 20–23 and 19 sessions respectively, representing a 94% total compliance rate. 6-month XeQOLS scores were available for 35 patients; 30 (86%) achieved a positive treatment response with a mean reduction of 35.9% (SD 36.1). Five patients developed grade 1–2 gastrointestinal toxicity and one had grade 1 pain event. Conclusions ALTENS treatment for radiation-induced xerostomia can be uniformly delivered in a cooperative multicenter setting and has possible beneficial treatment response. Given these results, the phase III component of this study was initiated. PMID:22252927

  15. Expression and prognostic significance of APAF-1, caspase-8 and caspase-9 in stage II/III colon carcinoma: caspase-8 and caspase-9 is associated with poor prognosis.

    PubMed

    Sträter, Jörn; Herter, Ines; Merkel, Gaby; Hinz, Ulf; Weitz, Jürgen; Möller, Peter

    2010-08-15

    Apoptosis protease activating factor-1 (APAF-1), caspase-8 and caspase-9 are important factors in the execution of death signals. To study their prognostic influence in colon carcinoma, expression of APAF-1, caspase-8 and caspase-9 was determined by immunohistochemistry in normal colon mucosa (n = 8) and R0-resected stage II/III colon carcinomas (n >or= 124) using a semiquantitative score. Staining results were correlated with disease-free survival by Kaplan-Meier estimates, and multivariate Cox analyses were performed. In normal colon, APAF-1 and caspase-8 are most strongly expressed in the luminal surface epithelium, whereas caspase-9 is expressed all along the crypt axis. In colon carcinomas, there is considerable variability in the expression of these proapoptotic factors, although complete loss of caspase-8 and caspase-9 is rare. APAF-1 expression did not correlate with disease-free survival. Instead, both expression of caspase-9 and high-level expression of caspase-8 in a majority of tumor cells were significantly associated with adverse prognosis (p = 0.004 and p = 0.029, respectively). The influence of caspase-8 expression was mainly seen in patients with stage III colon carcinoma (p = 0.011), whereas the prognostic influence of caspase-9 expression was significant in stage II cases (p = 0.037) and just failed to be significant in stage III tumors (p = 0.0581). After adjusting for confounding factors in a multivariate Cox analysis, the effect of caspase-9 in predicting disease-free survival was confirmed (p = 0.003). Our data suggest that, in colon carcinomas, expression of caspase-8 and caspase-9 is significantly associated with poor survival. Caspase-9 may be an independent prognosticator in colon carcinoma.

  16. Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE.

    PubMed

    Cohen, H; Doré, C J; Clawson, S; Hunt, B J; Isenberg, D; Khamashta, M; Muirhead, N

    2015-09-01

    The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism (VTE) in major phase III prospective, randomized controlled trials (RCTs), but the results may not be directly generalizable to patients with APS. The primary aim is to demonstrate, in patients with APS and previous VTE, with or without systemic lupus erythematosus (SLE), that the intensity of anticoagulation achieved with rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare rates of recurrent thrombosis, bleeding and the quality of life in patients on rivaroxaban with those on warfarin. Rivaroxaban in antiphospholipid syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which eligible patients with APS, with or without SLE, who are on warfarin, target international normalized ratio (INR) 2.5 for previous VTE, will be randomized either to continue warfarin (standard of care) or to switch to rivaroxaban. Intensity of anticoagulation will be assessed using thrombin generation (TG) testing, with the primary outcome the percentage change in endogenous thrombin potential (ETP) from randomization to day 42. Other TG parameters, markers of in vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin complex and D-dimer, will also be assessed. If RAPS demonstrates i) that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin and ii) the absence of any adverse effects that cause concern with regard to the use of rivaroxaban, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of APS patients with previous VTE, requiring a target INR of 2.5. © The Author(s) 2015.

  17. Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer.

    PubMed

    Coleman, R; Woodward, E; Brown, J; Cameron, D; Bell, R; Dodwell, D; Keane, M; Gil, M; Davies, C; Burkinshaw, R; Houston, S J; Grieve, R J; Barrett-Lee, P J; Thorpe, H

    2011-06-01

    The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3-1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ.

  18. The prognostic value of preoperative inflammation-based prognostic scores and nutritional status for overall survival in resected patients with nonmetastatic Siewert type II/III adenocarcinoma of esophagogastric junction.

    PubMed

    Zhang, Lixiang; Su, Yezhou; Chen, Zhangming; Wei, Zhijian; Han, Wenxiu; Xu, Aman

    2017-07-01

    Immune and nutritional status of patients have been reported to predict postoperative complications, recurrence, and prognosis of patients with cancer. Therefore, this retrospective study aimed to explore the prognostic value of preoperative inflammation-based prognostic scores [neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR)] and nutritional status [prognostic nutritional index (PNI), body mass index (BMI), hemoglobin, albumin, and prealbumin] for overall survival (OS) in adenocarcinoma of esophagogastric junction (AEG) patients. A total of 355 patients diagnosed with Siewert type II/III AEG and underwent surgery between October 2010 and December 2011 were followed up until October 2016. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values of NLR, PLR, and PNI. Kaplan-Meier curves and Cox regression analyses were used to calculate the OS characteristics. The ideal cutoff values for predicting OS were 3.5 for NLR, 171 for PLR, and 51.3 for PNI according to the ROC curve. The patients with hemoglobin <120 g/L (P = .001), prealbumin <180 mg/L (P = .000), PNI <51.3 (P = .010), NLR >3.5 (P = .000), PLR >171 (P = .006), and low BMI group (P = .000) had shorter OS. And multivariate survival analysis using the Cox proportional hazards model showed that the tumor-node-metastasis stage, BMI, NLR, and prealbumin levels were independent risk factors for the OS. Our study demonstrated that preoperative prealbumin, BMI, and NLR were independent prognostic factors of AEG patients.

  19. A randomized, multicenter, phase II/III study to determine the optimal dose and to evaluate the efficacy and safety of pegteograstim (GCPGC) on chemotherapy-induced neutropenia compared to pegfilgrastim in breast cancer patients: KCSG PC10-09.

    PubMed

    Lee, Ki Hyeong; Kim, Ji-Yeon; Lee, Moon Hee; Han, Hye Sook; Lim, Joo Han; Park, Keon Uk; Park, In Hae; Cho, Eun Kyung; Yoon, So Young; Kim, Jee Hyun; Choi, In Sil; Park, Jae Hoo; Choi, Young Jin; Kim, Hee-Jun; Jung, Kyung Hae; Kim, Si-Young; Oh, Do-Youn; Im, Seock-Ah

    2016-04-01

    Pegylated granulocyte-colony-stimulating factor (G-CSF) is frequently used to prevent febrile neutropenia (FN) in patients undergoing chemotherapy with a high risk of myelosuppression. This phase II/III study was conducted to determine the adequate dose of pegteograstim, a new formulation of pegylated G-CSF, and to evaluate the efficacy and safety of pegteograstim compared to pegfilgrastim. In the phase II part, 60 breast cancer patients who were undergoing DA (docetaxel and doxorubicin) or TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy were randomly selected to receive a single subcutaneous injection of 3.6 or 6.0 mg pegteograstim on day 2 of each chemotherapy cycle. The phase III part was seamlessly started to compare the dose of pegteograstim at selected in phase II with 6.0 mg pegfilgrastim in 117 breast cancer patients. The primary endpoint of both the phase II and III parts was the duration of grade 4 neutropenia in the chemotherapy cycle 1. The mean duration of grade 4 neutropenia for the 3.6 mg pegteograstim (n = 33) was similar to that for the 6.0 mg pegteograstim (n = 26) (1.97 ± 1.79 days vs. 1.54 ± 0.95 days, p = 0.33). The 6.0 mg pegteograstim was selected to be compared with the 6.0 mg pegfilgrastim in the phase III part. In the phase III part, the primary analysis revealed that the efficacy of pegteograstim (n = 56) was non-inferior to that of pegfilgrastim (n = 59) [duration of grade 4 neutropenia, 1.64 ± 1.18 days vs. 1.80 ± 1.05 days; difference, -0.15 ± 1.11 (p = 0.36, 97.5 % confidence intervals = 0.57 and 0.26)]. The time to the absolute neutrophil count (ANC) recovery of pegteograstim (≥2000/μL) was significantly shorter than that of pegfilgrastim (8.85 ± 1.45 days vs. 9.83 ± 1.20 days, p < 0.0001). Other secondary endpoints showed no significant difference between the two groups. The safety profiles of the two groups did not differ significantly. Pegteograstim was shown to be as effective as pegfilgrastim in the

  20. Construction of a database for published phase II/III drug intervention clinical trials for the period 2009-2014 comprising 2,326 records, 90 disease categories, and 939 drug entities.

    PubMed

    Jeong, Sohyun; Han, Nayoung; Choi, Boyoon; Sohn, Minji; Song, Yun-Kyoung; Chung, Myeon-Woo; Na, Han-Sung; Ji, Eunhee; Kim, Hyunah; Rhew, Ki Yon; Kim, Therasa; Kim, In-Wha; Oh, Jung Mi

    2016-06-01

    To construct a database of published clinical drug trials suitable for use 1) as a research tool in accessing clinical trial information and 2) in evidence-based decision-making by regulatory professionals, clinical research investigators, and medical practitioners. Comprehensive information obtained from a search of design elements and results of clinical trials in peer reviewed journals using PubMed (http://www.ncbi.nlm.ih.gov/pubmed). The methodology to develop a structured database was devised by a panel composed of experts in medical, pharmaceutical, information technology, and members of Ministry of Food and Drug Safety (MFDS) using a step by step approach. A double-sided system consisting of user mode and manager mode served as the framework for the database; elements of interest from each trial were entered via secure manager mode enabling the input information to be accessed in a user-friendly manner (user mode). Information regarding methodology used and results of drug treatment were extracted as detail elements of each data set and then inputted into the web-based database system. Comprehensive information comprising 2,326 clinical trial records, 90 disease states, and 939 drugs entities and concerning study objectives, background, methods used, results, and conclusion could be extracted from published information on phase II/III drug intervention clinical trials appearing in SCI journals within the last 10 years. The extracted data was successfully assembled into a clinical drug trial database with easy access suitable for use as a research tool. The clinically most important therapeutic categories, i.e., cancer, cardiovascular, respiratory, neurological, metabolic, urogenital, gastrointestinal, psychological, and infectious diseases were covered by the database. Names of test and control drugs, details on primary and secondary outcomes and indexed keywords could also be retrieved and built into the database. The construction used in the database

  1. Axillary Management of Stage II/III Breast Cancer in Patients Treated with Neoadjuvant Systemic Therapy: Results of CALGB 40601 (HER2-Positive) and CALGB 40603 (Triple-Negative).

    PubMed

    Ollila, David W; Cirrincione, Constance T; Berry, Donald A; Carey, Lisa A; Sikov, William M; Hudis, Clifford A; Winer, Eric P; Golshan, Mehra

    2017-04-01

    Management of the axilla in stage II/III breast cancer undergoing neoadjuvant systemic therapy (NST) is controversial. To understand current patterns of care, we collected axillary data from 2 NST trials: HER2-positive (Cancer and Leukemia Group B [CALGB] 40601) and triple-negative (CALGB 40603). Axillary evaluation pre- and post-NST was per the treating surgeon and could include sentinel node biopsy. Post-NST, node-positive patients were recommended to undergo axillary lymph node dissection (ALND). We report pre-NST histopathologic nodal evaluation and post-NST axillary surgical procedures with correlation to clinical and pathologic nodal status. Seven hundred and forty-two patients were treated, 704 had complete nodal data pre-NST and post-NST. Pre-NST, 422 (60%) of 704 patients underwent at least 1 procedure for axillary node evaluation (total of 468 procedures): fine needle aspiration (n = 234; 74% positive), core needle biopsy (n = 138; 72% positive), and sentinel node biopsy (n = 96; 33% positive). Pre-NST, 304 patients were considered node-positive. Post-NST, 304 of 704 patients (43%) underwent sentinel node biopsy; 44 were positive and 259 were negative (29 and 36 patients, respectively, had subsequent ALND). Three hundred and ninety-one (56%) patients went directly to post-NST ALND and 9 (1%) pre-NST node-positive patients had no post-NST axillary procedure. Post-NST, 170 (24%) of the 704 patients had residual axillary disease. Agreement between post-NST clinical and radiologic staging and post-NST histologic staging was strongest for node-negative (81%) and weaker for node-positive (N1 31%, N2 29%), with more than half of the clinically node-positive patients found to be pathologic negative (p < 0.001). Our results suggest there is no widely accepted standard for axillary nodal evaluation pre-NST. Post-NST staging was highly concordant in patients with N0 disease, but poorly so in node-positive disease. Accurate methods are needed to identify post

  2. Ozone loss rates in the Arctic winter stratosphere during 1994-2000 derived from POAM II/III and ILAS observations: Implications for relationships among ozone loss, PSC occurrence, and temperature

    NASA Astrophysics Data System (ADS)

    Terao, Yukio; Sugita, Takafumi; Sasano, Yasuhiro

    2012-03-01

    Quantitative chemical ozone loss rates at the 475 K isentropic surface inside the Arctic polar vortex are evaluated for six winters (January through March) using a satellite-based Match technique. Satellite observational data are taken from the Polar Ozone and Aerosol Measurement (POAM) II for 1994-1996, the Improved Limb Atmospheric Spectrometer (ILAS) for 1997, and the POAM III for 1999-2000. The largest ozone loss rates were observed in the end of January 1995 (˜50 ± 20 ppbv d-1), February 1996 (˜40-50 ± 15 ppbv d-1), February 1997 (˜40 ± 8 ppbv d-1), January 2000 (˜60 ± 30 ppbv d-1), and early March 2000 (˜40 ± 10 ppbv d-1). The probability of polar stratospheric cloud (PSC) existence is estimated using aerosol extinction coefficient data from POAM II/III and ILAS. Ozone loss and the PSC probability are strongly correlated and an absolute increase of 10% in the PSC probability is found to amplify the chemical ozone loss rate during Arctic winter by approximately 25 ± 6 ppbv per day or 3.2 ± 0.7 ppbv per sunlit hour. Relationships between average Arctic winter ozone loss rates and various PSC- and temperature-related indices are investigated, including the area of polar vortex that is colder than the threshold temperature for PSC existence (APSC), the PSC formation potential (PFP), and the potential for activation of chlorine (PACl). Of these three, PACl provides the best proxy representation of interannual variability in Arctic ozone loss at the 475 K level. Large ozone loss occurred primarily for air masses that experienced low temperatures between 187 K and 195 K within the previous 10 days and the ozone loss rates clearly increase with decreasing the minimum temperature. The particularly large ozone losses of ˜9 ± 3 ppbv per sunlit hour in February 1996 and January 2000 were associated with low minimum temperatures of 187-189 K, simultaneously with high PSC probabilities.

  3. Adult Education in Israel, II-III.

    ERIC Educational Resources Information Center

    Kirmayer, Paul, Ed.; Pinnes, Noy, Ed.

    This is the second booklet in English that deals with adult education in Israel. The following papers are included: "Editors' Notes" (Paul Kirmayer, Noy Pinnes); "Introduction" (Meir Peretz); "Defining 'Adult Education'" (Yehezkel Cohen); "Planning Study Programs for Adults" (Rachel Tokatli); "The Role…

  4. Evaluation of safety and immunogenicity of HNVAC, an MDCK-based H1N1 pandemic influenza vaccine, in Phase I single centre and Phase II/III multi-centre, double-blind, randomized, placebo-controlled, parallel assignment studies.

    PubMed

    Basavaraj, V H; Sampath, G; Hegde, Nagendra R; Mohan, V Krishna; Ella, Krishna M

    2014-07-31

    The clinical evaluation of the MDCK-based H1N1 pandemic influenza vaccine HNVAC in adults aged 18-65 years is reported. In the Phase I randomized, double-blind, placebo-controlled, single-centre study, 160 subjects were parallelly assigned 3:1 to vaccine:placebo groups (n=60:20) with both the aluminium hydroxide adjuvanted and non-adjuvanted vaccine formulations. A single dose of both the formulations containing 15 μg of haemagglutinin protein showed minimal adverse reactions, the most common of which were pain at injection site (11.67%) and fever (10.00%). Both formulations produced 74-81% seroprotection (SRP: titre of ≥40), 67-70% seroconversion (SRC: four-fold increase in titres between days 0 and 21), and a four-fold increase in geometric mean titres (GMT). Aluminium hydroxide did not have a significant effect either on immunogenicity or on reactogenicity. Nevertheless, based on its recognized positive effects on the stability and immunogenicity of many vaccines, and its marginal benefit in both pre-clinical and Phase I studies of HNVAC, alum adjuvanted HNVAC was further tested in a staggered Phase II/III randomized, double-blind, placebo-controlled, multi-centre study of 200 and 195 subjects, respectively, parallelly assigned 4:1 to adjuvanted vaccine and placebo groups. In these studies, the most common adverse reactions were pain at injection site (6.88% and 5.77% in Stage 1 and Stage 2, respectively) and fever (7.50% and 7.05%, respectively), and a single dose resulted in 87-90% SRP, 85-86% SRC, and a nearly six-fold increase in GMT, meeting or exceeding licensing criteria. It is concluded that HNVAC is safe and immunogenic to adults of 18-65 years.

  5. Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial.

    PubMed

    Yardley, Denise A; Brufsky, Adam; Coleman, Robert E; Conte, Pierfranco F; Cortes, Javier; Glück, Stefan; Nabholtz, Jean-Mark A; O'Shaughnessy, Joyce; Beck, Robert M; Ko, Amy; Renschler, Markus F; Barton, Debora; Harbeck, Nadia

    2015-12-16

    Triple-negative breast cancer is an aggressive disease with unmet clinical needs. In a phase III study of patients with metastatic triple-negative breast cancer, first-line gemcitabine/carboplatin resulted in a median progression-free survival of 4.6 months. nab-paclitaxel-based regimens (with gemcitabine or carboplatin±bevacizumab) also demonstrated efficacy and safety in first-line phase II trials of human epidermal growth factor receptor 2-negative metastatic breast cancer. In this international, multicenter, open-label, randomized phase II/III trial, the efficacy and safety of first-line nab-paclitaxel with gemcitabine or with carboplatin will be compared with gemcitabine/carboplatin (control arm) for metastatic triple-negative breast cancer. In the phase II portion, 240 patients with measurable metastatic triple-negative breast cancer and treatment-naive for metastatic disease will be randomized 1:1:1 (stratified by disease-free interval: ≤1 versus>1 year) to nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2, nab-paclitaxel 125 mg/m2 plus carboplatin area under the curve 2 mg×min/mL, or gemcitabine 1000 mg/m2 plus carboplatin area under the curve 2 mg×min/mL, all given on days 1 and 8 of a 21-day cycle. Investigator-assessed progression-free survival (primary endpoint), overall response rate, overall survival, and safety will be assessed. A ranking algorithm of five efficacy and safety parameters will be used to pick the "winner" of the nab-paclitaxel regimens. In the phase III portion, 550 patients will be randomized 1:1 (stratified by disease-free interval: ≤1 versus >1 year, and prior adjuvant/neoadjuvant taxane use) to the nab-paclitaxel combination arm selected from the phase II portion or to the control arm. Patients in phase II will not be part of the phase III population. The phase III primary endpoint is blinded, independently-assessed progression-free survival; secondary endpoints include blinded, independently-assessed overall response

  6. Play the winner for phase II/III clinical trials.

    PubMed

    Yao, Q; Wei, L J

    In comparing two treatments under a typical sequential clinical trial setting, a 50-50 randomization design generates reliable data for making efficient inferences about the treatment difference for the benefit of patients in the general population. However, if the treatment difference is large and the endpoint of the study is potentially fatal, it does not seem appropriate to sacrifice a large number of study patients who are assigned to the inferior arm. An adaptive design is a data-dependent treatment allocation rule that sequentially uses accumulating information about the treatment difference during the trial to modify the allocation rule for new study patients. In this article, we utilize real trials from AIDS and cancer to illustrate the advantage of using adaptive designs. Specifically we show that, with adaptive designs, the loss of power for testing the equality of two treatments is negligible. Moreover, the study patients do not have to pay a handsome price for the benefit of future patients. We also propose multi-stage adaptive rules to relax the administrative burden of implementing the study and to handle continuous response variables, such as the failure time in survival analysis.

  7. CHEMICAL INTERACTIONS OF ARSENATE, ARSENITE, PHOSPHATE, AND SILICATE WITH IRON (II,III) HYDROXYCARBONATE GREEN RUST

    EPA Science Inventory

    Granular zerovalent iron has been proposed to be used as a medium in permeable reactive barriers (PRBs) to remove arsenic from contaminated groundwater. Iron(II, III) hydroxycarbonate green rust (carbonate green rust, or CGR) is a major corrosion product of zerovalent iron under ...

  8. Prognostic and predictive significance of MSI in stages II/III colon cancer.

    PubMed

    Saridaki, Zacharenia; Souglakos, John; Georgoulias, Vassilis

    2014-06-14

    In colon cancer, classic disease staging remains the key prognosis and treatment determinant. Although adjuvant chemotherapy has an established role in stage III colon cancer patients, in stage II it is still a subject of controversy due to its restriction to a small subgroup of patients with high-risk histopathologic features. Patients with stage II tumors form a highly heterogeneous group, with five-year relative overall survival rates ranging from 87.5% (IIA) to 58.4% (IIC). Identifying those for whom adjuvant chemotherapy would be appropriate and necessary has been challenging, and prognostic markers which could serve in the selection of patients more likely to recur or benefit from adjuvant chemotherapy are eagerly needed. The stronger candidate in this category seems to be microsatellite instability (MSI). The recently reported European Society for Medical Oncology guidelines suggest that MSI should be evaluated in stage II colorectal cancer patients in order to contribute in treatment decision-making regarding chemotherapy administration. The hypothetical predictive role of MSI regarding its response to 5-fluorouracil-based adjuvant chemotherapy has proven a much more difficult issue to address. Almost every possible relation between MSI and chemotherapy outcome has been described in the adjuvant colon cancer setting in the international literature, and the matter is far from being settled. In this current report we critically evaluate the prognostic and predictive impact of MSI status in patients with stage II and stage III colon cancer patients.

  9. Low-metallicity Star Formation and Pop III-II Transition

    NASA Astrophysics Data System (ADS)

    Omukai, Kazuyuki

    2010-10-01

    The first stars in the universe were typically very massive, but those near us are not. The metallicity in the star-forming gas is thought to have played a key role in this transition of characteristic stellar mass scale. By studying the evolution of low-metallicity star-forming clouds up to the formation of protostars by way of radiation hydrodynamics with spherical symmetry, we discuss their fragmentation mass scales. The critical metallicity for low-mass fragmentation is in the range of Zcr = 10-6-10-5Zsolar. Although the exact value is still unknown due to uncertain dust nature in the early universe, the small value of Zcr means that low-mass star formation begun just after the first episode of metal enrichment. We also evaluate the upper limit on the stellar mass by the stellar feedback. Owing to the higher density in the envelope and thus higher protostellar accretion rate, the upper limit of stellar mass increases toward lower matallicity.

  10. CHEMICAL INTERACTIONS OF ARSENATE, ARSENITE, PHOSPHATE, AND SILICATE WITH IRON (II,III) HYDROXYCARBONATE GREEN RUST

    EPA Science Inventory

    Granular zerovalent iron has been proposed to be used as a medium in permeable reactive barriers (PRBs) to remove arsenic from contaminated groundwater. Iron(II, III) hydroxycarbonate green rust (carbonate green rust, or CGR) is a major corrosion product of zerovalent iron under ...

  11. 40 CFR Table 8 to Subpart IIIii of... - Requirements for Cell Room Monitoring Program

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... Extractive cold vapor spectroscopy system a. Mercury vapor analyzer Be capable of continuously monitoring the... absorption spectroscopy system a. Mercury vapor analyzer Be capable of continuously monitoring the...

  12. 40 CFR Table 8 to Subpart IIIii of... - Requirements for Cell Room Monitoring Program

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... Extractive cold vapor spectroscopy system a. Mercury vapor analyzer Be capable of continuously monitoring the... absorption spectroscopy system a. Mercury vapor analyzer Be capable of continuously monitoring the...

  13. 40 CFR Table 8 to Subpart IIIii of... - Requirements for Cell Room Monitoring Program

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... Extractive cold vapor spectroscopy system a. Mercury vapor analyzer Be capable of continuously monitoring the... absorption spectroscopy system a. Mercury vapor analyzer Be capable of continuously monitoring the...

  14. Use of theragnostic markers to select drugs for phase II/III trials for Alzheimer disease

    PubMed Central

    2010-01-01

    In a slowly progressive disorder like Alzheimer disease, evaluation of the clinical effect of novel drug candidates requires large numbers of patients and extended treatment periods. Current cell- and animal-based disease models of Alzheimer disease are poor at predicting a positive treatment response in patients. To help bridge the gap between disease models and large and costly clinical trials with high failure rates, biomarkers for the intended biochemical drug effect may be of value. Such biomarkers may be called 'theragnostic'. Here, we review the literature addressing the prospective value of these biomarkers. PMID:21122172

  15. Alpha Trianguli Australis (K2 II-III) - Hybrid or composite?

    NASA Technical Reports Server (NTRS)

    Ayres, T. R.

    1985-01-01

    The prototype hybrid-spectrum giant Alpha Trianguli Australis exhibits a far-ultraviolet continuum which is considerably bluer than would be expected of a star of its optical colors, suggesting the presence of a previously unrecognized companion. If the K-type primary is as luminous as indicated by the widths of its Ca II and H-alpha lines, the companion could be an early F-type dwarf that only recently has arrived on the main sequence. Indeed, the flux of C IV from Alpha TrA - an important measure of hybridness - would not be inconsistent with that expected from a very young chromospherically active F star.

  16. Clinical Outcome From Oxaliplatin Treatment in Stage II/III Colon Cancer According to Intrinsic Subtypes

    PubMed Central

    Song, Nan; Pogue-Geile, Katherine L.; Gavin, Patrick G.; Yothers, Greg; Kim, S. Rim; Johnson, Nicole L.; Lipchik, Corey; Allegra, Carmen J.; Petrelli, Nicholas J.; O’Connell, Michael J.; Wolmark, Norman; Paik, Soonmyung

    2016-01-01

    IMPORTANCE Oxaliplatin added to fluorouracil plus leucovorin therapy for patients with colon cancer has been shown to provide significant but modest absolute benefit for disease-free survival. However, acute and chronic neurotoxic effects from this regimen underscore the need for markers that predict oxaliplatin benefit. OBJECTIVE To test our hypothesis that molecular subtypes of colon cancer would be associated with differential prognosis and benefit from oxaliplatin added to fluorouracil plus leucovorin therapy. DESIGN, SETTING, AND PARTICIPANTS Participants in the NSABP C-07 trial were divided into discovery (n = 848) and validation (n = 881) cohorts based on the order of tissue block submission. A reestimated centroid using 72 genes was used to determine Colorectal Cancer Assigner subtypes and their association with oxaliplatin benefit in the discovery cohort. The validation cohort was examined with a locked-down algorithm for subtype classification and statistical analysis plan. Post hoc analysis included examination of the entire cohort with Colorectal Cancer Assigner, Colorectal Cancer Subtype (CCS), and Consensus Molecular Subtype (CMS) methods. INTERVENTIONS Fluorouracil plus leucovorin with or without oxaliplatin. MAIN OUTCOMES AND MEASURES Percent recurrence-free survival. RESULTS Among 1729 patients, 744 (43%) were female and mean (SD) age was 58 (11) years. Although C-07 participants with stage III disease with an enterocyte subtype showed a statistically significant benefit from oxaliplatin in the discovery cohort (hazard ratio, 0.22 [95% CI, 0.09–0.56]; P = .001 [N = 65]), no statistically significant benefit was observed in the validation cohort (hazard ratio, 0.53 [95% CI, 0.22–1.24]; P = .14 [N = 70]). The stemlike subtype was associated with poor prognosis and lack of benefit from oxaliplatin treatment (HR, 0.99 [95% CI, 0.73–1.34]; P = .96 [N = 367]). Examination of the different subtyping methods shows that all 3 methods robustly identified patients with poor prognosis (stemlike, CCS-3, and CMS-4) in both stage II and III. CONCLUSIONS AND RELEVANCE Patients with stemlike tumors may be appropriate for clinical trials testing experimental therapies because stemlike tumors were robustly identified and associated with a poor prognosis regardless of stage or chemotherapy regimen. The clinical utility of using subtyping for the identification of patients for treatment with oxaliplatin requires validation in independent clinical trial cohorts. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00004931 PMID:27270348

  17. Multipurpose Wetlands Phase II/III: final design and ongoing research investigations

    USGS Publications Warehouse

    Babbitt, Bruce; Beard, Daniel P.; Hancock, Lawrence F.

    1994-01-01

    The Eastern Municipal Water District (EMWD), the Bureau of Reclamation (USBR), and the National Biological Survey (NBS), in consultation with other governmental agencies, the academic community, and environmental groups, are involved in a cooperative wetlands research and demonstration effort. This report reflects progress through the first 3 years of a 5-year program. The goal of the Multipurpose Wetlands Research and Demonstration Project is to evaluate and expand the use of reclaimed water and contaminated ground water through the incorporation of multipurpose constructed wetlands into EMWD's total water resources management program. The focus of the wetlands is the development of design, construction, and operation criteria that will provide a cost-effective and innovative alternative for managing water resources and provide other public benefits in arid areas. The program also recognizes the fact that naturally-occurring wetlands, both coastal and inland, have been disappearing at an alarming rate.

  18. Microsatellite instability & survival in patients with stage II/III colorectal carcinoma

    PubMed Central

    Srdjan, Markovic; Jadranka, Antic; Ivan, Dimitrijevic; Branimir, Zogovic; Daniela, Bojic; Petar, Svorcan; Velimir, Markovic; Zoran, Krivokapic

    2016-01-01

    Background & objectives: The two key aspects associated with the microsatellite instability (MSI) as genetic phenomenon in colorectal cancer (CRC) are better survival prognosis, and the varying response to 5-fluorouracil (5-FU)-based chemotherapy. This study was undertaken to measure the survival of surgically treated patients with stages II and III CRC based on the MSI status, the postoperative 5-FU treatment as well as clinical and histological data. Methods: A total of 125 consecutive patients with stages II and III (American Joint Committee on Cancer, AJCC staging) primary CRCs, were followed prospectively for a median time of 31 months (January 2006 to December 2009). All patients were assessed, operated and clinically followed. Tumour samples were obtained for cytopathological verification and MSI grading. Results: Of the 125 patients, 21 (20%) had high MSI (MSI-H), and 101 patients (80%) had MSI-L or MSS (low frequency MSI or stable MSI). Patients with MSS CRC were more likely to have recurrent disease (P=0.03; OR=3.2; CI 95% 1-10.2) compared to those with MSI-H CRC. Multi- and univariate Cox regression analysis failed to show a difference between MSI-H and MSS groups with respect to disease-free, disease-specific and overall survival. However, the disease-free survival was significantly lower in patients with MSI-H CRC treated by adjuvant 5-FU therapy (P=0.03). Interpretation & conclusions: MSI-H CRCs had a lower recurrence rate, but the prognosis was worse following adjuvant 5-FU therapy. PMID:27748284

  19. Structure and function of the ESCRT II-III interface in multivesicular body biogenesis

    PubMed Central

    Im, Young Jun; Wollert, Thomas; Boura, Evzen; Hurley, James H.

    2009-01-01

    SUMMARY The ESCRT-II-ESCRT-III interaction coordinates the sorting of ubiquitinated cargo with the budding and scission of intralumenal vesicles into multivesicular bodies. The interacting regions of these complexes were mapped to the second winged-helix domain of human ESCRT-II subunit VPS25 and the first helix of ESCRT-III subunit VPS20. The crystal structure of this complex was determined at 2.0 Å resolution. Residues involved in structural interactions explain the specificity of ESCRT-II for Vps20, and are critical for cargo sorting in vivo. ESCRT-II directly activates ESCRT-III driven vesicle budding and scission in vitro via these structural interactions. VPS20 and ESCRT-II bind membranes with nanomolar affinity, explaining why binding to ESCRT-II is dispensable for the recruitment of Vps20 to membranes. Docking of the ESCRT-II -VPS202 supercomplex reveals a convex membrane-binding surface, suggesting a hypothesis for negative membrane curvature induction in the nascent intralumenal vesicle. PMID:19686684

  20. Role of Postmastectomy Radiation After Neoadjuvant Chemotherapy in Stage II-III Breast Cancer

    SciTech Connect

    Fowble, Barbara L.; Einck, John P.; Kim, Danny N.; McCloskey, Susan; Mayadev, Jyoti; Yashar, Catheryn; Chen, Steven L.; Hwang, E. Shelley

    2012-06-01

    Purpose: To identify a cohort of women treated with neoadjuvant chemotherapy and mastectomy for whom postmastectomy radiation therapy (PMRT) may be omitted according to the projected risk of local-regional failure (LRF). Methods and Materials: Seven breast cancer physicians from University of California cancer centers created 14 hypothetical clinical case scenarios, identified, reviewed, and abstracted the available literature (MEDLINE and Cochrane databases), and formulated evidence tables with endpoints of LRF, disease-free survival, and overall survival. Using the American College of Radiology appropriateness criteria methodology, appropriateness ratings for postmastectomy radiation were assigned for each scenario. Finally, an overall summary risk assessment table was developed. Results: Of 24 sources identified, 23 were retrospective studies from single institutions. Consensus on the appropriateness rating, defined as 80% agreement in a category, was achieved for 86% of the cases. Distinct LRF risk categories emerged. Clinical stage II (T1-2N0-1) patients, aged >40 years, estrogen receptor-positive subtype, with pathologic complete response or 0-3 positive nodes without lymphovascular invasion or extracapsular extension, were identified as having {<=}10% risk of LRF without radiation. Limited data support stage IIIA patients with pathologic complete response as being low risk. Conclusions: In the absence of randomized trial results, existing data can be used to guide the use of PMRT in the neoadjuvant chemotherapy setting. Using available studies to inform appropriateness ratings for clinical scenarios, we found a high concordance of treatment recommendations for PMRT and were able to identify a cohort of women with a low risk of LRF without radiation. These low-risk patients will form the basis for future planned studies within University of California Athena Breast Health Network.

  1. Alpha Trianguli Australis (K2 II-III) - Hybrid or composite?

    NASA Technical Reports Server (NTRS)

    Ayres, T. R.

    1985-01-01

    The prototype hybrid-spectrum giant Alpha Trianguli Australis exhibits a far-ultraviolet continuum which is considerably bluer than would be expected of a star of its optical colors, suggesting the presence of a previously unrecognized companion. If the K-type primary is as luminous as indicated by the widths of its Ca II and H-alpha lines, the companion could be an early F-type dwarf that only recently has arrived on the main sequence. Indeed, the flux of C IV from Alpha TrA - an important measure of hybridness - would not be inconsistent with that expected from a very young chromospherically active F star.

  2. Aging and Surveillance Program MINUTEMAN II/III Stage II Program Progress.

    DTIC Science & Technology

    1985-11-01

    130 Firing Adapters Used to Fire VECP Igniters 58 132 Squib Arrangement Used in Both KR80000 Safe and Arm and FFTFs 59 133 Bladder Permeation vs Age...hydrolytic liner degradation as the primary mechanism leading ; . " to failure for the motor. Kinetic projections for service life ranged from 14 to 17...the igniter following assembly . In general, propellant in the bulk of the web is slightly harder than that measured in the fin. Propellant in the slot

  3. 40 CFR Table 6 to Subpart IIIii of... - Examples of Techniques for Equipment Problem Identification, Leak Detection and Mercury Vapor

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... inspections b. Portable mercury vapor analyzer—ultraviolet light absorption detector A sample of gas is drawn... vapor in the cell room and other areas a. Portable mercury vapor analyzer—ultraviolet light...

  4. Current Advancement in Multidisciplinary Treatment for Resectable cStage II/III Esophageal Squamous Cell Carcinoma in Japan

    PubMed Central

    Matsuda, Satoru; Kawakubo, Hirofumi; Ando, Nobutoshi; Kitagawa, Yuko

    2016-01-01

    Multidisciplinary treatment comprising surgery, chemotherapy, and radiotherapy for resectable esophageal squamous cell carcinoma (ESCC) is widely used with improved prognosis. Transthoracic esophagectomy (TTE) with extended lymph node (LN) dissection, known as three field LN dissection, has been recommended for ESCC using open thoracotomy or the thoracoscopic approach. The Japan Clinical Oncology Group (JCOG) trial (JCOG1409) is investigating the patients’ long term survival using the thoracoscopic approach that has been shown to reduce the incidence of postoperative respiratory complication. For perioperative treatment, neoadjuvant chemotherapy using cisplatin plus 5-fluorouracil (5-FU), has been accepted as the standard of care in Japan based on the JCOG9907 trial. In Western countries, neoadjuvant chemoradiotherapy was shown to prolong overall survival for esophageal cancer, including ESCC. Although surgery has been recognized as an initial curative treatment for esophageal cancer, definitive chemoradiotherapy is an alternative treatment for patients who are unable to undergo thoracotomy or who decline to undergo surgery. This article reviews multidisciplinary treatment advances for ESCC. However, current standard treatments are country dependent and the ongoing trial may help standardize ESCC treatment across various societies. PMID:27384595

  5. Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery

    ClinicalTrials.gov

    2017-09-29

    Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  6. Multiparametric MRI-based differentiation of WHO grade II/III glioma and WHO grade IV glioblastoma

    PubMed Central

    Wiestler, Benedikt; Kluge, Anne; Lukas, Mathias; Gempt, Jens; Ringel, Florian; Schlegel, Jürgen; Meyer, Bernhard; Zimmer, Claus; Förster, Stefan; Pyka, Thomas; Preibisch, Christine

    2016-01-01

    Non-invasive, imaging-based examination of glioma biology has received increasing attention in the past couple of years. To this end, the development and refinement of novel MRI techniques, reflecting underlying oncogenic processes such as hypoxia or angiogenesis, has greatly benefitted this research area. We have recently established a novel BOLD (blood oxygenation level dependent) based MRI method for the measurement of relative oxygen extraction fraction (rOEF) in glioma patients. In a set of 37 patients with newly diagnosed glioma, we assessed the performance of a machine learning model based on multiple MRI modalities including rOEF and perfusion imaging to predict WHO grade. An oblique random forest machine learning classifier using the entire feature vector as input yielded a five-fold cross-validated area under the curve of 0.944, with 34/37 patients correctly classified (accuracy 91.8%). The most important features in this classifier as per bootstrapped feature importance scores consisted of standard deviation of T1-weighted contrast enhanced signal, maximum rOEF value and cerebral blood volume (CBV) standard deviation. This study suggests that multimodal MRI information reflects underlying tumor biology, which is non-invasively detectable through integrative data analysis, and thus highlights the potential of such integrative approaches in the field of radiogenomics. PMID:27739434

  7. Bevacizumab, Fluorouracil, Leucovorin Calcium, and Oxaliplatin Before Surgery in Treating Patients With Stage II-III Rectal Cancer

    ClinicalTrials.gov

    2017-04-11

    Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

  8. Intramolecular electronic couplings in class II/III organic mixed-valence systems of bis(1,4-dimethoxybenzene).

    PubMed

    Yang, Juanhua; Zhang, Weiwei; Si, Yubing; Zhao, Yi

    2012-12-06

    The intramolecular electronic couplings in organic mixed-valence systems [D-(ph)(n)-D](•+) (D = 2,5-dimethoxy-4-methylphenyl, n = 0, 1, and 2) are calculated by dominantly using density functional theory to investigate their dependence of functionals. Since these systems have the property that the charge is from localization to delocalization, the optimized structures are sensitive to the functionals. The geometric optimizations show that CAM-B3LYP and ωB97X-D functionals are good choices for delocalized systems and LC-ωPBE and M06HF are suitable for the systems from charge almost localization to localization. The calculations of electronic couplings demonstrate that the pure functional generally underestimates the electronic couplings whereas the pure HF overestimates them. Furthermore, the electronic couplings from the conventional generalized Mulliken-Hush method are very sensitive to the HF component in functionals, which makes it a challenge to accurately estimate the values. A new reduced two-state method is thus proposed to overcome the deficiency, and the obtained electronic couplings are less sensitive to the ω value in LC-ω PBE functional and they are also consistent with the experimental data.

  9. Two-staged revision with custom made prosthesis in septic failure of massive allograft reconstruction after type II-III pelvic resection.

    PubMed

    Bekmez, Senol; Ayvaz, Mehmet; Mermerkaya, M Uğur; Tokgozoglu, A Mazhar

    2014-01-01

    Reconstruction of defects occurring during periacetabular resections of pelvic tumors is required particularly in young and functionally active persons. Allograft reconstruction provides good functional outcomes in restoration of normal pelvic anatomy. A 24-year-old male patient was reconstructed with an allograft-prosthesis composite after periacetabular resection due to pelvic chondrosarcoma. After four years, a two-staged revision with a custom-made pelvic prosthesis was performed due to septic failure. Successful radiographic and functional outcomes were achieved at two-year follow-up. In conclusion, we suggest a two-staged revision with a custom-made pelvic prosthesis as a satisfactory option in case of septic failure of allograft reconstruction after periacetabular resection.

  10. 40 CFR Table 3 to Subpart IIIii of... - Work Practice Standards-Required Actions for Liquid Mercury Spills and Accumulations and Hydrogen...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) National Emission Standards for Hazardous Air Pollutants: Mercury Emissions From Mercury Cell... that you cannot repair the leaking equipment without taking the cell off line, provided that you contain the dripping mercury at all times as described above, and take the cell off line as soon...

  11. Electron transfer rate on mixed valence states of Class II/III transition for N, N'-diphenyl-1,4-phenylenediamine structures as a polyaniline unit

    NASA Astrophysics Data System (ADS)

    Nishiumi, Toyohiko; Nomura, Yasuhiro; Higuchi, Masayoshi; Yamamoto, Kimihisa

    2003-08-01

    The first example of the determination of the electron transfer rate ( λ, V, Δ G*, kth) for N, N'-diphenyl-1,4-phenylenediamine derivatives using the Marcus-Hush theory is described. These results were in good agreement with the ones obtained using variable-temperature IR spectra measurements.

  12. Bevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II-III Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-12-21

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  13. A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer†

    PubMed Central

    O'Neil, B. H.; Scott, A. J.; Ma, W. W.; Cohen, S. J.; Aisner, D. L.; Menter, A. R.; Tejani, M. A.; Cho, J. K.; Granfortuna, J.; Coveler, L.; Olowokure, O. O.; Baranda, J. C.; Cusnir, M.; Phillip, P.; Boles, J.; Nazemzadeh, R.; Rarick, M.; Cohen, D. J.; Radford, J.; Fehrenbacher, L.; Bajaj, R.; Bathini, V.; Fanta, P.; Berlin, J.; McRee, A. J.; Maguire, R.; Wilhelm, F.; Maniar, M.; Jimeno, A.; Gomes, C. L.; Messersmith, W. A.

    2015-01-01

    Background Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small-molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcinoma. Materials and methods Patients with metastatic pancreatic adenocarcinoma were randomized in a 2:1 fashion to gemcitabine 1000 mg/m2 weekly for 3 weeks of a 4-week cycle plus rigosertib 1800 mg/m2 via 2-h continuous IV infusions given twice weekly for 3 weeks of a 4-week cycle (RIG + GEM) versus gemcitabine 1000 mg/m2 weekly for 3 weeks in a 4-week cycle (GEM). Results A total of 160 patients were enrolled globally and randomly assigned to RIG + GEM (106 patients) or GEM (54). The most common grade 3 or higher adverse events were neutropenia (8% in the RIG + GEM group versus 6% in the GEM group), hyponatremia (17% versus 4%), and anemia (8% versus 4%). The median overall survival was 6.1 months for RIG + GEM versus 6.4 months for GEM [hazard ratio (HR), 1.24; 95% confidence interval (CI) 0.85–1.81]. The median progression-free survival was 3.4 months for both groups (HR = 0.96; 95% CI 0.68–1.36). The partial response rate was 19% versus 13% for RIG + GEM versus GEM, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40 cases). Other mutations detected included TP53 (13 cases) and PIK3CA (1 case). No correlation between mutational status and efficacy was detected. Conclusions The combination of RIG + GEM failed to demonstrate an improvement in survival or response compared with GEM in patients with metastatic pancreatic adenocarcinoma. Rigosertib showed a similar safety profile to that seen in previous trials using the IV formulation. PMID:26091808

  14. Concomitant boost IMRT-based neoadjuvant chemoradiotherapy for clinical stage II/III rectal adenocarcinoma: results of a phase II study

    PubMed Central

    2014-01-01

    Aim This study was designed to evaluate the efficacy and toxicities of concomitant boost intensity-modulated radiation therapy (IMRT) along with capecitabine and oxaliplatin, followed by a cycle of Xelox, in neoadjuvant course for locally advanced rectal cancer. Materials and methods Patients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received IMRT to the pelvis of 50 Gy and a concomitant boost of 5 Gy to the primary tumor in 25 fractions, and concurrent with oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 bid d1–5 weekly). One cycle of Xelox (oxaliplatin 130 mg/m2 on d1 and capecitabine 1000 mg/m2 twice daily d1–14) was given two weeks after the completion of chemoradiation, and radical surgery was scheduled eight weeks after chemoradiation. Tumor response was evaluated by tumor regression grade (TRG) system and acute toxicities were evaluated by NCI-CTC 3.0 criteria. Survival curves were estimated using the Kaplan-Meier method and compared with Log-rank test. Results A total of 78 patients were included between March 2009 and May 2011 (median age 54 years; 62 male). Seventy-six patients underwent surgical resection. Twenty-eight patients underwent sphincter-sparing lower anterior resection and 18 patients (23.7%) were evaluated as pathological complete response (pCR). The incidences of grade 3 hematologic toxicity, diarrhea, and radiation dermatitis were 3.8%, 10.3%, and 17.9%, respectively. The three-year LR (local recurrence), DFS (disease-free survival) and OS (overall survival) rates were 14.6%, 63.8% and 77.4%, respectively. Initial clinical T stage and tumor regression were independent prognostic factors to DFS. Conclusion An intensified regimen of concomitant boost radiotherapy plus concurrent capecitabine and oxaliplatin, followed by one cycle of Xelox, can be safely administered in patients with locally advanced rectal cancer, and produces a high rate of pCR. A prognostic score model is helpful to distinguish different long-term prognosis groups in early stage. PMID:24606870

  15. Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-10-10

    Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Breast Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Breast Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Breast Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Breast Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  16. Pegylated Liposomal Doxorubicin Hydrochloride and Carboplatin Followed by Surgery and Paclitaxel in Treating Patients With Triple Negative Stage II-III Breast Cancer

    ClinicalTrials.gov

    2017-01-19

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  17. Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups.

    PubMed

    Weller, Michael; Weber, Ruthild G; Willscher, Edith; Riehmer, Vera; Hentschel, Bettina; Kreuz, Markus; Felsberg, Jörg; Beyer, Ulrike; Löffler-Wirth, Henry; Kaulich, Kerstin; Steinbach, Joachim P; Hartmann, Christian; Gramatzki, Dorothee; Schramm, Johannes; Westphal, Manfred; Schackert, Gabriele; Simon, Matthias; Martens, Tobias; Boström, Jan; Hagel, Christian; Sabel, Michael; Krex, Dietmar; Tonn, Jörg C; Wick, Wolfgang; Noell, Susan; Schlegel, Uwe; Radlwimmer, Bernhard; Pietsch, Torsten; Loeffler, Markus; von Deimling, Andreas; Binder, Hans; Reifenberger, Guido

    2015-05-01

    Cerebral gliomas of World Health Organization (WHO) grade II and III represent a major challenge in terms of histological classification and clinical management. Here, we asked whether large-scale genomic and transcriptomic profiling improves the definition of prognostically distinct entities. We performed microarray-based genome- and transcriptome-wide analyses of primary tumor samples from a prospective German Glioma Network cohort of 137 patients with cerebral gliomas, including 61 WHO grade II and 76 WHO grade III tumors. Integrative bioinformatic analyses were employed to define molecular subgroups, which were then related to histology, molecular biomarkers, including isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation, 1p/19q co-deletion and telomerase reverse transcriptase (TERT) promoter mutations, and patient outcome. Genomic profiling identified five distinct glioma groups, including three IDH1/2 mutant and two IDH1/2 wild-type groups. Expression profiling revealed evidence for eight transcriptionally different groups (five IDH1/2 mutant, three IDH1/2 wild type), which were only partially linked to the genomic groups. Correlation of DNA-based molecular stratification with clinical outcome allowed to define three major prognostic groups with characteristic genomic aberrations. The best prognosis was found in patients with IDH1/2 mutant and 1p/19q co-deleted tumors. Patients with IDH1/2 wild-type gliomas and glioblastoma-like genomic alterations, including gain on chromosome arm 7q (+7q), loss on chromosome arm 10q (-10q), TERT promoter mutation and oncogene amplification, displayed the worst outcome. Intermediate survival was seen in patients with IDH1/2 mutant, but 1p/19q intact, mostly astrocytic gliomas, and in patients with IDH1/2 wild-type gliomas lacking the +7q/-10q genotype and TERT promoter mutation. This molecular subgrouping stratified patients into prognostically distinct groups better than histological classification. Addition of gene expression data to this genomic classifier did not further improve prognostic stratification. In summary, DNA-based molecular profiling of WHO grade II and III gliomas distinguishes biologically distinct tumor groups and provides prognostically relevant information beyond histological classification as well as IDH1/2 mutation and 1p/19q co-deletion status.

  18. Paleoecological crisis in the steppes of the Lower Volga region in the Middle of the Bronze Age (III-II centuries BC)

    NASA Astrophysics Data System (ADS)

    Demkina, T. S.; Borisov, A. V.; Demkin, V. A.; Khomutova, T. E.; Kuznetsova, T. V.; El'tsov, M. V.; Udal'tsov, S. N.

    2017-07-01

    Diagnostic features of a catastrophic aridization of climate, desertification, and paleoecological crisis in steppes of the Lower Volga region have been identified on the basis of data on the morphological, chemical, and microbiological properties of paleosols under archeological monuments (burial mounds) of the Middle Bronze Age. These processes resulted in a certain convergence of the soil cover with transformation of zonal chestnut (Kastanozems) paleosols and paleosolonetzes (Solonetz Humic) into specific chestnut-like eroded saline calcareous paleosols analogous to the modern brown desert-steppe soils (Calcisols Haplic) that predominated in this region 4300-3800 years ago.1 In the second millennium BC, humidization of the climate led to the divergence of the soil cover with secondary formation of the complexes of chestnut soils and solonetzes. This paleoecological crisis had a significant effect on the economy of the tribes in the Late Catacomb and Post-Catacomb time stipulating their higher mobility and transition to the nomadic cattle breeding.

  19. Chlorine and temperature directed self-assembly of Mg-Ru2(ii,iii) carbonates and particle size dependent magnetic properties.

    PubMed

    Yang, Jian-Hui; Cheng, Ru-Mei; Jia, Yan-Yan; Jin, Jin; Yang, Bing-Bing; Cao, Zhi; Liu, Bin

    2016-02-21

    A series of heterometallic magnesium diruthenium(ii,iii) carbonates, namely K{Mg(H2O)6}2[Ru2(CO3)4Cl2]·4H2O (1), K2[{Mg(H2O)4}2Ru2(CO3)4(H2O)Cl]Cl2·2H2O (2), K[Mg(H2O)5Ru2(CO3)4]·5H2O (3) and K[Mg(H2O)4Ru2(CO3)4]·H2O (4), were synthesized from the reaction of Ru2(CO3)4(3-) and Mg(2+) in aqueous solution. Compound 1 is composed of ionic crystals with the Ru2(CO3)4Cl2(5-) : Mg(H2O)6(2+) : K(+) ratio of 1 : 2 : 1. Compound 2 consists of two dimensional layer structures, in which each octahedral environment Mg(H2O)4(2+) bonds to two [Ru2(CO3)4(H2O)Cl](4-) units in a cis manner forming a neutral square-grid layer {Mg(H2O)4Ru2(CO3)4(H2O)Cl}n. For compound 3, one water molecule of each Mg(H2O)6(2+) is substituted by an oxygen atom of Ru2(CO3)4(3-) forming [Mg(H2O)5Ru2(CO3)4](-), and then the neighboring Ru2 dimers are linked together by the rest of the two oxygen atoms of carbonates to form a layer structure {Mg(H2O)5Ru2(CO3)4}n(n-). In compound 4, the neighboring squared-grid layers {Ru2(CO3)4}n(3n-), similar to those in compound 3, are linked by each octahedral environment Mg(H2O)4(2+) in a cis manner forming the three-dimensional network {Mg(H2O)4Ru2(CO3)4}n(n-). Compound 3 shows ferromagnetic coupling between Ru2 dimers, and a long-range ordering is observed below 3.8 K. Compound 4 displays a magnetic ordering below 3.5 K, and a systematic study of the size-dependent magnetic properties of compound 4 reveals that the coercivity of 4 has been improved with reduced sample particle size from the micrometer to the nanometer scale.

  20. Genetic variants within obesity-related genes are associated with tumor recurrence in patients with stages II/III colon cancer.

    PubMed

    Sebio, Ana; Gerger, Armin; Matsusaka, Satoshi; Yang, Dongyun; Zhang, Wu; Stremitzer, Stefan; Stintzing, Sebastian; Sunakawa, Yu; Yamauchi, Shinichi; Ning, Yan; Fujimoto, Yoshiya; Ueno, Masashi; Lenz, Heinz-Josef

    2015-01-01

    Obesity is an established risk factor for colorectal cancer (CRC) incidence and it is also linked to CRC recurrence and survival. Polymorphisms located in obesity-related genes are associated with an increased risk of developing several cancer types including CRC. We evaluated whether single-nucleotide polymorphisms in obesity-related genes may predict tumor recurrence in colon cancer patients. Genotypes were obtained from germline DNA from 207 patients with stage II or III colon cancer at the Norris Comprehensive Cancer Center. Nine polymorphisms in eight obesity-related genes (PPAR, LEP, NFKB, CD36, DRG1, NGAL, REGIA, and DSCR1) were evaluated. The primary endpoint of the study was the 3-year recurrence rate. Positive associations were also tested in an independent Japanese cohort of 350 stage III CRC patients. In univariate analysis, for PPARrs1801282, patients with a CC genotype had significantly lower recurrence probability (29 ± 4% SE) compared with patients with a CG genotype (48 ± 8% SE) [hazard ratio (HR): 1.77; 95% confidence interval (CI), 1.01-3.10; P = 0.040]. For DSCR1rs6517239, patients with an AA genotype had higher recurrence probability than patients carrying at least one allele G (37 ± 4% SE vs. 15 ± 6% SE) (HR: 0.51; 95% CI, 0.27-0.94; P = 0.027). This association was stronger in the patients bearing a left-sided tumor (HR: 0.34; 95% CI, 0.13-0.88; P = 0.018). In the Japanese cohort, no associations were found. This hypothesis-generating study suggests a potential influence of polymorphisms within obesity-related genes in the recurrence probability of colon cancer. These interesting results should be evaluated further.

  1. Effect of cariprazine across the symptoms of mania in bipolar I disorder: Analyses of pooled data from phase II/III trials.

    PubMed

    Vieta, Eduard; Durgam, Suresh; Lu, Kaifeng; Ruth, Adam; Debelle, Marc; Zukin, Stephen

    2015-11-01

    Bipolar I disorder is a chronic disorder characterized by episodic recurrences of mania, depression, and mixed affective states interspersed with periods of full or partial remission; subsyndromal residual symptoms between episodes are common and disabling. Cariprazine, an atypical antipsychotic, is a potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors. Post-hoc analyses of pooled data from 3 positive trials were conducted to evaluate the effect of cariprazine 3-12 mg/d on the symptoms of mania in inpatients (18-65 years) with bipolar I disorder and a current manic episode. Analyses were based on the pooled intent-to-treat (ITT) population (placebo=429; cariprazine=608). Mean change from baseline to the end of treatment on individual Young Mania Rating Scale (YMRS) items was analysed using a mixed-effects model for repeated measures (MMRM); categorical symptom severity shifts were analysed using logistic regression. Statistically significant improvement in mean change was seen for cariprazine versus placebo on all 11 YMRS items (p<0.0001); significantly more cariprazine- versus placebo-treated patients had mild/no symptoms at the end of treatment on 11 YMRS items (p<0.0001) and concurrently on the 4 YMRS core symptoms (irritability, speech, content, and disruptive-aggressive behaviour) (p<0.0001). Significantly more cariprazine- versus placebo-treated patients shifted from a Moderate/Worse or Marked/Worse Symptoms categories to Mild/No Symptoms on all 11 (p<0.0001) and 9 of 11 YMRS items (p<0.05), respectively. Results suggest that cariprazine treatment improved mania across YMRS symptoms; a significant percentage of cariprazine- versus placebo-treated patients had mild/no symptoms at the end of treatment. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  2. Tolerability of cariprazine in the treatment of acute bipolar I mania: A pooled post hoc analysis of 3 phase II/III studies.

    PubMed

    Earley, Willie; Durgam, Suresh; Lu, Kaifeng; Debelle, Marc; Laszlovszky, István; Vieta, Eduard; Yatham, Lakshmi N

    2017-06-01

    Atypical antipsychotics have broad-spectrum efficacy against core symptoms of acute mania/mixed states in bipolar disorder; however, they are associated with clinically significant adverse effects (AEs). This post hoc analysis evaluated the safety and tolerability of the atypical antipsychotic cariprazine in the treatment of adult patients with acute manic/mixed episodes of bipolar I disorder. Data were taken from three 3-week randomized, double-blind, placebo-controlled, flexible-dose trials of cariprazine 3-12mg/d. Patient subgroups categorized by modal daily dose (3-6mg/d; 9-12mg/d) were used to assess dose response. The pooled safety population comprised 1065 patients (placebo=442; cariprazine 3-6mg/d=263; cariprazine 9-12mg/d=360). More cariprazine- than placebo-treated patients reported double-blind treatment-emergent AEs; the overall AE incidence was similar among cariprazine-dose groups. AEs reported in ≥5% of cariprazine patients overall with at least twice the incidence of placebo were akathisia, extrapyramidal symptoms, restlessness, and vomiting. The incidence of SAEs was low and similar between the placebo- and cariprazine-treatment groups. Metabolic parameter changes were small and generally similar between cariprazine and placebo groups; mean increases in fasting glucose levels were greater with cariprazine (3-6mg/d=6.6mg/dL; 9-12mg/d=7.2mg/dL) than placebo (1.7mg/dL). Mean weight change was 0.54kg and 0.17kg for cariprazine and placebo, respectively; weight increase ≥7% was <3% in all treatment groups. Cariprazine was not associated with clinically meaningful changes in electrocardiogram parameters. Post hoc analysis, flexible-dose design, short trial duration. Cariprazine was generally safe and well-tolerated in patients with manic/mixed episodes associated with bipolar I disorder. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Treatment of Plaque-Type Psoriasis With Oral CF101: Data from a Phase II/III Multicenter, Randomized, Controlled Trial.

    PubMed

    David, Michael; Gospodinov, Dimitar Konstantinov; Gheorghe, Nicola; Mateev, Grisha Stefanov; Rusinova, Mariyana Venelinova; Hristakieva, Evgeniya; Solovastru, Laura Gheuca; Patel, Rita V; Giurcaneanu, Calin; Hitova, Mariela Chepileva; Purcaru, Anca Ioana; Horia, Beti; Tsingov, Iliya Iliev; Yankova, Rumyana Kaloferova; Kadurina, Miroslava Ilieva; Ramon, Michael; Rotaru, Maria; Simionescu, Olga; Benea, Vasile; Demerdjieva, Zdravka Velichkova; Cosgarea, Maria Rodica; Morariu, Horia Silviu; Michael, Ziv; Cristodor, Patricia; Nica, Carmen; Silverman, Michael H; Bristol, David R; Harpaz, Zivit; Farbstein, Motti; Cohen, Shira; Fishman, Pnina

    2016-08-01

    CF101, an adenosine A3 receptor agonist, is an orally bioavailable small molecule drug presenting an anti-psoriatic effect demonstrated in a Phase 2 clinical trial in psoriasis patients.
    To evaluate the safety and efficacy of CF101 treatment in a Phase 2/3 study in patients with moderate to severe plaque-type psoriasis.
    This multicenter, double-blind, 2-segment, placebo-controlled study randomized subjects with moderate to severe plaque psoriasis to CF101 1 or 2 mg, or placebo twice daily. At either week 12 (Segment 1) or 16 (Segment 2), the placebo group crossed over to CF101 BID through week 32 in an open-label fashion. At week 12, following an interim analysis, the CF101 1mg group was discontinued due to futility. The primary endpoint was proportion of patients achieving ≥75% improvement in Psoriasis Area Severity Index (PASI 75). Efficacy testing was performed using the Cochran-Mantel Haenszel test, the primary analysis of PASI 75 was performed at the 0.035 significance level.
    CF101 had an excellent safety profile at all tested dosages with a profile similar to the placebo group. The most common adverse events were infections and gastrointestinal events, and there was no cumulative intolerance over the 32-week dosing period. The study did not meet the primary endpoint of PASI 75 at week 12 (2 mg: 8.5% vs. placebo: 6.9%, P=0.621). However, at week 32, PASI mean percent improvement with CF101 2 mg was 57% (P<0.001) compared to baseline, with linear improvement in PASI 50 (63.5%), 75 (35.5%), 90 (24.7%), and 100 (10.6%).
    Oral CF101 was found to be safe and very well tolerated, demonstrating evidence of efficacy in patients with moderate to severe plaque psoriasis through 32 weeks of treatment.

    J Drugs Dermatol. 2016;15(8):931-938.

  4. 7Li and 14N NMR studies of phase II-III transition in LiNH4SO4 single crystals

    NASA Astrophysics Data System (ADS)

    Lim, Ae Ran

    2016-12-01

    The NMR spectra of 7Li and 14N nuclei in LiNH4SO4 crystals were obtained near the phase transition temperature TC2=284.5 K. Below TC2, the two physically inequivalent Li groups in phase III were distinguished in 7Li NMR spectra. Meanwhile, the 14N NMR spectra in phase II above TC2 showed four pairs of lines, where as those in phase III showed eight pairs. These changes in the resonance frequencies near TC2 were attributed to the structural phase transition. The 7Li and 14N nuclei in the structure are coordinated through the Li-O-H-N skeleton. Therefore, changes in their NMR spectra with temperature are correlated. The displacements of 7Li and 14N in LiNH4SO4 crystals play important roles in the phase transition near TC2.

  5. Whole genome sequencing of a recombinant type II/III Toxoplasma gondii strain from Uganda reveals chromosome sorting and local allelic variants.

    USDA-ARS?s Scientific Manuscript database

    Toxoplasma gondii is a zoonotic parasite of global importance. In common with many protozoan parasites it has the capacity for sexual recombination, but current evidence suggests this is rarely employed. The global population structure is dominated by a small number of clonal genotypes, which exhib...

  6. Can we eliminate neoadjuvant chemoradiotherapy in favor of neoadjuvant multiagent chemotherapy for select stage II/III rectal adenocarcinomas: Analysis of the National Cancer Data base.

    PubMed

    Cassidy, Richard J; Liu, Yuan; Patel, Kirtesh; Zhong, Jim; Steuer, Conor E; Kooby, David A; Russell, Maria C; Gillespie, Theresa W; Landry, Jerome C

    2017-03-01

    Stage II and III rectal cancers have been effectively treated with neoadjuvant chemoradiotherapy (NCRT) followed by definitive resection. Advancements in surgical technique and systemic therapy have prompted investigation of neoadjuvant multiagent chemotherapy (NMAC) regimens with the elimination of radiation (RT). The objective of the current study was to investigate factors that predict for the use of NCRT versus NMAC and compare outcomes using the National Cancer Data Base (NCDB) for select stage II and III rectal cancers. In the NCDB, 21,707 patients from 2004 through 2012 with clinical T2N1 (cT2N1), cT3N0, or cT3N1 rectal cancers were identified who had received NCRT or NMAC followed by low anterior resection. Kaplan-Meier analyses, log-rank tests, and Cox-proportional hazards regression analyses were conducted along with propensity score matching analysis to reduce treatment selection bias. The 5-year actuarial overall survival (OS) rate was 75% for patients who received NCRT versus 67.2% for those who received NMAC (P < .01). On MVA, those who received NCRT had improved OS (hazard ratio, 0.77. P < .01), and this effect was confirmed on propensity score matching analysis (hazard ratio, 0.72; P = .01). In the same model, the following variables improved OS: age < 65 years, having private insurance, treatment at an academic center, living in an affluent zip code, a low comorbidity score, receipt of adjuvant chemotherapy, and a shorter interval before surgery (all P < .05). African Americans, men, patients with high-grade tumors, those with cT3N1 tumors, and those who underwent incomplete (R1) resection had worse OS (all P < .05). In this series, the elimination of neoadjuvant RT for select patients with stage II and III rectal adenocarcinoma was associated with worse OS and should not be recommended outside of a clinical trial. Cancer 2017;123:783-93. © 2016 American Cancer Society. © 2016 American Cancer Society.

  7. Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial.

    PubMed

    Goorin, Allen M; Harris, Michael B; Bernstein, Mark; Ferguson, William; Devidas, Meenakshi; Siegal, Gene P; Gebhardt, Mark C; Schwartz, Cindy L; Link, Michael; Grier, Holcombe E

    2002-01-15

    The objectives of this trial were to estimate the response rate, progression-free survival, and overall survival of patients who received therapy with etoposide and high-dose ifosfamide, and to define the toxicity of this combination when provided with standard chemotherapy in patients with newly diagnosed metastatic osteosarcoma. Eligible patients received infusions of 100 mg/m(2) per day of etoposide and 3.5 g/m(2) per day of ifosfamide for 5 days. Therapy with granulocyte colony-stimulating factor was begun on day 6. This was repeated 3 weeks after therapy was begun. Response was determined at week 6 by both standard World Health Organization response criteria and by pathologic determination of tumor necrosis of the primary tumor. Forty-three patients were registered; 39 were assessable for response and 41 for toxicity and survival. Twenty-eight (68%) of 41 had metastatic sites only in the lung; 12 (29%) had metastatic sites in other bones with or without lung involvement. Four patients (10%) experienced complete response, and 19 patients (49%) experienced partial response, for an overall response rate of 59% +/- 8%. The projected 2-year progression-free survival (PFS) for the 28 patients with metastases to lungs was 39% +/- 11%. The projected 2-year PFS for the 12 patients with metastases to other bones (with or without pulmonary metastases) was 58% +/- 17%. Two patients died as a result of therapy toxicity. Eighty-three percent of patients had grade 4 neutropenia, and 29% had grade 4 thrombocytopenia. Ten patients (24%) had sepsis. Fanconi's syndrome was observed in five patients. The combination of etoposide and high-dose ifosfamide is effective induction chemotherapy for patients with metastatic osteosarcoma, despite significant associated myelosuppression sometimes complicated by infection and renal toxicity.

  8. Transthoracic versus abdominal-transhiatal resection for treating Siewert type II/III adenocarcinoma of the esophagogastric junction: a meta-analysis

    PubMed Central

    Zheng, Zhi; Cai, Jun; Yin, Jie; Zhang, Jun; Zhang, Zhong-Tao; Wang, Kang-Li

    2015-01-01

    Our study aimed to explore the differences in short and long-term outcomes about the transthoracic (TH) and abdominal-transhiatal (TH) approaches for treating esophagogastric junction (AEG). A systematic review of PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure and CBMdisc was performed. All original articles comparing TH with TA were included in the study. Meta-analysis was conducted using odd ratios (OR) and weighted mean differences (WMDs).Thirteen studies including 2489 patients with adenocarcinoma of the esophagogastric junction, with 1050 patients underwent TA and 1437 patients underwent TH were pooled for this study. There were no significant difference between two approaches concerning duration of operation, blood loss, anastomotic leakage and positive of proximal incisal margin. Lymph node excised also showed no significant differences between two procedures in RCTs while in TA group of Non-RCTs, the number of lymph node dissection is higher. TH approach was associated with a longer length of hospital stay and had higher incidence of respiratory and cardiovascular complications and early postoperative mortality. Overall analysis of 1, 3, 5-year survival showed no significant difference between two approaches. Based on the study, TA approach had a positive impact than TH for AEG with respect to respiratory and cardiovascular complications, hospital stay and early mortality rates. There were no significant differences between the two approaches for long-term survival. Therefore, two surgical approaches are acceptable, and the elders with poor cardiopulmonary function, we recommended TA approach for treating it. PMID:26770310

  9. Postoperative radiotherapy and tumor recurrence after complete resection of stage II/III thymic tumor: a meta-analysis of cohort studies

    PubMed Central

    Ma, Jietao; Sun, Xin; Huang, Letian; Xiong, Zhicheng; Yuan, Meng; Zhang, Shuling; Han, Cheng-Bo

    2016-01-01

    Background Whether postoperative radiotherapy (PORT) is effective for reducing the recurrence risk in patients who received complete resection of the stage II or III thymic tumors has not been determined. A meta-analysis was performed by combining the results of all available controlled trials. Methods PubMed, Cochrane’s Library, and the Embase databases were searched for studies which compared the recurrence data for patients with complete resection of the stage II or III thymic tumors assigned to an observing group, or a PORT group. A random effect model was applied to combine the results. Results Nineteen studies, all designed as retrospective cohort studies were included. These studies included 663 patients of PORT group and 617 patients of observing group. The recurrence rate for the patients in PORT group and observing group were 12.4% and 11.5%, respectively. Results of our study indicated that PORT has no significant influence on recurrent risk in patients with stage II or III thymic tumor after complete resection (odds ratio 1.02, 95% confidence interval 0.55–1.90, P=0.96). When stratified by stages, our meta-analyses did not indicate any significant effects of PORT on recurrent outcomes in either the stage II or the stage III patients. Moreover, subsequent analysis limited to studies only including patients with thymoma or thymic carcinoma also did not support the benefits of PORT on recurrent outcomes. Conclusion Although derived from retrospective cohort studies, current evidence did not support any benefit of PORT on recurrent risk in patients with complete resection of the stage II or III thymic tumors. PMID:27524907

  10. Akt Inhibitor MK-2206 and Anastrozole With or Without Goserelin Acetate in Treating Patients With Stage II-III Breast Cancer

    ClinicalTrials.gov

    2017-04-24

    Estrogen Receptor Positive; HER2/Neu Negative; Recurrent Breast Carcinoma; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  11. Phase II Study of Intraperitoneal Paclitaxel Plus Cisplatin and Intravenous Paclitaxel Plus Bevacizumab As Adjuvant Treatment of Optimal Stage II/III Epithelial Ovarian Cancer

    PubMed Central

    Konner, Jason A.; Grabon, Diana M.; Gerst, Scott R.; Iasonos, Alexia; Thaler, Howard; Pezzulli, Sandra D.; Sabbatini, Paul J.; Bell-McGuinn, Katherine M.; Tew, William P.; Hensley, Martee L.; Spriggs, David R.; Aghajanian, Carol A.

    2011-01-01

    Purpose Intraperitoneal (IP) cisplatin and intravenous (IV) or IP paclitaxel constitute a standard therapy for optimally debulked ovarian cancer. Bevacizumab prolongs progression-free survival (PFS) when included in first-line IV chemotherapy. In this study, the safety and feasibility of adding bevacizumab to a first-line IP regimen were assessed. Patients and Methods Treatment was as follows: paclitaxel 135 mg/m2 IV over 3 hours day 1, cisplatin 75 mg/m2 IP day 2, and paclitaxel 60 mg/m2 IP day 8. Bevacizumab 15 mg/kg IV was given after paclitaxel on day 1 beginning in cycle 2. After six cycles of chemotherapy, bevacizumab was given every 3 weeks for 17 additional treatments. The primary end point was safety and tolerability determined by whether 60% of patients completed six cycles of IV/IP chemotherapy. Results Of 41 treated patients, 30 (73%) received six cycles of IV/IP chemotherapy and 35 (85%) received at least four cycles. Three (27%) of those who discontinued chemotherapy did so because of complications related to bevacizumab (hypertension, n = 2; perforation, n = 1). Grades 3 to 4 toxicities included neutropenia (34%), vasovagal syncope (10%), hypertension (7%), nausea/vomiting (7%), hypomagnesemia (7%), and abdominal pain (7%). There were three grade 3 small bowel obstructions (7%) during cycles 3, 9, and 15. One patient died following rectosigmoid anastomotic dehiscence during cycle 4. Estimated median PFS is 28.6 months (95% CI, 19.1 to 38.9 months). Three patients (7%) had IP port malfunction. Conclusion The addition of bevacizumab to this IP regimen is feasible; however, bevacizumab may increase the risk of bowel obstruction/perforation. The observed median PFS is similar to that seen with IP/IV chemotherapy alone. PMID:22067389

  12. Carboplatin and Paclitaxel With or Without Atezolizumab Before Surgery in Treating Patients With Newly Diagnosed, Stage II-III Triple-Negative Breast Cancer

    ClinicalTrials.gov

    2017-01-31

    Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  13. Comparative effectiveness of combined therapy inhibiting EGFR and VEGF pathways in patients with advanced non-small-cell lung cancer: a meta-analysis of 16 phase II/III randomized trials

    PubMed Central

    Cai, Shangli; Wu, Tongwei; Yan, Guangyue; Cheng, Sijin; Cui, Kang; Xi, Ying; Qi, Xiaolong; Zhang, Jie; Ma, Wang

    2017-01-01

    Background & Aims Combined therapy inhibiting EGFR and VEGF pathways is becoming a promising therapy in the treatment of advanced non-small-cell lung cancer (NSCLC), however, with controversy. The study aims to compare the efficacy of combined inhibition therapy versus control therapy (including placebo, single EGFR inhibition and single VEGF inhibition) in patients with advanced NSCLC. Materials and Methods An adequate literature search in EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) was conducted. Phase II or III randomized controlled trials (RCTs) that compared effectiveness between combined inhibition therapy and control therapy in patients with advanced NSCLC were eligible. The endpoint was overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Results Sixteen phase II or III RCTs involving a total of 7,109 patients were included. The results indicated that the combined inhibition therapy significantly increased the ORR (OR = 1.59, 95% CI = 1.36-1.87, p<0.00001; I2 = 36%) when compared to control therapy. In the subgroup analysis, the combined inhibition therapy clearly increased the ORR (OR = 2.04, 95% CI = 1.60-2.60, p<0.00001; I2 = 0%) and improved the PFS (HR = 0.78, 95% CI = 0.71-0.85, p<0.00001;I2 = 0%) when compared with the placebo, and similar results was detected when compared with the single EGFR inhibition in terms of ORR (OR = 1.39, 95% CI = 1.12-1.74, p = 0.003; I2 = 30%) and PFS (HR = 0.73, 95% CI = 0.67-0.81, p<0.0001; I2 = 50%). No obvious difference was found between the combined inhibition therapy and single VEGF inhibition in term of ORR, however, combined inhibition therapy significantly decreased the PFS when compared to the single VEGF inhibition therapy (HR = 1.70, 95% CI = 1.34-2.17, p<0.0001; I2 = 50%). Besides, no significant difference was observed between the combined inhibition therapy and control therapy in term of OS (including placebo, single EGFR inhibition and single VEGF inhibition) (HR = 0.98, 95% CI = 0.92-1.04, p = 0.41; I2 = 0%). Conclusions Combined inhibition therapy was superior to placebo and single EGFR inhibition in terms of ORR, PFS for advanced NSCLC, however, no statistical difference were found in term of OS. Besides, combined inhibition therapy was not superior to single VEGF inhibition in terms of ORR, PFS and OS. Therefore, combined inhibition therapy is recommended to treat advanced NSCLC patients. PMID:27690345

  14. Analysis of mucolipidosis II/III GNPTAB missense mutations identifies domains of UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase involved in catalytic function and lysosomal enzyme recognition.

    PubMed

    Qian, Yi; van Meel, Eline; Flanagan-Steet, Heather; Yox, Alex; Steet, Richard; Kornfeld, Stuart

    2015-01-30

    UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase tags newly synthesized lysosomal enzymes with mannose 6-phosphate recognition markers, which are required for their targeting to the endolysosomal system. GNPTAB encodes the α and β subunits of GlcNAc-1-phosphotransferase, and mutations in this gene cause the lysosomal storage disorders mucolipidosis II and III αβ. Prior investigation of missense mutations in GNPTAB uncovered amino acids in the N-terminal region and within the DMAP domain involved in Golgi retention of GlcNAc-1-phosphotransferase and its ability to specifically recognize lysosomal hydrolases, respectively. Here, we undertook a comprehensive analysis of the remaining missense mutations in GNPTAB reported in mucolipidosis II and III αβ patients using cell- and zebrafish-based approaches. We show that the Stealth domain harbors the catalytic site, as some mutations in these regions greatly impaired the activity of the enzyme without affecting its Golgi localization and proteolytic processing. We also demonstrate a role for the Notch repeat 1 in lysosomal hydrolase recognition, as missense mutations in conserved cysteine residues in this domain do not affect the catalytic activity but impair mannose phosphorylation of certain lysosomal hydrolases. Rescue experiments using mRNA bearing Notch repeat 1 mutations in GNPTAB-deficient zebrafish revealed selective effects on hydrolase recognition that differ from the DMAP mutation. Finally, the mutant R587P, located in the spacer between Notch 2 and DMAP, was partially rescued by overexpression of the γ subunit, suggesting a role for this region in γ subunit binding. These studies provide new insight into the functions of the different domains of the α and β subunits.

  15. Twelve-week, multicenter, placebo-controlled, randomized, double-blind, parallel-group, comparative phase II/III study of benzoyl peroxide gel in patients with acne vulgaris: A secondary publication.

    PubMed

    Kawashima, Makoto; Sato, Shinichi; Furukawa, Fukumi; Matsunaga, Kayoko; Akamatsu, Hirohiko; Igarashi, Atsuyuki; Tsunemi, Yuichiro; Hayashi, Nobukazu; Yamamoto, Yuki; Nagare, Toshitaka; Katsuramaki, Tsuneo

    2017-03-11

    A placebo-controlled, randomized, double-blind, parallel-group, comparative, multicenter study was conducted to investigate the efficacy and safety of benzoyl peroxide (BPO) gel, administrated once daily for 12 weeks to Japanese patients with acne vulgaris. Efficacy was evaluated by counting all inflammatory and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. All 609 subjects were randomly assigned to receive the study products (2.5% and 5% BPO and placebo), and 607 subjects were included in the full analysis set, 544 in the per protocol set and 609 in the safety analyses. The median rates of reduction from baseline to the last evaluation of the inflammatory lesion counts, the primary end-point, in the 2.5% and 5% BPO groups were 72.7% and 75.0%, respectively, and were significantly higher than that in the placebo group (41.7%). No deaths or other serious adverse events were observed. The incidences of adverse events in the 2.5% and 5% BPO groups were 56.4% and 58.8%, respectively; a higher incidence than in the placebo group, but there was no obvious difference between the 2.5% and 5% BPO groups. All adverse events were mild or moderate in severity. Most adverse events did not lead to study product discontinuation. The results suggested that both 2.5% and 5% BPO are useful for the treatment of acne vulgaris.

  16. IgE and IgG cross-reactivity among Lol p I and Lol p II/III. Identification of the C-termini of Lol p I, II, and III as cross-reactive structures.

    PubMed

    van Ree, R; van Leeuwen, W A; van den Berg, M; Weller, H H; Aalberse, R C

    1994-04-01

    In this study, the homologous C-termini of Lol p I, Lol p II, and Lol p III were shown to contain cross-reactive B-cell epitopes. This was demonstrated by inhibition studies with purified Lol p I, II, and III and synthetic peptides of their C-termini. It was ruled out that the observed cross-reactivity was caused by cross-contamination of the purified allergens. Both human IgE and IgG bound to the C-terminus of Lol p I. These antibodies were cross-reactive with Lol p II and, more specifically, with its C-terminus. Within a small panel of allergic patients, no cross-reactivity with Lol p III was found. A hyperimmune polyclonal rabbit antiserum against Lol p I also recognized the Lol p I C-terminus. As for human antibodies, cross-reactivity with Lol p II and its C-terminus was demonstrated. Cross-reactivity with Lol p III was demonstrated with C-terminal peptides, but not with native Lol p III. A polyclonal rabbit antiserum against Lol p II bound to the C-terminal peptides of both Lol p II and III. This binding was inhibited with Lol p I, confirming that cross-reactive structures exist not only on the C-termini of Lol p II and Lol p I, but also of Lol p III and Lol p I. The existence of cross-reactivity between Lol p I and Lol p II and III possibly contributes to the frequently observed cosensitization for these allergens in grass-pollen-allergic patients.

  17. Valproic acid, compared to other antiepileptic drugs, is associated with improved overall and progression-free survival in glioblastoma but worse outcome in grade II/III gliomas treated with temozolomide.

    PubMed

    Redjal, Navid; Reinshagen, Clemens; Le, Andrew; Walcott, Brian P; McDonnell, Erin; Dietrich, Jorg; Nahed, Brian V

    2016-05-01

    Valproic acid (VPA) is an anti-epileptic drug with properties of a histone deacetylase inhibitor (HDACi). HDACi play a key role in epigenetic regulation of gene expression and have been increasingly used as anticancer agents. Recent studies suggest that VPA is associated with improved survival in high-grade gliomas. However, effects on lower grade gliomas have not been examined. This study investigates whether use of VPA correlates with tumor grade, histological progression, progression-free and overall survival (OS) in grade II, III, and IV glioma patients. Data from 359 glioma patients (WHO II-IV) treated with temozolomide plus an antiepileptic drug (VPA or another antiepileptic drug) between January 1997 and June 2013 at the Massachusetts General Hospital was analyzed retrospectively. After confounder adjustment, VPA was associated with a 28 % decrease in hazard of death (p = 0.031) and a 28 % decrease in the hazard of progression or death (p = 0.015) in glioblastoma. Additionally, VPA dose correlated with reduced hazard of death by 7 % (p = 0.002) and reduced hazard of progression or death by 5 % (p < 0.001) with each 100 g increase in total dose. Conversely, in grade II and III gliomas VPA was associated with a 118 % increased risk of tumor progression or death (p = 0.014), and every additional 100 g of VPA raised the hazard of progression or death by 4 %, although not statistically significant (p = 0.064). Moreover, grade II and III glioma patients taking VPA had 2.17 times the risk of histological progression (p = 0.020), although this effect was no longer significant after confounder adjustment. In conclusion, VPA was associated with improved survival in glioblastoma in a dose-dependent manner. However, in grade II and III gliomas, VPA was linked to histological progression and decrease in progression-free survival. Prospective evaluation of VPA treatment for glioma patients is warranted to confirm these findings.

  18. Relationship Between Tumor Gene Expression and Recurrence in Four Independent Studies of Patients With Stage II/III Colon Cancer Treated With Surgery Alone or Surgery Plus Adjuvant Fluorouracil Plus Leucovorin

    PubMed Central

    O'Connell, Michael J.; Lavery, Ian; Yothers, Greg; Paik, Soonmyung; Clark-Langone, Kim M.; Lopatin, Margarita; Watson, Drew; Baehner, Frederick L.; Shak, Steven; Baker, Joffre; Cowens, J. Wayne; Wolmark, Norman

    2010-01-01

    Purpose These studies were conducted to determine the relationship between quantitative tumor gene expression and risk of cancer recurrence in patients with stage II or III colon cancer treated with surgery alone or surgery plus fluorouracil (FU) and leucovorin (LV) to develop multigene algorithms to quantify the risk of recurrence as well as the likelihood of differential treatment benefit of FU/LV adjuvant chemotherapy for individual patients. Patients and Methods We performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) on RNA extracted from fixed, paraffin-embedded (FPE) tumor blocks from patients with stage II or III colon cancer who were treated with surgery alone (n = 270 from National Surgical Adjuvant Breast and Bowel Project [NSABP] C-01/C-02 and n = 765 from Cleveland Clinic [CC]) or surgery plus FU/LV (n = 308 from NSABP C-04 and n = 508 from NSABP C-06). Overall, 761 candidate genes were studied in C-01/C-02 and C-04, and a subset of 375 genes was studied in CC/C-06. Results A combined analysis of the four studies identified 48 genes significantly associated with risk of recurrence and 66 genes significantly associated with FU/LV benefit (with four genes in common). Seven recurrence-risk genes, six FU/LV-benefit genes, and five reference genes were selected, and algorithms were developed to identify groups of patients with low, intermediate, and high likelihood of recurrence and benefit from FU/LV. Conclusion RT-qPCR of FPE colon cancer tissue applied to four large independent populations has been used to develop multigene algorithms for estimating recurrence risk and benefit from FU/LV. These algorithms are being independently validated, and their clinical utility is being evaluated in the Quick and Simple and Reliable (QUASAR) study. PMID:20679606

  19. Phase II-I-II Study of Two Different Doses and Schedules of Pralatrexate, a High-Affinity Substrate for the Reduced Folate Carrier, in Patients With Relapsed or Refractory Lymphoma Reveals Marked Activity in T-Cell Malignancies

    PubMed Central

    O'Connor, Owen A.; Horwitz, Steven; Hamlin, Paul; Portlock, Carol; Moskowitz, Craig H.; Sarasohn, Debra; Neylon, Ellen; Mastrella, Jill; Hamelers, Rachel; MacGregor-Cortelli, Barbara; Patterson, Molly; Seshan, Venkatraman E.; Sirotnak, Frank; Fleisher, Martin; Mould, Diane R.; Saunders, Mike; Zelenetz, Andrew D.

    2009-01-01

    Purpose To determine the maximum-tolerated dose (MTD) and efficacy of pralatrexate in patients with lymphoma. Patients and Methods Pralatrexate, initially given at a dose of 135 mg/m2 on an every-other-week basis, was associated with stomatitis. A redesigned, weekly phase I/II study established an MTD of 30 mg/m2 weekly for six weeks every 7 weeks. Patients were required to have relapsed/refractory disease, an absolute neutrophil greater than 1,000/μL, and a platelet count greater than 50,000/μL for the first dose of any cycle. Results The every-other-week, phase II experience was associated with an increased risk of stomatitis and hematologic toxicity. On a weekly schedule, the MTD was 30 mg/m2 weekly for 6 weeks every 7 weeks. This schedule modification resulted in a 50% reduction in the major hematologic toxicities and abrogation of the grades 3 to 4 stomatitis. Stomatitis was associated with elevated homocysteine and methylmalonic acid, which were reduced by folate and vitamin B12 supplementation. Of 48 assessable patients, the overall response rate was 31% (26% by intention to treat), including 17% who experienced complete remission (CR). When analyzed by lineage, the overall response rates were 10% and 54% in patients with B- and T-cell lymphomas, respectively. All eight patients who experienced CR had T-cell lymphoma, and four of the six patients with a partial remission were positron emission tomography negative. The duration of responses ranged from 3 to 26 months. Conclusion Pralatrexate has significant single-agent activity in patients with relapsed/refractory T-cell lymphoma. PMID:19652067

  20. Elemental abundance analyses with DAO spectrograms: XXX. The middle B through early A stars ξ2 Ceti (B9 III), 21 Aquilae (B8 II-III), ι Aquilae (B5 III), and ι Delphini (A2V)

    NASA Astrophysics Data System (ADS)

    Adelman, S. J.; Westbrook, P. C.; Gulliver, A. F.

    2010-04-01

    This series of high quality elemental abundance analyses of mostly main-sequence band normal and peculiar B, A, and F stars defines their properties and provides data for the comparison with the analyses of somewhat similar stars and with theoretical predictions. Most use high dispersion and high S/N (≥ 200) spectrograms obtained with CCD detectors at the long camera of the Coudé spectrograph of the 1.22-m Dominion Astrophysical Observatory telescope. Here we reanalyze 21 Aql with better quality spectra and increase the number of stars consistently analyzed in the spectral range B5 to A2 by analyzing three new stars for this series. In the early A stars the normal and non-mCP stars have abundances with overlapping ranges. But more stars are needed especially in the B5 to B9 range. ξ2 Cet on average has a solar composition with a few abundances outside the solar range while both 21 Aql and ι Aql have abundances marginally less than solar. The abundances of ι Del are greater than solar with a few elements such as Ca being less than solar. It is an Am star. Table 3 is only available in electronic form at the CDS via http://cdsarc.u-strasbg.fr/ftp/cats/J/other/AN/331/378

  1. Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia: a pooled analysis of four phase II/III randomized, double-blind, placebo-controlled studies.

    PubMed

    Earley, Willie; Durgam, Suresh; Lu, Kaifeng; Laszlovszky, István; Debelle, Marc; Kane, John M

    2017-07-07

    Cariprazine, a potent dopamine D3 and D2 receptor partial agonist antipsychotic with preferential binding to D3 receptors, is Food and Drug Administration approved for treating schizophrenia and manic or mixed episodes of bipolar I disorder. A post-hoc safety/tolerability analysis of data from the four acute trials in the cariprazine schizophrenia clinical development program (NCT00404573; NCT00694707; NCT01104766; NCT01104779) was carried out using the overall safety population (all patients who received ≥1 dose of study drug) and modal daily dose subgroups (1.5-3, 4.5-6, and 9-12 mg/day). These exploratory findings were summarized using descriptive statistics. Cariprazine was generally well tolerated. The incidence of treatment-emergent adverse events versus placebo was similar for cariprazine 1.5-3 mg/day and higher for cariprazine 4.5-6 and 9-12 mg/day; a dose-response relationship was observed for akathisia, extrapyramidal symptoms, and diastolic blood pressure. The mean changes in metabolic parameters were generally similar in cariprazine-treated and placebo-treated patients. There was no prolactin level increase or QTc value greater than 500 ms; small increases in mean body weight (∼1to2 kg) versus placebo were observed. Within the Food and Drug Administration-approved dose range (1.5-6 mg/day), cariprazine was generally safe and well tolerated in patients with schizophrenia.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  2. Safety profile of combined therapy inhibiting EFGR and VEGF pathways in patients with advanced non-small-cell lung cancer: A meta-analysis of 15 phase II/III randomized trials.

    PubMed

    Ma, Wang; Xu, Mingxin; Liu, Yiqian; Liu, Hao; Huang, Jiale; Zhu, Yanjie; Ji, Li-Juan; Qi, Xiaolong

    2015-07-15

    The efficacy of combined vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibition in patients with advanced non-small-cell lung cancer (NSCLC) was well studied. However, few studies focused on the risk and adverse events (AEs) of combined targeted therapy. The aim of this meta-analysis was to evaluate the safety profile of combined targeted therapy against EFGR and VEGF in patients with advanced NSCLC. A comprehensive literature search in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ASCO Abstracts and ESMO Abstracts was conducted. Eligible studies were randomized clinical trials (RCTs) that compared safety profile of combined therapy inhibiting EFGR and VEGF pathways with control groups (placebo, single EGFR or VEGF inhibition therapy, chemotherapy or a combination of them) in patients with advanced NSCLC. The endpoints included treatment discontinuation, treatment-related deaths and AEs. The search identified 15 RCTs involving 6,919 patients. The outcomes showed that three of four pairwise comparisons detected more discontinuation due to AEs in combined targeted therapy, with odds ratio (OR) compared with the control groups ranged from 1.97 to 2.29. Treatment with combined inhibition therapy was associated with several all-grade and grade 3 or 4 AEs (e.g. rash, diarrhea and hypertension). Also, there was a significantly higher incidence of treatment-related deaths in combined inhibition using vandetanib versus single EGFR inhibition therapy (OR = 1.97, 95% CI 1.19-3.28). In conclusion, combined inhibition therapy against EGFR and VEGF in patients with advanced NSCLC was associated with increased toxicity. Increased AEs hinder patient compliance and reduce their quality of life, leading to dose reduction or discontinuation. © 2014 UICC.

  3. BREATHER (PENTA 16) short-cycle therapy (SCT) (5 days on/2 days off) in young people with chronic human immunodeficiency virus infection: an open, randomised, parallel-group Phase II/III trial.

    PubMed

    Butler, Karina; Inshaw, Jamie; Ford, Deborah; Bernays, Sarah; Scott, Karen; Kenny, Julia; Klein, Nigel; Turkova, Anna; Harper, Lynda; Nastouli, Eleni; Paparini, Sara; Choudhury, Rahela; Rhodes, Tim; Babiker, Abdel; Gibb, Diana

    2016-06-01

    For human immunodeficiency virus (HIV)-infected adolescents facing lifelong antiretroviral therapy (ART), short-cycle therapy (SCT) with long-acting agents offers the potential for drug-free weekends, less toxicity, better adherence and cost savings. To determine whether or not efavirenz (EFV)-based ART in short cycles of 5 days on and 2 days off is as efficacious (in maintaining virological suppression) as continuous EFV-based ART (continuous therapy; CT). Secondary objectives included the occurrence of new clinical HIV events or death, changes in immunological status, emergence of HIV drug resistance, drug toxicity and changes in therapy. Open, randomised, non-inferiority trial. Europe, Thailand, Uganda, Argentina and the USA. Young people (aged 8-24 years) on EFV plus two nucleoside reverse transcriptase inhibitors and with a HIV-1 ribonucleic acid level [viral load (VL)] of < 50 copies/ml for > 12 months. Young people were randomised to continue daily ART (CT) or change to SCT (5 days on, 2 days off ART). Follow-up was for a minimum of 48 weeks (0, 4 and 12 weeks and then 12-weekly visits). The primary outcome was the difference between arms in the proportion with VL > 50 copies/ml (confirmed) by 48 weeks, estimated using the Kaplan-Meier method (12% non-inferiority margin) adjusted for region and age. In total, 199 young people (11 countries) were randomised (n = 99 SCT group, n = 100 CT group) and followed for a median of 86 weeks. Overall, 53% were male; the median age was 14 years (21% ≥ 18 years); 13% were from the UK, 56% were black, 19% were Asian and 21% were Caucasian; and the median CD4% and CD4 count were 34% and 735 cells/mm(3), respectively. By week 48, only one participant (CT) was lost to follow-up. The SCT arm had a 27% decreased drug exposure as measured by the adherence questionnaire and a MEMSCap(™) Medication Event Monitoring System (MEMSCap Inc., Durham, NC, USA) substudy (median cap openings per week: SCT group, n = 5; CT group, n = 7). By 48 weeks, six participants in the SCT group and seven in the CT group had a confirmed VL > 50 copies/ml [difference -1.2%, 90% confidence interval (CI) -7.3% to 4.9%] and two in the SCT group and four in the CT group had a confirmed VL > 400 copies/ml (difference -2.1%, 90% CI -6.2% to 1.9%). All six participants in the SCT group with a VL > 50 copies/ml resumed daily ART, of whom five were resuppressed, three were on the same regimen and two with a switch; two others on SCT resumed daily ART for other reasons. Overall, three participants in the SCT group and nine in the CT group (p = 0.1) changed ART regimen, five because of toxicity, four for simplification reasons, two because of compliance issues and one because of VL failure. Seven young people (SCT group, n = 2; CT group, n = 5) had major non-nucleoside reverse transcriptase inhibitor mutations at VL failure, of whom two (n = 1 SCT group, n = 1 CT group) had the M184V mutation. Two young people had new Centers for Disease Control B events (SCT group, n = 1; CT group, n = 1). There were no significant differences between SCT and CT in grade 3/4 adverse events (13 vs. 14) or in serious adverse events (7 vs. 6); there were fewer ART-related adverse events in the SCT arm (2 vs. 14; p = 0.02). At week 48 there was no evidence that SCT led to increased inflammation using an extensive panel of markers. Young people expressed a strong preference for SCT in a qualitative substudy and in pre- and post-trial questionnaires. In total, 98% of the young people are taking part in a 2-year follow-up extension of the trial. Non-inferiority of VL suppression in young people on EFV-based first-line ART with a VL of < 50 copies/ml was demonstrated for SCT compared with CT, with similar resistance, safety and inflammatory marker profiles. The SCT group had fewer ART-related adverse events. Further evaluation of the immunological and virological impact of SCT is ongoing. A limitation of the trial is that the results cannot be generalised to settings where VL monitoring is either not available or infrequent, nor to use of low-dose EFV. Two-year extended follow-up of the trial is ongoing to confirm the durability of the SCT strategy. Further trials of SCT in settings with infrequent VL monitoring and with other antiretroviral drugs such as tenofovir alafenamide, which has a long intracellular half-life, and/or dolutegravir, which has a higher barrier to resistance, are planned. Current Controlled Trials ISRCTN97755073; EUDRACT 2009-012947-40; and CTA 27505/0005/001-0001. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (projects 08/53/25 and 11/136/108), the European Commission through EuroCoord (FP7/2007/2015), the Economic and Social Research Council, the PENTA Foundation, the Medical Research Council and INSERM SC10-US19, France, and will be published in full in Health Technology Assessment; Vol. 20, No. 49. See the NIHR Journals Library website for further project information.

  4. Image-Guided Hypofractionated Radiation Therapy With Stereotactic Body Radiation Therapy Boost and Combination Chemotherapy in Treating Patients With Stage II-III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2017-06-12

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  5. Evidence-based nutritional recommendations for the prevention and treatment of overweight and obesity in adults (FESNAD-SEEDO consensus document). The role of diet in obesity prevention (II/III).

    PubMed

    Gargallo Fernández, M; Quiles Izquierdo, J; Basulto Marset, J; Breton Lesmes, I; Formiguera Sala, X; Salas-Salvadó, J

    2012-01-01

    This study is a consensus document of two Spanish scientific associations, FESNAD (Spanish Federation of Nutrition, Food and Dietetetic Associations) and SEEDO (Spanish Association for the Study of Obesity), about the role of the diet in the prevention and of overweight and obesity in adults. It is the result of a careful and systematic review of the data published in the medical literature from January 1st 1996 to January 31st 2011 concerning the role of the diet on obesity prevention. The conclusions obtained have been classified according several evidence levels. Subsequently, in agreement with these evidence levels, different degree recommendations are established. These recommendations could be potentially useful to design food guides as part of strategies to prevent overweight and obesity.

  6. REVIEW OF THE NEGOTIATION OF THE MODEL PROTOCOL ADDITIONAL TO THE AGREEMENT(S) BETWEEN STATE(S) AND THE INTERNATIONAL ATOMIC ENERGY AGENCY FOR THE APPLICATION OF SAFEGUARDS, INFCIRC/540 (Corrected) VOLUME II/III IAEA COMMITTEE 24, Major Issues Underlying the Model Additional Protocol (1996-1997).

    SciTech Connect

    Rosenthal, M.D.; Saum-Manning, L.; Houck, F.

    2010-01-01

    Volume I of this Review traces the origins of the Model Additional Protocol. It covers the period from 1991, when events in Iraq triggered an intensive review of the safeguards system, until 1996, when the IAEA Board of Governors established Committee 24 to negotiate a new protocol to safeguards agreement. The period from 1991-1996 set the stage for this negotiation and shaped its outcome in important ways. During this 5-year period, many proposals for strengthening safeguards were suggested and reviewed. Some proposals were dropped, for example, the suggestion by the IAEA Secretariat to verify certain imports, and others were refined. A rough consensus was established about the directions in which the international community wanted to go, and this was reflected in the draft of an additional protocol that was submitted to the IAEA Board of Governors on May 6, 1996 in document GOV/2863, Strengthening the Effectiveness and Improving the Efficiency of the Safeguards System - Proposals For Implementation Under Complementary Legal Authority, A Report by the Director General. This document ended with a recommendation that, 'the Board, through an appropriate mechanism, finalize the required legal instrument taking as a basis the draft protocol proposed by the Secretariat and the explanation of the measures contained in this document.'

  7. Induction of Pro-Angiogenic Factors by Pregnancy-Specific Glycoproteins and Studies on Receptor Usage

    DTIC Science & Technology

    2008-01-01

    Genovac, Freiburg, Germany), anti-Flag BioM2 (Sigma, St. Louis, MO), rat anti-mouse IgG1 phycoerythrin and CD16/ CD32 (Fc III/II receptor, BD...peritoneal macrophages, cells were first blocked with anti-mouse CD16/ CD32 (Fc III/II receptor, BD Biosciences) antibody prior to incubation with the...phycoerythrin and CD16/ CD32 (Fc III/II receptor, BD Biosciences, San Jose, CA), GST (B-14) antibody (clone sc-138, Santa Cruz Biotechnology, Inc., Santa

  8. National Dam Safety Program. Inventory of Dams. New Jersey. Volume 1.

    DTIC Science & Technology

    1981-09-01

    IIIII.. ..III..IIIIII. ..... I..IIIII.*uuIIIuuIuuIum I I ’ ’ 𔃻 13 6 1 - L 1011112. - . IIIII 8 ljjll_1.25 . 6 MICROCOPY RESOLUTION TESI CHART...Us N Qm - -4 1 % 0Nc ’.. .. c - a I -t-*_ 0m C Z I.;N w 4I: CL 1 (%J OO X m IQ ’ w0 j44 M .4 I.-U C M 01. L% 46 -- - 0 u~ w- - 00 03 p( Px uaM

  9. Is obesity stigmatizing? Body weight, perceived discrimination, and psychological well-being in the United States.

    PubMed

    Carr, Deborah; Friedman, Michael A

    2005-09-01

    We investigate the frequency and psychological correlates of institutional and interpersonal discrimination reported by underweight, normal weight, overweight, obese I, and obese II/III Americans. Analyses use data from the Midlife Development in the United States study, a national survey of more than 3,000 adults ages 25 to 74 in 1995. Compared to normal weight persons, obese II/III persons (body mass index of 35 or higher) are more likely to report institutional and day-to-day interpersonal discrimination. Among obese II/III persons, professional workers are more likely than nonprofessionals to report employment discrimination and interpersonal mistreatment. Obese II/III persons report lower levels of self-acceptance than normal weight persons, yet this relationship is fully mediated by the perception that one has been discriminated against due to body weight or physical appearance. Our findings offer further support for the pervasive stigma of obesity and the negative implications of stigmatized identities for life chances.

  10. Interleukin-1 Blockade With Canakinumab to Improve Exercise Capacity in Patients With Chronic Systolic Heart Failure and Elevated High Sensitivity C-reactive Protein (Hs-CRP)

    ClinicalTrials.gov

    2017-09-14

    Prior Acute Myocardial Infarction; Evidence of Systemic Inflammation (C Reactive Protein Plasma >2 mg/l); Reduced Left Ventricle Ejection Fraction (<50%); Symptoms of Heart Failure (NYHA Class II-III)

  11. NEW BEDFORD, DRAFT 100% DESIGN PLANS FOR ...

    EPA Pesticide Factsheets

    2013-06-11

    E D c B A \\ \\ \\ I I I I \\ I I \\ I I I I I I I I I ~x i\\ . I I I I \\ II I I I \\ \\ I I \\ \\ I I I \\ ' I \\ · ~ I I I I I \\ \\ ' \\ \\ I \\ \\ I \\ ,_ I' I \\ I I I I I I I I I J I" I ;:J J J I •IIIIIIIIII I I I I I ~'{; '29''\\N /~ ...

  12. Chronic shin splints. Classification and management of medial tibial stress syndrome.

    PubMed

    Detmer, D E

    1986-01-01

    A clinical classification and treatment programme has been developed for chronic medial tibial stress syndrome. Medial tibial stress syndrome has been reported to be either tibial stress fracture or microfracture, tibial periostitis, or distal deep posterior chronic compartment syndrome. Three chronic types exist and may coexist: Type I (tibial microfracture, bone stress reaction or cortical fracture); type II (periostalgia from chronic avulsion of the periosteum at the periosteal-fascial junction); and type III (chronic compartment syndrome syndrome). Type I disease is treated nonoperatively. Operations for resistant types II and III medial tibial stress syndrome were performed in 41 patients. Bilaterality was common (type II, 50% type III, 88%). Seven had coexistent type II/III; one had type I/II. Preoperative symptoms averaged 24 months in type II, 6 months in type III, and 33 months in types II/III. Mean age was 22 years (15 to 51). Resting compartment pressures were normal in type II (mean 12 mm Hg) and elevated in type III and type II/III (mean 23 mm Hg). Type II and type II/III patients received fasciotomy plus periosteal cauterisation. Type III patients had fasciotomy only. All procedures were performed on an outpatient basis using local anaesthesia. Follow up was complete and averaged 6 months (2 to 14 months). Improved performance was as follows: type II, 93%, type III, 100%; type II/III, 86%. Complete cures were as follows: type II, 78%; type III, 75%; and type II/III, 57%. This experience suggests that with precise diagnosis and treatment involving minimal risk and cost the athlete has a reasonable chance of return to full activity.

  13. Cognitive Effort and Decision Making Strategies: A Componential Analysis of Choice.

    DTIC Science & Technology

    1986-07-31

    COMPONENTIAL ANALYSIS OF CHOICE(U) DUKE UNIV DURNA NC J R DETTNAN ET AL. 31 JUL 86 RR-96-2 NSWI4-6S-C- S ±14 UNCLASSIFIED F/O 5/𔃻@ M IIIII IIIII1 0 5...CLASSIFICATION OF THIS PAGE M%0on DOM Entored) REPORT DOCUMENTATION PAGE BEFRED COMLEIGM 1. REPORT NUMBER G2. OVT ACCES&ION NO S . RECIPIENT’S CATALOG...NUMBER86-2 D /4CJ 4. TITLE (and Subtitle) S . TYPE OF REPORT & PERIOD COVERED COGNITIVE EFFORT AND DECISION MAKING STRATEGIES: Research A COMPONENTIAL

  14. Solar Occultation Retrieval Algorithm Development

    NASA Technical Reports Server (NTRS)

    Lumpe, Jerry D.

    2004-01-01

    This effort addresses the comparison and validation of currently operational solar occultation retrieval algorithms, and the development of generalized algorithms for future application to multiple platforms. initial development of generalized forward model algorithms capable of simulating transmission data from of the POAM II/III and SAGE II/III instruments. Work in the 2" quarter will focus on: completion of forward model algorithms, including accurate spectral characteristics for all instruments, and comparison of simulated transmission data with actual level 1 instrument data for specific occultation events.

  15. Balancing Accession and Retention: The Disaggregate Model.

    DTIC Science & Technology

    1982-08-01

    MENDEZ ET AL. AUG 82 CNA- PP -374 UNCLSSIFIED N80814-76-C -888i F/G 5/9 N IIIII._____ m~j~2 111112.2 11.6 140 1111120 1II’.8 IIIII 25 11 A1. 1.6 MICROCOPY...Introduction ...........00........ . 00.. . ..... 0............ .0 .1 ;.The Modelo ... ... ... .... ... ... ... o................ ... ..... - 2 The Flow of...34 by Matthew S. Goldberg and Michael F. Hager, Unclassified, 10 June 1981 K -1 .1 I LI -- 4 .1 CNA PROFESSIDNL PAPS - 1978 ID RFlSENT" PP 211 PP 222

  16. Cluster of infections caused by methicillin-resistant Staphylococcus pseudintermedius in humans in a tertiary hospital.

    PubMed

    Starlander, Gustaf; Börjesson, Stefan; Grönlund-Andersson, Ulrika; Tellgren-Roth, Christian; Melhus, Asa

    2014-08-01

    The dog-associated Staphylococcus pseudintermedius is a rare pathogen in humans. Here we describe a cluster of infections caused by the methicillin-resistant S. pseudintermedius clone ST71-J-t02-II-III. It involved four elderly patients at a tertiary hospital. Three patients had wound infections, and the strain had a tendency to cause bullous skin lesions.

  17. Greenhouse evaluation of commercial soybean cultivars adapted to the northern United States for resistance to charcoal rot

    USDA-ARS?s Scientific Manuscript database

    Thirty (30) and sixty-seven (67) commercially available soybean (Glycine max (L.) Merr) cultivars from Wisconsin (Maturity group (MG) I-II) and Indiana (MG II-III), respectively, were evaluated for charcoal rot (CR; Macrophomina phaseolina (Tassi) Goid) resistance using a cut-stem greenhouse assay. ...

  18. US EPA, Pesticide Product Label, , 09/09/1975

    EPA Pesticide Factsheets

    2011-04-13

    ... 111!jo..·!;II\\ :';' III \\IJI \\ ," \\\\1' IIt"I'I .. : :; l ;" :'.1 .\\1 i !il' ,! ,. ... II hI[ ha,h1 Jpplh.JtI,· li lJ ... C ;l' ,t', "IIIII,lll·1\\ 11..' .. IIT tlr~JflI\\. rTlJ!tl'1 . >fl!l'!t' ~ll·! ...

  19. US EPA, Pesticide Product Label, FLIGHT BRAND ...

    EPA Pesticide Factsheets

    2011-04-14

    • \\ " I II H ) I 1\\ , I) , If{, I \\ II' I \\{ I \\: \\ \\. I! \\ ""Y',I(I\\,, \\: 1'·(1" \\11 (,"iI'" III \\1 "i1'1( '11>1',' ;IIIII\\' I'f)lse."''' SY\\'l'lo'o., \\11 l'II'''i1( 1\\"" ,UI' 1;1, ',. ...

  20. US EPA, Pesticide Product Label, , 11/26/1982

    EPA Pesticide Factsheets

    2011-04-19

    ... It 15 I vic with lU 10 SAIIITl ZING IN FOOD CON equl .... t. ... It ••• 1 ..... driAk prlllljltiy I IIrIll qllllllity II milk •• gg wlIiIH. gelatin nItIIIII; or II ..... IrI lilt Ivlillllll. ...

  1. CORRIGENDUM: Optical and electronic properties of ZnO:P/n+-Si heterostructures fabricated by metalorganic chemical vapour deposition

    NASA Astrophysics Data System (ADS)

    Zhu, H.; Du, G.; Li, X.; Zhang, Y.; Cui, Y.; Huang, K.; Xia, X.; Yang, T.; Zhang, B.; Chang, Y.

    2007-04-01

    There is a mistake in the first sentence of the paper, where 'II-III' should read as 'II-IV'. The corrected sentence is: Zinc oxide (ZnO) is a II-IV compound semiconductor with a hexagonal wurtzite-type crystal structure.

  2. 40 CFR 63.11494 - What are the applicability requirements and compliance dates?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Mercury Cell Chlor-Alkali Plants, subject to subpart IIIII of this part. (iii) Polyvinyl Chloride and.../quality control laboratories. (5) Ancillary activities, as defined in § 63.11502(b). (6) Metal HAP in... total CAA section 112(b) organic HAP. A CMPU using only Table 1 metal HAP is required to control only...

  3. 40 CFR 63.11494 - What are the applicability requirements and compliance dates?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Mercury Cell Chlor-Alkali Plants, subject to subpart IIIII of this part. (iii) Polyvinyl Chloride and.../quality control laboratories. (5) Ancillary activities, as defined in § 63.11502(b). (6) Metal HAP in... total CAA section 112(b) organic HAP. A CMPU using only Table 1 metal HAP is required to control only...

  4. 40 CFR 63.11494 - What are the applicability requirements and compliance dates?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Mercury Cell Chlor-Alkali Plants, subject to subpart IIIII of this part. (iii) Polyvinyl Chloride and.../quality control laboratories. (5) Ancillary activities, as defined in § 63.11502(b). (6) Metal HAP in... total CAA section 112(b) organic HAP. A CMPU using only Table 1 metal HAP is required to control only...

  5. US EPA, Pesticide Product Label, DZN DIAZINON AG500, 06 ...

    EPA Pesticide Factsheets

    2011-04-13

    ... "Il fit-I'llt'" Apply;' ;r '. ph pt'r dt ... Hop" A("lt.,', M",,<. Apply I ql PI" iH ff' D" flfll .11'1,11' W'~"''1 140.\\1'''' III 'l,IIIII".1 ()I ,11""l'" rt",'~'Jf'" m,ly "'~,Irll ... (.1'.17 4 (;I~, ...

  6. Rediscovery of Hyalinobatrachium chirripoi (Anura: Centrolenidae) in southeastern Costa Rica.

    PubMed

    Kubicki, Brian

    2004-03-01

    The Suretka glass frog, Hyalinobatrachium chirripoi, has been recently rediscovered in the southeastern region of Costa Rica. This species was last reported in Costa Rica in the 1950's. H. chirripoi is distinguished from H. colymbiphyllum, which appears to be its most closely Costa Rican related taxon, by having extensive webbing between fingers II-III.

  7. A macrocyclic approach to tetracycline natural products. Investigation of transannular alkylations and Michael additions.

    PubMed

    Wzorek, Joseph S; Knöpfel, Thomas F; Sapountzis, Ioannis; Evans, David A

    2012-12-07

    A new approach to the tetracycline core structure is presented. The pivotal intermediate is identified as macrocycle III. The two interior bonds (C4a-C12a and C5a-C11a) are to be constructed through sequential transannular Michael additions (III-II) and compression-promoted transannular isoxazole alkylations from intermediate II.

  8. Symmetrical osteoporosis (spongy hyperostosis) in a prehistoric skull from New Mexico.

    PubMed

    Jarcho, S; Simon, N; Jaffe, H L

    1965-01-01

    Fragments of an Anasazi skull (Pueblo II-III) from New Mexico are described. Lesions of symmetrical osteoporosis were found and their anatomical and roentgenographic characteristics are discussed. The term symmetrical osteoporosis has led to confusion with the unrelated disease osteoporosis and should be replaced by the designation spongy hyperostosis.

  9. NEW BEDFORD, MAPS OF FINAL DESANDING AND ...

    EPA Pesticide Factsheets

    2012-05-04

    ... m US Army Cor~ at Eno1,-a ... EnolCJld DIa1rlct i I J ~~ ~ ~ IU I~i B ~lI il& ~ ~ ~ I ; I IS II! h iii U H H! IIIII .,N - 0 • ~., t~ "- I .!Q I iii :;:t!J .11 j~ 2' li .1 I ~~! ...

  10. Is Obesity Stigmatizing? Body Weight, Perceived Discrimination, and Psychological Well-Being in the United States

    ERIC Educational Resources Information Center

    Carr, Deborah; Friedman, Michael A.

    2005-01-01

    We investigate the frequency and psychological correlates of institutional and interpersonal discrimination reported by underweight, normal weight, overweight, obese I, and obese II/III Americans. Analyses use data from the Midlife Development in the United States study, a national survey of more than 3,000 adults ages 25 to 74 in 1995. Compared…

  11. Evidence of nosocomial transmission of human rhinovirus in a neonatal intensive care unit.

    PubMed

    Reese, Sara M; Thompson, Meredyth; Price, Connie S; Young, Heather L

    2016-03-01

    Nosocomial respiratory infections cause significant morbidity and mortality, especially among the extremely susceptible neonatal population. Human rhinovirus C is a common viral respiratory illness that causes significant complications in children <2 years old. We describe a nosocomial outbreak of human rhinovirus C in a level II-III neonatal intensive care unit in an urban public safety net hospital.

  12. New Bedford, Tidal Cycle and PCB Mass Transport Study ...

    EPA Pesticide Factsheets

    2012-04-22

    ... Sill iri cii! ... ti clliii1 c: j c 1 ts iiillin "I iiiiili zes t (rue ip [it ent1 a "1 fo i iii c: na 1 iesi i c: te 11 :i a 1 c:;; ;1 » t: ob 1 as ci (»in ii"III "1 stiiclli] i ii!i"!i 11 ts Com ...

  13. US EPA, Pesticide Product Label, SA-50 BRAND 25% ...

    EPA Pesticide Factsheets

    2011-04-14

    ... 111\\ ,11,>1- in'·~II·ra ... ,· IlIlrihilllr \\Illlw nil ll1rll1"r '·'I"I'''rt· IIlIlil Itrll.· tllr ;, ,'h .. IIII,',I, I '" fI'g-('III'ralillll h:! ... 1"';'11 ;01111\\\\('" 1 ... ""I·rllllll,·" III "1",,11 1",1 -

  14. Qualitative Analysis: The Current Status.

    ERIC Educational Resources Information Center

    Cole, G. Mattney, Jr.; Waggoner, William H.

    1983-01-01

    To assist in designing/implementing qualitative analysis courses, examines reliability/accuracy of several published separation schemes, notes methods where particular difficulties arise (focusing on Groups II/III), and presents alternative schemes for the separation of these groups. Only cation analyses are reviewed. Figures are presented in…

  15. US EPA, Pesticide Product Label, , 02/22/1974

    EPA Pesticide Factsheets

    2011-04-14

    ... lll'd ,trip' in Ihl' fi,'ld. hp,',ien<,' h •• , ,1111\\1 n Ih.ll lh('m il.11 mi\\ing in Ih(' ,"i I Il(I Ul\\ 10 .I d"plh .IpIIIII\\im.II,'lv unl' ... di ... ( rn~ to " dt'plh 01 loUr IIH IH· .... ...

  16. Dendrites and Cognition: A Negative Pilot Study in the Rat.

    ERIC Educational Resources Information Center

    Anderson, Britt

    1995-01-01

    The dendritic structure of layer II-III pyramidal neurons of the parietal cortex in 41 Long-Evans rats was compared to behavioral assessments of attention to novelty, response flexibility, and reasoning. A significant correlation between dendritic arborization and behavioral performance was not demonstrated. (SLD)

  17. US EPA, Pesticide Product Label, TASCO BRAND 8LB. ...

    EPA Pesticide Factsheets

    2011-04-13

    ... nell II ~ .. 1 •• lde ., , .. t,," WIll., " .. H ... er ,I,.., Clnthllt ••• tc. ThIlCll n t. ,art III ..... 3) A ..... bIM " , ... U.II •• 111. ~iI • ..." trlldI ... .. tIIIII tilt ... If .. ...

  18. Mediterranean and Black Sea organisms and algae from mariculture as sources of antitumor drugs.

    PubMed

    Apryshko, Galina N; Ivanov, Valeriy N; Milchakova, Natalya A; Nekhoroshev, Mikhail V

    2005-06-01

    Mussels and tunicates cultivated in Mediterranean and Black Sea are the sources of antitumor drugs. Three compounds isolated from these animals (ET-743, aplidin and bryostatin-1) are on the II-III stages of clinical trials. Carotenoid fucoxantin that is present in edible brown algae possesses antitumor activity. The consumption of brown macrophyts decreases the risk of cancer development.

  19. 77 FR 18793 - Spectrum Sharing Innovation Test-Bed Pilot Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-28

    ... National Telecommunications and Information Administration Spectrum Sharing Innovation Test-Bed Pilot... conduct in Phase II/III of the Spectrum Sharing Innovation Test-Bed pilot program to assess whether devices employing Dynamic Spectrum Access techniques can share the frequency spectrum with land...

  20. US EPA, Pesticide Product Label, MOGUL A-422, 08/27/1968

    EPA Pesticide Factsheets

    2011-04-21

    ... Ill'l'i,,,li, """,L'-"'' 1 III "I'''iin.! ''; j()(;t'l,:\\ I.!~ fIJI' ("-1'1','- J,IIIII/p-;tll"Il" "I' ("illtainl'd "-,tll'l'. ;:l~-~tl·. ifl 11!'tit'l' 'II !,lll~l:!l (, ,!- 1111'''' ,1' (!lli),!i, ...

  1. United States Army Medical Materiel Development Activity - 1989

    DTIC Science & Technology

    1990-01-31

    other reports. They also provided a review of the enpiroline clinical data collected to date which served as the basis for the Government’s declsior tQ...e A Milestone II/III IPR for the antimalarial drug Enpiroline will be held 1Q90. e A Topical Skin Protectant will transition to advanced development

  2. Study of three-dimensional morphology of the proximal femur in developmental adult dysplasia of the hip suggests that the on-shelf modular prosthesis may not be an ideal choice for patients with Crowe type IV hips.

    PubMed

    Liu, Shuanglu; Zuo, Jianlin; Li, Zhizhou; Yang, Yuhui; Liu, Tong; Xiao, Jianlin; Gao, Zhongli

    2017-04-01

    The purpose of this study was to investigate the three-dimensional morphological features of the proximal femur of developmental dysplasia of the hip (DDH). From January 2012 to December 2014, 38 patients (47 hips) of DDH were admitted and 30 normal hips were selected as controls. All hips from both groups were examined by CT scan. CT data were imported into Mimics 17.0. Three-dimensional models of the proximal femur were then reconstructed, and the following parameters were measured: neck-shaft angle, neck length, offset, height of the centre of femoral head, level of isthmus, height of the tip of greater trochanter, the medullary canal diameter of isthmus(Di), the medullary canal diameter 10 mm above the apex of the lesser trochanter(DT + 10), the medullary canal diameter 20 mm below the apex of the lesser trochanter(DT-20), and then DT + 10/Di, DT-20/Di and DT + 10/DT-20 were calculated. There was no significant difference in neck-shaft angle between Crowe I, Crowe II-III DDH and the control group, while the neck-shaft angle was much smaller in Crowe IV DDH. The neck length of Crowe IV DDH was also much smaller than those of Crowe I and Crowe II-III DDH. Height of the tip greater trochanter in Crowe IV was greater than that in Crowe I, Crowe II-III DDH and the control group. The centre of femoral head in Crowe IV DDH was lower than those in Crowe I, Crowe II-III DDH and the control group. The level of isthmus in Crowe IV was much higher than those in Crowe I, Crowe II-III DDH and the control group. DT + 10, DT-20, DT + 10/Di and DT-20/Di were much smaller in Crowe IV DDH than those in Crowe I, Crowe II-III and the control group. Neck-shaft angle in the DDH groups was not larger than that in the control group. Comparing to Crowe I, Crowe II-III DDH and the control group, Crowe IV DDH had a dramatic change in the intramedullary and extramedullary parameters, especially the dramatic narrowing of medullary canal around the level of the lesser

  3. HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials.

    PubMed

    Richman, Susan D; Southward, Katie; Chambers, Philip; Cross, Debra; Barrett, Jennifer; Hemmings, Gemma; Taylor, Morag; Wood, Henry; Hutchins, Gordon; Foster, Joseph M; Oumie, Assa; Spink, Karen G; Brown, Sarah R; Jones, Marc; Kerr, David; Handley, Kelly; Gray, Richard; Seymour, Matthew; Quirke, Philip

    2016-03-01

    HER2 overexpression/amplification is linked to trastuzumab response in breast/gastric cancers. One suggested anti-EGFR resistance mechanism in colorectal cancer (CRC) is aberrant MEK-AKT pathway activation through HER2 up-regulation. We assessed HER2-amplification/overexpression in stage II-III and IV CRC patients, assessing relationships to KRAS/BRAF and outcome. Pathological material was obtained from 1914 patients in the QUASAR stage II-III trial and 1342 patients in stage IV trials (FOCUS and PICCOLO). Tissue microarrays were created for HER2 immunohistochemistry. HER2-amplification was assessed using FISH and copy number variation. KRAS/BRAF mutation status was assessed by pyrosequencing. Progression-free survival (PFS) and overall survival (OS) data were obtained for FOCUS/PICCOLO and recurrence and mortality for QUASAR; 29/1342 (2.2%) stage IV and 25/1914 (1.3%) stage II-III tumours showed HER2 protein overexpression. Of the HER2-overexpressing cases, 27/28 (96.4%) stage IV tumours and 20/24 (83.3%) stage II-III tumours demonstrated HER2 amplification by FISH; 41/47 (87.2%) also showed copy number gains. HER2-overexpression was associated with KRAS/BRAF wild-type (WT) status at all stages: in 5.2% WT versus 1.0% mutated tumours (p < 0.0001) in stage IV and 2.1% versus 0.2% in stage II-III tumours (p = 0.01), respectively. HER2 was not associated with OS or PFS. At stage II-III, there was no significant correlation between HER2 overexpression and 5FU/FA response. A higher proportion of HER2-overexpressing cases experienced recurrence, but the difference was not significant. HER2-amplification/overexpression is identifiable by immunohistochemistry, occurring infrequently in stage II-III CRC, rising in stage IV and further in KRAS/BRAF WT tumours. The value of HER2-targeted therapy in patients with HER2-amplified CRC must be tested in a clinical trial. © 2015 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society

  4. Analysis of pramipexole dose-response relationships in Parkinson's disease.

    PubMed

    Wang, Ying; Sun, Sheng-Gang; Zhu, Sui-Qiang; Liu, Chun-Feng; Liu, Yi-Ming; Di, Qing; Shang, Hui-Fang; Ren, Yan; Xiang, Wei; Chen, Sheng-Di

    2017-01-01

    Pramipexole (PPX), a non-ergot dopamine receptor agonist, is a first-line treatment for Parkinson's disease (PD). A critical dose level above which a better benefit-to-harm ratio exists has not been examined. Chinese PD patients (n=464) were retrospectively analyzed by PPX maintenance dose, PD stage, combined levodopa dose, and baseline tremor contribution. The sum score of Baseline Activities of Daily Living (part II) and Motor Examination (III) of the Unified Parkinson's Disease Rating Scale (UPDRS II+III) was used as a covariate for final score adjustment. Sustained-release (SR) and immediate-release (IR) PPX showed similar efficacy based on score changes at 18 weeks, with comparable tolerability. Approximately two-third of patients received PPX at ≥1.5 mg/d, and one fourth of patients had ≥20% tremor contribution to UPDRS II+III. After treatment, patients receiving PPX ≥1.5 mg/d showed better improvement in UPDRS II+III scores (P=0.0025), with similar trends with the IR and SR formulations. Patients with ≥20% tremor contribution showed better improvement in UPDRS II+III scores (P=0.0017). No differences were seen based on PD stage or combined levodopa dose. The overall proportions of adverse events (AEs) were similar. More patients discontinued because of intolerable side effects, and more investigator-defined drug-related AEs were recorded in the <1.5 mg/d subgroup. UPDRS II+III improvement was better with PPX ≥1.5 than with <1.5 mg/d in Chinese PD patients after 18 weeks of treatment, with similar trends seen with IR and SR formulations. The frequency of AEs in PPX ≥1.5 and <1.5 mg/d subgroups was similar.

  5. Diverse action of repeated corticosterone treatment on synaptic transmission, neuronal plasticity, and morphology in superficial and deep layers of the rat motor cortex.

    PubMed

    Kula, Joanna; Gugula, Anna; Blasiak, Anna; Bobula, Bartosz; Danielewicz, Joanna; Kania, Alan; Tylko, Grzegorz; Hess, Grzegorz

    2017-07-27

    One of the adverse effects of prolonged stress in rats is impaired performance of skilled reaching and walking tasks. The mechanisms that lead to these abnormalities are incompletely understood. Therefore, we compared the effects of twice daily repeated corticosterone injections for 7 days on miniature excitatory postsynaptic currents (mEPSCs), as well as on synaptic plasticity and morphology of layers II/III and V pyramidal neurons of the primary motor cortex (M1) of male Wistar rats. Corticosterone treatment resulted in increased frequency, but not amplitude, of mEPSCs in layer II/III neurons accompanied by increased complexity of the apical part of their dendritic tree, with no changes in the density of dendritic spines. The frequency and amplitude of mEPSCs as well as the parameters characterizing the complexity of the dendritic tree were not changed in layer V cells; however, their dendritic spine density was increased. While corticosterone treatment resulted in an increase in the amplitude of field potentials evoked in intralaminar connections within layer II/III, it did not influence field responses in layer V intralaminar connections, as well as the extent of chemically induced layer V long-term potentiation (chemLTP) by the application of tetraethylammonium (TEA, 25 mM). However, chemLTP induction in layer II/III was impaired in slices prepared from corticosterone-treated animals. These data indicate that repeated 7-day administration of exogenous corticosterone induces structural and functional plasticity in the M1, which occurs mainly in layer II/III pyramidal neurons. These findings shed light on potential sites of action and mechanisms underlying stress-induced impairment of motor functions.

  6. Fluorescence resonance energy transfer (FRET) indicates that association with the type I ryanodine receptor (RyR1) causes reorientation of multiple cytoplasmic domains of the dihydropyridine receptor (DHPR) α(1S) subunit.

    PubMed

    Polster, Alexander; Ohrtman, Joshua D; Beam, Kurt G; Papadopoulos, Symeon

    2012-11-30

    The skeletal muscle dihydropyridine receptor (DHPR) in the t-tubular membrane serves as the Ca(2+) channel and voltage sensor for excitation-contraction (EC) coupling, triggering Ca(2+) release via the type 1 ryanodine receptor (RyR1) in the sarcoplasmic reticulum (SR). The two proteins appear to be physically linked, and both the α(1S) and β(1a) subunits of the DHPR are essential for EC coupling. Within α(1S), cytoplasmic domains of importance include the I-II loop (to which β(1a) binds), the II-III and III-IV loops, and the C terminus. However, the spatial relationship of these domains to one another has not been established. Here, we have taken the approach of measuring FRET between fluorescent proteins inserted into pairs of α(1S) cytoplasmic domains. Expression of these constructs in dyspedic (RyR1 null) and dysgenic (α(1S) null) myotubes was used to test for function and targeting to plasma membrane/SR junctions and to test whether the presence of RyR1 caused altered FRET. We found that in the absence of RyR1, measureable FRET occurred between the N terminus and C terminus (residue 1636), and between the II-III loop (residue 626) and both the N and C termini; the I-II loop (residue 406) showed weak FRET with the II-III loop but not with the N terminus. Association with RyR1 caused II-III loop FRET to decrease with the C terminus and increase with the N terminus and caused I-II loop FRET to increase with both the II-III loop and N terminus. Overall, RyR1 appears to cause a substantial reorientation of the cytoplasmic α(1S) domains consistent with their becoming more closely packed.

  7. Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

    SciTech Connect

    Nakayama, Hidetsugu; Satoh, Hiroaki; Sugahara, Shinji; Kurishima, Koichi; Tsuboi, Koji; Sakurai, Hideyuki; Ishikawa, Shigemi; Tokuuye, Koichi

    2011-11-15

    Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

  8. Analysis of pramipexole dose–response relationships in Parkinson’s disease

    PubMed Central

    Wang, Ying; Sun, Sheng-Gang; Zhu, Sui-Qiang; Liu, Chun-Feng; Liu, Yi-Ming; Di, Qing; Shang, Hui-Fang; Ren, Yan; Xiang, Wei; Chen, Sheng-Di

    2017-01-01

    Background Pramipexole (PPX), a non-ergot dopamine receptor agonist, is a first-line treatment for Parkinson’s disease (PD). A critical dose level above which a better benefit-to-harm ratio exists has not been examined. Methods Chinese PD patients (n=464) were retrospectively analyzed by PPX maintenance dose, PD stage, combined levodopa dose, and baseline tremor contribution. The sum score of Baseline Activities of Daily Living (part II) and Motor Examination (III) of the Unified Parkinson’s Disease Rating Scale (UPDRS II+III) was used as a covariate for final score adjustment. Results Sustained-release (SR) and immediate-release (IR) PPX showed similar efficacy based on score changes at 18 weeks, with comparable tolerability. Approximately two-third of patients received PPX at ≥1.5 mg/d, and one fourth of patients had ≥20% tremor contribution to UPDRS II+III. After treatment, patients receiving PPX ≥1.5 mg/d showed better improvement in UPDRS II+III scores (P=0.0025), with similar trends with the IR and SR formulations. Patients with ≥20% tremor contribution showed better improvement in UPDRS II+III scores (P=0.0017). No differences were seen based on PD stage or combined levodopa dose. The overall proportions of adverse events (AEs) were similar. More patients discontinued because of intolerable side effects, and more investigator-defined drug-related AEs were recorded in the <1.5 mg/d subgroup. Conclusion UPDRS II+III improvement was better with PPX ≥1.5 than with <1.5 mg/d in Chinese PD patients after 18 weeks of treatment, with similar trends seen with IR and SR formulations. The frequency of AEs in PPX ≥1.5 and <1.5 mg/d subgroups was similar. PMID:28096656

  9. Outcome in 212 anti-Ro/SSA-positive pregnancies and population-based incidence of congenital heart block.

    PubMed

    Skog, Amanda; Lagnefeldt, Linda; Conner, Peter; Wahren-Herlenius, Marie; Sonesson, Sven-Erik

    2016-01-01

    We investigated the effects of maternal autoimmune disease and fetal congenital heart block (CHB) on pregnancy outcomes in anti-Ro/SSA-positive women and assessed the population-based incidence of isolated CHB. One hundred and ninety nine anti-Ro/SSA-positive pregnancies were prospectively followed at our center (2000-2013). Seven fetuses developed atrioventricular block (AVB) II-III. In this period, another 13 anti-Ro/SSA-positive pregnancies were referred for fetal bradycardia, subsequently diagnosed with AVB II-III. Cesarean section rates, gestational age, body measurements at birth, and the incidence of CHB in these 212 pregnancies were analyzed in relation to fetal atrioventricular conduction and maternal diagnosis and compared with data from the Medical Birth Registry on 352,104 pregnancies in the Stockholm County. The prevalence of maternal systemic lupus erythematosus (SLE) and primary Sjögren's syndrome and the outcomes at birth were similar in normal conduction and AVB I cases. Only 1/20 AVB II-III cases (0/7 in the surveillance group) had a mother diagnosed with SLE, compared with 73/192 in cases with normal conduction or AVB I. Excluding cases with AVB II-III, SLE mothers more frequently delivered by cesarean section (31% vs. 20%, p < 0.05) and had a higher incidence of preterm birth (13% vs. 5.8%, p < 0.05) than the county population. Both SLE and primary Sjögren's syndrome mothers had a fourfold greater rate of growth-retarded babies (10.11% vs. 2.2%, p < 0.001). The incidence of autoantibody-related AVB II-III in Stockholm County was 1/23 300. This study of CHB provides new information on the incidence of CHB and outcome of pregnancy in anti-Ro/SSA-positive women, which has clinical relevance when counseling rheumatic patients considering pregnancy. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  10. Electrical properties and gustatory responses of various taste disk cells of frog fungiform papillae.

    PubMed

    Sato, Toshihide; Nishishita, Kazuhisa; Okada, Yukio; Toda, Kazuo

    2008-04-01

    We compared the electrical properties and gustatory response profiles of types Ia cell (mucus cell), Ib cell (wing cell), and II/III cell (receptor cell) in the taste disks of the frog fungiform papillae. The large depolarizing responses of all types of cell induced by 1 M NaCl were accompanied by a large decrease in the membrane resistance and had the same reversal potential of approximately +5 mV. The large depolarizing responses of all cell types for 1 mM acetic acid were accompanied by a small decrease in the membrane resistance. The small depolarizing responses of all cell types for 10 mM quinine-HCl (Q-HCl) were accompanied by an increase in the membrane resistance, but those for 1 M sucrose were accompanied by a decrease in the membrane resistance. The reversal potential of sucrose responses in all cell types were approximately +12 mV. Taken together, depolarizing responses of Ia, Ib, and II/III cells for each taste stimulus are likely to be generated by the same mechanisms. Gustatory depolarizing response profiles indicated that 1) each of Ia, Ib, and II/III cells responded 100% to 1 M NaCl and 1 mM acetic acid with depolarizing responses, 2) approximately 50% of each cell type responded to 10 mM Q-HCl with depolarizations, and 3) each approximately 40% of Ia and Ib cells and approximately 90% of II/III cells responded to 1 M sucrose with depolarizations. These results suggest that the receptor molecules for NaCl, acid, and Q-HCl stimuli are equivalently distributed on all cell types, but the receptor molecules for sugar stimuli are richer on II/III cells than on Ia and Ib cells. Type III cells having afferent synapses may play a main role in gustatory transduction and transmission.

  11. RubisCO of a nucleoside pathway known from Archaea is found in diverse uncultivated phyla in bacteria

    SciTech Connect

    Wrighton, Kelly C.; Castelle, Cindy J.; Varaljay, Vanessa A.; Satagopan, Sriram; Brown, Christopher T.; Wilkins, Michael J.; Thomas, Brian C.; Sharon, Itai; Williams, Kenneth H.; Tabita, F. Robert; Banfield, Jillian F.

    2016-05-03

    Metagenomic studies recently uncovered form II/III RubisCO genes, originally thought to only occur in archaea, from uncultivated bacteria of the candidate phyla radiation (CPR). There are no isolated CPR bacteria and these organisms are predicted to have limited metabolic capacities. Here we expand the known diversity of RubisCO from CPR lineages. We report a form of RubisCO, distantly similar to the archaeal form III RubisCO, in some CPR bacteria from the Parcubacteria (OD1), WS6 and Microgenomates (OP11) phyla. In addition, we significantly expand the Peregrinibacteria (PER) II/III RubisCO diversity and report the first II/III RubisCO sequences from the Microgenomates and WS6 phyla. To provide a metabolic context for these RubisCOs, we reconstructed near-complete ( > 93%) PER genomes and the first closed genome for a WS6 bacterium, for which we propose the phylum name Dojkabacteria. Genomic and bioinformatic analyses suggest that the CPR RubisCOs function in a nucleoside pathway similar to that proposed in Archaea. Detection of form II/III RubisCO and nucleoside metabolism gene transcripts from a PER supports the operation of this pathway in situ. We demonstrate that the PER form II/III RubisCO is catalytically active, fixing CO2 to physiologically complement phototrophic growth in a bacterial photoautotrophic RubisCO deletion strain. We propose that the identification of these RubisCOs across a radiation of obligately fermentative, small-celled organisms hints at a widespread, simple metabolic platform in which ribose may be a prominent currency.

  12. RubisCO of a nucleoside pathway known from Archaea is found in diverse uncultivated phyla in bacteria

    DOE PAGES

    Wrighton, Kelly C.; Castelle, Cindy J.; Varaljay, Vanessa A.; ...

    2016-05-03

    Metagenomic studies recently uncovered form II/III RubisCO genes, originally thought to only occur in archaea, from uncultivated bacteria of the candidate phyla radiation (CPR). There are no isolated CPR bacteria and these organisms are predicted to have limited metabolic capacities. Here we expand the known diversity of RubisCO from CPR lineages. We report a form of RubisCO, distantly similar to the archaeal form III RubisCO, in some CPR bacteria from the Parcubacteria (OD1), WS6 and Microgenomates (OP11) phyla. In addition, we significantly expand the Peregrinibacteria (PER) II/III RubisCO diversity and report the first II/III RubisCO sequences from the Microgenomates andmore » WS6 phyla. To provide a metabolic context for these RubisCOs, we reconstructed near-complete ( > 93%) PER genomes and the first closed genome for a WS6 bacterium, for which we propose the phylum name Dojkabacteria. Genomic and bioinformatic analyses suggest that the CPR RubisCOs function in a nucleoside pathway similar to that proposed in Archaea. Detection of form II/III RubisCO and nucleoside metabolism gene transcripts from a PER supports the operation of this pathway in situ. We demonstrate that the PER form II/III RubisCO is catalytically active, fixing CO2 to physiologically complement phototrophic growth in a bacterial photoautotrophic RubisCO deletion strain. We propose that the identification of these RubisCOs across a radiation of obligately fermentative, small-celled organisms hints at a widespread, simple metabolic platform in which ribose may be a prominent currency.« less

  13. RubisCO of a nucleoside pathway known from Archaea is found in diverse uncultivated phyla in bacteria

    PubMed Central

    Wrighton, Kelly C; Castelle, Cindy J; Varaljay, Vanessa A; Satagopan, Sriram; Brown, Christopher T; Wilkins, Michael J; Thomas, Brian C; Sharon, Itai; Williams, Kenneth H; Tabita, F Robert; Banfield, Jillian F

    2016-01-01

    Metagenomic studies recently uncovered form II/III RubisCO genes, originally thought to only occur in archaea, from uncultivated bacteria of the candidate phyla radiation (CPR). There are no isolated CPR bacteria and these organisms are predicted to have limited metabolic capacities. Here we expand the known diversity of RubisCO from CPR lineages. We report a form of RubisCO, distantly similar to the archaeal form III RubisCO, in some CPR bacteria from the Parcubacteria (OD1), WS6 and Microgenomates (OP11) phyla. In addition, we significantly expand the Peregrinibacteria (PER) II/III RubisCO diversity and report the first II/III RubisCO sequences from the Microgenomates and WS6 phyla. To provide a metabolic context for these RubisCOs, we reconstructed near-complete (>93%) PER genomes and the first closed genome for a WS6 bacterium, for which we propose the phylum name Dojkabacteria. Genomic and bioinformatic analyses suggest that the CPR RubisCOs function in a nucleoside pathway similar to that proposed in Archaea. Detection of form II/III RubisCO and nucleoside metabolism gene transcripts from a PER supports the operation of this pathway in situ. We demonstrate that the PER form II/III RubisCO is catalytically active, fixing CO2 to physiologically complement phototrophic growth in a bacterial photoautotrophic RubisCO deletion strain. We propose that the identification of these RubisCOs across a radiation of obligately fermentative, small-celled organisms hints at a widespread, simple metabolic platform in which ribose may be a prominent currency. PMID:27137126

  14. Extended radical mastectomy versus simple mastectomy followed by radiotherapy in primary breast cancer. A fifty-year follow-up to the Copenhagen Breast Cancer randomised study.

    PubMed

    Johansen, Helge; Kaae, Sigvard; Jensen, Maj-Britt; Mouridsen, Henning T

    2008-01-01

    From November 1951 to December 1957, 666 consecutive patients with untreated primary breast cancer admitted to the Radium Center in Copenhagen were randomised before their operability was evaluated into two groups, simple mastectomy with postoperative radiotherapy or extended radical mastectomy. Following physical examination 241 of the patients were excluded, primarily due to tumours deemed inoperable due to clinical criteria (n =107) and due to poor general condition (n =69). Twenty-five years results of disease-free free survival and fifty years results of survival are presented, showing no difference between the two groups. Patients with clinical stage I did significantly better than patients with stage II-III tumours. Patients with grade I tumours had a better survival than patients with grade II-III. The breast cancer associated mortality was lower in premenopausal patients compared to postmenopausal patients. An excess mortality due to breast cancer was evident up to 20-25 years following the primary diagnosis.

  15. General Aviation Avionics Statistics: 1977.

    DTIC Science & Technology

    1980-06-01

    UNCLASSIFIED TSC-FAA-80-13 FAA-MS-SO-6 NL IIIII."IIE -INEIlllllll 1111 Q 8 j11. 5 j III� 111112- IIIII 8 1111.25 H .II 4 jl 6 MICROCOPY...i t y_ ’ *rout . E - Radi ;Ct A t L I hi I Ir I IidI C C’,,V t I A \\ 1 ’ 1J A ’ III L’,. th\\ l II, Ad l l Q ,"C ) L’ it - t W I 11 t F I! L’ ia I I...Cq . P. N. *Vgw~ .-. P. C ~ e .- 4 C ** C w * . * * - C* N * C c C C g fF- In - * , CC * C; C 0 * P g P *g ’ e q . Fn N1 CN N1 VP N K) cc 4N T N u- a

  16. Diffusion-Weighted Imaging in Meningioma: Prediction of Tumor Grade and Association with Histopathological Parameters.

    PubMed

    Surov, Alexey; Gottschling, Sebastian; Mawrin, Christian; Prell, Julian; Spielmann, Rolf Peter; Wienke, Andreas; Fiedler, Eckhard

    2015-12-01

    To analyze diffusion-weighted imaging (DWI) findings of meningiomas and to compare them with tumor grade, cell count, and proliferation index and to test a possibility of use of apparent diffusion coefficient (ADC) to differentiate benign from atypical/malignant tumors. Forty-nine meningiomas were analyzed. DWI was done using a multislice single-shot echo-planar imaging sequence. A polygonal region of interest was drawn on ADC maps around the margin of the lesion. In all lesions, minimal ADC values (ADCmin) and mean ADC values (ADCmean) were estimated. Normalized ADC (NADC) was calculated in every case as a ratio ADCmean meningioma/ADCmean white matter. All meningiomas were surgically resected and analyzed histopathologically. The tumor proliferation index was estimated on Ki-67 antigen-stained specimens. Cell density was calculated. Collected data were evaluated by means of descriptive statistics. Analyses of ADC/NADC values were performed by means of two-sided t tests. The mean ADCmean value was higher in grade I meningiomas in comparison to grade II/III tumors (0.96 vs 0.80 × 10(-3) mm(2)s(-1), P = .006). Grade II/III meningiomas showed lower NADC values in comparison to grade I tumors (1.05 vs 1.26, P = .015). There was no significant difference in ADCmin values between grade I and II/III tumors (0.69 vs 0.63 × 10(-3) mm(2)s(-1), P = .539). The estimated cell count varied from 486 to 2091 (mean value, 1158.20 ± 333.74; median value, 1108). There were no significant differences in cell count between grade I and grade II/III tumors (1163.93 vs 1123.86 cells, P = .77). The mean level of the proliferation index was 4.78 ± 5.08%, the range was 1% to 18%, and the median value was 2%. The proliferation index was statistically significant higher in grade II/III meningiomas in comparison to grade I tumors (15.43% vs 3.00%, P = .001). Ki-67 was negatively associated with ADCmean (r = -0.61, P < .001) and NADC (r = -0.60, P < .001). No significant correlations between

  17. Hydrocarbon source potential of the Tanezzuft Formation, Murzuq Basin, south-west Libya: An organic geochemical approach

    NASA Astrophysics Data System (ADS)

    El Diasty, W. Sh.; El Beialy, S. Y.; Anwari, T. A.; Batten, D. J.

    2017-06-01

    A detailed organic geochemical study of 20 core and cuttings samples collected from the Silurian Tanezzuft Formation, Murzuq Basin, in the south-western part of Libya has demonstrated the advantages of pyrolysis geochemical methods for evaluating the source-rock potential of this geological unit. Rock-Eval pyrolysis results indicate a wide variation in source richness and quality. The basal Hot Shale samples proved to contain abundant immature to early mature kerogen type II/III (oil-gas prone) that had been deposited in a marine environment under terrigenous influence, implying good to excellent source rocks. Strata above the Hot Shale yielded a mixture of terrigenous and marine type III/II kerogen (gas-oil prone) at the same maturity level as the Hot Shale, indicating the presence of only poor to fair source rocks.

  18. The Effects of Climatological and Transient Wind Forcing on Eddy Generation in the California Current System

    DTIC Science & Technology

    1989-09-01

    M.L. Batteen (408) 646- 2768 I 54Ss DD Form 1473, JUN 86 Prevous editions are obsolete SECURITY CLASS FICATION OF T’,S PAGE S/N 0102-LF-014-6603...34". .. ................. .. ’ " 2 T ISO - 250 .-- 192 36 ---------- - ----. - 32 -- --- ii~iii 326 64 4 532 440 564 520 2 2 3 44I -- 0 312 448 364 320

  19. Prevalence of canine methicillin resistant Staphylococcus pseudintermedius in a veterinary diagnostic laboratory in Italy.

    PubMed

    De Lucia, M; Moodley, A; Latronico, F; Giordano, A; Caldin, M; Fondati, A; Guardabassi, L

    2011-12-01

    The overall prevalence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) was 2% (10/590) among 590 canine specimens submitted to an Italian veterinary diagnostic laboratory during a two-month period, and 21% (10/48) among Staphylococcus intermedius group (SIG) isolates. All methicillin-resistant strains exhibited additional resistance to fluoroquinolones, gentamicin, lincosamides, tetracyclines, and potentiated sulfonamides, belonged predominantly to spa type t02 and harboured SCCmec type II-III cassette.

  20. Toward a New "New Triad"

    DTIC Science & Technology

    2009-04-01

    ii-iii. 50 Rumsfeld, ―Nuclear Posture Review Report: Forward.‖ 51 DOD, ―Findings of the Nuclear Posture Review,‖ 9. 52 Pilat , ―The end of the...28 Pilat , Joseph F. ―The end of the NPT regime?‖ International Affairs 83:3 (2007): 469-482. Raser, John R. ―Deterrence Research: Past

  1. [Surface architectonic of the peripheral red blood cells in cancer patients].

    PubMed

    Novitskiĭ, V V; Chasovskikh, N Iu; Stepovaia, E A; Gol'dberg, V E; Kitsmaniuk, Z D; Kolosova, M V; Mikhaĭlenko, A N; Koreshkova, K G; Bazhenova, N G; Petrova, I V; Sokolova, I B

    1997-08-01

    Scanning electron microscopy of the relief of the surface of peripheral red blood cells in patients with tumors of the head and neck (cancer of the tongue, larynx, and fundal buccal mucosa) of stages II-III and with stages III-IV lung cancer revealed similar changes, characterized by a manifest drop in the count of discocytes and increased share of transitional, prehemolytic, and degenerative forms of cells.

  2. The three most common human papillomavirus oncogenic types and their integration state in Thai women with cervical precancerous lesions and carcinomas.

    PubMed

    Aromseree, Sirinart; Chaiwongkot, Arkom; Ekalaksananan, Tipaya; Kongyingyoes, Bunkerd; Patarapadungkit, Natcha; Pientong, Chamsai

    2014-11-01

    To understand the potential role in cervical cancer development of the three most common high-risk human papillomavirus (HR-HPVs) in Thai women, HPV genotypes and viral genome statuses in different cervical lesions were investigated. Cervical tissues consisting of no cervical intraepithelial neoplasia (84 cases), grade I cervical intraepithelial neoplasia (176 cases), grade II-III cervical intraepithelial neoplasia (91 cases), and squamous cell carcinoma (66 cases) were subjected for HPV genotyping by polymerase chain reaction (PCR) and reverse line blot hybridization assay and for HPV genome status determination by amplification of papillomavirus oncogene transcripts (APOT) assay. HPV prevalence was 28.6% in no cervical intraepithelial neoplasia, 40.3% in grade I cervical intraepithelial neoplasia, 70.3% in grade II-III cervical intraepithelial neoplasia and 86.4% in squamous cell carcinoma cases. The three most common HR-HPV types were HPV 16, 58, and 18 which were distributed in all cervical lesions. HPV physical statuses could be investigated in 4 no cervical intraepithelial neoplasias, 2 grade I cervical intraepithelial neoplasias, 28 grade II-III cervical intraepithelial neoplasias and 31 squamous cell carcinomas. The integrated-derived transcripts were found 3.6% in grade II-III cervical intraepithelial neoplasia and 48.4% in squamous cell carcinoma, whereas no viral genome integration was found in the group of no cervical intraepithelial neoplasia or grade I cervical intraepithelial neoplasia samples. The frequencies of HR-HPV integration in squamous cell carcinoma were found 40%, 100%, 20% of HPV 16, 18, and 58. This study indicates the oncogenic potential ability of the three most common HR-HPVs associated with cervical cancer progression. © 2014 Wiley Periodicals, Inc.

  3. Downsizing Information Systems: Framing the Issues for the Office of Naval Intelligence (ONI)

    DTIC Science & Technology

    1994-03-01

    AD-A279 888lBr Ii AI IN itlt IIIII EllH NAVAL POSTGRADUATE SCHOOL Monterey, California SOTTO UN Q I’ý, . THESIS DOWNSIZING INFORMATION SYSTEMS...Master’s Thesis 4. TITLE AND SUBTITLE S. FUNDING NUMBERS DOWNSIZING INFORMATION SYSTEMS: FRAMING THE ISSUES FOR THE OFFICE OF NAVAL INTELLIGENCE (ONI...13. ABSTRACT (Maximum 200 words) Downsizing information systems from large and centralized mainframe computing architectures to smaller and

  4. First International Conference on Winter Vehicle Mobility, Santa Barbara, California, June 1991

    DTIC Science & Technology

    1993-07-01

    low temperatures are discussed in reference 6. a way that water is drawn in from a point near the bottom Thermoelectric generators are very reliable...both k tIlter 111(1 IN dies ILictii as a1 xx ok-hors Nx PC ti~elit IIIII \\ chile IL ICrn %ninc CINAN UVlrCOtiditiotIs. hiI t11e %% liter thle N% shIII

  5. The Impact of Data Rates on the Design of a Fiber Optics Guidance System.

    DTIC Science & Technology

    1982-07-01

    function.5 A thorough study has been performed of the effects of video bandwidth, sensor resolution, sensor field of view, sensor video truncation...when fields of view greater than 1.8 degrees are used. Note also that video zoom levels need to be determined for target and artillery burst...recover the baseband signal. 7 j ii II__iii_,,_ The problem addressed by rate-distortion theory is the minimi- zation of channel-capacity requirement qhile

  6. Inhibition of TRPV1 channels enables long-term potentiation in the entorhinal cortex.

    PubMed

    Banke, Tue G

    2016-04-01

    The transient receptor potential vanilloid 1 (TRPV1) channel is a non-selective cation channel that is mainly found in nociceptive neurons of the peripheral nervous system; however, these channels have also been located within the CNS, including the entorhinal cortex. Whole-cell patch-clamp recordings of principal entorhinal cortex (EC) layers II/III neurons revealed that evoked inhibitory postsynaptic currents were depressed by application of the TRPV1 agonist capsaicin (CAP), accompanied by a change in the pair-pulse ratio (PPR). In addition, recordings of miniature inhibitory postsynaptic currents (mIPSCs) revealed that inter-event intervals but not amplitude were decreased in wild-type (WT) after application of CAP. This suggests that TRPV1 channels are functional in the entorhinal cortex and are located on inhibitory neurons with their axonal arborization within layers II/III. In order to study TRPV1 channels and their involvement in long-term potentiation (LTP) induction in a more intact circuit, extracellular field potential recordings were performed in EC layers II/III. It was found that activated TRPV1 channels preclude induction of long-term potentiation. In sharp contrast, clear LTP was observed when antagonizing TRPV1 channels or recording from TRPV1 knock-out mice. Thus, these results suggests that signaling through activating inhibitory presynaptic TRPV1 channels represents a novel mechanism by which a shift in feed-forward inhibition of layers II/III cortical principal neurons prompt changes in synaptic strength and thereby contribute to a change of information storage within the brain.

  7. Use and Care of the Extended Cold Weather Clothing System (ECWCS).

    DTIC Science & Technology

    1986-01-01

    SPOT REMOVAL 42G. WATER REPELLENCY 43 Section IV: REPAIR OF ECWCS 44 A. RIPSANDTEARS 44 , [ Il I I IIII ...... . . I - -• • II II II I L IIIJ I IIIII...clean and rinse as required. For thorough cleaning and restoring of water repellency , return to laundry unit for machine washing in accordance with...for additional instructions on stain/spot removal. 42 G. WATER REPELLENCY . If the fourth layer (Parka/Trousers, Extended Cold Weather, Camou- flage) of

  8. Spatial Range Munitions Constituents (MC) Modeling Capabilities

    DTIC Science & Technology

    2011-05-01

    reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of...runoff, interflow, baseflow and streamflow discharge, quantifies sediment rates of each grain size fraction for erosion from the soil surface and bed...Dissolved .... Sorption J Sorbed j Contaminant l.oo .. Contaminant I Dispersion Di spersion Dissolution I Separate I IIIII .. Ioiii .. I I I Kinoll

  9. Fluorescence Resonance Energy Transfer-based Structural Analysis of the Dihydropyridine Receptor α1S Subunit Reveals Conformational Differences Induced by Binding of the β1a Subunit.

    PubMed

    Mahalingam, Mohana; Perez, Claudio F; Fessenden, James D

    2016-06-24

    The skeletal muscle dihydropyridine receptor α1S subunit plays a key role in skeletal muscle excitation-contraction coupling by sensing membrane voltage changes and then triggering intracellular calcium release. The cytoplasmic loops connecting four homologous α1S structural domains have diverse functions, but their structural arrangement is poorly understood. Here, we used a novel FRET-based method to characterize the relative proximity of these intracellular loops in α1S subunits expressed in intact cells. In dysgenic myotubes, energy transfer was observed from an N-terminal-fused YFP to a FRET acceptor, ReAsH (resorufin arsenical hairpin binder), targeted to each α1S intracellular loop, with the highest FRET efficiencies measured to the α1S II-III loop and C-terminal tail. However, in HEK-293T cells, FRET efficiencies from the α1S N terminus to the II-III and III-IV loops and the C-terminal tail were significantly lower, thus suggesting that these loop structures are influenced by the cellular microenvironment. The addition of the β1a dihydropyridine receptor subunit enhanced FRET to the II-III loop, thus indicating that β1a binding directly affects II-III loop conformation. This specific structural change required the C-terminal 36 amino acids of β1a, which are essential to support EC coupling. Direct FRET measurements between α1S and β1a confirmed that both wild type and truncated β1a bind similarly to α1S These results provide new insights into the role of muscle-specific proteins on the structural arrangement of α1S intracellular loops and point to a new conformational effect of the β1a subunit in supporting skeletal muscle excitation-contraction coupling. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Fluorescence Resonance Energy Transfer-based Structural Analysis of the Dihydropyridine Receptor α1S Subunit Reveals Conformational Differences Induced by Binding of the β1a Subunit*

    PubMed Central

    Mahalingam, Mohana; Perez, Claudio F.; Fessenden, James D.

    2016-01-01

    The skeletal muscle dihydropyridine receptor α1S subunit plays a key role in skeletal muscle excitation-contraction coupling by sensing membrane voltage changes and then triggering intracellular calcium release. The cytoplasmic loops connecting four homologous α1S structural domains have diverse functions, but their structural arrangement is poorly understood. Here, we used a novel FRET-based method to characterize the relative proximity of these intracellular loops in α1S subunits expressed in intact cells. In dysgenic myotubes, energy transfer was observed from an N-terminal-fused YFP to a FRET acceptor, ReAsH (resorufin arsenical hairpin binder), targeted to each α1S intracellular loop, with the highest FRET efficiencies measured to the α1S II-III loop and C-terminal tail. However, in HEK-293T cells, FRET efficiencies from the α1S N terminus to the II-III and III-IV loops and the C-terminal tail were significantly lower, thus suggesting that these loop structures are influenced by the cellular microenvironment. The addition of the β1a dihydropyridine receptor subunit enhanced FRET to the II-III loop, thus indicating that β1a binding directly affects II-III loop conformation. This specific structural change required the C-terminal 36 amino acids of β1a, which are essential to support EC coupling. Direct FRET measurements between α1S and β1a confirmed that both wild type and truncated β1a bind similarly to α1S. These results provide new insights into the role of muscle-specific proteins on the structural arrangement of α1S intracellular loops and point to a new conformational effect of the β1a subunit in supporting skeletal muscle excitation-contraction coupling. PMID:27129199

  11. Field Surveys, IOC Valleys. Volume III, Part II. Cultural Resources Survey, Pine and Wah Wah Valleys, Utah.

    DTIC Science & Technology

    1981-08-01

    including horse, camel, mammoth, Ertm E-TR-48-III-II 20 musk ox, and certain species of bison, goat, and bear, which had previously inhabited the marsh and...34 - - -9,$.. 𔄃 Im I I I Si to * Location lype/Contents Affiliation 42B@644 rid e over cr ek - P/J depression, cleared areas, Fr elon (f4-5-18-92) ground

  12. Evidence that the inhibitory effects of guanidinoacetate on the activities of the respiratory chain, Na+,K+-ATPase and creatine kinase can be differentially prevented by taurine and vitamins E and C administration in rat striatum in vivo.

    PubMed

    Zugno, Alexandra I; Scherer, Emilene B S; Mattos, Cristiane; Ribeiro, César A J; Wannmacher, Clovis M D; Wajner, Moacir; Wyse, Angela T S

    2007-05-01

    Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of guanidinoacetate (GAA) and depletion of creatine. Affected patients present epilepsy and mental retardation whose etiopathogeny is unclear. In a previous study we showed that instrastriatal administration of GAA caused a reduction of Na(+),K(+)-ATPase and creatine kinase (CK) activities, as well as an increase in TBARS (an index of lipid peroxidation). In the present study we investigated the in vitro and in vivo effects of GAA on glucose uptake from [U-(14)C] acetate (citric acid cycle activity) and on the activities of complexes II, II-III, III and IV of the respiratory chain in striatum of rats. Results showed that 50 and 100 microM GAA (in vitro studies) and GAA administration (in vivo studies) significantly inhibited complexes II and II-III, respectively, but did not alter complexes III and IV, as well as CO(2) production. We also studied the influence of taurine or vitamins E and C on the inhibitory effects caused by intrastriatal administration of GAA on complexes II and II-III, Na(+),K(+)-ATPase and CK activities, and on TBARS in rat striatum. Pre-treatment with taurine and vitamins E and C revealed that taurine prevents the effects of intrastriatal administration of GAA on the inhibition of complex II, complex II-III, and Na(+),K(+)-ATPase activities. Vitamins E and C prevent the effects of intrastriatal administration of GAA on the inhibition of CK and Na(+),K(+)-ATPase activities, and on the increase of TBARS. The data suggest that GAA in vivo and in vitro treatment disturbs important parameters of striatum energy metabolism and that oxidative damage may be mediating these effects. It is presumed that defects in striatum bioenergetics might be involved in the pathophysiology of striatum damage characteristic of patients with GAMT-deficiency.

  13. Three Dimensional Fire Extinguishant

    DTIC Science & Technology

    1985-09-01

    IIIII docu111e111. •r ( ( G. ADDITIONAL INFORMATION J. Walker, Chief, Fire Technology Branch, HQ AFESC/RDCF Tyndall AFB FL 32043, Telephone: 904/283...6283, AUTOVON 970-6283. Request copies of publication from NTIS. JOSEPH L. WALKER Chief, Fire Technology Branch LAWRENCE D. HOKANSON, Lt Col, USAF...publication . JOSEPH L. WALKER Chief, Fire Technology Branch LAWRENCE D. HOKANSON, Lt Col, USAF Director of Engineering & S ervices Laboratory

  14. Mapping Emplaced Articulated Concrete Mattress Using Geoelectrical and Electromagnetic Techniques.

    DTIC Science & Technology

    1998-08-01

    2450 2200 1760 2800 2491 2378 1745 1823 2015 11 (mV/ft) +.0055 +.0500 +.0055 +.00618 +.0105 ÷.00832 +.08484 +.0070 4.01 HI (depth to source, ft) 115...Calculated value NIf ) >V E 0 _J < I Iw - MODEL, , 0-10 Line XMID Depth Current I no. (ft (ft) (mA/f’n1 2450 10O0 .0055 Is 1 -d-- iiiiI 2160 44.1

  15. [Gastric esophagoplasty in cancer of the middle third of the esophagus].

    PubMed

    Mamontov, A S; Orokhovskiĭ, V I; Ivanov, P A; Vasilenko, L I

    1986-08-01

    The examination of 119 corpses, experiments in 67 dogs and clinical management of 127 patients with the II-III degrees of cancer of the middle third of the esophagus have supported new methods of esophagoplasty by a tube from the greater curvature of the stomach with highly germetic sutures, longer transplants and diaphragmo-percutaneous conduction of it onto the neck. The method is shown to be more safe, less traumatic, not followed by functional alterations of the heart, lungs, diaphragm.

  16. A Vertical Wind Angle Standard Deviation Calculation Method for the Unstable Surface Boundary Layer.

    DTIC Science & Technology

    1983-08-01

    UT C ILTOFT RUG 63 UNCLASSIFIED DPG-TR -3 41 F6 4/ 2L .41 L5.04 1111LA. 1 1112.0- 11111 .5 ~ ?"IIIII 111111. MICROCOPY RESOLUTION TEST CHART NATIONAL ...equation (16). R-Fg = F1 + Fh (16) Swinbank (1964) tabulated R and F data taken at an open field near Kerang, Australia under a variety of weater ...Addressee Copies Di rector 1 National Oceanic and Atmospheric Administration Environmental Research Laboratories Boulder, CO 80302 Cooperative

  17. Spaceflight induces changes in the synaptic circuitry of the postnatal developing neocortex

    NASA Technical Reports Server (NTRS)

    DeFelipe, J.; Arellano, J. I.; Merchan-Perez, A.; Gonzalez-Albo, M. C.; Walton, K.; Llinas, R.

    2002-01-01

    The establishment of the adult pattern of neocortical circuitry depends on various intrinsic and extrinsic factors, whose modification during development can lead to alterations in cortical organization and function. We report the effect of 16 days of spaceflight [Neurolab mission; from postnatal day 14 (P14) to P30] on the neocortical representation of the hindlimb synaptic circuitry in rats. As a result, we show, for the first time, that development in microgravity leads to changes in the number and morphology of cortical synapses in a laminar-specific manner. In the layers II/III and Va, the synaptic cross-sectional lengths were significantly larger in flight animals than in ground control animals. Flight animals also showed significantly lower synaptic densities in layers II/III, IV and Va. The greatest difference was found in layer II/III, where there was a difference of 344 million synapses per mm(3) (15.6% decrease). Furthermore, after a 4 month period of re-adaptation to terrestrial gravity, some changes disappeared (i.e. the alterations were transient), while conversely, some new differences also appeared. For example, significant differences in synaptic density in layers II/III and Va after re-adaptation were no longer observed, whereas in layer IV the density of synapses increased notably in flight animals (a difference of 185 million synapses per mm(3) or 13.4%). In addition, all the changes observed only affected asymmetrical synapses, which are known to be excitatory. These results indicates that terrestrial gravity is a necessary environmental parameter for normal cortical synaptogenesis. These findings are fundamental in planning future long-term spaceflights.

  18. Shots ABLE to EASY. The First Five Tests of the BUSTER-JANGLE Series, 22 October - 5 November 1951.

    DTIC Science & Technology

    1982-06-22

    ONA-6024F UNCLASSIFIED ONACO -7-C-0473 F/O 1/3 NL m/I/IIIII iimmhhiiII,hI- Ehm "𔃻E/ - £S~- OWO~fS C fnvbe IVNO ,VN 18VHD IS31 NOJinl1OS36 AdOO8DIVY 97 JI...forces into retreat. The aggressor then established a line of strong defensive positions that resisted breakthrough by friendly forces using conventional

  19. US EPA, Pesticide Product Label, , 03/13/1968

    EPA Pesticide Factsheets

    2011-04-14

    ... '.liim4b Rla)j !It.'t, •• nh.' lr\\l~Jttt'nt;.i ,,~' th., ","I.III.I •• r..1 ('001 II\\'nn\\III" fl('the: ~Pl!\\r: 'Thi~ i"a It'blP''rary r"!l~i')n IInll IlIUIIU~Wm Il'Jt ... n • f~ EP t: LS l::lic ...

  20. A Review of the Literature on Memory Enhancement: The Potential and Relevance of Mnemotechnics for Military Training

    DTIC Science & Technology

    1979-12-01

    and Social Sciences j DecIIIII11179 Approved for public release, distribution unlimited. 80 7 10 0 2 1, 44 U. S. ARMY RESEARCH INSTITUTE FOR THE...REPORT DOCUMENTATION PAGE BEFORE COMPLETI FORM I. REPORT NUMBER 2 .GOVT ACCESSIN NO. 3. RCIPIENT’S CATALOG NUMBER Technical Report 436 4. TITLE (amd...potential for increasing military trainin8 eifectiveness and consequent operational proficiency is obvious. ( 2 ) A wide range of mnemotechnics currently

  1. US EPA, Pesticide Product Label, PYRENONE DAIRY ...

    EPA Pesticide Factsheets

    2011-04-14

    ... l'na~,I!\\1: - IC.q:lsh'lI·11 TI-hi.· ... l .... uf r,1l,rlt'ld Amt'r 1,'.11. [,.rIIPI".ll ~f_,1 'Ihl ... l'I".III.·1 r,'IIt.lllI:-> thluru(llI(1ro".IIIII.u-11 .111.1 Chll'lo.1 ,UI'II" ,HI"H;-I~ ...

  2. Spaceflight induces changes in the synaptic circuitry of the postnatal developing neocortex

    NASA Technical Reports Server (NTRS)

    DeFelipe, J.; Arellano, J. I.; Merchan-Perez, A.; Gonzalez-Albo, M. C.; Walton, K.; Llinas, R.

    2002-01-01

    The establishment of the adult pattern of neocortical circuitry depends on various intrinsic and extrinsic factors, whose modification during development can lead to alterations in cortical organization and function. We report the effect of 16 days of spaceflight [Neurolab mission; from postnatal day 14 (P14) to P30] on the neocortical representation of the hindlimb synaptic circuitry in rats. As a result, we show, for the first time, that development in microgravity leads to changes in the number and morphology of cortical synapses in a laminar-specific manner. In the layers II/III and Va, the synaptic cross-sectional lengths were significantly larger in flight animals than in ground control animals. Flight animals also showed significantly lower synaptic densities in layers II/III, IV and Va. The greatest difference was found in layer II/III, where there was a difference of 344 million synapses per mm(3) (15.6% decrease). Furthermore, after a 4 month period of re-adaptation to terrestrial gravity, some changes disappeared (i.e. the alterations were transient), while conversely, some new differences also appeared. For example, significant differences in synaptic density in layers II/III and Va after re-adaptation were no longer observed, whereas in layer IV the density of synapses increased notably in flight animals (a difference of 185 million synapses per mm(3) or 13.4%). In addition, all the changes observed only affected asymmetrical synapses, which are known to be excitatory. These results indicates that terrestrial gravity is a necessary environmental parameter for normal cortical synaptogenesis. These findings are fundamental in planning future long-term spaceflights.

  3. Differential effect of dark rearing on long-term potentiation induced by layer IV and white matter stimulation in rat visual cortex.

    PubMed

    Salami, M; Fathollahi, Y; Semnanian, S; Atapour, N

    2000-12-01

    In the earlier work, we showed that primed-burst stimulation (PBs) is an effective protocol to induce long-term potentiation (LTP) in layer II/III of adult rat visual cortex in vitro. In the present study, we investigated effects of dark rearing on potentiation of layer II/III responses to stimulation of layer IV or the underlying white matter in the visual cortex in vitro. Long-term potentiation was induced by PBs applied to white matter or layer IV of the cortex in light and dark reared rats. Regardless of the stimulation site, layer II/III field potentials consisted of two components. In general, the latency of responses in dark reared rats was shorter than that in light reared ones. Whereas PBs of layer IV produced LTP of two components in both the groups, that of white matter induced an appreciable potentiation of the second component in both groups and the first component only in dark reared rats. These results indicate that PBs of either white matter or layer IV can gain access to the modifiable synapses that are related to the second component of layer II/III responses in light and dark reared visual cortex, but accessibility of the modifiable synapses that are related to first component depends on the tetanization site. The dark rearing enhances accessibility of the modifiable synapses that are related to the first component following PBs of the white matter. It is suggested that the immaturity of inhibitory circuits and/or better function of excitatory ones in the visual cortex of dark reared rats may contribute to the enhanced accessibility of the first component.

  4. Recurrence and risk of progression to lower genital tract malignancy in women with high grade VAIN.

    PubMed

    Hodeib, Melissa; Cohen, Joshua G; Mehta, Sukrant; Rimel, B J; Walsh, Christine S; Li, Andrew J; Karlan, Beth Y; Cass, Ilana

    2016-06-01

    High-grade vaginal intraepithelial neoplasia (VAIN) II-III has a variable clinical course. Due to the rarity of VAIN, existing data on the efficacy of treatment, risk of recurrence and progression to carcinoma is limited. Our objective was to evaluate predictors of recurrent disease and describe the risk of progression to carcinoma. Under an IRB-approved protocol 42 patients with biopsy-proven VAIN II-III from 1995 to 2015 were retrospectively identified. Demographics, treatment, and clinical course were abstracted from medical records. Patients were followed with semi-annual colposcopy and biopsies at physician discretion. Standard statistical analyses were applied. Median patient age was 58years old (range 20-81). Median follow-up time was 45months (range 9-195). Management included excision (31%), laser ablation (33%), topical agents (19%), and observation (10%), with the following rates of recurrence: 38%, 43%, 75%, and 50% (p=0.26). 20 patients (48%) had recurrent or persistent disease during treatment follow-up. No specific primary treatment was significantly more effective in preventing recurrence. Recurrence of VAIN II-III occurred at a median of 17.4months (7-78months) from time of initial diagnosis. Five (12%) patients developed invasive cancer of the lower genital tract. Median time to cancer diagnosis was 64months (30 to 101months). Patients with VAIN II-III are at high risk of recurrence and progression, suggesting the need for ongoing evaluation with cytology and comprehensive colposcopy by a skilled specialist. There were no clear risk factors or histopathologic criteria which predicted recurrence or progression to cancer. Published by Elsevier Inc.

  5. Impact of Turbine Modulation on Variable-Cycle Engine Performance. Phase 4. Additional Hardware Design and Fabrication, Engine Modification, and Altitude Test. Part 3 B

    DTIC Science & Technology

    1974-12-01

    the follow- ing equation: Appendix A 7 mmmmma^ -—’■■ umtämmimmm -"^’■""-"-■ ’*■’—■ -■---■ii|-| ■ mini M ■ HWIWWWP^W—llnpipi^l^fPW—mil,mii|i|iiiii...Taaparatura HP Turbina mXat Tmparatura Cockpit Dlaplay Traporatuta (intarturbina Taaparatura) Prinary Exhaust plow Total Tanparatura Bypaaa Bxhauat Flow

  6. Algorithmic Approximation of Optimal Value Differential Stability Bounds in Nonlinear Programming,

    DTIC Science & Technology

    1981-08-01

    NCLASSIFIED RANO/PA6659 N IN *~4 112.0.0 ~11111,.. I32 111 IIIII 111111.25 MICROCOPY RESOLUTION TESI CHART NATIOt AL BJRLAU Of SIANDARD 1964 A * LEVEL 00 o pm...Sensitivity Analysis in Parametric Nonlinear Programming, Doctoral Dissertation, School of Engineering and Applied Science, The George Washington University...Differential Stability of the Optimal Value Function in Constrained Nonlinear Programing, Doctoral Disser- tation, School of Engineering and Applied

  7. [Role of myocardial micropump function in the pathogenesis of ischemic heart disease].

    PubMed

    Feketa, V P

    1996-01-01

    Myocardial vibrational activity examined in 40 patients with functional classes II-III coronary heart disease and in 20 apparently healthy individuals, which indirectly reflects the status of its micropump function has been studied by using a spectral analysis of the first heart sound. Inhibition of the micropump function of the myocardium with its higher oxygen demands has been found to substantially contribute to the pathogenesis of myocardial ischemia.

  8. Adjusted blood requirement index as indicator of failure to control acute variceal bleeding.

    PubMed

    Duvnjak, Marko; Barsić, Neven; Tomasić, Vedran; Virović Jukić, Lucija; Lerotić, Ivan; Pavić, Tajana

    2006-06-01

    To estimate the clinical value of adjusted blood requirement index (ABRI) in relation to other criteria for failure of variceal bleeding control proposed at Baveno consensus workshops and to evaluate ABRI as an early predictor of occurrence of other Baveno criteria and identification of possible predictors of unfavorable ABRI. We retrospectively analyzed the data on 60 patients admitted to the hospital due to acute variceal bleeding. Number of treatment failures according to Baveno II-III and Baveno IV definitions and criteria was compared. We tested the ABRI's predictability of other Baveno IV and Baveno II-III criteria. Logistic regression analysis was performed to ascertain independent variables that predict ABRI> or =0.75. Failure to control variceal bleeding occurred in 40 of 60 patients according to Baveno II-III criteria, and in 35 of 60 patients according to Baveno IV criteria. Excluding the criterion of "transfusion of 2 units of blood or more (over and above the previous transfusions)" and ABRI criterion, failure to control variceal bleeding was observed in 17 and 14 of 60 patients, respectively. Congruence of ABRI with other criteria was present in about two-thirds of the cases. ABRI> or =0.75 was associated with increased risk of positive other Baveno criteria, particularly modified Baveno II-III (odds ratio [OR] 4.10; 95% confidence interval [CI], 1.11-15.05) and Baveno IV without ABRI (OR 4.37; 95% CI, 1.04-18.28). Independent predictors of ABRI> or =0.75 identified in logistic regression analysis were male sex (P<0.001) and higher hematocrit values (P=0.004). We found low congruence between ABRI and other Baveno criteria and the incidence of treatment failure in our study was higher than the previously reported frequencies of early rebleeding. It seems that criteria related to the quantity of blood transfusions are not reliable indicators of treatment failure.

  9. Adjusted Blood Requirement Index as Indicator of Failure to Control Acute Variceal Bleeding

    PubMed Central

    Duvnjak, Marko; Baršić, Neven; Tomašić, Vedran; Virović Jukić, Lucija; Lerotić, Ivan; Pavić, Tajana

    2006-01-01

    Aim To estimate the clinical value of adjusted blood requirement index (ABRI) in relation to other criteria for failure of variceal bleeding control proposed at Baveno consensus workshops and to evaluate ABRI as an early predictor of occurrence of other Baveno criteria and identification of possible predictors of unfavorable ABRI. Methods We retrospectively analyzed the data on 60 patients admitted to the hospital due to acute variceal bleeding. Number of treatment failures according to Baveno II-III and Baveno IV definitions and criteria was compared. We tested the ABRI’s predictability of other Baveno IV and Baveno II-III criteria. Logistic regression analysis was performed to ascertain independent variables that predict ABRI≥0.75. Results Failure to control variceal bleeding occurred in 40 of 60 patients according to Baveno II-III criteria, and in 35 of 60 patients according to Baveno IV criteria. Excluding the criterion of “transfusion of 2 units of blood or more (over and above the previous transfusions)” and ABRI criterion, failure to control variceal bleeding was observed in 17 and 14 of 60 patients, respectively. Congruence of ABRI with other criteria was present in about two-thirds of the cases. ABRI≥0.75 was associated with increased risk of positive other Baveno criteria, particularly modified Baveno II-III (odds ratio [OR] 4.10; 95% confidence interval [CI], 1.11-15.05) and Baveno IV without ABRI (OR 4.37; 95% CI, 1.04-18.28). Independent predictors of ABRI≥0.75 identified in logistic regression analysis were male sex (P<0.001) and higher hematocrit values (P=0.004). Conclusion We found low congruence between ABRI and other Baveno criteria and the incidence of treatment failure in our study was higher than the previously reported frequencies of early rebleeding. It seems that criteria related to the quantity of blood transfusions are not reliable indicators of treatment failure. PMID:16758517

  10. Unusual Presentation of Hydatid Cyst in Breast with Magnetic Resonance Imaging Findings

    PubMed Central

    Koc, Ali; Vurdem, Umit Erkan; Karabiyik, Ozgur; Gumus, Ummugulsum Ozgul

    2017-01-01

    We report a case of 59-year-old woman with a painful left breast mass, compatible with types II-III hydatid cyst. Lesion was evaluated with mammography, ultrasound, computed tomography, and magnetic resonance imaging modalities. Magnetic resonance imaging had important diagnostic role with demonstrating characteristic features of the lesion and had capability of showing complications. Surgery also confirmed the diagnosis of a hydatid cyst. PMID:28167966

  11. A Study of Financial Management Training of Coast Guard Junior Officers in Command Afloat and Ashore.

    DTIC Science & Technology

    1980-12-01

    IIII.’."’II IEEE"o IIIIIIIIIII lllllllll, II...... II 11-1 1c 12-0 11111= 5-3- IIUI lill iiIII MICROCOPY RESOLUTION TESI CHART NATIONAL BURLAIJ OF...importance of financial management on tightening fiscal purse strings, this thesis will examine financial management as it is viewed and practiced by...general research by 16 the author has indicated that fiscal techniques utilizing operations research, statistical studies, computer applica- tion or

  12. US EPA, Pesticide Product Label, PYRIK 40 EMULSIFIABLE ...

    EPA Pesticide Factsheets

    2011-04-14

    ... 11'1,110 .. 111'11' 0' "f'.r" .• " I.· "',1;111.,1 II ~~" II,'I"II:}, .• J "ior .• lr·j "'1,"11110.' ,ltr 11"r·,r.! .• :r.' t lI"I~"dl\\ ", .. ... p" r, 101 fIJI .IPI.hl,llt.,1I I" 11 .. l1d·lu",vr, ...

  13. Bd +60 73 = Igr J00370+6122

    NASA Astrophysics Data System (ADS)

    Negueruela, Ignacio; Reig, Pablo

    2004-05-01

    A classification spectrum of BD +60 73, reported to be the optical counterpart to IGR J00370+6122 (ATel #281), was taken on the night of 2003 July 7th with the 2.5-m Issac Newton telescope at La Palma. The derived spectral type is BN0.5II-III, where the composite luminosity class indicates an intermediate luminosity. The Nitrogen enhancement is moderately high, with numerous NII lines being rather stronger than corresponds to the spectral type.

  14. Comparative study of postoperative morbidity in dental treatment under general anesthesia in pediatric patients with and without an underlying disease.

    PubMed

    Escanilla-Casal, Alejandro; Ausucua-Ibáñez, Martina; Aznar-Gómez, Mireia; Viaño-García, José M; Sentís-Vilalta, Joan; Rivera-Baró, Alejandro

    2016-03-01

    To identify and quantify the variables and their influence on postoperative morbidity in dental treatment under general anesthesia (GA) in pediatric patients with and without an underlying disease. A prospective, descriptive, and comparative analysis was conducted of healthy (n = 49) and disabled/medically compromised (n = 81) children treated under GA. Intra-/post-surgical, clinical epidemiology, technical, care-related, and pharmacologic data were gathered, as were postoperative complications. The average age of ASA I patients (6.7 ± 4.4 years) was younger than that of ASA II-III patients (9.0 ± 4.5 years). Average hospitalization time was 4.27 ± 6.5 h in ASA I and 7.41 ± 6.8 h in ASA II-III. Significant differences were found between the two groups in fillings, pulpotomies, oral surgery, and scaling. Postoperative morbidity in ASA I and ASA II-III was similar both in frequency and severity and decreased during the first 72 h. The most common complication in both groups was toothache. Postoperative morbidity is high after dental treatment under GA, but it is not higher in disabled/medically compromised patients. © 2015 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Statewide land cover derived from multiseasonal Landsat TM data: A retrospective of the WISCLAND project

    USGS Publications Warehouse

    Reese, H.M.; Lillesand, T.M.; Nagel, D.E.; Stewart, J.S.; Goldmann, R.A.; Simmons, T.E.; Chipman, J.W.; Tessar, P.A.

    2002-01-01

    Landsat Thematic Mapper (TM) data were the basis in production of a statewide land cover data set for Wisconsin, undertaken in partnership with U.S. Geological Survey's (USGS) Gap Analysis Program (GAP). The data set contained seven classes comparable to Anderson Level I and 24 classes comparable to Anderson Level II/III. Twelve scenes of dual-date TM data were processed with methods that included principal components analysis, stratification into spectrally consistent units, separate classification of upland, wetland, and urban areas, and a hybrid supervised/unsupervised classification called "guided clustering." The final data had overall accuracies of 94% for Anderson Level I upland classes, 77% for Level II/III upland classes, and 84% for Level II/III wetland classes. Classification accuracies for deciduous and coniferous forest were 95% and 93%, respectively, and forest species' overall accuracies ranged from 70% to 84%. Limited availability of acceptable imagery necessitated use of an early May date in a majority of scene pairs, perhaps contributing to lower accuracy for upland deciduous forest species. The mixed deciduous/coniferous forest class had the lowest accuracy, most likely due to distinctly classifying a purely mixed class. Mixed forest signatures containing oak were often confused with pure oak. Guided clustering was seen as an efficient classification method, especially at the tree species level, although its success relied in part on image dates, accurate ground troth, and some analyst intervention. ?? 2002 Elsevier Science Inc. All rights reserved.

  16. Plasma melatonin is reduced in Huntington's disease.

    PubMed

    Kalliolia, Eirini; Silajdžić, Edina; Nambron, Rajasree; Hill, Nathan R; Doshi, Anisha; Frost, Chris; Watt, Hilary; Hindmarsh, Peter; Björkqvist, Maria; Warner, Thomas T

    2014-10-01

    This study was undertaken to determine whether the production of melatonin, a hormone regulating sleep in relation to the light/dark cycle, is altered in Huntington's disease. We analyzed the circadian rhythm of melatonin in a 24-hour study of cohorts of control, premanifest, and stage II/III Huntington's disease subjects. The mean and acrophase melatonin concentrations were significantly reduced in stage II/III Huntington's disease subjects compared with controls. We also observed a nonsignificant trend toward reduced mean and acrophase melatonin in premanifest Huntington's disease subjects. Onset of melatonin rise was significantly more temporally spread in both premanifest and stage II/III Huntington's disease subjects compared with controls. A nonsignificant trend also was seen for reduced pulsatile secretion of melatonin. Melatonin concentrations are reduced in Huntington's disease. Altered melatonin patterns may provide an explanation for disrupted sleep and circadian behavior in Huntington's disease, and represent a biomarker for disease state. Melatonin therapy may help the sleep disorders seen in Huntington's disease.

  17. Cannabinoid-Induced Changes in the Activity of Electron Transport Chain Complexes of Brain Mitochondria.

    PubMed

    Singh, Namrata; Hroudová, Jana; Fišar, Zdeněk

    2015-08-01

    The aim of this study was to investigate changes in the activity of individual mitochondrial respiratory chain complexes (I, II/III, IV) and citrate synthase induced by pharmacologically different cannabinoids. In vitro effects of selected cannabinoids on mitochondrial enzymes were measured in crude mitochondrial fraction isolated from pig brain. Both cannabinoid receptor agonists, Δ(9)-tetrahydrocannabinol, anandamide, and R-(+)-WIN55,212-2, and antagonist/inverse agonists of cannabinoid receptors, AM251, and cannabidiol were examined in pig brain mitochondria. Different effects of these cannabinoids on mitochondrial respiratory chain complexes and citrate synthase were found. Citrate synthase activity was decreased only by Δ(9)-tetrahydrocannabinol and AM251. Significant increase in the complex I activity was induced by anandamide. At micromolar concentration, all the tested cannabinoids inhibited the activity of electron transport chain complexes II/III and IV. Stimulatory effect of anandamide on activity of complex I may participate on distinct physiological effects of endocannabinoids compared to phytocannabinoids or synthetic cannabinoids. Common inhibitory effect of cannabinoids on activity of complex II/III and IV confirmed a non-receptor-mediated mechanism of cannabinoid action on individual components of system of oxidative phosphorylation.

  18. Test-retest reliability of the 20-sec Wingate test to assess anaerobic power in children with cerebral palsy.

    PubMed

    Dallmeijer, Annet J; Scholtes, Vanessa A B; Brehm, Merel-Anne; Becher, Jules G

    2013-09-01

    The aim of this study was to determine the test-retest reliability of the 20-sec Wingate anaerobic test in children with cerebral palsy. Participants were 22 ambulant children with cerebral palsy, with Gross Motor Function Classification System levels I (limitations in advanced motor skills, n = 11), II (limitations in walking, n = 7), and III (walking with walking aids, n = 4), aged 7-13 yrs. All children performed two 20-sec full-out sprint tests on a bicycle ergometer within 1-3 wks. Mean power and peak power (W/kg) were calculated as an estimate of anaerobic power. Test-retest reliability was determined by calculating the intraclass correlation coefficient (ICC) and standard error of measurement (SEM). Values were shown for the total group and Gross Motor Function Classification System I and II/III separately. The test-retest reliability of mean power output was excellent for children with Gross Motor Function Classification System level I (ICC, 0.96; SEM, 5.4%) and II/III (ICC, 0.99; SEM, 6.1%). Peak power output showed a lower reliability in both Gross Motor Function Classification System I (ICC, 0.87; SEM, 9.4%) and II/III (ICC, 0.96; SEM, 11.7%). Anaerobic testing using a 20-sec Wingate bicycle test is reliable in ambulant school-aged children with cerebral palsy.

  19. [Primary risk of hemorrhage due to esophageal varices in cirrhotic patients: significance of the associated endoscopic signs and hepatic functional reserve].

    PubMed

    Jmelnitzky, A; Palazzolo, A; Viola, L; Landoni, N; Morgante, P; Chopita, N; Romero, G; Giulioni, P

    1991-01-01

    Significance of endoscopic findings associated to esophageal varices (Japanese Research Society for Portal Hypertension) and hepatic dysfunction (Child-Pough classification) as predictive factors of variceal bleeding in cirrhotic patients is analyzed. In a cooperative prospective experience 137 cirrhotic patients with esophageal varices were examined in the period May 1987/89: 83 out of them had never bled from their varices (VENS group) while 54 recently had (VES group). A highly significative association was found between variceal size over 3 mm (grade II-III) and bleeding: 96.3% vs. 34.9% in VENS group (p = 0.01); similar association was found with regard to endoscopic detection of "red signs": 92.6% in bleeding group vs. 20.5% in VENS one (p = 0.01). "Red signs" were found on grade II-III varices in 98.5% of cases, and this association were related to variceal bleeding in 75.5%. Hepatic dysfunction was not directly related to bleeding episodes but "red signs" endoscopic detection in VENS group increased with liver function deterioration: 9.1% in Child A class, 27.3% in Child B, and 41.2% in Child C (p = 0.01). The strong association founded between bleeding and both grade II-III variceal size and "red signs" detection, suggest the possibility to identify a high risk group of cirrhotic patients candidate to prophylactic methodologies.

  20. Perceived Interpersonal Mistreatment Among Obese Americans: Do Race, Class, and Gender Matter?

    PubMed Central

    Carr, Deborah; Jaffe, Karen J.; Friedman, Michael A.

    2010-01-01

    Objective: We examine the extent to which body weight affects three types of perceived interpersonal mistreatment, and evaluate whether these patterns vary by race, social class, and gender in a large sample of American men and women. Methods and Procedures: We use data from the first wave (1995) of the Midlife Development in the United States (N = 3,511), a survey of persons aged 25–74, to contrast underweight, normal weight, overweight, obese I, and obese II/III persons' reports of three types of perceived interpersonal mistreatment: disrespectful treatment; harassment/teasing; and being treated as if one has a character flaw. We assess whether these relationships are contingent upon one's gender, race, and occupational status. We control for possible confounding influences, including physical and mental health. Results: In the total sample, obese I and obese II/III persons report significantly higher levels of all three types of perceived mistreatment (compared to normal weight persons), even when demographic, socioeconomic status, and health characteristics are controlled. Among black men, however, obese II/III persons report significantly lower levels of all three types of perceived mistreatment, compared to their normal weight peers. Among both men and women, obese professional workers report significantly more perceived interpersonal mistreatment, compared to obese persons of lower socioeconomic status. Discussion: These findings reveal the ways that intersecting social identities may shape obese Americans' perceptions of stigmatizing interpersonal encounters. PMID:18978765

  1. Perceived interpersonal mistreatment among obese Americans: do race, class, and gender matter?

    PubMed

    Carr, Deborah; Jaffe, Karen J; Friedman, Michael A

    2008-11-01

    We examine the extent to which body weight affects three types of perceived interpersonal mistreatment, and evaluate whether these patterns vary by race, social class, and gender in a large sample of American men and women. We use data from the first wave (1995) of the Midlife Development in the United States (N = 3,511), a survey of persons aged 25-74, to contrast underweight, normal weight, overweight, obese I, and obese II/III persons' reports of three types of perceived interpersonal mistreatment: disrespectful treatment; harassment/teasing; and being treated as if one has a character flaw. We assess whether these relationships are contingent upon one's gender, race, and occupational status. We control for possible confounding influences, including physical and mental health. In the total sample, obese I and obese II/III persons report significantly higher levels of all three types of perceived mistreatment (compared to normal weight persons), even when demographic, socioeconomic status, and health characteristics are controlled. Among black men, however, obese II/III persons report significantly lower levels of all three types of perceived mistreatment, compared to their normal weight peers. Among both men and women, obese professional workers report significantly more perceived interpersonal mistreatment, compared to obese persons of lower socioeconomic status. These findings reveal the ways that intersecting social identities may shape obese Americans' perceptions of stigmatizing interpersonal encounters.

  2. Rotigotine in Combination with the MAO-B Inhibitor Selegiline in Early Parkinson’s Disease: A Post Hoc Analysis

    PubMed Central

    Giladi, Nir; Asgharnejad, Mahnaz; Bauer, Lars; Grieger, Frank; Boroojerdi, Babak

    2016-01-01

    Background: Monoamine oxidase B (MAO-B) inhibitors and dopamine receptor agonists are common first-line treatment options in early Parkinson’s disease (PD). Objective: To evaluate the efficacy and safety of rotigotine transdermal patch as an add-on therapy to an MAO-B inhibitor in patients with early-PD. Methods: In two Phase III, randomized, double-blind, placebo-controlled studies in early-PD (SP512, SP513), patients were randomized to rotigotine (titrated to optimal dose ≤8 mg/24 h) or placebo, and maintained for 24 (SP512) or 33 (SP513) weeks. Post hoc analyses were performed on pooled data for patients receiving an MAO-B inhibitor (selegiline) at a stable dose at randomization and throughout the studies, with groups defined as “Selegiline+Rotigotine” and “Selegiline+Placebo”. Outcome measures included change from baseline in Unified Parkinson’s Disease Rating Scale (UPDRS) II (activities of daily living), III (motor), UPDRS II+III and responders (patients achieving ≥20%, ≥25% or ≥30% decrease in UPDRS II+III). As post hoc analyses, p-values are exploratory. Results: 130 patients were evaluable for efficacy analyses (“Selegiline+Rotigotine”: 84, “Selegiline+Placebo”: 46). Combined treatment with rotigotine and selegiline improved UPDRS III and UPDRS II+III scores versus selegiline alone (LS-mean [95% CI] treatment difference for UPDRS III: –4.89 [–7.87 to –1.91], p = 0.0015; for UPDRS II+III: –5.76 [–9.71 to –1.82], p = 0.0045). Higher proportion of patients in the “Selegiline+Rotigotine” group were classified as ≥20%, ≥25% or ≥30% responders (all p < 0.001). Combined treatment appeared more effective in patients aged ≤65 years versus > 65 years (although patient numbers in the subgroups were low). Adverse event profile was consistent with the known safety profile of rotigotine. Conclusions: In these post hoc analyses, adjunctive treatment with rotigotine in patients already receiving an

  3. [Three dimensional reconstruction and measurement of the proximal femur in adult developmental dysplasia of the hip].

    PubMed

    Liu, Shuanglu; Liu, Lanbo; Zuo, Jianlin; Xiao, Jianlin; Yang, Yuhui; Gao, Zhongli

    2016-04-01

    To investigate characteristics and the differences of the anatomical parameters of the proximal femur of the developmental dysplasia of the hip (DDH). A total of 38 patients(47 hips) diagnosed as DDH with CT scan data and the pelvis radiograph from January 2012 to December 2014 in China-Japan Union Hospital of Jilin University were retrospectively analyzed. All the hips were divided into 3 groups according to Crowe classification method. Thirty normal hips were selected as controls who admitted at the same time. CT data of the patients were imported into Mimics 17.0. The three-dimensional models of the proximal femur were then reconstructed, and the following parameters were measured: neck-shaft angle, neck length, offset, height of the centre of femoral head, height of the isthmus, height of greater trochanter, the medullary canal diameter of isthmus (Di), the medullary canal diameter 10 mm above the apex of the lesser trochanter (DT+ 10), the medullary canal diameter 20 mm below the apex of the lesser trochanter (DT-20), and then DT+ 10/Di, DT-20/Di and DT+ 10/DT-20 were calculated.Variance discrepancy analysis was used to compare the difference among the four groups, and LSD method was used to compare the difference between either two groups. The parameters of neck-shaft angle of DDH with Crowe I, Crowe II-III, Crowe IV and the control group were (131.8°±7.1°), (131.7°±6.5°), (122.8°±11.4°) and (131.8°±5.9°), respectively; the parameters of neck-shaft angle of DDH with Crowe IV was smaller than that of DDH with Crowe I, Crowe II-III and control group (all P<0.05). The parameters of the neck length of DDH with Crowe IV ((44.6±6.6) mm) was smaller than that of DDH with Crowe I ((48.6±6.7) mm), Crowe II-III ((50.4±4.7) mm) (all P<0.05). There is no statistic difference in the offset among the groups (F=2.392, P>0.05). The parameters of the height of greater trochanter of DDH with Crowe IV ((12.1±6.1) mm) was bigger than that of DDH with Crowe I ((8

  4. Layer I neurons of rat neocortex. I. Action potential and repetitive firing properties.

    PubMed

    Zhou, F M; Hablitz, J J

    1996-08-01

    1. Whole cell patch-clamp techniques, combined with direct visualization of neurons, were used to study action potential (AP) and repetitive firing properties of layer I neurons in slices of rat neocortex. 2. Layer I neurons had resting membrane potentials (RMP) of -59.8 +/- 4.7 mV (mean +/- SD) and input resistances (RN) of 592 +/- 284 M Omega. Layer II/III pyramidal neurons had RMPs and RNs of -61.5 +/- 5.6 mV and 320 +/- 113 M omega, respectively. A double exponential function was needed to describe the charging curves of both neuron types. In layer I neurons, tau(0) was 45 +/- 22 ms and tau(1) was 5 +/- 3.3 ms whereas in layer II/III pyramidal neurons, tau(0) was 41 +/- 11 ms and tau(1) was 3 +/- 2.6 ms. Estimates of specific membrane resistance (Rm) for layer I and layer II/III cells were 45 +/- 22 and 41 +/- 11 k omega cm2, respectively (Cm was assumed to be 1 microF/cm2). 3. AP threshold was -41 +/- 2 mV in layer I neurons. Spike amplitudes, measured from threshold to peak, were 90.6 +/- 7.7 mV. AP durations, measured both at the base and half maximal amplitude, were 2.5 +/- 0.4 and 1.1 +/- 0.2 ms, respectively. AP 10-90% rise and repolarization times were 0.6 +/- 0.1 and 1.1 +/- 0.2 ms, respectively. In layer II/III pyramidal neurons, AP threshold was -41 +/- 2.5 mV and spike amplitude was 97 +/- 9.7 mV. AP duration at base and half maximal amplitude was 5.4 +/- 1.1 ms and 1.8 +/- 0.2 ms, respectively. AP 10-90% rise and decay times were 0.6 +/- 0.1 ms and 2.8 +/- 0.6 ms, respectively. 4. Layer I neurons were fast spiking cells that showed little frequency adaptation, a large fast afterhyperpolarization (fAHP), and no slow afterhyperpolarization (sAHP). Some cells had a medium afterhyperpolarization (mAHP) and a slow afterdepolarization (sADP). All pyramidal cells in layer II/III and "atypical" pyramidal neurons in upper layer II showed regular spiking behavior, prominent frequency adaptation, and marked sAHPs. 5. In both layer I neurons and layer II/III

  5. DISTINCT COPY NUMBER ALTERATIONS AND INCIDENCE OF CHROMOTHRIPSIS ASSOCIATED WITH GRADE AND PROGNOSIS IN IDH MUTANT AND WILD-TYPE GLIOMAS

    PubMed Central

    Colman, Howard; Cohen, Adam; Aldape, Ken; Sato, Mariko; Mason, Clint; Diefes, Kristin; Heathcock, Lindsey; Abegglen, Lisa; Shrieve, Dennis; Couldwell, William; Schiffman, Joshua

    2014-01-01

    BACKGROUND: Both IDH mutated (IDHmut) and wild-type (IDHwt) lower grade gliomas can progress to GBM. However, a detailed study of alterations associated with progression of these molecularly distinct tumor types has not been described. Here we perform an analysis of copy number alterations (CNA) across all grades (Grade II-II and Grade IV) IDHmut vs IDHwt infiltrating gliomas. METHODS: DNA was extracted from 94 patient FFPE glioma samples from 4 clinical and molecular groups: Grade II-III IDHwt (n = 17), Grade II-III IDHmut (n = 28), Grade IV IDHwt (n = 25), and Grade IV IDHmut (n = 24). CNA were detected by molecular inversion probes (OncoScan FFPE Express, Affymetrix) and analyzed with Nexus Copy Number Software (BioDiscovery). GISTIC was used to define deletions and amplifications. Chromothripsis (“chromosomal shattering”) was defined using stringent criteria of at least ten switches of CNA in individual chromosomes. RESULTS: Unsupervised clustering of CNAs demonstrated distinct clusters within IDHmut gliomas that correlated with grade. However, within IDHwt gliomas all grades clustered together regardless of grade, with Chr7 amplification (including EGFR) and loss of Chr10 (including PTEN) seen in most tumors. IDHwt Grade II-III and Grade IV tumors both displayed relatively poor prognosis (median survivals of 65.4 and 37.4 weeks). However, IDHmut gliomas had better survival for all grades (604.3 weeks for Grade II-III and 270.3 weeks for Grade IV). Grade IV IDHmut gliomas were more likely to have gains of 1q25.3 (SMG7, NCF2), 1q32.1 (KIF14, DDX59, BTG2), 6p21.1 (HSP90AB1 and other genes) and loss of 3p21 compared with Grade II-III. Functional analyses showed that IDHwt tumors had more amplifications in receptor tyrosine kinases and their downstream pathways. In terms of novel prognostic markers within IDHmut Grade II-III tumors, multivariate analysis identified loss of estrogen receptor B and loss of 10q26.3 containing part of GLRX3 as poor prognostic

  6. Cervical neoplasia after diagnosis and follow-up of women with atypical squamous cells of undetermined significance.

    PubMed

    Murta, E F C; Da Silva, C S; Vieira, J B; Khabbaz, K M; Adad, S J

    2007-01-01

    Although the cytological finding of atypical squamous cells of undetermined significance (ASCUS) occurs in around 5% of women undergoing cytological screening, the clinical evolution is unknown. The objective of this study was to evaluate women with a diagnosis of ASCUS and compare the histological findings and clinical evolution over six and 12 months. 1244 patients with ASCUS (two diagnostic cytologists) were evaluated in this study with Pap Smears and colposcopy (biopsy if necessary) at the first visit, and thereafter at second and third visits (6 and 12 months after the first visit). Comparisons were made between cytological findings and histological diagnoses at every visit during the study and during evolution. At the first visit, 60.3% of the biopsied patients presented histological findings of CIN I, 17.46% CIN II/III and 6.3% invasive neoplasia. At the second visit, 48.3% of the biopsied patients presented CIN I, 24.1% CIN II/III and none invasive neoplasia. At the third visit, 68.9% of the biopsied patients presented CIN I, 13.8% CIN II/III and none invasive carcinoma. If we consider all visits, a total of 213 colposcopy-guided biopsies were performed, representing 17.1% of all the patients included. Of these, 164 (13.2%) presented a histological diagnosis of cervical intraepithelial neoplasia (CIN) and eight (0.6%) presented with invasive carcinoma. We conclude that CIN or invasive lesions frequently occur in women with a diagnosis of ASCUS. Immediate review of the thin sections, new cytological tests or colposcopy and rigorous follow-up should be considered when making a diagnosis of ASCUS.

  7. Extended-release pramipexole in advanced Parkinson disease: a randomized controlled trial.

    PubMed

    Schapira, Anthony H V; Barone, P; Hauser, R A; Mizuno, Y; Rascol, O; Busse, M; Salin, L; Juhel, N; Poewe, W

    2011-08-23

    In advanced Parkinson disease (PD), immediate-release pramipexole, taken 3 times daily, improves symptoms and quality of life. A once-daily extended-release formulation may be an effective and simple alternative therapy. For a multicenter randomized, double-blind, parallel trial of extended- and immediate-release pramipexole vs placebo, patients experiencing motor fluctuations while taking levodopa underwent flexible study drug titration and then maintenance at optimized dosage (0.375-4.5 mg/day). The primary endpoint was a change in the Unified Parkinson's Disease Rating Scale (UPDRS) part II+III score at 18 weeks, with further assessments at 33 weeks in a subset of patients. Adverse events were recorded throughout. Among 507 patients in the 18-week analyses, UPDRS II+III scores decreased (from baseline means of 40.0-41.7) by an adjusted mean of -11.0 for extended-release pramipexole and -12.8 for immediate-release pramipexole vs -6.1 for placebo (p = 0.0001 and p < 0.0001) and off-time decreased (from baseline means of 5.8-6.0 hours/day) by an adjusted mean of -2.1 and -2.5 vs -1.4 hours/day (p = 0.0199 and p < 0.0001). Other outcomes were largely corroborative, including a significant improvement in early morning off symptoms. Among 249 pramipexole patients completing 33 weeks, UPDRS II+III and off-time findings showed ≤10.1% change from 18-week values. Both formulations were well-tolerated. Extended-release pramipexole significantly improved UPDRS score and off-time compared with placebo, with similar efficacy, tolerability, and safety of immediate-release pramipexole compared with placebo. This study provides Class I evidence that the extended-release form of pramipexole, taken once daily, is efficacious as an adjunct to levodopa in advanced PD.

  8. Extended-release pramipexole in early Parkinson disease: a 33-week randomized controlled trial.

    PubMed

    Poewe, W; Rascol, O; Barone, P; Hauser, R A; Mizuno, Y; Haaksma, M; Salin, L; Juhel, N; Schapira, A H V

    2011-08-23

    To assess the clinical efficacy of a novel once-daily extended-release (ER) formulation of the dopamine agonist pramipexole as monotherapy in patients with early Parkinson disease (PD) and establish its noninferiority vs standard immediate-release (IR) pramipexole. This was a multicenter, double-blind, parallel study of patients with early PD not receiving levodopa or dopamine agonists, randomly assigned to pramipexole IR, pramipexole ER, or placebo. Seven-week flexible titration was followed by 26-week maintenance, with levodopa permitted as rescue medication. The primary analysis was to test pramipexole ER noninferiority to pramipexole IR based on a change in the Unified Parkinson's Disease Rating Scale (UPDRS) part II+III score at 33 weeks, with noninferiority predefined as a treatment group difference for which the lower bound of the 95% confidence interval (CI) did not exceed -3 points. Among 213 ER and 207 IR recipients, the adjusted mean 33-week UPDRS II+III change (excluding levodopa rescue effects) was -8.2 for ER and -8.7 for IR, a difference of -0.5 with a 95% CI of -2.3 to 1.3. Compared with placebo (n = 103), pramipexole ER and pramipexole IR were significantly superior on UPDRS II+III score, all key secondary outcomes, and almost all other endpoints. On the 39-item Parkinson Disease Questionnaire, superiority of pramipexole ER failed to reach statistical significance. Both formulations were equally safe and well-tolerated. As monotherapy for early PD, pramipexole ER was noninferior to pramipexole IR and significantly more effective than placebo. Tolerability and safety did not differ between the formulations. This study provides Class I evidence that pramipexole ER is not inferior to pramipexole IR in patients with early PD.

  9. ZEB1 expression is increased in IDH1-mutant lower-grade gliomas.

    PubMed

    Nesvick, Cody L; Zhang, Chao; Edwards, Nancy A; Montgomery, Blake K; Lee, Michaela; Yang, Chunzhang; Wang, Herui; Zhu, Dongwang; Heiss, John D; Merrill, Marsha J; Ray-Chaudhury, Abhik; Zhuang, Zhengping

    2016-10-01

    Transcription factors that induce epithelial-mesenchymal transition (EMT) promote invasion, chemoresistance and a stem-cell phenotype in epithelial tumors, but their roles in central nervous system tumors are not well-understood. We hypothesized these transcription factors have a functional impact in grades II-III gliomas. Using the National Cancer Institute (NCI) Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the Cancer Genome Atlas (TCGA) Lower-Grade Glioma (LGG) data, we determined the impact of EMT-promoting transcription factors (EMT-TFs) on overall survival in grades II-III gliomas, compared their expression across common genetic subtypes and subsequently validated these findings in a set of 31 tumors using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. Increased expression of the gene coding for the transcriptional repressor Zinc Finger E box-binding Homeobox 1 (ZEB1) was associated with a significant increase in overall survival (OS) on Kaplan-Meier analysis. Genetic subtype analysis revealed that ZEB1 expression was relatively increased in IDH1/2-mutant gliomas, and IDH1/2-mutant gliomas expressed significantly lower levels of many ZEB1 transcriptional targets. Similarly, IDH1/2-mutant tumors expressed significantly higher levels of targets of microRNA 200C (MIR200C), a key regulator of ZEB1. In a validation study, ZEB1 mRNA was significantly increased in IDH1-mutant grades II-III gliomas, and ZEB1 protein expression was more pronounced in these tumors. Our findings demonstrate a novel relationship between IDH1/2 mutations and expression of ZEB1 and its transcriptional targets. Therapy targeting ZEB1-associated pathways may represent a novel therapeutic avenue for this class of tumors.

  10. Cell-cycle and suppressor proteins expression in uterine cervix in HIV/HPV co-infection: comparative study by tissue micro-array (TMA)

    PubMed Central

    Nicol, Alcina F; Pires, Andréa Rodrigues Cordovil; de Souza, Simone R; Nuovo, Gerard J; Grinsztejn, Beatriz; Tristão, Aparecida; Russomano, Fabio B; Velasque, Luciane; e Silva, José R Lapa; Pirmez, Claude

    2008-01-01

    Background The oncoproteins of human papillomavirus (HPVs) directly effect cell-cycle control. We hypothesize that regulatory and cell cycle protein expression might be additionally modified in the cervix of HIV/HPV co-infected women. Methods We analyzed the expression of Rb, p27, VEGF and Elf-1 transcriptor factor by immunohistochemistry in 163 paraffin-embeded cervical samples using Tissue Micro-Array (TMA) and correlated this to HIV-1 and HPV infection. Results HIV/HPV co-infection was associated with a significant increase in expression (p < 0.001) of VEGF and p27 in both low and high grade CIN when compared to the cervices of women infected by HPV alone. Decreased Rb expression was evident with increased CIN grade in the cervices of women infected with HPV alone (p = 0.003 average of cells/mm2 in CIN I: 17.9, CIN II/III: 4.8, and tumor 3.9). Rb expression increased 3-fold for both low and high grade CIN with HPV/HIV-1 co-infection compared to HPV infection alone but did not reach statistical significance. There was a significant increase in Elf-1 expression in HPV+/HIV- women with CIN II/III and tumor (average of cells/mm2 in CIN I: 63.8; CIN II/III: 115.7 and tumor: 112.0, p = 0.005), in comparison to controls. Conclusion Co-infection of HPV and HIV leads to significant increase in the VEGF and p27 expression when compared to HPV+/HIV-negative infection that could facilitate viral persistence and invasive tumor development. PMID:18840277

  11. De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer

    PubMed Central

    2012-01-01

    Background MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. Methods The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers. Results More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients. Conclusions Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications. PMID:22400902

  12. A Metabolic Study of Huntington's Disease.

    PubMed

    Nambron, Rajasree; Silajdžić, Edina; Kalliolia, Eirini; Ottolenghi, Chris; Hindmarsh, Peter; Hill, Nathan R; Costelloe, Seán J; Martin, Nicholas G; Positano, Vincenzo; Watt, Hilary C; Frost, Chris; Björkqvist, Maria; Warner, Thomas T

    2016-01-01

    Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III) and controls. Control (n = 15), premanifest (n = 14) and stage II/III (n = 13) participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a), fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test. We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington's disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine) there is a suggestion (p values between 0.02 and 0.05) that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious. Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington's disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington's disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that the majority

  13. Association between geographic access to cancer care and receipt of radiation therapy for rectal cancer

    PubMed Central

    Lin, Chun Chieh; Bruinooge, Suanna S.; Kirkwood, M. Kelsey; Hershman, Dawn L.; Jemal, Ahmedin; Guadagnolo, B. Ashleigh; Yu, James B.; Hopkins, Shane; Goldstein, Michael; Bajorin, Dean; Giordano, Sharon H.; Kosty, Michael; Arnone, Anna; Hanley, Amy; Stevens, Stephanie; Olsen, Christine

    2016-01-01

    Purpose Trimodality therapy (chemoradiation and surgery) is standard of care for Stage II/III rectal cancer but nearly one third of patients do not receive radiation therapy (RT). We examined the relationship between density of radiation oncologist and travel distance to receipt of RT. Materials/Methods A retrospective study based on the National Cancer Data Base identified 26,845 patients aged 18–80 with Stage II/III rectal cancer diagnosed between 2007–2010. Radiation oncologists were identified through Physician Compare Dataset. Generalized Estimating Equations clustering by Hospital Service Area was utilized to examine the association between geographic access and receipt of RT, controlling for patient sociodemographic and clinical characteristics. Results 70% of patients received RT within 180 days of diagnosis or within 90 days of surgery. Compared to travel distance <12.5 miles, patients diagnosed at reporting facility who traveled ≥50 miles had a decreased likelihood of receipt of RT (50–249 miles: adjusted Odds Ratio [aOR] 0.75, p<.001; ≥250 miles: aOR 0.46, p=.002), all else being equal. Density level of radiation oncologists was not significantly associated with receipt of RT. Patients who were female, nonwhites, ≥50 years, and with comorbidities were less likely to receive RT (p<.05). Patients who were uninsured but self-paid for their medical services, initially diagnosed elsewhere but treated at reporting facility, and resided in Midwest had increased likelihood of receipt of RT (p<.05). Conclusions Increased travel burden was associated with a decreased likelihood of receiving RT for stage II/III rectal cancer patients when all else being equal, but radiation oncologist density was not. Further research in geographic access and establishing transportation assistance programs, or lodging services for patients with unmet need may help decrease geographic barriers and improve the quality of rectal cancer care. PMID:26972644

  14. Efficacy of Rotigotine at Different Stages of Parkinson’s Disease Symptom Severity and Disability: A Post Hoc Analysis According to Baseline Hoehn and Yahr Stage

    PubMed Central

    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

  15. Thyroglobulin From Molecular and Cellular Biology to Clinical Endocrinology

    PubMed Central

    2016-01-01

    Thyroglobulin (Tg) is a vertebrate secretory protein synthesized in the thyrocyte endoplasmic reticulum (ER), where it acquires N-linked glycosylation and conformational maturation (including formation of many disulfide bonds), leading to homodimerization. Its primary functions include iodide storage and thyroid hormonogenesis. Tg consists largely of repeating domains, and many tyrosyl residues in these domains become iodinated to form monoiodo- and diiodotyrosine, whereas only a small portion of Tg structure is dedicated to hormone formation. Interestingly, evolutionary ancestors, dependent upon thyroid hormone for development, synthesize thyroid hormones without the complete Tg protein architecture. Nevertheless, in all vertebrates, Tg follows a strict pattern of region I, II-III, and the cholinesterase-like (ChEL) domain. In vertebrates, Tg first undergoes intracellular transport through the secretory pathway, which requires the assistance of thyrocyte ER chaperones and oxidoreductases, as well as coordination of distinct regions of Tg, to achieve a native conformation. Curiously, regions II-III and ChEL behave as fully independent folding units that could function as successful secretory proteins by themselves. However, the large Tg region I (bearing the primary T4-forming site) is incompetent by itself for intracellular transport, requiring the downstream regions II-III and ChEL to complete its folding. A combination of nonsense mutations, frameshift mutations, splice site mutations, and missense mutations in Tg occurs spontaneously to cause congenital hypothyroidism and thyroidal ER stress. These Tg mutants are unable to achieve a native conformation within the ER, interfering with the efficiency of Tg maturation and export to the thyroid follicle lumen for iodide storage and hormonogenesis. PMID:26595189

  16. Thyroglobulin From Molecular and Cellular Biology to Clinical Endocrinology.

    PubMed

    Di Jeso, Bruno; Arvan, Peter

    2016-02-01

    Thyroglobulin (Tg) is a vertebrate secretory protein synthesized in the thyrocyte endoplasmic reticulum (ER), where it acquires N-linked glycosylation and conformational maturation (including formation of many disulfide bonds), leading to homodimerization. Its primary functions include iodide storage and thyroid hormonogenesis. Tg consists largely of repeating domains, and many tyrosyl residues in these domains become iodinated to form monoiodo- and diiodotyrosine, whereas only a small portion of Tg structure is dedicated to hormone formation. Interestingly, evolutionary ancestors, dependent upon thyroid hormone for development, synthesize thyroid hormones without the complete Tg protein architecture. Nevertheless, in all vertebrates, Tg follows a strict pattern of region I, II-III, and the cholinesterase-like (ChEL) domain. In vertebrates, Tg first undergoes intracellular transport through the secretory pathway, which requires the assistance of thyrocyte ER chaperones and oxidoreductases, as well as coordination of distinct regions of Tg, to achieve a native conformation. Curiously, regions II-III and ChEL behave as fully independent folding units that could function as successful secretory proteins by themselves. However, the large Tg region I (bearing the primary T4-forming site) is incompetent by itself for intracellular transport, requiring the downstream regions II-III and ChEL to complete its folding. A combination of nonsense mutations, frameshift mutations, splice site mutations, and missense mutations in Tg occurs spontaneously to cause congenital hypothyroidism and thyroidal ER stress. These Tg mutants are unable to achieve a native conformation within the ER, interfering with the efficiency of Tg maturation and export to the thyroid follicle lumen for iodide storage and hormonogenesis.

  17. EphA2 expression is a key driver of migration and invasion and a poor prognostic marker in colorectal cancer

    PubMed Central

    Blayney, Jaine K.; McArt, Darragh G.; Redmond, Keara L.; Weir, Jessica-Anne; Bradley, Conor A.; Sasazuki, Takehiko; Shirasawa, Senji; Wang, Tingting; Srivastava, Supriya; Ong, Chee Wee; Arthur, Ken; Salto-Tellez, Manuel; Wilson, Richard H.

    2015-01-01

    Purpose EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumour initiation, neo-vascularization and metastasis in a wide range of epithelial and mesenchymal cancers, however its role in colorectal cancer (CRC) recurrence and progression is unclear. Experimental Design EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumours (N=338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive CRC cell line models. Results Colorectal tumours displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III CRC tissues, in both univariate and multivariate analyses. Pre-clinically, we found that EphA2 was highly expressed in KRASMT CRC cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines and down-regulation of EphA2 using RNAi or recombinant EFNA1, suppressed migration and invasion of KRASMT CRC cells. Conclusions These data show that EpHA2 is a poor prognostic marker in stage II/III CRC, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. PMID:26283684

  18. Functional analysis of a frame-shift mutant of the dihydropyridine receptor pore subunit (alpha1S) expressing two complementary protein fragments.

    PubMed

    Ahern, C A; Vallejo, P; Mortenson, L; Coronado, R

    2001-01-01

    The L-type Ca2+ channel formed by the dihydropyridine receptor (DHPR) of skeletal muscle senses the membrane voltage and opens the ryanodine receptor (RyR1). This channel-to-channel coupling is essential for Ca2+ signaling but poorly understood. We characterized a single-base frame-shift mutant of alpha1S, the pore subunit of the DHPR, that has the unusual ability to function voltage sensor for excitation-contraction (EC) coupling by virtue of expressing two complementary hemi-Ca2+ channel fragments. Functional analysis of cDNA transfected dysgenic myotubes lacking alpha1S were carried out using voltage-clamp, confocal Ca2+ indicator fluoresence, epitope immunofluorescence and immunoblots of expressed proteins. The frame-shift mutant (fs-alpha1S) expressed the N-terminal half of alpha1S (M1 to L670) and the C-terminal half starting at M701 separately. The C-terminal fragment was generated by an unexpected restart of translation of the fs-alpha1S message at M701 and was eliminated by a M701I mutation. Protein-protein complementation between the two fragments produced recovery of skeletal-type EC coupling but not L-type Ca2+ current. A premature stop codon in the II-III loop may not necessarily cause a loss of DHPR function due to a restart of translation within the II-III loop, presumably by a mechanism involving leaky ribosomal scanning. In these cases, function is recovered by expression of complementary protein fragments from the same cDNA. DHPR-RyR1 interactions can be achieved via protein-protein complementation between hemi-Ca2+ channel proteins, hence an intact II-III loop is not essential for coupling the DHPR voltage sensor to the opening of RyR1 channel.

  19. Association of tibialis posterior tendon pathology with other radiographic findings in the foot: a case-control study.

    PubMed

    Shibuya, Naohiro; Ramanujam, Crystal L; Garcia, Glenn M

    2008-01-01

    The purpose of this study was to analyze the prevalence of spring ligament pathology and other radiographic changes related to flatfoot deformity in the presence of different degrees of tibialis posterior tendon pathology. A total of 72 patients (24 with tibialis posterior tendon abnormality and 48 sex- and age-matched controls) were evaluated for tibialis posterior tendon pathology, spring ligament pathology, and plain pedal radiographic angles, including cuboid abduction, talar declination, calcaneal inclination, and Meary's angles. The patients with tibialis posterior tendon pathology were subdivided into either minor (Type I) or severe (Type II/III), according to the Conti classification of tibialis posterior tendon pathology on MRI. All the continuous data of radiographic angles were dichotomized into either a flatfoot group or normal/cavus foot group. Associations between these nominal variables were analyzed. There was no association between Type I tibialis posterior tendon pathology and spring ligament pathologies (OR = 0.8, 95% CI = 0.15-4.65). Conversely, every patient with Type II/III tibialis posterior tendon pathology had spring ligament abnormality. Type II/III group also showed statistically significant associations with both increased talar declination angle (OR = 10.4, 95% CI = 1.62-109.22) and Meary's angle (OR = 7.5, 95% CI = 1.35-51.12), while no such associations were found with Type I tibialis posterior tendon pathology (OR = 1.0, 95% CI = 0.18-6.18 with talar declination angle; OR = 3.9, 95% CI = 0.65-27.71 with Meary's angle). In this investigation, only advanced tibialis posterior tendon pathology was statistically significantly associated with adult-acquired flatfoot deformity and spring ligament pathology.

  20. Multiple functional involvement of thymosin beta-4 in tooth germ development.

    PubMed

    Ookuma, Yukiko F; Kiyoshima, Tamotsu; Kobayashi, Ieyoshi; Nagata, Kengo; Wada, Hiroko; Fujiwara, Hiroaki; Yamaza, Haruyoshi; Nonaka, Kazuaki; Sakai, Hidetaka

    2013-02-01

    Thymosin beta-4 (Tβ4) is known to be ubiquitously involved in the actin monomer sequestering on the cytoskeleton. Our previous study showed specific temporal and special in situ expression pattern of Tβ4 mRNA in dental epithelial and mesenchymal cells in the developing tooth germ of the mouse lower first molar. In this study, we examined the functional implications of Tβ4 in the developmental course of the mouse lower first molar. An inhibition assay using Tβ4 antisense sulfur-substituted oligodeoxynucleotide (AS S-ODN) in cultured embryonic day 11.0 (E11.0) mandibles showed a significant growth inhibition of the tooth germ. However, no growth arrest of the cultured E15.0 tooth germ was observed by using Tβ4 AS S-ODN. The Tβ4 knockdown led to significantly decreased expression levels of type II/III runt-related transcription factor 2 (Runx2) and nucleolin (Ncl) in the cultured E11.0 mandibles. Since our previous studies proved that the inhibition of type II/III Runx2 and Ncl translations resulted in the developmental arrest of the tooth germ in the cultured E11.0 mandible, Tβ4 appears to play roles in tooth germ development via the regulation of the type II/III Runx2 and Ncl expressions. Tβ4 knockdown also resulted in decreased secretion of matrix metalloproteinase (Mmp)-2, a reduced cell motility activity and upregulation of E-cadherin in dental epithelial mDE6 cells. These results suggest that Tβ4 plays multiple functional roles in odontogenic epithelial cells in the early stages of tooth germ development by regulating the expression of odontogenesis-related genes.

  1. Marine Corps Combat Readiness Evaluation System. Software Applications (MCCRESSA) Subroutine Library.

    DTIC Science & Technology

    1985-08-01

    SCIE W E CAVESIUNCLASSIFIED AUG 85 GWU/IMSE/SERIAL-T-58i/85 F/G 9/2 UL EEEEEEEEEEEEEE EEEEEEEEEEEEEE EEEEEIIIIEEE 32 I:.0 11,1.I I I IIIIi I ~~~Ill...J . ; - - - - t [ " ’ "" " " " " " " " "" " " T-501 CNTSEL 4. CNTSEL 4.1. Description: Tr. Z2KJ sjbroitine wiA.: builc a crCoC refe- ence table

  2. Raman spectra of solid benzene under high pressure

    NASA Technical Reports Server (NTRS)

    Thiery, M.-M.; Kobashi, K.; Spain, I. L.

    1985-01-01

    Raman spectra of solid benzene have been measured at room temperature up to about 140 kbar, using the diamond anvil cell. Effort has been focused upon the lattice vibration spectra at pressures above that of phase II. It is found that a change in slopes occurs in the frequency-pressure curves at about 40 kbar. Furthermore, a new band appears above 90 kbar. These features probably correspond respectively to the II-III phase transition, which has been reported previously, and a III-IV phase transition, reported here for the first time.

  3. The Archaeological Potential of Pool Number 10, Upper Mississippi River: A Geomorphological Perspective.

    DTIC Science & Technology

    1984-03-15

    D-17 935 H AMJLgp 0104 I M E i 1~i jn U14CLASSIFIE 15 ifnr U/ Gi ~suG~GIT. F/ /6 ED t4sYf IE I H L S) iii1,.__ 10 ,l2 00 . 13-16 2-22. iiiiI,. K K4...the floodplain, and have steeper downvalley gradients upstream toward St. Paul. The contribution of postglacial isostatic rebound to this phenomena is...erosional outliers of Woodfordian alluvium (e.g., Plate 3, Sec. 12, T7N, R7W). Postglacial entrenchment created an irregular erosional surface that passes

  4. Interface Specifications for SCR (Software Cost Reduction) (A-7E) Extended Computer Module. Revised.

    DTIC Science & Technology

    1984-12-31

    DC D L PRRNAS ET AL. |BIIE3E4L-2V62 mhmhhhhhhhhmmu mmhhhhhhhhhhhl EhhlllllllIIhl mIIIIIIIIIIIIII 1 .’ II 111NMI -7 11112. - IIII1.8 IIIII125 11111...CLASiiFIED ’a;E "A7 DN A-Oi 3 DISTRIBUTION AVAiLA8I~lTY OF REPORT ’ D DECASS; CA’ ON DOWNGRADING SC.IEOUIE Approved for public release; distribution...IDENTIFICATION %UMBER ORGANIZATION (if applicable ) Naval Electronic Systems Command Code 613 ______________________ Sc ADORE SS (City. State, and ZIP Code) 10

  5. An Analysis of a Finite Element Method for Convection-Diffusion Problems. Part II. A Posteriori Error Estimates and Adaptivity.

    DTIC Science & Technology

    1983-03-01

    UNCLASSIFIED N G SZYMCZAK ET AL. MAR 83 BN-i@82 F/G 12/1 NL I hhhhhhh EhhhhhhhhhhhE mhhhhomhhlhhhEIEEIEEEEEIlUso o.4 Q.8 L-A -J1 IIIII1 L MICROCOPY...AN ANALYSIS OF A FINITE ELEMENT METHOD FOR CONVECTION-DIFFUSION PROBLEMS PART II: A POSTERIORI ERROR ESTIMATES AND ADAPTIVITY by W. G. Szymczak Y 6a...ESTIMATES AND ADAPTIVITY 6. PERFORMING OR. REPORT NMBER 7. AUTNOR(e) S. CONTRACT OR GRANT NUM11CR’ s) W. G. Szymczak and I. Babu~ka ONR N00014-77-0623 S

  6. Social and Economic Impacts of Selected Potential Dredged Material Containment Facilities in Long Island Sound.

    DTIC Science & Technology

    1981-09-01

    DREDGING/DISPOSAL PERMlITS Pt/TaIm/Cfty pemitI~ ~ Suft. Aaajaav S . rtf M~l M9?3 0 Rover I". -I IlS to1 e~ cftI1 for ____ bwimimd. 196 10182 of Tida w~et...NORTHRDP SEP RI UNCLASSIFED CEM _4280-0OR735 DACW33-AG0-C 61 F/ S 13/2 NL .EIIIIIIIIIIIl EIIIIIIIIIIIIl IIfhhffffflllf L3= L2 11111 1. I iiiii 18...8217AGE ("oen Date &.**d) READ INSTRUCTIONSREPORT DOCU AENTATION PAGE BEFORE COMPLETING FORM 1. REPORT NUMBER z.OT ACCESSION No . Ot TS CATALOG NUMISER S

  7. Valvular dysplasia and congestive heart failure in a juvenile African penguin (Spheniscus demersus).

    PubMed

    McNaughton, Allyson; Frasca, Salvatore; Mishra, Neha; Tuttle, Allison D

    2014-12-01

    Abstract: An aquarium-housed, 6-mo-old African penguin (Spheniscus demersus) presented with acute respiratory distress. Auscultation revealed a grade II-III systolic murmur in the absence of adventitial sounds, and an enlarged heart without pulmonary edema was seen radiographically. Echocardiographic evaluation revealed atrioventricular (AV) valvular dysplasia and ventricular enlargement. The penguin was treated with enalapril, furosemide, and pimobendan but died within 3 wk of detection of the murmur. Congenital dysplasia of the right AV valve with right atrial and ventricular dilation and ventricular hypertrophy were diagnosed on postmortem examination.

  8. Transcatheter Embolization of a Renal Artery Aneurysm Using Ethylene Vinyl Alcohol Copolymer

    SciTech Connect

    Rautio, Riitta Haapanen, Arto

    2007-04-15

    Our aim was to treat a clinically silent renal artery aneurysm. The patient was a 76-year-old man with elevated prostate-specific antigen and prostata biopsies with a gradus II-III adenocarcinoma who was incidentally found to have an aneurysm in his right renal artery. We performed a successful transcatheter embolization of the aneurysm using ethylene vinyl alcohol copolymer (Onyx). To avoid migration of the liquid material into the parent artery, a balloon was inflated in the orifice of the neck of the aneurysm while the liquid was injected. Five-month follow-up computed tomography (CT) imaging confirmed total occlusion of the aneurysm.

  9. The association between body mass index and outcome after coronary artery bypass grafting operations.

    PubMed

    Devarajan, Jagan; Vydyanathan, Amaresh; You, Jing; Xu, Meng; Sessler, Daniel I; Sabik, Joseph F; Bashour, C Allen

    2016-08-01

    This investigation was undertaken to analyse the association between body mass index (BMI) and morbidity after coronary artery bypass graft (CABG) operations. The setting was a cardiovascular intensive care unit (ICU) of a tertiary medical referral centre. This was a retrospective review; patients were classified according to their BMI into five groups: underweight <18.5 kg/m(2); normal weight 18.5-24.9 kg/m(2); overweight 25-29.9 kg/m(2); Class I obesity 3034.9 kg/m(2); and Class II/III obesity >35 kg/m(2). We included patients who underwent isolated CABG between January 3, 2006 and March 8, 2011. After including only the initial operation or admission in patients with more than one operation or hospital admission and excluding patients with any missing variable, 3470 patients remained in the analyses. The primary outcomes analysed were hospital mortality and pulmonary and infection morbidities. We secondarily assessed the association between BMI category and each of the three outcomes. Respective mortality, and pulmonary and infection morbidity occurrence rates were: 8.7, 13.0 and 13.0% for the underweight; 2.4, 8.0 and 4.8% for the overweight; 1.8, 10.9 and 5.6% for the Class I obesity group; and 2.7, 11.1 and 5.7% for the Class II/III obesity group, vs 2.3, 7.0 and 6.2% for the normal weight group. Class I and II/III obesity patients were more likely to have pulmonary morbidity compared with the normal weight group, after adjusting for the potential confounding variables. Class I and Class II/III obesity (BMI ≥30 kg/m(2)) was associated with increased pulmonary morbidity after CABG operations. There was no difference in mortality or infection morbidity in any BMI group compared with the normal group. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  10. Electrooptic Crystal Growth and Properties

    DTIC Science & Technology

    1994-02-04

    the Applications of Ferroelectnics. ISAF 󈨠, Greenville, SC, 374 (1993). 9. A . M . Gadalla , Texas A & M University, unpublished results (1991). 10. B. D...TEES) for this work; Grant no. NAGW- 1194. We express our sincere thanks to Dr. A . M . Gadalla for the DTA and TGA expreiments. We also express our...AD-A276 023 *Texs Eginerin Exprimnt Satin Th Teas AM U Ivers I ity IIIII !11111 IilI li "*Texas Engineering Experiment Station The Texas A & M

  11. Evaluation Test of Radar Chronograph Set, NM87

    DTIC Science & Technology

    1974-12-01

    i.wppvR^nnnwpmqiliPV^^V^P pr IIIW«IIIII. .fp^t^, wi "Jn.’IHI ITW^LASSIFIED »ECUWTV CLM1IFICATI0M Of TMH ^ACC (***> t>— Bnfn4) REPORT DOCUMENTATION...through March 1974 to determine the capability of the NM87 to chrono graph standard cannon artillery. The NM87 «as subjected to laboratory...on the chrono - graph readout are valid muasle velocity measurements. The chronographlng range for this system, a maximum of 3* metera, will be

  12. Implementing the UCSD PASCAL system on the MODCOMP computer. [deep space network

    NASA Technical Reports Server (NTRS)

    Wolfe, T.

    1980-01-01

    The implementation of an interactive software development system (UCSD PASCAL) on the MODCOMP computer is discussed. The development of an interpreter for the MODCOMP II and the MODCOMP IV computers, written in MODCOMP II assembly language, is described. The complete Pascal programming system was run successfully on a MODCOMP II and MODCOMP IV under both the MAX II/III and MAX IV operating systems. The source code for an 8080 microcomputer version of the interpreter was used as the design for the MODCOMP interpreter. A mapping of the functions within the 8080 interpreter into MODCOMP II assembly language was the method used to code the interpreter.

  13. Listing of Army Fuel-Consuming Nonautomotive Ground Support Equipment.

    DTIC Science & Technology

    1981-08-01

    W Z(55I(00W(.J...J0((55(5 X55(S NNN. .6uu m xv~ 00d0. . -z 00 0 0a0 e~ W 0 0 1fl 0 40.28 QUf0=Q lS59uuIIIII 4 a a acca N0QgI %q c a It, 4t 0 0 0 - !3...ATDO-S FORT MONROE VA 23651 DIR US ARMY MATERIALS & MECHANICS CDR RSCH CTR US ARMY NATICK RES & DEV CMD ATTN: DRXMR-E 1 ATTN: DRDNA-YEP ( DR KAPLAN

  14. Network Management in an Emergency Communications System.

    DTIC Science & Technology

    1986-03-01

    EhhohhohEohhEI ANEOEEhh * . * - - 11112 I. ROC".,. ’. 11111 IIIII+ m "I’ _.__ .+4 .... a ..• .. 7 .7 R.- ’- ’c -’ 00 NAVAN NAVAL POSTGRADUAIE SCHOOL 0...re uirements for a generic emerrceoc: jommuni cat ic _!i tem,a .vell as specul1aItion oIn po te nt ialI r e clu ir e m enIts " Ur f -I t11r a - r a...network monitoring tells management processors and personnel what is happe .:ning throughout the network, where problems are devel- oping, and what is the

  15. Oil Module Working Paper

    DTIC Science & Technology

    1973-12-01

    data from veils drilled for that purpose. But in the Middle Last, at least, any pool or field which would add significantly to proved reserves would...generally are injected into the fields to replace the oil ■,.^ ..-- - .^.■.■.—»-^ —1I1II ■iiiiiMmw |f«HMPil"<Hn«inn*M^ Tl vap" mmmmmmm removed...develop these large pools in optimal fashion, drilling only the necessary numbers of wells for the desired rate of production, and drilling them in

  16. Historic Properties Report: Picatinny Arsenal, Dover, New Jersey.

    DTIC Science & Technology

    1985-03-01

    7D-A175 865 HISTORIC PROPERTIES REPORT: PICATINNY ARSENAL DOVER NEW liA JERSEY(U) DEPARTMENT OF THE INTERIOR MASHINOTON DC P THURBER ET AL. MAR...85UNCLASSIFIED F/6 5/6 ML III"."IIIII IIIIIIIII iiJJ,. 122 131 ! 4Ŗ L mom I- <L U. Lfl Lfl HISTORIC PROPERTIES REPORT PICATINNY ARSENAL DOVER, NEW JERSEY...Engineering Record of the National Park Service, U.S. Department of the Interior. d137 1 -~8 001 .1t EXECUTIVE SUMMARY Picatinny Arsenal is located in northern

  17. Understanding the Soviet Threat: The Necessity of Analyzing Soviet Military Thought and Actions from a Soviet Perspective.

    DTIC Science & Technology

    1987-12-01

    UNCL SSIFIEDD F / /6 L smmomhhmmohmlm i lflfflfllflfflfllflf 0 Xmin IlI"- ti , )0 368 111111.1- 11. MICROCOPY RESOLUTION TEST CHARI - A ,)RIlib -;A~r...to discriminate friends from enemies is a sign of intellectual maturity. . . some qualities of American mentality look like signs of emotional and...1516 ML mhhmohmohmhI S S 0 S 11111 1.0 ~’~J""~ liii.- IML IIIII~ LI~ I" 111111.1 ~ SIII" 11111 1.411111 S MICROCOPY RESOLUTION TEST CHART ’)R~AU

  18. Representing and Reasoning about Change in Geologic Interpretation.

    DTIC Science & Technology

    1983-12-01

    LAB R 6 SIMMONS DEC 83 UNCLASSIFIED AIl-TR-749 NGO014-80- C -9505 F/G 8/7 N ILEhhh hmmlEhmm hmhmhhhum o - IIII IIIIII 1__ _ _ 11 32-- IIIII ’ 2 MICROCOPY...NYS C T L G UM E AI-TR-749 7-ś_-_.’-0 4. TITLE (end Subtitle) S. TYPE OF REPORT & PERIOD COVERED Representing and Reasoning About Change in Technical...report Geologic Interpretation S. PERFORMING ONG. REPORT NUMBER 7. AuTmOR(m) S. CONTRACT OR GRANT NUMBER(e) Reid Gordon Simmons N00014-80- C -0505 9

  19. Analytical Prediction of Motor Component Vibrations Driven by Acoustic Combustion Instability

    DTIC Science & Technology

    1976-02-01

    34 i" ’ C 0 tD L\\ u U:u01 -’I C)-OzUU0 C.0UC-I.)4CJ 0CC0 0 0~ 0 : 4L4 1- OZ-ONM An11 0(- II, .II IhIOIICIOiIII NM4IIIII ICO 0C) us ~ Y.I-A 8-32 D...Modes for Symmetry Boundary Conditions. 1-26 f10 =206 HZ f 9 = 189 HZ f 8 164 HZj f7 161] HZ f = 140. HZ f 5 = 125. HZ -=f4 =97.4 HZ f3 =79.7 HZ LI f2

  20. Titan IIIC Transtage/Stage 2 Separation-Shock Bench Test. Volume 3

    DTIC Science & Technology

    1975-11-01

    2 6 15o I Frequency, HzJ Bench Shock Test - Stage II/III Separation, Run 10Measurement No. 4 - Longitudinal axis longeron nearstation 117 !• , 149 A...6I 5 5 4 33 3 10CC- O-10 I--L 87 8 i5 5 : -- 6 1ench Sh c- es -t ge I / I Se a a i n Ru02 1 2~w Me srm n No L N Lo g td n l0xsIn eo

  1. National Dam Inspection Program. Upper Castanea Reservoir Dam. (NDI I.D. Number PA-00393 Pennder I.D. Number 18-7) Susquehanna River Basin. Harvey’s Run, Clinton County, Pennsylvania. Phase I Inspection Report,

    DTIC Science & Technology

    1980-07-01

    b - 8-.. it8 b - -1 . . w -4 4C - aa V3 I.1 A. ’ +ua~e BAN. sAF rT"( " UL+ TTAJ . DAEUBJE-C HET NO. l LF( L" OFUPE9 CASTAkJEA R.ES .LVT, UAM By DATE...NL22llllllllllum//l2 liii- IIIII 11H 11 14 MICROCOPY RESOLUIION TESI CHARI NA11_N AL N I , 4t 𔃾 II APPENDIX E FIGURES LIST OF FIGURES Figure Description/Title

  2. Respiratory chain enzyme activities in spermatozoa from untreated Parkinson's disease patients.

    PubMed

    Molina, J A; Ruiz-Pesini, E; Jiménez-Jiménez, F J; López-Pérez, M J; Alvarez, E; Berbel, A; Ortí-Pareja, M; Zurdo, M; Tallón-Barranco, A; de Bustos, F; Arenas, J

    1999-01-01

    We studied respiratory chain enzyme activities in spermatozoa homogenates from 12 untreated Parkinson's disease (PD) male patients and from 23 age matched healthy male controls. When compared with controls, PD patients showed significantly lower specific activities for complexes I+ III, II+III, and IV. However, citrate synthase corrected activities were similar in patients and controls. Values for enzyme activities in the PD group did not correlate with age at onset, duration, scores of the Unified Parkinson's Disease Rating Scales and Hoehn and Yahr staging. These results suggest that this tissue cannot be used to develop a diagnostic test for PD.

  3. Synthesis and Reactivity of Backfluorinated NHC Carbene Complexes (Briefing Charts)

    DTIC Science & Technology

    2015-07-01

    19F Spectrum of pfme-SIMes-IrCOD-Cl Suggestion: two isomers Distribution A: Approved for public release 19 1H Spectrum of pfme-SIMes-Ir(CO)2-Cl...Conclusion: two isomers Distribution A: Approved for public release 20 • Ligand rotation observed upon heating in toluene-d8 Potential Isomers in...Solution Distribution A: Approved for public release Isomer A Isomer C /"cF3 •IIIII III H I Mes f’’’’ ,,,,,cl 1 -~lryN N I Mes Isomer B I Mes

  4. VizieR Online Data Catalog: Teff against colours calibrations (Huang+, 2015)

    NASA Astrophysics Data System (ADS)

    Huang, Y.; Liu, X.-W.; Yuan, H.-B.; Xiang, M.-S.; Chen, B.-Q.; Zhang, H.-W.

    2016-07-01

    Based on nearly two hundred dwarf (luminosity classes: IV/V) and giant (luminosity classes: II/III) stars with direct effective temperature measurements of better than 2.5 per cent collected from the literature, we have derived metallicity-dependent Teff-colour relations in twenty-one colours for dwarfs and eighteen colours for giants in four photometric systems (the Johnson, Cousins, SDSS and 2MASS). The compiled data of dwarf and giant sample stars employed in the current work is presented. (1 data file).

  5. Aerodynamics of Vortical Type Flows in Three Dimensions: Conference Proceedings Held at Rotterdam, Netherlands on 25-28 April 1983.

    DTIC Science & Technology

    1983-07-01

    JUt 83 A C ; S F E D A G A R ) -(F 3 4 2 / 2 0 4 N 1 -"-III".. IIEI IIIII."I 111111 11.11U~ 1,22 1.5 1. 1206 MICROCOPY RESOLUTION TEST CHART v.v...Flow Simulations Past Wings Using the Euler- Equations. 4 * T I | , ... , - COPOIENT PART NOTICE (CON’T) AD#: P002 259 TITLE: Numerical Solutions of the...Vortical Flows. - 4 final but regrettably brief period was devoted to a review of main impressions of the Symposium preseted.. J JB.Smith followed by a

  6. Oesophageal burn caused by sucking a 1.5 volt battery.

    PubMed

    Untersweg, U; Mayr, J; Schmidt, B

    1996-11-01

    We report the case of a 4-year-old boy who sustained an oesophageal burn grade II-III due to ingestion of an alkaline substance from a leaking cylindric 3.3 cm diameter battery, by putting the battery to his mouth and sucking the caustic solution. Lye ingestion by sucking a big cylindrical alkaline battery has not yet been reported in the medical literature. We recommend the production of safer alkaline battery cover tubes in order to eliminate any possibility of leakage. Accidents like this might occur more often, since battery collecting and recycling is becoming more common.

  7. Rapid Melting and Solidification of a Surface Due to a Moving Heat Flux,

    DTIC Science & Technology

    1979-03-22

    HSU, R MEHRABIAN N00014-78-C-0 75 U7NCLASSIFIED NL*nuu..nn...I m hEhhhhE EllElllllEEE-mu.!IIIII .. ..........- 7 FŘ RAPID MELTING AND...JOLIDIFICATION OF AJURFACE DUE TO; S. iou,4"S. C./Hsu *m tR ,ehrabian ~~~~~ABST RA CT.. // /{a ’ \\Rapid melting and solidification of a semi-infinite substrate...constant and equal. It is also assumed that the substrate, pure aluminum used as example, melts and solidifies at a single temperature. Temperature

  8. Dermal Sensitization Potential of DIGL-RP Solid Propellant in Guinea Pigs

    DTIC Science & Technology

    1989-10-01

    y ’,c. ADM$$ S (ft, SWOt , &Wd ZIP Cod 7b. ADDRESS (City, State, arid ZIP Code) Letterman Army Institute of Research Fort Detrick Presidio of San...The opinions or assertions contained herein -are the private views of the author( s ) and are not to be construed as official or as reflecting the...AVAILARlII Ily Of RFPORT 01. DELFICATION IOOWNGRAOINSHELEI’IVM oI li.IIIII:A.; DISTRJ13LITION I:;IN.IM 4. PERFORMING ORGANIZATION REMR NUMBER( S ) S

  9. Geokinetic Effects on Motion Sensitive Instrumentation, Systems and Facilities.

    DTIC Science & Technology

    1984-01-15

    7 RD-i42 682 GEO"INETIC EFFECT ON MOTION SENSITIVE INSTRUMENTATION 1/2 SYSTEMS AND FACILITJES(J) WESTON OBSERVATORY MA F A CROWLEY ET AL. 15 JAN 84...IIIII lfl m mI 25III 1ii MICROCOPY RESOLUTION TEST CHART NATIONAL BUREAU OF STANDARDS-1963-A !H- - .. .. - .-. AFGL-TR-84- 0031 Geokinetic Effects on...CATALOG NUMBER -. 4. TITLE (and Subtitie) 5. TYPE OF REPORT a PERIOD COVFRED Final Report Geokinetic Effects on Motion Sensitive 15 Oct 1980-30 Sep

  10. Therapy for Clostridium difficile infection - any news beyond Metronidazole and Vancomycin?

    PubMed

    Manthey, C F; Eckmann, L; Fuhrmann, V

    2017-08-11

    Infections with Clostridium difficile (CDI) represent a major burden for the health care system. Treatment is generally by antibiotic therapy with metronidazole and vancomycin, but efficacy remains suboptimal. Areas covered: This review discusses established and emerging treatment options for CDI, and current therapeutic guidelines, taking into account disease severity and risk of relapse. Expert commentary: New therapeutic approaches, including antibodies and new classes of antibiotics, and new measures for preventing infection with vaccines are under development in phase II/III clinical trials. We performed a systematic literature review using the search terms 'Clostridium difficile' and 'treatment'.

  11. Some Recent Results on Graph Matching,

    DTIC Science & Technology

    1987-06-01

    VJ and • work supported by ONR Contract # N00014-85-K-0488 I 1 1JI IIIII 2 the line-coloring problem [H]), there are others the polynomial -time sol...theorem of Tutte [T]. 2.1. THEOREM. A graph G has a perfect matching if and only if for every X 9_ V(G), the number of odd components of G - X is at most...here because our approach is different, being based upon the work of Edmonds, Lovasz and PuUeyblank [ELP], who gave a polynomial -time algorithm to com

  12. Persanura hyrcanica, a new genus and species of Neanurinae (Collembola: Neanuridae) from Iran, with a key to genera of the tribe Neanurini.

    PubMed

    Mayvan, Mahmood Mehrafroz; Shayanmehr, Masoumeh; Smolis, Adrian; Skarżyński, Dariusz

    2015-02-13

    Persanura hyrcanica, a new genus and species of Neanurini from Iran is described and illustrated. It has a unique suite of morphological characters: labrum with only 4 chaetae, fusion of tubercles So and L on head, tubercle Di on th. II-III with 2 chaetae and separation of tubercles Di on abd. V. The erected genus is closely related to Neanura MacGillivray, 1893, Kalanura Smolis, 2007 and Xylanura Smolis, 2011. An updated key to genera of the tribe Neanurini is given.

  13. Has the rescheduling of hydrocodone changed ED prescribing practices?

    PubMed

    Oehler, Elizabeth C; Day, Rachel L; Robinson, David B; Brown, Lawrence H

    2016-12-01

    The objective was to examine the effect of hydrocodone-containing product (HCP) rescheduling on the proportion of prescriptions for HCPs given to patients discharged from the emergency department (ED). Electronic queries of ED records were used to identify patients aged 15 years and older discharged with a pain-related prescription in the 12 months before and after HCP rescheduling. Prescriptions were classified as HCPs; other Schedule II medications (eg, oxycodone products); other Schedule III medications (eg, codeine products); and non-Schedule II/III products (eg, nonsteroidal anti-inflammatory drugs). We compared the proportions of patients receiving each type of prescription before and after rescheduling using χ(2) analysis and used logistic regression to explore the relationship between prescription type and time period while controlling for age, sex, race, and ethnicity. Before rescheduling, 58.1% (95% confidence interval [CI], 57.4-58.7) of patients receiving a pain-related prescription received an HCP; after rescheduling, 13.2% (95% CI, 12.7-13.7) received an HCP (P < .001). Concurrently, other Schedule III prescriptions increased (pre: 11.7% [CI, 11.3-12.2] vs post: 44.9% [CI, 44.2-45.6], P < .001)), as did non-Schedule II/III prescriptions (pre: 51.8% [CI, 51.2-52.5] vs post: 59.3% [CI, 58.6-60.0], P < .001). When controlling for demographic characteristics, patients remained less likely to receive an HCP after rescheduling (adjusted odds ratio [AOR], 0.11; CI, 0.10-0.11) and more likely to receive other Schedule III (AOR, 6.1; CI, 5.8-6.5) and non-Schedule II/III (AOR, 1.4; CI, 1.3-1.4) products. Rescheduling HCPs from Schedule III to Schedule II led to a substantial decrease in HCP prescriptions in our ED and an increase in prescriptions for other Schedule III and non-Schedule II/III products. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Regional but fatal: Intraperitoneal metastasis in gastric cancer

    PubMed Central

    Wei, Jia; Wu, Nan-Die; Liu, Bao-Rui

    2016-01-01

    Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase II-III studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition, proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients. PMID:27672270

  15. The Effect of Operating Temperature on Open, Multimegawatt Space Power Systems

    DTIC Science & Technology

    1988-04-01

    Idaho Falls, ID 83415 Attn: M. L . Stanley EG& G Idaho, Inc./INEL P.O. Box 1625 Idaho Falls, ID 83415 Attn: R. D. Struthers EG& G Idaho, Inc./INEL...School Road, NE Albuquerque, NM 87110 Attn: G . L . Zigler SDI Organization The Pentagon Washington, DC 20301-7100 Attn: R. Verga SDI...CTO« TIMF 1ÜIIIII FLY- WHEEL oimiiiToi y MY DKOatM Ft O« L »OWE« CONDITIONING »OWE« HO« REFftlOEIiaTO* Figure 1. Burst-Mode, Reactor

  16. Waterborne Transportation Lines of the United States 1987

    DTIC Science & Technology

    1988-10-01

    COAST I TER $ EIII l tIIII E D I 1 11/UI POlO I LINE-I IAO! LINE-1 I BUILT I VESSEL NAME AND HIJRBC4 I plato I TON_ IPAGel OVER-|OVER IIIII1 HORSE! PASS...30.11 110001 159171 114.8115 TON-t 66 TON ILA NEW 1 1972 I1 1 592.61 69.01 12.51 121 IELECTRIC BOONS I ORLEANS I I SOLON TURMAN 1285fS9 I7760|1A03! 567.61

  17. [Alternative of laser treatment optimization in retinoschisis].

    PubMed

    Bagdasarova, T A; Il'ina, T S

    2010-01-01

    In this study a new original technique is proposed for treatment of II-III retinoschisis using diode laser Milon Lachta (Saint-Petersburg). Laser radiation parameters were wave length 0,83 microm, energy 350-850 m W, time 0,2-0,3 s, spot diameter 150-200 microm. Original technique of gradual progressive laser coagulation was performed in 72 patients with II-I1 retinoschisis using diode laser. This treatment allowed to preserve macular function to the maximum.

  18. Influence of ASA score and Charlson Comorbidity Index on the surgical site infection rates.

    PubMed

    Khan, Mansoor; Rooh-ul-Muqim; Zarin, Mohammad; Khalil, Jawad; Salman, Muhammad

    2010-08-01

    To compare the frequencies of surgical site infections (SSI) in ASA class-I (American Society of Anaesthesiologists-I) with ASA class II-III and CCI-0 (Charlson Co-morbidity Index-0) with CCI 1-6 in clean (C) and clean contaminated (CC) surgeries. Analytical study. This study was conducted in a General Surgical Unit of Khyber Teaching Hospital, Peshawar, from December 2008 to April 2009. A total of 310 clean and clean contaminated general surgical interventions with pre-operative ASA score of I-III, were included in the study, excluding anal and cystoscopic procedures. On the basis of past medical record, patients were grouped into ASA-I (patients without any co-morbidity) and ASA II-III (patients with co-morbidities) on the basis of their ASA score pre-operatively. In the same way patients were divided into CCI-0 (patients without co-morbidities) and CC 1-6 (patients with co-morbidities) according to CCI score. All the patients were operated in the same environment by the same set of surgeons. Postoperatively the surgical wounds were observed for SSI by using ASEPSIS daily scoring system for one month prospectively. SSI rates in ASA-I was compared with SSI rates in ASA II-III. Similar comparison of SSI rates was performed in CCI-0 and CCI 1-6. Data was tested by using the Fisher's exact test with confidence interval of 95%. The overall SSI rate was 6.1% (n=19) with 4.23% (n=5) in clean cases (C) and 7.29% (n=14) in clean contaminated cases (CC). There were significantly higher surgical site infection rates among patients in ASA II-III than those with ASA-I in clean contaminated surgeries (p=0.003). There were also significantly higher surgical site infection rates among patients with CCI score 1-6 than those with CCI-0 in clean (p=0.024) and clean contaminated (p=0.002). American Society of Anaesthesiologists (ASA) score and Charlson comorbidity index (CCI) has strong influence on SSI rates in clean and clean contaminated cases. Patients' with co

  19. Specification and Design Methodologies for High-Speed Fault-Tolerant Array Algorithms and Structures for VLSI.

    DTIC Science & Technology

    1987-06-01

    A182 772 SPECIFICATION AND DESIGN METHODOLOGIES FOR NIGH-SPEED 11 FAULT-TOLERANT ARRA.. CU) CALIFORNIA UNIY LOS ANGELES DEPT OF COMPUTER SCIENCE M D ...ERCEGOVAC ET AL. JUN 0? UNLASSIFIED N611-03--K-S49 F/ 91 ML Ji 1 2. ~ iiii -i ’IfIhIN I_______ IIIII .l n. ’ 3 ’ 3 .3 .5 *. .. w w, - .. .J’. ~ d ...STRUCTURES FOR VLSI Office of Naval Research Contract No. N00014-83-K-0493 Principal Investigator Milo D . Ercegovac ELECTE Co-Principal Ivestigator S AUG 0

  20. Plan to be flexible: a commentary on adaptive designs.

    PubMed

    Shih, Weichung Joe

    2006-08-01

    This is a discussion of the following three papers appearing in this special issue on adaptive designs: 'Nested repeated confidence intervals and switching between noninferiority and superiority' by Joachim Hartung and Guido Knapp; 'Confirmatory Seamless Phase II/III Clinical trials with Hypotheses Selection at Interim: General Concepts' by Frank Bretz, Heinz Schmidli, Franz König, Amy Racine and Willi Maurer; and 'Confirmatory Seamless Phase Il/III Clinical Trials with Hypotheses Selection at Interim: Applications and Practical Considerations' by Heinz Schmidli, Frank Bretz, Amy Racine and Willi Maurer.

  1. Photochemical properties of Yt base in aqueous solution.

    PubMed Central

    Paszyc, S; Rafalska, M

    1979-01-01

    Photoreactivity of Yt base [I] has been studied in aqueous solution [pH approximately 6] saturated with oxygen. Two photoproducts (II,III], resulting from irradiation at lambda = 253.7 nm and lambda greater than or equal to 290 nm, were isolated and their structures determined. The quantum yield for Yt base disappearance [zeta dis] is 0.002 [lambda = 313 nm]. It was shown that dye-sensitized photooxidation of Yt base in aqueous solution occurs according to a Type I mechanism, as well as with participation of singlet state oxygen. Quantum yields, fluorescence decay times and phosphorescence of Yt base have been also determined. PMID:424298

  2. [Post-radiotherapy complications in malignant tumors of the nasopharynx. Analysis of 141 cases].

    PubMed

    Pastore, G; Krengli, M; Gambaro, G; Turri, L; Pisani, P

    1990-10-01

    This study was aimed at retrospectively analyzing the incidence and severity of the complications occurred in 141 patients affected with nasopharyngeal carcinomas treated with exclusive radiotherapy from 1960 to 1986. The acute complications were analyzed (85/141 grade II-III mucositis which generally came to a complete remission) which occurred during and immediately after radiation treatment. The late damage was then studied which occurred in 74/141 patients (52.5%) and which may worsen patients' quality of life. Finally, the incidence and severity of damage were correlated with some parameters: sex, age, performance status, risk factors (tabagism, alcoholism, diabetes), stage, total dose, fractionation, and processing techniques for treatment planning.

  3. Miniature Precision Detonator

    DTIC Science & Technology

    1974-06-01

    r o LTNM a . . . aj V • • « • &, t--CTi ro A o> CM romoo o < w O LPv vo CM on ^T in CM K O Z P- M oo M CM (M E 2 H CO Ci] H- • Ü... waa imm «ÜW n.,J.I.,kfl«WWiP.Wi™ "WfW" mmm HI iiiiiMU(jmiw<im>i.w J’IMI mi TABLE C-3 TEST DATA RECORDS Sheet 29 r v P i o* i t

  4. Embankment Criteria and Performance Report, Missouri River, Fort Peck Lake, Montana. Volume I. Text Appendix A, Appendix B.

    DTIC Science & Technology

    1982-09-01

    lt I i I I . .. . . . , . . . . . . TABULATION AND I ,. L RF DR =2. MLE LM P R 1MMAIOM IM=IGATIONS P0R F0N PECK DAM - Contd Peld . ;% Role Book ’ook...I EllIhlllIhl!Il EIIIIIIIIIiil IIIIIIIEEIIIIE IIIIIIIE--EEI 11111j8 13 2 L11L11 2.2IIIIII 1111.25 IlI41. 6IIIII l llt IIl’ MICROCOPY RESOLUTION...AM, MNTAN EMBANKENT CITERI AND PEFORMACE REORT PAT1 son& I IS L ’It K,4 FORT T0 -, DA.MOTN WflAtiK*f NT* CRTE IAN t-i RMNEREOTPLT -- - - --- FORT PECK

  5. Recovery Following Orthognathic Surgery

    DTIC Science & Technology

    1993-01-01

    AD-A267 PAGE Form Approved IJIIIJi PAGEll IIIIiBlll0MB No. 0204-0 US ONL (LWv bl0nk 2.; REjR DATE t0, P .• ~ ~ ~ ~ ~ ~ 1 ’o M"• >’lr.n , . mll.r ,t9 co...SPONSORING/ MONITORING DEPARTMENT OF THE AIR FORCE AGENCY REPORT NUMBER 2 P TIC WRIGHT-PATTERSON AFB OH 45433-7765 _E L ,bCTE- 11. SUPPLEMENTARY NOTES 12a...DISTRIBUTION ’ AVAILABILITY STATEMENT I12b. DISTRIBUTION CODE Approved for Public Release IAW 190-1 Distribution Unlimited MICHAEL M. BRICKER, SMSgt

  6. Neuroprotective effects of metabotropic glutamate receptor group II and III activators against MPP(+)-induced cell death in human neuroblastoma SH-SY5Y cells: the impact of cell differentiation state.

    PubMed

    Jantas, D; Greda, A; Golda, S; Korostynski, M; Grygier, B; Roman, A; Pilc, A; Lason, W

    2014-08-01

    Recent studies have documented that metabotropic glutamate receptors from group II and III (mGluR II/III) are a potential target in the symptomatic treatment of Parkinson's disease (PD), however, the neuroprotective effects of particular mGluR II/III subtypes in relation to PD pathology are recognized only partially. In the present study, we investigated the effect of various mGluR II/III activators in the in vitro model of PD using human neuroblastoma SH-SY5Y cell line and mitochondrial neurotoxin MPP(+). We demonstrated that all tested mGluR ligands: mGluR II agonist - LY354740, mGluR III agonist - ACPT-I, mGluR4 PAM - VU0361737, mGluR8 agonist - (S)-3,4-DCPG, mGluR8 PAM - AZ12216052 and mGluR7 allosteric agonist - AMN082 were protective against MPP(+)-evoked cell damage in undifferentiated (UN-) SH-SY5Y cells with the highest neuroprotection mediated by mGluR8-specific agents. However, in retinoic acid- differentiated (RA-) SH-SY5Y cells we found protection mediated only by mGluR8 activators. We also demonstrated the cell proliferation stimulating effect for mGluR4 and mGluR8 PAMs. Next, we showed that the protection mediated by mGluR II/III activators in UN-SH-SY5Y was not accompanied by the modulation of caspase-3 activity, however, a decrease in the number of apoptotic nuclei was found. Finally, we showed that the inhibitor of necroptosis, necrostatin-1 blocked the mGluR III-mediated protection. Altogether our comparative in vitro data add a further proof to neuroprotective effects of mGluR agonists or PAMs and point to mGluR8 as a promising target for neuroprotective interventions in PD. The results also suggest the participation of necroptosis-related molecular pathways in neuroprotective effects of mGluR III activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. A Stable Adaptive Numerical Scheme for Hyperbolic Conservation Laws.

    DTIC Science & Technology

    1983-05-01

    REERHCNE UIE A 3MCTR21 UNLSSFE hEEEE0-C001hhEEI/ N EhofhEE hE]h iiiii ,__ 12 L2 III’’,. 1iii.- 1 11"--- 110 11111-11111 11111=6 MICROCOPY RESOLUTION TEST...0041. This material is based upon work partially supported by the National Science Foundation under Grant No. MCS-7927062, Mod. 1 . SIGNIFICANCE AND...Stable Adaptive Numerical Scheme for Hyperbolic Conservation Laws * Bradey J. Lucter 1 . Intrduton Our focus in this paper is the efficient solution of

  8. A Study of the World’s Naval Surface-to-Air Missile Defense Systems.

    DTIC Science & Technology

    1984-12-01

    NCASFE F/a 16/4. 2 L • IlU ,. ___ LLU I". iiiii~ 1.8 MICROCOPY RESOLUTION TEST CHART NATIONAL BUREAU OF STANDARDS-1963-A ,0 -. - .1, -. ’., m r - -t... 2 ELECTE MAY 31 W8E Thesis Advisor: Robert E. Bal 85 5 28 072 Unclassified SIECURITY CLASSIFICATION OF THIS PAGE (Ifha, Does Enteed REPORT...POSTGRADUATE SCHOOL December 1984 Author: Approved by: ’ . N7F~Ii!WF7Cir man, Department of Aeronautics A---- DK7 T r, Dean of Science and Engineering 2 2 , 2

  9. CpG and TpA frequencies in the plant system.

    PubMed Central

    Boudraa, M; Perrin, P

    1987-01-01

    Higher plant nuclear sequences reveal avoidance of CpG and TpA doublets. Chloroplast sequences avoid the TpA doublet in all codon positions. The chloroplast genome is not methylated but codon positions II-III and untranslated regions avoid CpG. The mitochondrial genome, also unmethylated, avoids CpG in all codon positions. We therefore deduce that methylation is not sufficient to explain CpG avoidance in the higher plant systems. Other factors must be taken into account such as amino acid composition, codon choices and perhaps stability of the DNA helix. PMID:3497385

  10. Atypical squamous cells of undetermined significance: Bethesda classification and association with Human Papillomavirus.

    PubMed

    Barcelos, Ana Cristina Macêdo; Michelin, Márcia Antoniazi; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2011-01-01

    To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed. Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031). ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN.

  11. Neonatal sensory deprivation and the development of cortical function: unilateral and bilateral sensory deprivation result in different functional outcomes.

    PubMed

    Popescu, Maria V; Ebner, Ford F

    2010-07-01

    The normal development of sensory perception in mammals depends on appropriate sensory experience between birth and maturity. Numerous reports have shown that trimming some or all of the large mystacial vibrissa (whiskers) on one side of the face after birth has a detrimental effect on the maturation of cortical function. The objective of the present study was to understand the differences that occur after unilateral whisker trimming compared with those that occur after bilateral deprivation. Physiological deficits produced by bilateral trimming (BD) of all whiskers for 2 mo after birth were compared with the deficits produced by unilateral trimming (UD) for the same period of time using extracellular recording under urethan anesthesia from single cells in rat barrel cortex. Fast spiking (FSUs) and regular spiking (RSUs) units were separated and their properties compared in four subregions identified by histological reconstructions of the electrode penetrations, namely: layer IV barrel and septum, and layers II/III above a barrel and above a septum. UD upregulated responses in layer IV septa and in layers II/III above septa and perturbed the timing of responses to whisker stimuli. After BD, nearly all responses were decreased, and poststimulus latencies were increased. Circuit changes are proposed as an argument for how inputs arising from the spared whiskers project to the undeprived cortex and, via commissural fibers, could upregulate septal responses after UD. Following BD, more global neural deficits create a signature difference in the outcome of UD and BD in rat barrel cortex.

  12. Cellular and Molecular Basis for Stress-Induced Depression

    PubMed Central

    Seo, Ji-Seon; Wei, Jing; Qin, Luye; Kim, Yong; Yan, Zhen

    2016-01-01

    Chronic stress plays a crucial role in the development of psychiatric diseases, such as anxiety and depression. Dysfunction of the medial prefrontal cortex (mPFC) has been linked to the cognitive and emotional deficits induced by stress. However, little is known about the molecular and cellular determinants in mPFC for stress-associated mental disorders. Here we show that chronic restraint stress induces the selective loss of p11 (also known as annexin II light chain, S100A10), a multifunctional protein binding to 5-HT receptors, in layer II/III neurons of the prelimbic cortex (PrL), as well as depression-like behaviors, both of which are reversed by selective serotonin reuptake inhibitors (SSRIs) and the tricyclic class of antidepressant (TCA) agents. In layer II/III of the PrL, p11 is highly concentrated in dopamine D2 receptor-expressing (D2+) glutamatergic neurons. Viral expression of p11 in D2+ PrL neurons alleviates the depression-like behaviors exhibited by genetically manipulated mice with D2+ neuron-specific or global deletion of p11. In stressed animals, overexpression of p11 in D2+ PrL neurons rescues depression-like behaviors by restoring glutamatergic transmission. Our results have identified p11 as a key molecule in a specific cell type that regulates stress-induced depression, which provides a framework for the development of new strategies to treat stress-associated mental illnesses. PMID:27457815

  13. Interruptions and distractions in the gynaecological operating theatre: irritating or dangerous?

    PubMed

    Yoong, Wai; Khin, Ayemon; Ramlal, Navin; Loabile, Bogadi; Forman, Stephen

    2015-01-01

    Distractions and interference can include visual (e.g. staff obscuring monitors), audio (e.g. noise, irrelevant communication) and equipment problems. Level of distraction is usually defined as I: relatively inconsequential; II: > one member of the surgical team affected; III: the entire surgical team affected. The aim of this study was to observe the frequency and impact of distracting events and interruptions on elective gynaecology cases. Data from 35 cases were collected from 10 consecutive operating sessions. Mean number of interruptions was 26 episodes/case, while mean number of level II/III distractions was 17 episodes/case. Ninety per cent of interruptions occur in the first 30 minutes of the procedure and 80.9% lead to level II/III distraction. Although no complications were directly attributable to the observed distractions, the mean prolongation of operating time was 18.46 minutes/case. Understanding their effects on theatre environment enables appropriate measures to be taken so that theatre productivity and patient safety are optimised. This observational study of 35 elective cases shows a mean interruption rate of 26 episodes/case with 80.9% affecting > one member of operating team, leading to mean prolongation of 18.46 minutes/case. Theatre staff should be aware of these findings and appropriate measures taken to optimise theatre productivity and patient safety.

  14. Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.

    PubMed

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole

    2014-09-01

    A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Molecular basis for the modulation of native T-type Ca2+ channels in vivo by Ca2+ /calmodulin-dependent protein kinase II

    PubMed Central

    Yao, Junlan; Davies, Lucinda A.; Howard, Jason D.; Adney, Scott K.; Welsby, Philip J.; Howell, Nancy; Carey, Robert M.; Colbran, Roger J.; Barrett, Paula Q.

    2006-01-01

    Ang II receptor activation increases cytosolic Ca2+ levels to enhance the synthesis and secretion of aldosterone, a recently identified early pathogenic stimulus that adversely influences cardiovascular homeostasis. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a downstream effector of the Ang II–elicited signaling cascade that serves as a key intracellular Ca2+ sensor to feedback-regulate Ca2+ entry through voltage-gated Ca2+ channels. However, the molecular mechanism(s) by which CaMKII regulates these important physiological targets to increase Ca2+ entry remain unresolved. We show here that CaMKII forms a signaling complex with α1H T-type Ca2+ channels, directly interacting with the intracellular loop connecting domains II and III of the channel pore (II-III loop). Activation of the kinase mediated the phosphorylation of Ser1198 in the II-III loop and the positive feedback regulation of channel gating both in intact cells in situ and in cells of the native adrenal zona glomerulosa stimulated by Ang II in vivo. These data define the molecular basis for the in vivo modulation of native T-type Ca2+ channels by CaMKII and suggest that the disruption of this signaling complex in the zona glomerulosa may provide a new therapeutic approach to limit aldosterone production and cardiovascular disease progression. PMID:16917542

  16. Molecular basis for the modulation of native T-type Ca2+ channels in vivo by Ca2+/calmodulin-dependent protein kinase II.

    PubMed

    Yao, Junlan; Davies, Lucinda A; Howard, Jason D; Adney, Scott K; Welsby, Philip J; Howell, Nancy; Carey, Robert M; Colbran, Roger J; Barrett, Paula Q

    2006-09-01

    Ang II receptor activation increases cytosolic Ca2+ levels to enhance the synthesis and secretion of aldosterone, a recently identified early pathogenic stimulus that adversely influences cardiovascular homeostasis. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a downstream effector of the Ang II-elicited signaling cascade that serves as a key intracellular Ca2+ sensor to feedback-regulate Ca2+ entry through voltage-gated Ca2+ channels. However, the molecular mechanism(s) by which CaMKII regulates these important physiological targets to increase Ca2+ entry remain unresolved. We show here that CaMKII forms a signaling complex with alpha1H T-type Ca2+ channels, directly interacting with the intracellular loop connecting domains II and III of the channel pore (II-III loop). Activation of the kinase mediated the phosphorylation of Ser1198 in the II-III loop and the positive feedback regulation of channel gating both in intact cells in situ and in cells of the native adrenal zona glomerulosa stimulated by Ang II in vivo. These data define the molecular basis for the in vivo modulation of native T-type Ca2+ channels by CaMKII and suggest that the disruption of this signaling complex in the zona glomerulosa may provide a new therapeutic approach to limit aldosterone production and cardiovascular disease progression.

  17. Paternal deprivation during infancy results in dendrite- and time-specific changes of dendritic development and spine formation in the orbitofrontal cortex of the biparental rodent Octodon degus.

    PubMed

    Helmeke, C; Seidel, K; Poeggel, G; Bredy, T W; Abraham, A; Braun, K

    2009-10-20

    The aim of this study in the biparental rodent Octodon degus was to assess the impact of paternal deprivation on neuronal and synaptic development in the orbitofrontal cortex, a prefrontal region which is essential for emotional and cognitive function. On the behavioral level the quantitative comparison of parental behaviors in biparental and single-mother families revealed that (i) degu fathers significantly participate in parental care and (ii) single-mothers do not increase their maternal care to compensate the lack of paternal care. On the brain structural level we show in three-week-old father-deprived animals that layer II/III pyramidal neurons in the orbitofrontal cortex displayed significantly lower spine densities on apical and basal dendrites. Whereas biparentally raised animals have reached adult spine density values at postnatal day 21, fatherless animals seem "to catch up" by a delayed increase of spine density until reaching similar values as biparentally raised animals in adulthood. However, in adulthood reduced apical spine numbers together with shorter apical dendrites were observed in father-deprived animals, which indicates that dendritic growth and synapse formation (seen in biparental animals between postnatal day 21 and adulthood) were significantly suppressed. These results demonstrate that paternal deprivation delays and partly suppresses the development of orbitofrontal circuits. The retarded dendritic and synaptic development of the apical dendrites of layer II/III pyramidal neurons in the orbitofrontal cortex of adult fatherless animals may reflect a reduced excitatory connectivity of this cortical subregion.

  18. Dendritic morphology in epileptogenic cortex from TRPE patients, revealed by intracellular Lucifer Yellow microinjection and confocal laser scanning microscopy.

    PubMed

    Belichenko, P V; Sourander, P; Malmgren, K; Nordborg, C; von Essen, C; Rydenhag, B; Lindström, S; Hedström, A; Uvebrant, P; Dahlström, A

    1994-07-01

    Biopsy material was obtained from cortical epileptogenic zones (eight temporal, one occipital, one parietal and one frontal) of eleven patients aged 1.5-47 years with therapy-resistant partial epilepsy (TRPE) undergoing epilepsy surgery. Control autopsy material (two temporal, two occipital, one parietal and one frontal) was removed from six neurologically healthy cases within 6-10 hours postmortem delay. In each specimen, 100-300 pyramidal and non-pyramidal neurons were visualized by intracellular Lucifer Yellow microinjection. Single neurons were imaged using CLSM generated serial optical sections; 2-D reconstruction of each neuron was made using z-projection of serial optical images, and 3-D reconstructions and rotations were computerized. Neuronal maps from TRPE biopsies, compared to control autopsies, show markedly increased numbers of dendritic abnormalities of single pyramidal and non-pyramidal neurons in layers I, II-III, V-VII, and in the subcortical white matter. The abnormalities include: (1) increased number of non-pyramidal cells in layer I; (2) many pyramidal cells with two or three dendrites originating apically, rather than one single apical dendrite, in layers II-III; (3) atypical orientation of oblique apical and basal dendrites in pyramidal neurons of layers II-VII; (4) increased number of atypical 'dinosaur-like' and fusiform cells in layers V-VII; (5) numerous neurons in the white matter. These abnormalities may be etiological in cases with early onset, and predisposing in cases with late onset.

  19. Fluvoxamine alters the activity of energy metabolism enzymes in the brain.

    PubMed

    Ferreira, Gabriela K; Cardoso, Mariane R; Jeremias, Isabela C; Gonçalves, Cinara L; Freitas, Karolina V; Antonini, Rafaela; Scaini, Giselli; Rezin, Gislaine T; Quevedo, João; Streck, Emilio L

    2014-09-01

    Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent.

  20. Immunocytochemical localization of calcium-binding proteins, calbindin D28K-, calretinin-, and parvalbumin-containing neurons in the dog visual cortex.

    PubMed

    Yu, Song-Hee; Lee, Jea-Young; Jeon, Chang-Jin

    2011-09-01

    Although the dog is widely used to analyze the function of the brain, it is not known whether the distribution of calcium-binding proteins reflects a specific pattern in the visual cortex. The distribution of neurons containing calcium-binding proteins, calbindin D28K, calretinin, and parvalbumin in adult dog visual cortex were studied using immunocytochemistry. We also compared this labeling to that of gamma-aminobutyric acid (GABA). Calbindin D28K-immunoreactive (IR) neurons were predominantly located in layer II/III. Calretinin- and parvalbumin-IR neurons were located throughout the layers with the highest density in layers II/III and IV. The large majority of calbindin D28K-IR neurons were multipolar stellate cells. The majority of the calretinin-IR neurons were vertical fusiform cells with long processes traveling perpendicular to the pial surface. And the large majority of parvalbumin-IR neurons were multipolar stellate and round/oval cells. More than 90% of the calretinin- and parvalbumin-IR neurons were double-labeled with GABA, while approximately 66% of the calbindin D28K-IR neurons contained GABA. This study elucidates the neurochemical structure of calcium-binding proteins. These data will be informative in appreciating the functional significance of different laminar distributions of calcium-binding proteins between species and the differential vulnerability of calcium-binding proteins-containing neurons, with regard to calcium-dependent excitotoxic procedures.

  1. Association between obesity and prescribed medication use in England.

    PubMed

    Kinge, Jonas Minet; Morris, Stephen

    2014-12-01

    We investigate the association between obesity and use of prescribed medications in England. Data were taken from fourteen rounds of the Health Survey for England (1999-2012), which has measures of current prescribed medication use based on therapeutic classifications in the British National Formulary, and nurse-measured height and weight. We find that obesity has a statistically significant and positive association with use of a range of medicines for managing diseases associated with obesity. The mean probability of using any type of medication is 0.40 in those of normal weight, 0.44 in the overweight, 0.52 in obesity class I and 0.60 in obesity class II/III. Significant positive associations were found between obesity and the use of medication for diseases of the cardiovascular system, gastrointestinal system, respiratory system, and central nervous system, as well as for infections, endocrine system disorders, gynaecological/urinary disorders and musculoskeletal and joint disorders. Use of anti-obesity medication is low, even among those with class II/III obesity.

  2. [Effect of paidu baoshen pill in retarding the progression of chronic renal failure].

    PubMed

    Wang, Shui-hua; Deng, Hong-tao; Wang, Guo-bin

    2008-08-01

    To assess the impact of Paidu Baoshen Pill (PBP, modified Dahuang Zhechong Pill), in retarding the procession of chronic renal failure (CRF) of stage II-III. The 283 patients of CRF stage II-III were randomly assigned to two groups, 151 patients in the treatment group treated with oral administration of PBP 3 g twice a day, and 132 patients in the control group with oxidative amylase aldehyde enveloped capsule 5-10 capsules thrice a day after meal. The course for both groups was 2 months, and the changes after 1 or 2 courses treatment in scoring of quality of life (QOL) and clinical symptoms, also in laboratory indexes including serum levels of creatinine (Cr), urea nitrogen (UN), and intrinsic creatinine clearance rate were observed. The total effective rate was 70. 86% (107/151 cases) in the treatment group and 44.70% (59/132 cases) in the control group, showing significant difference between them (X2 = 18.69, P < 0.01). Significant differences between groups were also shown in comparisons of scores of QOL and clinical symptoms after treatment. Inter-group comparison showed no difference in all the three indexes detected before treatment, but they did show statistical significance respectively after 1 and 2 courses of treatment (P < 0.05 and P < 0.01). PBP could effectively retard the progression of chronic renal failure and significantly improve the QOL of patients.

  3. Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC

    PubMed Central

    Petersen, Lars F.; Klimowicz, Alexander C.; Otsuka, Shannon; Elegbede, Anifat A.; Petrillo, Stephanie K.; Williamson, Tyler; Williamson, Chris T.; Konno, Mie; Lees-Miller, Susan P.; Hao, Desiree; Morris, Don; Magliocco, Anthony M.; Bebb, D. Gwyn

    2017-01-01

    Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p < 0.01). This effect was pronounced in stage II/III patients, even after adjusting for other clinical co-variates (p < 0.001). Additionally, we provide evidence that ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients. PMID:28418844

  4. Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC.

    PubMed

    Petersen, Lars F; Klimowicz, Alexander C; Otsuka, Shannon; Elegbede, Anifat A; Petrillo, Stephanie K; Williamson, Tyler; Williamson, Chris T; Konno, Mie; Lees-Miller, Susan P; Hao, Desiree; Morris, Don; Magliocco, Anthony M; Bebb, D Gwyn

    2017-06-13

    Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p < 0.01). This effect was pronounced in stage II/III patients, even after adjusting for other clinical co-variates (p < 0.001). Additionally, we provide evidence that ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients.

  5. Histopathology of motor cortex in an experimental focal ischemic stroke in mouse model.

    PubMed

    de Oliveira, Juçara Loli; Crispin, Pedro di Tárique Barreto; Duarte, Elisa Cristiana Winkelmann; Marloch, Gilberto Domingos; Gargioni, Rogério; Trentin, Andréa Gonçalves; Alvarez-Silva, Marcio

    2014-05-01

    Experimental ischemia results in cortical brain lesion followed by ischemic stroke. In this study, focal cerebral ischemia was induced in mice by occlusion of the middle cerebral artery. We studied cortical layers I, II/III, V and VI in the caudal forelimb area (CFA) and medial agranular cortex (AGm) from control and C57BL/6 mice induced with ischemic stroke. Based on our analysis of CFA and AGm motor cortex, significant differences were observed in the numbers of neurons, astrocytes and microglia in the superficial II/III and deep V cortical layers. Cellular changes were more prominent in layer V of the CFA with nuclear pyknosis, chromatin fragmentation, necrosis and degeneration, as well as, morphological evidence of apoptosis, mainly in neurons. As result, the CFA was more severely impaired than the AGm in this focal cerebral ischemic model, as evidenced by the proliferation of astrocytes, potentially resulting in neuroinflammation by microglia-like cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Endoscopic monopolar coagulation of internal haemorrhoids: a surgeon's experience of the first 100 cases.

    PubMed

    Loh, W-L; Tan, S; Ngooi, M S; Ong, Z K; Ngoi, S S

    2017-01-01

    The purpose of this study was to evaluate one surgeon's initial experience with a novel technique of retroflexed endoscopic coagulation of internal haemorrhoids. Patients who presented with symptoms and signs indicating Grade II-III haemorrhoids were counselled before the procedure. Those who were assessed to require an examination of their colon, based on their age and symptoms, underwent a full colonoscopy before treatment of the haemorrhoids. After the procedure, patients were routinely prescribed nonsteroidal anti-inflammatory drugs, antibiotics and laxatives. The first 100 patients of median age 52.0 (20.8-78.5) years included 65 (65%) women. Five (5%) patients suffered from postprocedural complications, of which three (3%) were postprocedural bleeding and two (2%) were postprocedural pain, all treated conservatively. The recurrence rate was 6% at a median follow-up time of 36 (6-76) months. The median duration of follow-up was 36.5 (8.5-57.0) months. This novel technique appears to be safe and effective for the treatment of Grade II-III internal haemorrhoids, and can be incorporated seamlessly into the end of a colonoscopy for the evaluation of haematochezia. Comparative trials should be performed. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

  7. Feasibility of using the retroauricular approach without endoscopic or robotic assistance for excision of benign neck masses.

    PubMed

    Ahn, Dongbin; Sohn, Jin Ho; Lee, Gil Joon; Hwang, Ki Ha

    2017-04-01

    The purpose of this study was to present our evaluation of the feasibility of using a retroauricular approach for excision of benign upper neck mass lesions without assistance of an endoscopic or robotic system. We enrolled 23 patients with benign neck mass lesions of the parotid gland, submandibular gland, and the level II/III region who underwent surgery via a retroauricular approach. In 22 of 23 patients (95.7%), parotidectomies, submandibular gland resections, and mass excisions were successfully completed under direct vision, without endoscopic or robotic assistance. Mean operation time, drainage amount, and drainage duration were 99.1 minutes, 44.3 mL, and 2.9 days, respectively. For a total of 23 patients, the mean visual analog scale score for subjective satisfaction with the incision scar was 8.9. No serious or permanent complications occurred. Excision using a retroauricular approach under direct vision is technically feasible for many benign mass lesions of the parotid gland, submandibular gland, and levels II/III of the neck region. © 2017 Wiley Periodicals, Inc. Head Neck 39: 748-753, 2017. © 2017 Wiley Periodicals, Inc.

  8. Heterotopic Transcallosal Projections Are Present throughout the Mouse Cortex

    PubMed Central

    Chovsepian, Alexandra; Empl, Laura; Correa, Daphne; Bareyre, Florence M.

    2017-01-01

    Transcallosal projection neurons are a population of pyramidal excitatory neurons located in layers II/III and to a lesser extent layer V of the cortex. Their axons form the corpus callosum thereby providing an inter-hemispheric connection in the brain. While transcallosal projection neurons have been described in some detail before, it is so far unclear whether they are uniformly organized throughout the cortex or whether different functional regions of the cortex contain distinct adaptations of their transcallosal connectivity. To address this question, we have therefore conducted a systematic analysis of transcallosal projection neurons and their axons across six distinct stereotactic coordinates in the mouse cortex that cover different areas of the motor and somatosensory cortices. Using anterograde and retrograde tracing techniques, we found that in agreement with previous studies, most of the transcallosal projections show a precise homotopic organization. The somata of these neurons are predominantly located in layer II/III and layer V but notably smaller numbers of these cells are also found in layer IV and layer VI. In addition, regional differences in the distribution of their somata and the precision of their projections exist indicating that while transcallosal neurons show a uniform organization throughout the mouse cortex, there is a sizeable fraction of these connections that are heterotopic. Our study thus provides a comprehensive characterization of transcallosal connectivity in different cortical areas that can serve as the basis for further investigations of the establishment of inter-hemispheric projections in development and their alterations in disease. PMID:28270750

  9. The role of DMQ9 in the long-lived mutant clk-1

    PubMed Central

    Yang, Yu-Ying; Vasta, Valeria; Hahn, Sihoun; Gangoiti, Jon A.; Opheim, Elyce; Sedensky, Margaret M.; Morgan, Phil G.

    2011-01-01

    Introduction Ubiquinone (UQ) is a redox active lipid that transfers electrons from complex I or II to complex III in the electron transport chain (ETC). The long-lived C. elegans mutant clk-1 is unable to synthesize its native ubiquinone, and accumulates high amounts of its precursor, 5-demethoxyubiquinone-9 (DMQ9). In clk-1, complex I-III activity is inhibited while complex II-III activity is normal. We asked whether the complex I-III defect in clk-1 was caused by: 1) a defect in the ETC; 2) an inhibitory effect of DMQ9; or 3) a decreased amount of ubiquinone. Methods We extracted the endogenous quinones from wildtype (N2) and clk-1 mitochondria, replenished them with exogenous ubiquinones, and measured ETC activities. Results Replenishment of extracted mutant and wildtype mitochondria resulted in equal enzymatic activities for complex I-III and II-III ETC assays. Blue native gels showed that supercomplex formation was indistinguishable between clk-1 and N2. Addition of a pentane extract from clk-1 mitochondria containing DMQ9 to wildtype mitochondria specifically inhibited complex I-III activity. UQ in clk-1 mitochondria was oxidized compared to N2. Discussion Our results show that no measurable intrinsic ETC defect exists in clk-1 mitochondria. The data indicate that DMQ9 specifically inhibits electron transfer from complex I to ubiquinone. PMID:21745495

  10. Developmental Origin of Patchy Axonal Connectivity in the Neocortex: A Computational Model

    PubMed Central

    Bauer, Roman; Zubler, Frederic; Hauri, Andreas; Muir, Dylan R.; Douglas, Rodney J.

    2014-01-01

    Injections of neural tracers into many mammalian neocortical areas reveal a common patchy motif of clustered axonal projections. We studied in simulation a mathematical model for neuronal development in order to investigate how this patchy connectivity could arise in layer II/III of the neocortex. In our model, individual neurons of this layer expressed the activator–inhibitor components of a Gierer–Meinhardt reaction–diffusion system. The resultant steady-state reaction–diffusion pattern across the neuronal population was approximately hexagonal. Growth cones at the tips of extending axons used the various morphogens secreted by intrapatch neurons as guidance cues to direct their growth and invoke axonal arborization, so yielding a patchy distribution of arborization across the entire layer II/III. We found that adjustment of a single parameter yields the intriguing linear relationship between average patch diameter and interpatch spacing that has been observed experimentally over many cortical areas and species. We conclude that a simple Gierer–Meinhardt system expressed by the neurons of the developing neocortex is sufficient to explain the patterns of clustered connectivity observed experimentally. PMID:23131803

  11. [Posterior interbody fusion versus improved transforaminal lumbar interbody fusion in segmental spinal fixation for aged spondylolisthesis with lumbar spinal canal stenosis].

    PubMed

    Ma, Chao; Wu, Ji-bin; Zhao, Meng; Dai, Wei-xiang; Wu, De-hui; Wang, Zhao-hong; Feng, Jie; Liu, Chao; Zhao, Qing-hua; Tian, Ji-wei

    2012-03-06

    To assess the clinical and radiographic outcomes of posterior lumbar fixation and posterior interbody fusion or improved transforaminal lumbar interbody fusion for Meyerding grade II/III spondylolisthesis so as to address the suitability of a dynamic stabilization. A total of 28 consecutive patients underwent posterior lumbar fixation and posterior interbody fusion or improved transforaminal lumbar interbody fusion for Meyerding grade II/III spondylolisthesis. Among them, 13 patients underwent posterior interface fusion (PLIF) and pedicle screw fixation. And improved transforaminal lumbar interbody fusion (ITLIF) and placement of the same system were performed in 15 patients. Their clinical, economic, functional, and radiographic data were recorded both pre- and postoperatively. The average changes of economic and functional scores on the Prolo scale were 1.36 and 1.48 respectively. In patients with posterior interbody fusion; the average preoperative vertebral slippage was 46.9% (range: 25 - 75%) versus 14.6% (range: 15 - 25%) postoperatively. In patients with ITLIF, the average changes in economic and functional scores were 1.75 and 1.63 respectively. And the average preoperative vertebral slippage was 45.2% (range: 28 - 78%) compared with 26.3% (range: 14 - 28%) postoperatively. When two fusion techniques were compared, an overall superior reliability and resistance of systems was associated with the ITLIF procedure. But their clinical outcomes did not differ greatly (P > 0.05). The application of a segmental pedicle screw fixation is both feasible and efficacious.

  12. A call for more transparency of registered clinical trials on endometriosis

    PubMed Central

    Guo, Sun-Wei; Hummelshoj, Lone; Olive, David L.; Bulun, Serdar E.; D'Hooghe, Thomas M.; Evers, Johannes L.H.

    2009-01-01

    In response to the pressing need for more efficacious and safer therapeutics for endometriosis, there have been numerous reports in the last decade of positive results from animal and in vitro studies of various compounds as potential therapeutics for endometriosis. A handful of these have undergone phase II/III clinical trials. Since the announcement of the International Committee of Medical Journal Editors that mandated registration as a prerequisite for publication, 57 endometriosis-related clinical trials have been registered at ClinicalTrials.gov, an Internet-based public depository for information on drug studies. Among them, 25 are listed as completed, and 2 as suspended. There are 15 completed phase II/III trials, which evaluated the efficacy of various promising compounds. Yet only three of the 15 trials (20%) have published their results. The remaining 12 (80%) studies so far have not published their findings. We argue that this apparent lack of transparency will actually not benefit the trial sponsors or the public, and will ultimately prove detrimental to research efforts attempting to develop more efficacious and safer therapeutics for endometriosis. Thus we call for more transparency of clinical trials on endometriosis. PMID:19264712

  13. The characterization of neuroenergetic effects of chronic L-tyrosine administration in young rats: evidence for striatal susceptibility.

    PubMed

    Ferreira, Gabriela K; Carvalho-Silva, Milena; Gomes, Lara M; Scaini, Giselli; Teixeira, Leticia J; Mota, Isabella T; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

    2015-02-01

    Tyrosinemia type II is an inborn error of metabolism caused by a deficiency in hepatic cytosolic aminotransferase. Affected patients usually present a variable degree of mental retardation, which may be related to the level of plasma tyrosine. In the present study we evaluated effect of chronic administration of L-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase and complexes I, II, II-III and IV in cerebral cortex, hippocampus and striatum of rats in development. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old); rats were killed 12 h after last injection. Our results demonstrated that L-tyrosine inhibited the activity of citrate synthase in the hippocampus and striatum, malate dehydrogenase activity was increased in striatum and succinate dehydrogenase, complexes I and II-III activities were inhibited in striatum. However, complex IV activity was increased in hippocampus and inhibited in striatum. By these findings, we suggest that repeated administrations of L-tyrosine cause alterations in energy metabolism, which may be similar to the acute administration in brain of infant rats. Taking together the present findings and evidence from the literature, we hypothesize that energy metabolism impairment could be considered an important pathophysiological mechanism underlying the brain damage observed in patients with tyrosinemia type II.

  14. A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer

    PubMed Central

    Berdiel-Acer, Mireia; Berenguer, Antoni; Sanz-Pamplona, Rebeca; Cuadras, Daniel; Sanjuan, Xavier; Paules, Maria José; Santos, Cristina; Salazar, Ramon; Moreno, Victor; Capella, Gabriel; Villanueva, Alberto; Molleví, David G.

    2014-01-01

    Based on 108 differentially expressed genes between carcinoma-associated fibroblasts (CAFs) and paired normal colonic fibroblasts we recently reported, a 5-gene classifier for relapse prediction in Stage II/III colorectal cancer (CRC) was developed. Its predictive value was validated in datasets GSE17538, GSE33113 and GSE14095. An additional validation was performed in a metacohort (n=317) and 142 CRC patients by means of RT-PCR. The 5-gene classifier was significantly associated with increased relapse risk and death from CRC across all validation series of Stage II/III patients used. Multivariate Cox regression analyses confirmed the independent prognostic value of the stromal classifier (HR=2.67; P=0.002). Post-test probabilities provided evidence of the suitability of the 5-gene classifier in clinical practice, identifying a subgroup of Stage-II patients who were at high risk of relapse. Moreover, the a priory worst prognosis mesenchymal subtype of tumours can be stratified according to the physiological status of their carcinoma-associated fibroblasts. In conclusion the CAFs-derived 5-gene classifier provides more accurate information about outcome than conventional clinicopathological criteria and it could be useful to take clinical decisions, especially in Stage II. Additionally, the classifier put into relevance the CAF's intratumoral heterogeneity and might contribute to find relevant targets for depleting adequate CAFS subtypes. PMID:25115384

  15. Methamphetamine-induced inhibition of mitochondrial complex II: roles of glutamate and peroxynitrite.

    PubMed

    Brown, Jeffrey M; Quinton, Maria S; Yamamoto, Bryan K

    2005-10-01

    High-dose methamphetamine (METH) is associated with long-term deficits in dopaminergic systems. Although the mechanism(s) which contributes to these deficits is not known, glutamate and peroxynitrite are likely to play a role. These factors are hypothesized to inhibit mitochondrial function, increasing the free radical burden and decreasing neuronal energy supplies. Previous studies suggest a role for the mitochondrial electron transport chain (ETC) in mediating toxicity of METH. The purpose of the present studies was to determine whether METH administration selectively inhibits complex II of the ETC in rats. High-dose METH administration (10 mg/kg every 2 h x 4) rapidly (within 1 h) decreased complex II (succinate dehydrogenase) activity by approximately 20-30%. In addition, decreased activity of complex II-III, but not complex I-III, of the mitochondrial ETC was also observed 24 h after METH. This inhibition was not due to direct inhibition by METH or METH-induced hyperthermia and was specific to striatal brain regions. METH-induced decreases in complex II-III were prevented by MK-801 and the peroxynitrite scavenger 5,10,15,20-tetrakis (2,4,6-trimethyl-3,5-sulphonatophenyl) porphinato iron III. These findings provide the first evidence that METH administration, via glutamate receptor activation and peroxynitrite formation, selectively alters a specific site of the ETC.

  16. Layer-specific optogenetic activation of pyramidal neurons causes beta–gamma entrainment of neonatal networks

    PubMed Central

    Bitzenhofer, Sebastian H; Ahlbeck, Joachim; Wolff, Amy; Wiegert, J. Simon; Gee, Christine E.; Oertner, Thomas G.; Hanganu-Opatz, Ileana L.

    2017-01-01

    Coordinated activity patterns in the developing brain may contribute to the wiring of neuronal circuits underlying future behavioural requirements. However, causal evidence for this hypothesis has been difficult to obtain owing to the absence of tools for selective manipulation of oscillations during early development. We established a protocol that combines optogenetics with electrophysiological recordings from neonatal mice in vivo to elucidate the substrate of early network oscillations in the prefrontal cortex. We show that light-induced activation of layer II/III pyramidal neurons that are transfected by in utero electroporation with a high-efficiency channelrhodopsin drives frequency-specific spiking and boosts network oscillations within beta–gamma frequency range. By contrast, activation of layer V/VI pyramidal neurons causes nonspecific network activation. Thus, entrainment of neonatal prefrontal networks in fast rhythms relies on the activation of layer II/III pyramidal neurons. This approach used here may be useful for further interrogation of developing circuits, and their behavioural readout. PMID:28216627

  17. Colles' fracture treated with non-bridging external fixation: a 1-year follow-up.

    PubMed

    Andersen, J K; Høgh, A; Gantov, J; Vaesel, M T; Hansen, T Baek

    2009-08-01

    The results in 75 of 105 patients with Older type II/III (AO type A2.2, A3.1, A3.2) Colles' fractures, treated with non-bridging external fixation are presented. The mean age was 67.8 years, and all patients were followed prospectively for 12 months with radiological and functional assessment. No statistically significant loss of radial length, angulation or inclination was seen between the postoperative reduction and the 1-year follow-up examination. The clinical results after 1 year were 66 (88%) excellent/good, nine (12%) fair and 0 (0%) poor according to the modified Gartland and Werley score. Mean visual analogue scale pain score after 1 year was 0.8. In three patients (4%), re-displacement of the fracture occurred and was treated with plating. Non-bridging external fixation offers a reliable method of maintaining radiological reduction of Older type II/III fractures of the distal radius and gives a good functional outcome after 1 year.

  18. Docetaxel and cisplatin as first-line treatment for patients with metastatic esophageal cancer: a pilot study.

    PubMed

    Laack, Eckart; Andritzky, Birte; Dürk, Heinz; Burkholder, Iris; Edler, Lutz; Schuch, Gunter; Boeters, Ina; Görn, Michael; Lipp, Rainer; Horst, Hartmut; Popp, Johann; Hossfeld, Dieter K

    2005-12-01

    We investigated the combination of docetaxel and cisplatin as first-line chemotherapy in patients with metastatic esophageal cancer. 16 chemotherapy-naïve patients with distant metastases were included in the study (15 male, 1 female; median age: 58.5 years (range 37-69); median ECOG performance status: 1). 11 patients (69%) had esophageal cancer, and 5 patients (31%) had cancer of the gastroesophageal junction. Patients received docetaxel 75 mg/m2 and cisplatin 80 mg/m2 on day 1 every 3 weeks. A total of 55 chemotherapy cycles was administered. The median number of cycles was 3 (range 1-6). The overall response rate was 31.3%. 4 out of 10 patients (40%) with squamous cell carcinoma and 1 out of 5 patients (20%) with adenocarcinoma responded to chemotherapy. The median overall survival was 29.6 weeks, and the median progression-free survival was 18.6 weeks. Hematological and non-hematological toxicities were moderate (neutropenia WHO grade III/IV: 42.9%, alopecia grade II/III: 64.3%, nausea/vomiting grade II/III: 57.2%, neurotoxicity grade II: 14.3%). The combination of docetaxel and cisplatin is an active regimen with moderate toxicity in the treatment of patients with metastatic esophageal cancer. This pilot study demonstrates the feasibility of a combination treatment containing a taxane and cisplatin in metastatic esophageal cancer.

  19. Accident progression event tree analysis for postulated severe accidents at N Reactor

    SciTech Connect

    Wyss, G.D.; Camp, A.L.; Miller, L.A.; Dingman, S.E.; Kunsman, D.M. ); Medford, G.T. )

    1990-06-01

    A Level II/III probabilistic risk assessment (PRA) has been performed for N Reactor, a Department of Energy (DOE) production reactor located on the Hanford reservation in Washington. The accident progression analysis documented in this report determines how core damage accidents identified in the Level I PRA progress from fuel damage to confinement response and potential releases the environment. The objectives of the study are to generate accident progression data for the Level II/III PRA source term model and to identify changes that could improve plant response under accident conditions. The scope of the analysis is comprehensive, excluding only sabotage and operator errors of commission. State-of-the-art methodology is employed based largely on the methods developed by Sandia for the US Nuclear Regulatory Commission in support of the NUREG-1150 study. The accident progression model allows complex interactions and dependencies between systems to be explicitly considered. Latin Hypecube sampling was used to assess the phenomenological and systemic uncertainties associated with the primary and confinement system responses to the core damage accident. The results of the analysis show that the N Reactor confinement concept provides significant radiological protection for most of the accident progression pathways studied.

  20. Effects of acute and chronic treatment elicited by lamotrigine on behavior, energy metabolism, neurotrophins and signaling cascades in rats.

    PubMed

    Abelaira, Helena M; Réus, Gislaine Z; Ribeiro, Karine F; Zappellini, Giovanni; Ferreira, Gabriela K; Gomes, Lara M; Carvalho-Silva, Milena; Luciano, Thais F; Marques, Scherolin O; Streck, Emilio L; Souza, Cláudio T; Quevedo, João

    2011-12-01

    The present study was aimed to investigate the behavioral and molecular effects of lamotrigine. To this aim, Wistar rats were treated with lamotrigine (10 and 20 mg/kg) or imipramine (30 mg/kg) acutely and chronically. The behavior was assessed using forced swimming test. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), Proteina Kinase B (PKB, AKT), glycogen synthase kinase 3 (GSK-3) and B-cell lymphoma 2 (Bcl-2) levels, citrate synthase, creatine kinase and mitochondrial chain (I, II, II-III and IV) activities were assessed in the brain. The results showed that both treatments reduced the immobility time. The BDNF were increased in the prefrontal after acute treatment with lamotrigine (20 mg/kg), and the BDNF and NGF were increased in the prefrontal after chronic treatment with lamotrigine in all doses. The AKT increased and Bcl-2 and GSK-3 decreased after both treatments in all brain areas. The citrate synthase and creatine kinase increased in the amygdala after acute treatment with imipramine. Chronic treatment with imipramine and lamotrigine (10 mg/kg) increased the creatine kinase in the hippocampus. The complex I was reduced and the complex II, II-III and IV were increased, but related with treatment and brain area. In conclusion, lamotrigine exerted antidepressant-like, which can be attributed to its effects on pathways related to depression, such as neurotrophins, metabolism energy and signaling cascade. Copyright © 2011. Published by Elsevier Ltd.

  1. Treatment with enhanced external counterpulsation improves cognitive functions in chronic heart failure patients.

    PubMed

    Kozdağ, Güliz; Işeri, Pervin; Gökçe, Gökçen; Ertaş, Gökhan; Aygün, Fatih; Kutlu, Ayşe; Hebert, Kathy; Ural, Dilek

    2013-07-01

    Chronic heart failure (CHF) has been associated with an increased risk of poorer cognitive performance in older adults. Reversibility of cognitive impairment after medical treatment has been reported, although the restorative effects of enhanced external counterpulsation (EECP) on cognitive performance have not been studied. We investigated the effect of EECP on cognitive functions in CHF patients. Thirty-six individuals (mean age: 66±8 years) who were diagnosed with CHF and were New York Heart Association (NYHA) Class II-III and Canadian Cardiovascular Society (CCS) Class II-III participated in this study. Neuropsychological assessment was performed in these patients. Patients in the EECP treatment group showed a statistically significant improvement in spontaneous naming (p=0.011) and forward row score of the attention subset among domains of cognition (p=0.020) and interference time of executive function (p=0.012). Enhanced external counter pulsation resulted in improvement in all domains of cognitive functions except verbal and visual memory tests.

  2. Effects of Mood Stabilizers on Brain Energy Metabolism in Mice Submitted to an Animal Model of Mania Induced by Paradoxical Sleep Deprivation.

    PubMed

    Streck, Emilio L; Scaini, Giselli; Jeremias, Gabriela C; Rezin, Gislaine T; Gonçalves, Cinara L; Ferreira, Gabriela K; Réus, Gislaine Z; Resende, Wilson R; Valvassori, Samira S; Kapczinski, Flávio; Andersen, Mônica L; Quevedo, João

    2015-06-01

    There is a body of evidence suggesting that mitochondrial dysfunction is involved in bipolar disorder (BD) pathogenesis. Studies suggest that abnormalities in circadian cycles are involved in the pathophysiology of affective disorders; paradoxical sleep deprivation (PSD) induces hyperlocomotion in mice. Thus, the present study aims to investigate the effects of lithium (Li) and valproate (VPA) in an animal model of mania induced by PSD for 96 h. PSD increased exploratory activity, and mood stabilizers prevented PSD-induced behavioral effects. PSD also induced a significant decrease in the activity of complex II-III in hippocampus and striatum; complex IV activity was decreased in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex. Additionally, VPA administration was able to prevent PSD-induced inhibition of complex II-III and IV activities in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex, whereas Li administration prevented PSD-induced inhibition only in prefrontal cortex and hippocampus. Regarding the enzymes of Krebs cycle, only citrate synthase activity was increased by PSD in prefrontal cortex. We also found a similar effect in creatine kinase, an important enzyme that acts in the buffering of ATP levels in brain; its activity was increased in prefrontal cortex, hippocampus and cerebral cortex. These results are consistent with the connection of mitochondrial dysfunction and hyperactivity in BD and suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.

  3. Association Between Geographic Access to Cancer Care and Receipt of Radiation Therapy for Rectal Cancer.

    PubMed

    Lin, Chun Chieh; Bruinooge, Suanna S; Kirkwood, M Kelsey; Hershman, Dawn L; Jemal, Ahmedin; Guadagnolo, B Ashleigh; Yu, James B; Hopkins, Shane; Goldstein, Michael; Bajorin, Dean; Giordano, Sharon H; Kosty, Michael; Arnone, Anna; Hanley, Amy; Stevens, Stephanie; Olsen, Christine

    2016-03-15

    Trimodality therapy (chemoradiation and surgery) is the standard of care for stage II/III rectal cancer but nearly one third of patients do not receive radiation therapy (RT). We examined the relationship between the density of radiation oncologists and the travel distance to receipt of RT. A retrospective study based on the National Cancer Data Base identified 26,845 patients aged 18 to 80 years with stage II/III rectal cancer diagnosed from 2007 to 2010. Radiation oncologists were identified through the Physician Compare dataset. Generalized estimating equations clustering by hospital service area was used to examine the association between geographic access and receipt of RT, controlling for patient sociodemographic and clinical characteristics. Of the 26,845 patients, 70% received RT within 180 days of diagnosis or within 90 days of surgery. Compared with a travel distance of <12.5 miles, patients diagnosed at a reporting facility who traveled ≥50 miles had a decreased likelihood of receipt of RT (50-249 miles, adjusted odds ratio 0.75, P<.001; ≥250 miles, adjusted odds ratio 0.46; P=.002), all else being equal. The density level of radiation oncologists was not significantly associated with the receipt of RT. Patients who were female, nonwhite, and aged ≥50 years and had comorbidities were less likely to receive RT (P<.05). Patients who were uninsured but self-paid for their medical services, initially diagnosed elsewhere but treated at a reporting facility, and resided in Midwest had an increased the likelihood of receipt of RT (P<.05). An increased travel burden was associated with a decreased likelihood of receiving RT for patients with stage II/III rectal cancer, all else being equal; however, radiation oncologist density was not. Further research of geographic access and establishing transportation assistance programs or lodging services for patients with an unmet need might help decrease geographic barriers and improve the quality of rectal

  4. Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection.

    PubMed

    Qing, Song; Tulake, Wuniqiemu; Ru, Mingfang; Li, Xiaohong; Yuemaier, Reziwanguli; Lidifu, Dilare; Rouzibilali, Aierken; Hasimu, Axiangu; Yang, Yun; Rouziahong, Reziya; Upur, Halmurat; Abudula, Abulizi

    2017-04-01

    It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus-based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16-positive squamous cell carcinoma and human papillomavirus-negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16-positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix ( p < 0.05). In addition, the transcription of PCBP2, MCM5, hnRNPA1, TYPH, and CYC was also significantly increased in cervical intraepithelial neoplasia II-III compared to normal cervix. Immunohistochemistry staining further confirmed the overexpression of PCBP2, hnRNPA1, ASAH1, and DDX5 in squamous cell carcinoma and cervical intraepithelial neoplasia II-III compared to normal controls ( p < 0.05). Our data suggest that the expression of ASAH1, PCBP2, DDX5

  5. Age- and time-dependent effects on functional outcome and cortical activation pattern in patients with median nerve injury: a functional magnetic resonance imaging study.

    PubMed

    Fornander, Lotta; Nyman, Torbjörn; Hansson, Thomas; Ragnehed, Mattias; Brismar, Tom

    2010-07-01

    The authors conducted a study to determine age- and time-dependent effects on the functional outcome after median nerve injury and repair and how such effects are related to changes in the pattern of cortical activation in response to tactile stimulation of the injured hand. The authors studied 11 patients with complete unilateral median nerve injury at the wrist repaired with epineural suture. In addition, 8 patients who were reported on in a previous study were included in the statistical analysis. In the entire study cohort, the mean age at injury was 23.3 +/- 13.4 years (range 7-57 years) and the time after injury ranged from 1 to 11 years. Sensory perception was measured with the static 2-point discrimination test and monofilaments. Functional MR imaging was conducted during tactile stimulation (brush strokes) of Digits II-III and IV-V of both hands, respectively. Tactile sensation was diminished in the median territory in all patients. The strongest predictor of 2-point discrimination was age at injury (p < 0.0048), and when this was accounted for in the regression analysis, the other age- and time-dependent predictors had no effect. The activation ratios (injured/healthy hand) for Digit II-III and Digit IV-V stimulation were positively correlated (rho 0.59, p < 0.011). The activation ratio for Digit II-III stimulation correlated weakly with time after injury (p < 0.041). The activation ratio of Digits IV-V correlated weakly with both age at injury (p < 0.048) and time after injury (p < 0.033), but no predictor reached significance in the regression model. The mean ratio of ipsi- and contralateral hemisphere activation after stimulation of the injured hand was 0.55, which was not significantly different from the corresponding ratio of the healthy hand (0.66). Following a median nerve injury (1-11 years after injury) there may be an initial increase in the volume of the cortical representation, which subsequently declines during the restoration phase. These

  6. Cost-effectiveness of New Surgical Treatments for Hemorrhoidal Disease: A Multicentre Randomized Controlled Trial Comparing Transanal Doppler-guided Hemorrhoidal Artery Ligation With Mucopexy and Circular Stapled Hemorrhoidopexy.

    PubMed

    Lehur, Paul A; Didnée, Anne S; Faucheron, Jean-Luc; Meurette, Guillaume; Zerbib, Philippe; Siproudhis, Laurent; Vinson-Bonnet, Béatrice; Dubois, Anne; Casa, Christine; Hardouin, Jean-Benoit; Durand-Zaleski, Isabelle

    2016-11-01

    To compare Doppler-guided hemorrhoidal artery ligation (DGHAL) with circular stapled hemorrhoidopexy (SH) in the treatment of grade II/III hemorrhoidal disease (HD). DGHAL is a treatment option for symptomatic HD; existing studies report limited risk and satisfactory outcomes. DGHAL has never before been compared with SH in a large-scale multi-institutional randomized clinical trial. Three hundred ninety-three grade II/III HD patients recruited in 22 centers from 2010 to 2013 were randomized to DGHAL (n = 197) or SH (n = 196). The primary endpoint was operative-related morbidity at 3 months (D.90) based on the Clavien-Dindo surgical complications grading. Total cost, cost-effectiveness, and clinical outcome were assessed at 1 year. At D.90, operative-related adverse events occurred after DGHAL and SH, respectively, in 47 (24%) and 50 (26%) patients (P = 0.70). DGHAL resulted in longer mean operating time (44±16 vs 30±14 min; P < 0.001), less pain (postoperative and at 2 wks visual analogic scale: 2.2 vs 2.8; 1.3 vs 1.9; P = 0.03; P = 0.013) and shorter sick leave (12.3 vs 14.8 d; P = 0.045). At 1 year, DGHAL led to more residual grade III HD (15% vs 5%) and a higher reoperation rate (8% vs 4%). Patient satisfaction was >90% for both procedures. Total cost at 1 year was greater for DGHAL [&OV0556;2806 (&OV0556;2670; 2967) vs &OV0556;2538 (&OV0556;2386; 2737)]. The D.90, incremental cost-effectiveness ratio (ICER) was &OV0556;7192 per averted complication. At 1 year DGHAL strategy was dominated. DGHAL and SH are viable options in grade II/III HD with no significant difference in operative-related risk. Although resulting in less postoperative pain and shorter sick leave, DGHAL was more expensive, took longer, and provided a possible inferior anatomical correction suggesting an increased risk of recurrence.

  7. Receptive field scatter, topography and map variability in different layers of the hindpaw representation of rat somatosensory cortex.

    PubMed

    Haupt, S Shuichi; Spengler, Friederike; Husemann, Robert; Dinse, Hubert R

    2004-04-01

    We recorded neurons extracellularly in layers II/III, IV, and V of the hindpaw representation of primary somatosensory cortex in anesthetized rats and studied laminar features of receptive fields (RFs) and representational maps. On average, RFs were smallest in layer IV and largest in layer V; however, for individual penetrations we found substantial deviations from this rule. Within the hindpaw representation, a distinct rostrocaudal gradient of RF size was present in all layers. While layer V RFs were generally largest independent of this gradient, layer IV RFs recorded caudally representing the proximal portions of the paw were larger than layer II/III RFs recorded rostrally representing the digits. The individual scatter of the locations of RFs across laminar groups was in the range of several millimeters, corresponding to about 25% of the average RF diameter. The cutaneous representations of the hindpaw in extragranular layers were confined to the areal extent defined by responsive sites in layer IV. Comparison between RFs determined quantitatively and by handplotting showed a reliable correspondence. Repeated measurements of RFs revealed spontaneous fluctuations of RF size of no more than 5% of the initial condition over an observation period of several hours. The topography and variability of cortical maps of the hindpaw representation were studied with a quantitative interpolation method taking into account the geometric centers of RFs and the corresponding cortical recording sites. On average, the overall topography in terms of preservation of neighborhood relations was present in all layers, although some individual maps showed severe distortions of topography. Factors contributing to map variability were overall position of the representation on the cortical surface, internal topography and spatial extent. Interindividual variability of map layout was always highest in the digit representations. Local topographic orderliness was lowest in layer V, but

  8. Oxidative turnover increases the rate constant and extent of intramolecular electron transfer in the multicopper enzymes, ascorbate oxidase and laccase.

    PubMed

    Tollin, G; Meyer, T E; Cusanovich, M A; Curir, P; Marchesini, A

    1993-12-07

    Using laser flash photolysis of lumiflavin/EDTA solutions containing ascorbate oxidase, we find that the rate constant for intramolecular electron transfer varies from one enzyme preparation to another and is generally a more sensitive measure of the state of the active site than are steady-state assays. Thus, type I copper is initially reduced in a second-order reaction followed by first-order reoxidation by the type II-III trinuclear copper center. The observed rate constant for this intramolecular process in presumably native enzyme is 160 s-1 at pH 7, whereas an enzyme preparation which had less than 20% activity had a rate constant of 2.6 s-1. Other samples of relatively active enzyme showed biphasic intramolecular kinetics intermediate between the above values. The inactive enzyme sample could be reactivated by dialysis against ascorbate or by treatment with ferricyanide, resulting in a corresponding increase in the intramolecular rate constant for type I copper reoxidation to a value comparable to that of native enzyme. Using this same methodology, we have determined that the type I copper in Japanese lacquer tree laccase is reoxidized by the type II-III trinuclear copper center in a first-order (intramolecular) process with rate constants of 1 s-1 at pH 7.0 and 4.9 s-1 at pH 6.0, values which are approximately two orders of magnitude smaller than for ascorbate oxidase. The intramolecular rate constant and enzyme activity for laccase also increased, but only by a factor of 2-6, when the enzyme was treated with ascorbate or ferricyanide, respectively. We further found that intramolecular electron transfer in laccase was completely inhibited by fluoride ion, in contrast to ascorbate oxidase which is unaffected by this ion. These differences in behavior for these two very similar enzymes are rather remarkable, when it is considered that the distance between copper atoms is constrained by the location of the protein-derived copper ligands in the three

  9. Primary healthcare worker knowledge related to prenatal and immediate newborn care: a cross sectional study in Masindi, Uganda

    PubMed Central

    2014-01-01

    Background Global neonatal mortality remains unacceptably high. Health workers who attend to prenatal and postnatal mothers need to be knowledgeable in preventive and curative care for pregnant women and their newborn babies. This study aimed to determine the level of knowledge related to prenatal and immediate newborn care among primary healthcare workers in Masindi, Uganda. Methods A cross-sectional study was conducted. Interviews comprised of 25 multiple-choice questions were administered to health workers who were deployed to offer prenatal and postnatal care in Masindi in November 2011. Questions were related to four domains of knowledge: prenatal care, immediate newborn care, management of neonatal infections and identifying and stabilizing Low-Birth Weight (LBW) babies. Corresponding composite variables were derived; level of knowledge among health workers dichotomized as ‘adequate’ or ‘inadequate’. The chi-square statistic test was used to examine associations with independent variables including level of training (nursing assistant, general nurse or midwife), level of care (hospital/health centre level IV or health centre level III/II) and years of service (five years or less, six years or more). Results 183 health workers were interviewed: general nurses (39.3%), midwives (21.9%) and nursing assistants (38.8%). Respectively, 53.6%, 46.5%, 7.1% and 56.3% were considered to have adequate knowledge in prenatal care, newborn care, management of neonatal infections and identifying/stabilizing LBW babies. Being a general nurse was significantly associated with having adequate knowledge in identifying and stabilizing LBW babies (p < 0.001) compared to being a nursing assistant. Level of care being hospital/health centre level IV was not significantly associated with having adequate knowledge in prenatal or newborn care with reference to health centres of level III/II. Conclusion Knowledge regarding prenatal and newborn care among primary healthcare

  10. Primary healthcare worker knowledge related to prenatal and immediate newborn care: a cross sectional study in Masindi, Uganda.

    PubMed

    Ayiasi, Richard Mangwi; Criel, Bart; Orach, Christopher Garimoi; Nabiwemba, Elizabeth; Kolsteren, Patrick

    2014-02-11

    Global neonatal mortality remains unacceptably high. Health workers who attend to prenatal and postnatal mothers need to be knowledgeable in preventive and curative care for pregnant women and their newborn babies. This study aimed to determine the level of knowledge related to prenatal and immediate newborn care among primary healthcare workers in Masindi, Uganda. A cross-sectional study was conducted. Interviews comprised of 25 multiple-choice questions were administered to health workers who were deployed to offer prenatal and postnatal care in Masindi in November 2011. Questions were related to four domains of knowledge: prenatal care, immediate newborn care, management of neonatal infections and identifying and stabilizing Low-Birth Weight (LBW) babies. Corresponding composite variables were derived; level of knowledge among health workers dichotomized as 'adequate' or 'inadequate'. The chi-square statistic test was used to examine associations with independent variables including level of training (nursing assistant, general nurse or midwife), level of care (hospital/health centre level IV or health centre level III/II) and years of service (five years or less, six years or more). 183 health workers were interviewed: general nurses (39.3%), midwives (21.9%) and nursing assistants (38.8%). Respectively, 53.6%, 46.5%, 7.1% and 56.3% were considered to have adequate knowledge in prenatal care, newborn care, management of neonatal infections and identifying/stabilizing LBW babies. Being a general nurse was significantly associated with having adequate knowledge in identifying and stabilizing LBW babies (p < 0.001) compared to being a nursing assistant. Level of care being hospital/health centre level IV was not significantly associated with having adequate knowledge in prenatal or newborn care with reference to health centres of level III/II. Knowledge regarding prenatal and newborn care among primary healthcare workers in Masindi was very low. The highest

  11. Genetic markers associated with dihydroartemisinin–piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study

    PubMed Central

    Amato, Roberto; Lim, Pharath; Miotto, Olivo; Amaratunga, Chanaki; Dek, Dalin; Pearson, Richard D.; Almagro-Garcia, Jacob; Neal, Aaron T.; Sreng, Sokunthea; Suon, Seila; Drury, Eleanor; Jyothi, Dushyanth; Stalker, Jim; Kwiatkowski, Dominic P.; Fairhurst, Rick M.

    2017-01-01

    Summary Background As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong Subregion (GMS), emerging resistance to partner drugs in artemisinin combination therapies (ACTs) seriously threatens global efforts to treat and eliminate this disease. Molecular markers for ACT failure are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in Southeast Asia and beyond. Methods We performed a genome-wide association study (GWAS) of 297 P. falciparum isolates from Cambodia to investigate the relationship of 11,630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC50s), and tested whether these genetic variants are markers of dihydroartemisinin-piperaquine failures. We then performed a survival analysis of 133 patients to determine whether candidate molecular markers predicted parasite recrudescence following dihydroartemisinin-piperaquine treatment. Findings Piperaquine IC50s increased significantly from 2011 to 2013 in 3 Cambodian provinces. Genome-wide analysis of SNPs identified a chromosome 13 region that associates with elevated piperaquine IC50s. A nonsynonymous SNP (encoding a Glu415Gly substitution) in this region, within a gene encoding an exonuclease, associates with parasite recrudescence following dihydroartemisinin-piperaquine treatment. Genome-wide analysis of CNVs revealed that a single copy of the mdr1 gene on chromosome 5 and a novel amplification of the plasmepsin II and plasmepsin III genes on chromosome 14 also associate with elevated piperaquine IC50s. After adjusting for covariates, both exo-E415G and plasmepsin II-III markers significantly associate with decreased treatment efficacy (0.38 and 0.41 survival rates, respectively). Interpretation The exo-E415G SNP and plasmepsin II-III amplification are markers of piperaquine resistance and dihydroartemisinin

  12. Animal models of rheumatoid arthritis: How informative are they?

    PubMed

    McNamee, Kay; Williams, Richard; Seed, Michael

    2015-07-15

    Animal models of arthritis are widely used to de-convolute disease pathways and to identify novel drug targets and therapeutic approaches. However, the high attrition rates of drugs in Phase II/III rates means that a relatively small number of drugs reach the market, despite showing efficacy in pre-clinical models. There is also increasing awareness of the ethical issues surrounding the use of animal models of disease and it is timely, therefore, to review the relevance and translatability of animal models of arthritis. In this paper we review the most commonly used animal models in terms of their pathological similarities to human rheumatoid arthritis as well as their response to drug therapy. In general, the ability of animal models to predict efficacy of biologics in man has been good. However, the predictive power of animal models for small molecules has been variable, probably because of differences in the levels of target knockdown achievable in vivo.

  13. Project CHECO Southeast Asia Report. Rescue at Ban Phanop, 5-7 December 1969

    DTIC Science & Technology

    1970-02-15

    II II II • • • • • • • • • • • • • • DEC~SS PROJECT lillillti 1’ 1 ’ 11111[[1 , ~~ 1 :. 111 • 11 ·c’)l,,iltilil 111111111 l , ontemporary...8217lij 111 """.l.tllilllll,llllltlllll’ll ii · H ISior~cal 11 I " � i 111111 ! II . E,~~~0H~~~~ilfllnlll·l~t~!lltl 1 1111111111111111111111111...8217"’"� I IIIII 111111’ I ’ II ’ 1 0 perations I! I ’ll ;’ lllllll’’’’lllllllllllllllll I 1.1

  14. Main determinants of physical activity levels in individuals with Parkinson's disease.

    PubMed

    Lana, Raquel de Carvalho; de Araujo, Lysandra Nogueira; Cardoso, Francisco; Rodrigues-de-Paula, Fátima

    2016-02-01

    This study analyzed the relationship between patient characteristics, factors associated with Parkinson's disease (PD), and physical activity level of individuals affected by the disease. Forty-six volunteers with mild-to-moderate idiopathic PD were assessed using sections II/III of the Unified Parkinson's Disease Rating Scale and their motor functions were classified according to the modified Hoehn and Yahr (HY) scale. Data such as age, disease duration, the Human Activity Profile (HAP), the Fatigue Severity Scale were collected. Lower limb bradykinesia and clinical subtypes of PD were defined. Two models that explained 76% of the variance of the HAP were used. The first comprised age, ability to perform activities of daily living (ADL), and the HY scale; the second comprised age, ability to perform ADL, and lower limb bradykinesia. Possible modifiable factors such as the ability to perform ADL and lower limb bradykinesia were identified as predictors of physical activity level of individuals with PD.

  15. A simple technique to achieve bloodless excision of carotid body tumors.

    PubMed

    Spinelli, Francesco; Massara, Mafalda; La Spada, Michele; Stilo, Francesco; Barillà, David; De Caridi, Giovanni

    2014-05-01

    We describe a technique for Shamblin II-III carotid body tumor (CBT) resection to reduce bleeding and neurologic complications during surgery. The technique was based on the fact that CBTs are supplied almost exclusively from the external carotid artery. Therefore, we carefully isolated the origin of the external carotid artery and its distal branches outside the tumor and temporarily clamped all of these vessels after heparin administration. This allowed a safe and bloodless resection as the tumor was dissected from the internal carotid artery in the usual subadventitial plane. The internal carotid artery was never clamped, and respect of peripheral nerves was warranted in the clean and bloodless field. From 2007 to 2010, we treated 11 patients with a CBT: six had a Shamblin II and five had a Shamblin III lesion. Neither perioperative neurologic events nor recurrences occurred after a mean follow-up of 42 months.

  16. [Quality management in oncology supported by clinical cancer registries].

    PubMed

    Klinkhammer-Schalke, Monika; Gerken, Michael; Barlag, Hagen; Tillack, Anett

    2015-01-01

    Efforts in nationwide quality management for oncology have so far failed to comprehensively document all levels of care. New organizational structures such as population-based clinical cancer registries or certified organ cancer centers were supposed to solve this problem more sufficiently, but they have to be accompanied by valid trans-sectoral documentation and evaluation of clinical data. To measure feasibility and qualitative effectiveness of guideline implementation we approached this problem with a nationwide investigation from 2000 to 2011. The rate of neoadjuvant radio/chemotherapy in stage UICC II/III rectum cancer, cut-off point 80% for separating good from insufficient quality, was used as a quality indicator. The nationwide analysis indicates an increase from 45% to 70%, but only with the implementation strategy of CME. The combination of new structures, evidence-based quality indicators, organ cancer center and clinical cancer registries has shown good feasibility and seems promising.

  17. Fermentation, Hydrogen, and Sulfur Metabolism in Multiple Uncultivated Bacterial Phyla

    SciTech Connect

    Wrighton, Kelly C.; Thomas, BC; Sharon, I; Miller, CS; Castelle, Cindy J; Verberkmoes, Nathan C; Wilkins, Michael J.; Hettich, Robert {Bob} L; Lipton, Mary S; Williams, Ken; Long, Philip E; Banfield, Jillian F.

    2012-01-01

    BD1-5, OP11, and OD1 bacteria have been widely detected in anaerobic environments, but their metabolisms remain unclear owing to lack of cultivated representatives and minimal genomic sampling. We uncovered metabolic characteristics for members of these phyla, and a new lineage, PER, via cultivation-independent recovery of 49 partial to near-complete genomes from an acetate-amended aquifer. All organisms were nonrespiring anaerobes predicted to ferment. Three augment fermentation with archaeal-like hybrid type II/III ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO) that couples adenosine monophosphate salvage with CO2 fixation, a pathway not previously described in Bacteria. Members of OD1 reduce sulfur and may pump protons using archaeal-type hydrogenases. For six organisms, the UGA stop codon is translated as tryptophan. All bacteria studied here may play previously unrecognized roles in hydrogen production, sulfur cycling, and fermentation of refractory sedimentary carbon.

  18. Progress in corticotropin-releasing factor-1 antagonist development

    PubMed Central

    Zorrilla, Eric P.; Koob, George F.

    2010-01-01

    Corticotropin-releasing factor (CRF) receptor antagonists have been sought since the stress-secreted peptide was isolated in 1981. Although evidence suggests the limited efficacy of CRF1 antagonists as antidepressants, CRF1 antagonists might be novel pharmacotherapies for anxiety and addiction. Progress in understanding the two-domain model of ligand–receptor interactions for CRF family receptors might yield chemically novel CRF1 receptor antagonists, including peptide CRF1 antagonists, antagonists with signal transduction selectivity and nonpeptide CRF1 antagonists that act via the extracellular (rather than transmembrane) domains. Novel ligands that conform to prevalent pharmacophore and exhibit drug-like pharmacokinetic properties have been identified. The therapeutic utility of CRF1 antagonists should soon be clearer: several small molecules are currently in Phase II/III clinical trials for depression, anxiety and irritable bowel syndrome. PMID:20206287

  19. Progression of Ebola Therapeutics During the 2014-2015 Outbreak.

    PubMed

    Mendoza, Emelissa J; Qiu, Xiangguo; Kobinger, Gary P

    2016-02-01

    The recent Ebola virus (EBOV) outbreak in West Africa was the deadliest EBOV epidemic in history, highlighting the need for a safe and efficacious treatment against EBOV disease (EVD). In the absence of an approved treatment, experimental drugs were utilized under compassionate grounds hoping to diminish EVD-associated morbidity and mortality. As more data were collected from safety studies, Phase II/III clinical trials were introduced in Guinea, Sierra Leone, and Liberia to test promising candidates, including small-molecule drugs, RNA-based treatments, and antibody-based therapies. In this review, we summarize the use of, and preliminary observations from, current clinical trials with EVD therapeutics, shedding light on experimental drug selection, emergency clinical evaluation, and the impact these factors may have on future infectious disease outbreaks.

  20. Prevalence and genotype identification of Toxoplasma gondii in wild animals from southwestern Spain.

    PubMed

    Calero-Bernal, Rafael; Saugar, José M; Frontera, Eva; Pérez-Martín, Juan E; Habela, Miguel A; Serrano, Francisco J; Reina, David; Fuentes, Isabel

    2015-01-01

    We used PCR to detect Toxoplasma gondii in the principal game species in southwestern Spain. We detected T. gondii in 32.2% of animals tested. Prevalences varied from 14.7% in wild boar (Sus scrofa) to 51.2% in red fox (Vulpes vulpes). The most prevalent genotype was type II (50.0%), followed by type III (20.6%) and type I (5.9%). Mixed infections (11.8%) were detected in wild boar (types I+III) and red fox (types II+III). Polymorphic strains (11.8%) were detected in several species. The high prevalence and the genetic variability shown could have implications for infection of farm animals and humans.

  1. ``Blessed rain'' as a drive for the abandonment of ancient settlements along the Israeli coast

    NASA Astrophysics Data System (ADS)

    Ashkenazy, Y.; Faust, A.

    2005-12-01

    Previous studies suggested that arid conditions in the ancient Near-East altered settlement pattern and even triggered the collapse of empires; more humid conditions in the semi-arid Near-East are expected to be more favorite for living. Here we present archaeological evidence for a drastic decline in settlement along the Israeli coast during most of the fifth millennium BP (Early Bronze Age II-III). Based on archaeological and climatic evidence we link this decline to an environment change at that time. We propose that increased precipitation intensified the already existing drainage problems and resulted with flooding, which lead to transformation of arable land into marshes and to spread of diseases, gradually causing settlement decline and abandonment.

  2. A high burnup model developed for the DIONISIO code

    NASA Astrophysics Data System (ADS)

    Soba, A.; Denis, A.; Romero, L.; Villarino, E.; Sardella, F.

    2013-02-01

    A group of subroutines, designed to extend the application range of the fuel performance code DIONISIO to high burn up, has recently been included in the code. The new calculation tools, which are tuned for UO2 fuels in LWR conditions, predict the radial distribution of power density, burnup, and concentration of diverse nuclides within the pellet. The balance equations of all the isotopes involved in the fission process are solved in a simplified manner, and the one-group effective cross sections of all of them are obtained as functions of the radial position in the pellet, burnup, and enrichment in 235U. In this work, the subroutines are described and the results of the simulations performed with DIONISIO are presented. The good agreement with the data provided in the FUMEX II/III NEA data bank can be easily recognized.

  3. EVALUATING COSTS WITH UNMEASURED CONFOUNDING: A SENSITIVITY ANALYSIS FOR THE TREATMENT EFFECT

    PubMed Central

    Handorf, Elizabeth A.; Bekelman, Justin E.; Heitjan, Daniel F.; Mitra, Nandita

    2014-01-01

    Estimates of the effects of treatment on cost from observational studies are subject to bias if there are unmeasured confounders. It is therefore advisable in practice to assess the potential magnitude of such biases. We derive a general adjustment formula for loglinear models of mean cost and explore special cases under plausible assumptions about the distribution of the unmeasured confounder. We assess the performance of the adjustment by simulation, in particular, examining robustness to a key assumption of conditional independence between the unmeasured and measured covariates given the treatment indicator. We apply our method to SEER-Medicare cost data for a stage II/III muscle-invasive bladder cancer cohort. We evaluate the costs for radical cystectomy vs. combined radiation/chemotherapy, and find that the significance of the treatment effect is sensitive to plausible unmeasured Bernoulli, Poisson and Gamma confounders. PMID:24587844

  4. Development of InCVAX as a novel in situ autologous vaccine for metastatic cancers (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Hode, Tomas; Alleruzzo, Luciano; Raker, Joseph; Lam, Samuel Siu Kit; Nordquist, Robert E.; Chen, Wei R.

    2016-03-01

    A novel method, an in situ autologous whole-cell cancer vaccine (inCVAX), is being developed by Immunophotonics, Inc., for the treatment of metastatic cancers. inCVAX combines phototherapy and immunotherapy to potentially induce a systemic anti-tumor immune response in the hosts. Immunophotonics and its academic partners have spent years conducting nonclinical research, developing CMC techniques and conducting clinical research. In 2015 the company initiated a late-stage (II/III) clinical trial in South America for advanced breast cancer patients. The process of developing the inCVAX approach from a laboratory setting into clinical trials requires significant efforts from a group of dedicated engineers, scientists, and physicians. The growth of the company and its business advances demonstrated the determination of a group of visionary investors, entrepreneurs, and business leaders. This talk will chronicle the milestones of the scientific achievement, medical progress, and business development of Immunophotonics.

  5. Comparison of Machine Learning Methods for the Arterial Hypertension Diagnostics

    PubMed Central

    Belo, David; Gamboa, Hugo

    2017-01-01

    The paper presents results of machine learning approach accuracy applied analysis of cardiac activity. The study evaluates the diagnostics possibilities of the arterial hypertension by means of the short-term heart rate variability signals. Two groups were studied: 30 relatively healthy volunteers and 40 patients suffering from the arterial hypertension of II-III degree. The following machine learning approaches were studied: linear and quadratic discriminant analysis, k-nearest neighbors, support vector machine with radial basis, decision trees, and naive Bayes classifier. Moreover, in the study, different methods of feature extraction are analyzed: statistical, spectral, wavelet, and multifractal. All in all, 53 features were investigated. Investigation results show that discriminant analysis achieves the highest classification accuracy. The suggested approach of noncorrelated feature set search achieved higher results than data set based on the principal components. PMID:28831239

  6. Phase I-II clinical trial of Californium-252. Treatment of stage IB carcinoma of the cervix.

    PubMed

    Maruyama, Y; VanNagell, J R; Yoneda, J; Donaldson, E; Gallion, H; Rowley, K; Kryscio, R; Beach, J L

    1987-04-15

    Intracavitary Californium-252 combined with whole-pelvis photon radiotherapy was tested as the sole form of treatment for 22 patients with Stage IB carcinoma of the cervix. Californium-252 (Cf) is a fast neutron-emitting radioisotope currently being tested in trials of neutron brachytherapy (NT). The outcomes of the treated group of patients were traced for local tumor control, survival, patterns of failure, and complications. The Cf intracavitary therapy combined with whole-pelvis photon radiotherapy resulted in 95% 2-year and 91% 5-year actuarial survival. There were 9% Grade II-III complications by the Stockholm scale and 4% local failures. These results were obtained in an early clinical trial with a group of largely poor-risk patients with tumors of mean diameter of 4.3 cm.

  7. Physiological, Subjective, and Performance Correlates of Reported Boredom and Monotony while Performing a Simulated Radar Control Task

    DTIC Science & Technology

    1975-08-01

    use thereof. 4: .................................................................................. i. S. t I = a r. CO, as ’k,.4 - b *t C: E- -aI- r...Cd. 0d .p B * IIr3=- T =A CS c S-000 tx ca U2 r 5:d. I i *~~~~~ 3-.-= Lo0~d’c3I£::Iiiii wozao...Cs 0 -)2 s 0V 10 r - C: C30t :-- C ;- 24 " b =Okk 0 U2 ~ wi Io u~ 0. 0 = * d 0 Q e Q as 0 b44 W ml 10 4) CS )U SJ1r* Ud -i va-; a ’ cs S _= �( : 1

  8. CHEMINI: A new in situ CHEmical MINIaturized analyzer

    NASA Astrophysics Data System (ADS)

    Vuillemin, R.; Le Roux, D.; Dorval, P.; Bucas, K.; Sudreau, J. P.; Hamon, M.; Le Gall, C.; Sarradin, P. M.

    2009-08-01

    "CHEMINI" is a new instrument developed for the measurement of seawater chemical parameters. It is a mono-parameter in situ chemical analyzer based on flow injection analysis and colorimetric detection. The deep-sea version of CHEMINI combines two modules to perform the analysis of dissolved iron [Fe (II) or Fe (II+III)] and total sulphide (H 2S+HS -+S 2-) up to 6000 m depth. Detection limits are, respectively, 0.3 and 0.1 μM for iron and sulphide. The system proved highly reliable during the MoMARETO cruise on the Mid-Atlantic Ridge. The two CHEMINIs were used to describe the chemical environment in 12 mussel beds on the Tour Eiffel hydrothermal edifice.

  9. Efficient Ab initio Modeling of Random Multicomponent Alloys

    DOE PAGES

    Jiang, Chao; Uberuaga, Blas P.

    2016-03-08

    Here, we present in this Letter a novel small set of ordered structures (SSOS) method that allows extremely efficient ab initio modeling of random multi-component alloys. Using inverse II-III spinel oxides and equiatomic quinary bcc (so-called high entropy) alloys as examples, we also demonstrate that a SSOS can achieve the same accuracy as a large supercell or a well-converged cluster expansion, but with significantly reduced computational cost. In particular, because of this efficiency, a large number of quinary alloy compositions can be quickly screened, leading to the identification of several new possible high entropy alloy chemistries. Furthermore, the SSOS methodmore » developed here can be broadly useful for the rapid computational design of multi-component materials, especially those with a large number of alloying elements, a challenging problem for other approaches.« less

  10. Efficient Ab initio Modeling of Random Multicomponent Alloys

    SciTech Connect

    Jiang, Chao; Uberuaga, Blas P.

    2016-03-08

    Here, we present in this Letter a novel small set of ordered structures (SSOS) method that allows extremely efficient ab initio modeling of random multi-component alloys. Using inverse II-III spinel oxides and equiatomic quinary bcc (so-called high entropy) alloys as examples, we also demonstrate that a SSOS can achieve the same accuracy as a large supercell or a well-converged cluster expansion, but with significantly reduced computational cost. In particular, because of this efficiency, a large number of quinary alloy compositions can be quickly screened, leading to the identification of several new possible high entropy alloy chemistries. Furthermore, the SSOS method developed here can be broadly useful for the rapid computational design of multi-component materials, especially those with a large number of alloying elements, a challenging problem for other approaches.

  11. New species of Lepidocyrtus Bourlet and Entomobrya Rondani (Collembola: Entomobryoidea: Entomobryidae) from Brazil.

    PubMed

    Bellini, Bruno C; Cipola, Nikolas G; Godeiro, Nerivânia N

    2015-10-02

    The taxonomic comprehension of Brazilian entomobryids had several contributions during the last decade, but the absence of detailed chaetotaxic schemes to most of endemic species difficult identifications and probably hides undescribed species in surveys across the country. Herein we describe two new species of the family and provide detailed dorsal chaetotaxy of them, in hope to guide future identifications and descriptions within the genera in Brazil and Neotropical Region. Lepidocyrtus sotoi sp. nov. is possibly more related to L. biphasis due to the lack of antennal and leg scales, but presents a unique dorsal head chaetotaxy among the Neotropical species of the genus. Entomobrya bahiana sp. nov. presents an uncommon color pattern and dorsal chaetotaxy in Th. II-III, Abd. II and IV when compared to other Entomobrya spp. from Neotropical Region.

  12. Inhibition of indoleamine 2,3-dioxygenase 1/2 prevented cognitive impairment and energetic metabolism changes in the hippocampus of adult rats subjected to polymicrobial sepsis.

    PubMed

    Comim, Clarissa M; Freiberger, Viviane; Ventura, Letícia; Mina, Francielle; Ferreira, Gabriela K; Michels, Monique; Generoso, Jaqueline S; Streck, Emílio L; Quevedo, João; Barichello, Tatiana; Dal-Pizzol, Felipe

    2017-04-15

    Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection that may affect the brain. We investigated the role of indoleamine 2,3-dioxygenase (IDO-1/2) inhibition on long-term memory and energetic metabolism after experimental sepsis by caecal ligation and perforation (CLP). Experimental sepsis increased the activity of complexes I, II-III and IV at 24h after CLP, and IDO-1/2 inhibition normalized the activity of these complexes in the hippocampus. Wistar rats presented impairment of habituation and aversive memories 10days after CLP. Adjuvant treatment with the IDO inhibitor prevented long-term cognitive impairment triggered by sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Dendritic arborization patterns of cortical interneurons labeled with the lectin, Vicia villosa, and injected intracellularly with Lucifer yellow in aldehyde-fixed rat slices.

    PubMed

    Ojima, H

    1993-01-01

    Neurons whose cell bodies had been stained by a lectin, Vicia villosa, which recognizes terminal N-acetylgalactosamine residue, were intracellularly injected with Lucifer yellow (LY), in aldehyde-fixed slices of the parietal cortex of rats. LY was subsequently visualized immunocytochemically. All injected neurons had smooth or only sparsely spiny dendrites and resembled the various forms of gamma-aminobutyric acid-ergic neurons previously described in rat neocortex. In layers II/III, IV and V, most injected neurons were multipolar. In layer VI, most had vertically elongated dendritic fields. Some injected neurons in layer IV had an oval or vertically elongated soma and a bitufted dendritic arborization pattern. There was a gradual increase in the overall dendritic extent in deeper layers of the cortex.

  14. Emerging applications of stereotactic body radiotherapy.

    PubMed

    Lo, Simon S; Loblaw, Andrew; Chang, Eric L; Mayr, Nina A; Teh, Bin S; Huang, Zhibin; Yao, Min; Ellis, Rodney J; Biswas, Tithi; Sohn, Jason W; Machtay, Mitchell; Sahgal, Arjun

    2014-05-01

    Stereotactic body radiotherapy (SBRT) has been used extensively in patients with lung, liver and spinal tumors, and the treatment outcomes are very favorable. For certain conditions such as medically inoperable stage I non-small-cell lung cancer, liver and lung oligometastases, primary liver cancer and spinal metastases, SBRT is regarded as one of the standard therapies. In the recent years, the use of SBRT has been extended to other disease conditions and sites such as recurrent head and neck cancer, renal cell carcinoma, prostate cancer, adrenal metastasis, pancreatic cancer, gynecological malignancies, spinal cord compression, breast cancer, and stage II-III non-small-cell lung cancer. Preliminary data in the literature show promising results but the follow-up intervals are short for most studies. This paper will provide an overview of these emerging applications.

  15. [Clinical and metabolic effects of betaxolol (lokren) in treatment of patients with chronic cardiac insufficiency].

    PubMed

    Korzh, A N

    2003-01-01

    Effects were studied of a selective beta-adrenoblocker betaxolol on clinical, hemodynamic, and metabolic indices in patients with chronic cardiac insufficiency (ChCI). A total of 47 patients (27 men and 20 women) with functional class II-III ChCI by the classification of the New-York Association of Cardiologists and the left ventricular ejection fraction less than 40% were examined. The use of betaxolol in the conventional therapy of ChCI has been shown to be of significant clinical benefit in the above patient population, with the improvement in hemodynamic status, the functional class exercise-induces angina alleviated, the left ventricular ejection fraction significantly became greater. Moreover, long-term treatment with betaxolol tends to lower the degree of lipid peroxidation with no adverse effect being exerted on lipid and carbohydrate metabolism.

  16. All Prime Contract Awards by State or Country, Place, and Contractor. Part 21 (Stafford Virginia-Yellowstone Park)

    DTIC Science & Technology

    1990-01-01

    4 -1Z ..4z .4z .4zzi* -4iiiii* -6 OKI Co H c >- >is > a > a ->-. > >~ CI aOI uro No m af -0 mv) N M W q 0 -or-Go vinsm 10 a-ua. Hv NM 04 00 N 4 --I...i-ain LmI 01@001 sul 0M 00 0000 0 0 0 0 0 00 0 * 4 I06m 0. C.1. 06 .𔃾.4-4-4 06-4 a".00 06 0.-4 06-4 We4 0.0 0lu .4 lo Isla 04 0-4 0 6060600 00* a0

  17. Job Language Performance Requirements for MOS 62B, Construction Equipment Repairer, Reference Soldier’s Manual Dated 13 March 1978.

    DTIC Science & Technology

    1978-03-13

    the backgroun underlying the JLPR. Sections V and VI are the major substantive portions of the analysis. They are the results of the analysis and...Writing 25% II. JOB LANGUAGEp:;O.’ ANCE REQ1R.t"EI;TS TASK: Listen to learn and perform CONDITIONS: Given oral instructions or verbal comm:nds in any...performianc’IIIIi6II 1 ~ I~~ hN 111 S hands-on I,~I I L IIII S demonstratio;III’ I’M ~~=ec~~u~to jI 1,1 ilili II I II 09 i*~ ance difficul? t 11 Ill 11

  18. Understanding the C-pulse device and its potential to treat heart failure.

    PubMed

    Sales, Virna L; McCarthy, Patrick M

    2010-03-01

    The Sunshine Heart C-Pulse (C-Pulse; Sunshine Heart Inc., Tustin, CA) device is an extra-aortic implantable counterpulsation pump designed as a non-blood contacting ambulatory heart assist device, which may provide relief from symptoms for class II-III congestive heart failure patients. It has a comparable hemodynamic augmentation to intra-aortic balloon counterpulsation devices. The C-Pulse cuff is implanted through a median sternotomy, secured around the ascending aorta, and pneumatically driven by an external system controller. Pre-clinical studies in the acute pig model, and initial temporary clinical studies in patients undergoing off-pump coronary bypass surgery have shown substantial increase in diastolic perfusion of the coronary vessels, which translated to a favorable improvement in ventricular function. A U.S. prospective multi-center trial to evaluate the safety and efficacy of the C-Pulse in class III patients with moderate heart failure is now in progress.

  19. The 5-HT(7) receptor antagonist SB 269970 counteracts restraint stress-induced attenuation of long-term potentiation in rat frontal cortex.

    PubMed

    Tokarski, K; Bobula, B; Kusek, M; Hess, G

    2011-12-01

    The effects of restraint lasting for 10 min, repeated twice daily for 3 days, were studied ex vivo in rat frontal cortex slices prepared 24 h after the last stress session. In slices originating from stressed animals, the amplitude of extracellular field potentials recorded in cortical layer II/III was increased. Stress also resulted in a reduced magnitude of long-term potentiation (LTP) of field potentials. In a separate experimental group, rats were subjected to restraint lasting for 10 min, twice daily for 3 days but, additionally, animals received injections of 5-HT(7) receptor antagonist SB 269970 (1.25 mg/kg) before each restraint stress session. In this group, the amplitude of field potentials and the magnitude of LTP were not different from the control, indicating that stress-induced modifications of basal glutamatergic transmission and synaptic plasticity were prevented by the 5-HT(7) receptor antagonist.

  20. Sorafenib in radioactive iodine-refractory well-differentiated metastatic thyroid cancer

    PubMed Central

    McFarland, Daniel C; Misiukiewicz, Krzysztof J

    2014-01-01

    Recent Phase III data presented at the American Society of Clinical Oncology (ASCO) 2013 annual conference by Brose et al led to the US Food and Drug Administration (FDA) approval of sorafenib for the treatment of well-differentiated radioactive iodine-resistant metastatic thyroid cancer. This is the second drug in 40 years to be FDA approved for this indication. Recent reviews and a meta-analysis reveal a modest ability to induce a partial remission but substantial ability to halt disease progression. Given the significant activating mutations present in thyroid cancer, many of which are inhibited by sorafenib, the next logical approach may be to combine targeted rational therapies if permitted by collective toxicity profiles. This systematic review aims to summarize the recent Phase II/III data leading to the FDA approval of sorafenib for radioactive iodine therapy differentiated thyroid cancer and highlights recent novel combination therapy trials. PMID:25053887

  1. Measurement of Compression Factor and Error Sensitivity Factor of Facsimile Coding Techniques Submitted to the CCITT By Great Britain and the Federal Republic of Germany

    DTIC Science & Technology

    1979-10-01

    2. i. Pass mode This mode is identified when the position of bd lies to the left of a,. 11’ the position o b2 !,es directly above a,, then this does...43( OTBUF( I *OTCOD) 9P-1 *1) 00009 CALL M12-3 (PELL oPEL .2 932-3 .3) 00009 615 CONTINUE_ 00009 C 00009 IF44Tj&jjSP1).N!3) GO TO 1155 0000 INCEX...ATA 33S( to 39 6)9C 00S( 2o 396) *COOS( 3 3.96 bd 3. *Z000I/ 00016, DATA CODS (1 4 96).C305( 29 *.6)*CODS(39 490)/ ** boz0ooI/ 00016. soito iiiii t

  2. The n-CdSe photoelectrochemical cell: wavelength-dependent photostability

    SciTech Connect

    Rubin, H.D.; Arent, D.J.; Bocarsly, A.B.

    1985-02-01

    Much recent work has focused on Fe(CN)/sub 6/ /SUP 4-/3-/ as a stabilizing electrolyte for n-CdX(X=S,Se) based photoelectrochemical cells (1-5). Prior studies performed in this laboratory (6) showed that irradiation of n-CdS in an electrolyte containing Fe(CN)/sub 6/ /SUP 4-/3-/ can lead to formation of a surface layer of (Cd /SUP II/ Fe /SUP II/III/ (CN)/sub 6/) /SUP 2-/1-/ . In the presence of the appropriate cations, this layer was associated with improved cell output parameters. These studies have now been extended to include the n-CdSe system. In this letter we wish to report an unprecedented wavelength dependence of the n-CdSe photoelectrochemical cell.

  3. New species and records of Microveliinae and Veliinae (Hemiptera: Heteroptera: Veliidae) from Colombia.

    PubMed

    Molano, Fredy; Moreira, Felipe Ferraz Figueiredo; Morales, Irina

    2016-09-29

    Euvelia orinoquia sp. nov. and E. meta sp. nov. from eastern Colombia are described, illustrated, and included in an updated identification key to the species of the genus. The former can be diagnosed by body length 2.30-2.50 mm, male fore femur without tufts of setae, longitudinal black stripe of female pronotum almost twice as wide as length of antennomere I, and female connexiva grayish black with silvery pruinosity on mesal portion, reddish on lateral portion. Euvelia meta sp. nov. can be diagnosed by female body length about 1.50 mm and maximum body width 0.90 mm, patches of silvery setae on female abdominal terga II-III and V-VII, and connexival segments I and IV-VI. Additionally, new records from the country are presented for species of Euvelia Drake, Husseyella Herring, Microvelia Westwood (Microveliinae), Oiovelia Drake & Maldonado-Capriles, Platyvelia Polhemus & Polhemus, Stridulivelia Hungerford, and Veloidea Gould (Veliinae).

  4. Pathogenesis of Salmonellosis: Salmonella Exotoxins

    DTIC Science & Technology

    1982-03-08

    OVT ACCESSION NO. 3 . RECIPIENT’S CATALOG NUMBER 4 . TITLE (nd Subtitle) S. TYPE OF REPORT &PERIOD COVERED Pathogenesis of Salmonellosis: Salmonella...J .• ..- o . -. - ° "-o Figure 1 E a’. CL ’ u-E: U~ 0 (. 3 0 -0.- ".5 Clio CL! Ud Figure 2 0 X in 4 (D U - Untreated CHO cells 0...U. 3 o I- 2 00 0.001 0.01 0.1 1 10 Cholera Toxin (ng) lu I II I 1 11 IIII III I I III II I II IIIII II II I III I I I I I I Figure3 el , 4 "I

  5. Recombinant B domain deleted porcine factor VIII for the treatment of bleeding episodes in adults with acquired hemophilia A.

    PubMed

    Gomperts, Edward

    2015-08-01

    Hemophilia A is an inherited deficiency of clotting factor VIII (FVIII) often complicated by inhibitor development (CHAWI) in which neutralizing antibodies block the therapeutic benefit of replacement therapy. Inhibitors to FVIII can also be seen in an auto-immune disease known as acquired hemophilia A (AHA). 'Bypassing' therapies have been shown to provide hemostasis but dosing must be done empirically because current assays cannot measure objective markers of treatment efficacy and safety. A recombinant porcine sequence factor VIII (r-pFVIII) has been developed for the management of AHA. Preclinical, Phase I and Phase II clinical research studies in CHAWI subjects showed therapeutic potential and safety of this agent. A Phase II/III study in AHA with serious bleeding episodes shows a positive response in all subjects after administration. Based on current preclinical and clinical trial data, r-pFVIII should become the first line of treatment in the management of hemorrhage in patients with AHA.

  6. The potential for a controlled human infection platform in Singapore

    PubMed Central

    Balasingam, Shobana; Horby, Peter; Wilder-Smith, Annelies

    2014-01-01

    For over 100 years, controlled human infection (CHI) studies have been performed to advance the understanding of the pathogenesis, treatment and prevention of infectious diseases. This methodology has seen a resurgence, as it offers an efficient model for selecting the most promising agents for further development from available candidates. CHI studies are utilised to bridge safety and immunogenicity testing and phase II/III efficacy studies. However, as this platform is not currently utilised in Asia, opportunities to study therapeutics and vaccines for infections that are important in Asia are missed. This review examines the regulatory differences for CHI studies between countries and summarises other regulatory differences in clinical trials as a whole. We found that the regulations that would apply to CHI studies in Singapore closely mirror those in the United Kingdom, and conclude that the regulatory and ethical guidelines in Singapore are compatible with the conduct of CHI studies. PMID:25273928

  7. Ofatumumab for a rituximab-allergic child with chronic-relapsing paraneoplastic opsoclonus-myoclonus.

    PubMed

    Pranzatelli, Michael R; Tate, Elizabeth D; Shenoy, Shalini; Travelstead, Anna L

    2012-06-01

    Ofatumumab is a fully human anti-CD20 monoclonal antibody in phase II-III trials for various autoimmune and lymphoreticular diseases. We used it to treat a rituximab-allergic child with severe, chronic-relapsing, opsoclonus-myoclonus syndrome (OMS), characterized by persistent cerebrospinal fluid (CSF) B-cell expansion and T-cell dysregulation. He had relapsed despite chemotherapy, plasma exchange with immunoadsorption, and resection of ganglioneuroblastoma, detected 3 years after OMS onset. The four ofatumumab infusions (1,195 mg/m(2) total dose) were well tolerated, and CSF B-cell expansion was eliminated. No further relapses have occurred in 3 years, but he remains on low-dose ACTH with neuropsychiatric residuals of OMS.

  8. Paleopathology of the juvenile Pharaoh Tutankhamun-90th anniversary of discovery.

    PubMed

    Hussein, Kais; Matin, Ekatrina; Nerlich, Andreas G

    2013-09-01

    Modern paleopathology is a multidisciplinary field of research which involves archaeology, medicine and biology. The most common diseases of Ancient Egypt were traumatic injuries, malaria and tuberculosis. Exemplarily, an internistic and trauma surgery case of that time is reviewed: Pharaoh Tutankhamun (ca. 1330-1324 B.C.). Summarising all findings which have been collected between 1922 and 2010, including computed tomography and molecular pathology, a diversity of disease is verifiable: (1) chronic/degenerative diseases (mild kyphoscoliosis, pes planus and hypophalangism of the right foot, bone necrosis of metatarsal bones II-III of the left foot); (2) inflammatory disease (malaria tropica, verified by PCR analysis) and (3) acute trauma (complex fracture of the right knee shortly before death). The most likely cause of death is the severe acute knee fracture and/or the malaria, while a suspected eighteenth dynasty syndrome cannot be proven.

  9. Clinical pharmacology considerations in biologics development

    PubMed Central

    Zhao, Liang; Ren, Tian-hua; Wang, Diane D

    2012-01-01

    Biologics, including monoclonal antibodies (mAbs) and other therapeutic proteins such as cytokines and growth hormones, have unique characteristics compared to small molecules. This paper starts from an overview of the pharmacokinetics (PK) of biologics from a mechanistic perspective, the determination of a starting dose for first-in-human (FIH) studies, and dosing regimen optimisation for phase II/III clinical trials. Subsequently, typical clinical pharmacology issues along the corresponding pathways for biologics development are summarised, including drug-drug interactions, QTc prolongation, immunogenicity, and studies in specific populations. The relationships between the molecular structure of biologics, their pharmacokinetic and pharmacodynamic characteristics, and the corresponding clinical pharmacology strategies are summarised and depicted in a schematic diagram. PMID:23001474

  10. The use of capecitabine in the combined-modality therapy for rectal cancer.

    PubMed

    Liauw, Stanley L; Minsky, Bruce D

    2008-03-01

    Locally advanced rectal adenocarcinoma is treated by combined-modality therapy, which consists of surgery, chemotherapy, and radiation therapy. A series of randomized trials established a preferred treatment sequence of preoperative radiation therapy and 5-fluorouracil(5-FU)-based chemotherapy, total mesorectal excision, and adjuvant 5-FU-based chemotherapy for patients with stage II/III disease. Capecitabine is an oral prodrug of 5-FU that has potential advantages compared with intravenous 5-FU, including ease of administration and potentially increased therapeutic effect. Capecitabine is converted by a 3-step enzymatic process; the last step involves the enzyme thymidine phosphorylase, which is overexpressed in tumor tissues and is stimulated by concurrent radiation therapy. Over the past 5 years, several phase I/II trials of capecitabine-based therapy were reported. This review discusses the evolution of combined-modality therapy for rectal cancer with specific attention given to the use of capecitabine in conjunction with radiation therapy.

  11. Efficient Ab initio Modeling of Random Multicomponent Alloys.

    PubMed

    Jiang, Chao; Uberuaga, Blas P

    2016-03-11

    We present in this Letter a novel small set of ordered structures (SSOS) method that allows extremely efficient ab initio modeling of random multicomponent alloys. Using inverse II-III spinel oxides and equiatomic quinary bcc (so-called high entropy) alloys as examples, we demonstrate that a SSOS can achieve the same accuracy as a large supercell or a well-converged cluster expansion, but with significantly reduced computational cost. In particular, because of this efficiency, a large number of quinary alloy compositions can be quickly screened, leading to the identification of several new possible high-entropy alloy chemistries. The SSOS method developed here can be broadly useful for the rapid computational design of multicomponent materials, especially those with a large number of alloying elements, a challenging problem for other approaches.

  12. Abnormal Auditory Brainstem Response (ABR) Findings in a Near-Normal Hearing Child with Noonan Syndrome

    PubMed Central

    Jalaei, Bahram; Zakaria, Mohd Normani; Sidek, Dinsuhaimi

    2017-01-01

    Introduction: Noonan syndrome (NS) is a heterogeneous genetic disease that affects many parts of the body. It was named after Dr. Jacqueline Anne Noonan, a paediatric cardiologist. Case Report: We report audiological tests and auditory brainstem response (ABR) findings in a 5-year old Malay boy with NS. Despite showing the marked signs of NS, the child could only produce a few meaningful words. Audiological tests found him to have bilateral mild conductive hearing loss at low frequencies. In ABR testing, despite having good waveform morphology, the results were atypical. Absolute latency of wave V was normal but interpeak latencies of wave’s I-V, I-II, II-III were prolonged. Interestingly, interpeak latency of waves III-V was abnormally shorter. Conclusion: Abnormal ABR results are possibly due to abnormal anatomical condition of brainstem and might contribute to speech delay. PMID:28229064

  13. Molecular Markers in Low-Grade Glioma-Toward Tumor Reclassification.

    PubMed

    Olar, Adriana; Sulman, Erik P

    2015-07-01

    Low-grade diffuse gliomas are a heterogeneous group of primary glial brain tumors with highly variable survival. Currently, patients with low-grade diffuse gliomas are stratified into risk subgroups by subjective histopathologic criteria with significant interobserver variability. Several key molecular signatures have emerged as diagnostic, prognostic, and predictor biomarkers for tumor classification and patient risk stratification. In this review, we discuss the effect of the most critical molecular alterations described in diffuse (IDH1/2, 1p/19q codeletion, ATRX, TERT, CIC, and FUBP1) and circumscribed (BRAF-KIAA1549, BRAF(V600E), and C11orf95-RELA fusion) gliomas. These molecular features reflect tumor heterogeneity and have specific associations with patient outcome that determine appropriate patient management. This has led to an important, fundamental shift toward developing a molecular classification of World Health Organization grade II-III diffuse glioma.

  14. Parvalbumin- and vasoactive intestinal polypeptide-expressing neocortical interneurons impose differential inhibition on Martinotti cells

    PubMed Central

    Walker, F.; Möck, M.; Feyerabend, M.; Guy, J.; Wagener, R. J.; Schubert, D.; Staiger, J. F.; Witte, M.

    2016-01-01

    Disinhibition of cortical excitatory cell gate information flow through and between cortical columns. The major contribution of Martinotti cells (MC) is providing dendritic inhibition to excitatory neurons and therefore they are a main component of disinhibitory connections. Here we show by means of optogenetics that MC in layers II/III of the mouse primary somatosensory cortex are inhibited by both parvalbumin (PV)- and vasoactive intestinal polypeptide (VIP)-expressing cells. Paired recordings revealed stronger synaptic input onto MC from PV cells than from VIP cells. Moreover, PV cell input showed frequency-independent depression, whereas VIP cell input facilitated at high frequencies. These differences in the properties of the two unitary connections enable disinhibition with distinct temporal features. PMID:27897179

  15. Proposal for a "phase II" multicenter trial model for preclinical new antiepilepsy therapy development.

    PubMed

    O'Brien, Terence J; Ben-Menachem, Elinor; Bertram, Edward H; Collins, Stephen D; Kokaia, Merab; Lerche, Holger; Klitgaard, Henrik; Staley, Kevin J; Vaudano, Elisabetta; Walker, Matthew C; Simonato, Michele

    2013-08-01

    There is a pressing need to address the current major gaps in epilepsy treatment, in particular drug-resistant epilepsy, antiepileptogenic therapies, and comorbidities. A major concern in the development of new therapies is that current preclinical testing is not sufficiently predictive for clinical efficacy. Methodologic limitations of current preclinical paradigms may partly account for this discrepancy. Here we propose and discuss a strategy for implementing a "phase II" multicenter preclinical drug trial model based on clinical phase II/III studies designed to generate more rigorous preclinical data for efficacy. The goal is to improve the evidence resulting from preclinical studies for investigational new drugs that have shown strong promise in initial preclinical "phase I" studies. This should reduce the risk for expensive clinical studies in epilepsy and therefore increase the appeal for funders (industry and government) to invest in their clinical development.

  16. Re-entrant spin glass and stepped magnetization in mixed-valence SrFe3(PO4)3

    NASA Astrophysics Data System (ADS)

    Shang, Mingyu; Chen, Yan; Tian, Ge; Yuan, Hongming; Feng, Shouhua

    2013-01-01

    The 2 D channel mixed-valent iron (II/III) monophosphate SrFe3(PO4)3 was synthesized via one step mild hydrothermal method at 210 °C and characterized by X-ray diffraction techniques and magnetization measurements. Coexistence of antiferromagnetic superexchange and ferromagnetic superexchange interactions was supposed to be in the lattice according to the Goodenough-Kanamori-Anderson rules. Temperature dependent DC magnetization measurement shows that SrFe3(PO4)3 is ferrimagnet with three magnetic transitions between 2 and 350 K. Through AC magnetization measurement, re-entrant spin glass was observed due to the competition between ferromagnetic and antiferromagnetic interactions. Furthermore, an interesting field induced stepped magnetization was observed in SrFe3(PO4)3 at 2 K with the saturation magnetization Ms=2.4 μB/f.u. at 5 T.

  17. Atopic eczema.

    PubMed

    Brown, Sara J

    2016-02-01

    Atopic eczema is an itchy inflammatory skin disease with a chronic relapsing-remitting course; it has increased in prevalence in recent decades and now affects up to 25% of school-aged children in the developed world and up to 10% of adults. Recent advances in understanding the aetiology of eczema have focused interest on skin barrier dysfunction as a common precursor and pathological feature. In addition, genetically determined skin barrier dysfunction (associated with mutations in the gene encoding filaggrin) is known to predispose to multiple systemic atopic diseases. First-line treatments for atopic eczema focus on maintaining and repairing the skin barrier (emollients) and reducing inflammation (topical steroids); allergen and irritant avoidance are also important to achieve disease control. Second and third-line treatments include topical calcineurin inhibitors, ultraviolet light and systemic immunosuppressant therapies of which only ciclosporin is licenced for the treatment of atopic eczema in adults. Novel biological therapies are in phase II-III clinical trials.

  18. Ceftazidime-avibactam for the treatment of complicated urinary tract infections and complicated intra-abdominal infections.

    PubMed

    Mawal, Yogesh; Critchley, Ian A; Riccobene, Todd A; Talley, Angela K

    2015-01-01

    Treatment of complicated urinary tract infections and complicated intra-abdominal infections is increasingly difficult due to the rising prevalence of multidrug-resistant Gram-negative bacteria. Ceftazidime-avibactam is a combination of the established third-generation cephalosporin ceftazidime with avibactam, a novel non-β-lactam β-lactamase inhibitor, which restores the activity of ceftazidime against many β-lactamase-producing Gram-negative bacteria, including extended-spectrum β-lactamases and Klebsiella pneumoniae carbapenemases. Clinical and nonclinical studies supporting the safety and efficacy of ceftazidime-avibactam include microbiological surveillance studies of clinically relevant pathogens, in vivo animal models of infection, pharmacokinetic/pharmacodynamic target attainment analyses, Phase I clinical pharmacology studies, and Phase II/III studies in the treatment of complicated intra-abdominal infections and complicated urinary tract infections, including patients with ceftazidime-nonsusceptible Gram-negative infections.

  19. Clinical pharmacology considerations in biologics development.

    PubMed

    Zhao, Liang; Ren, Tian-hua; Wang, Diane D

    2012-11-01

    Biologics, including monoclonal antibodies (mAbs) and other therapeutic proteins such as cytokines and growth hormones, have unique characteristics compared to small molecules. This paper starts from an overview of the pharmacokinetics (PK) of biologics from a mechanistic perspective, the determination of a starting dose for first-in-human (FIH) studies, and dosing regimen optimisation for phase II/III clinical trials. Subsequently, typical clinical pharmacology issues along the corresponding pathways for biologics development are summarised, including drug-drug interactions, QTc prolongation, immunogenicity, and studies in specific populations. The relationships between the molecular structure of biologics, their pharmacokinetic and pharmacodynamic characteristics, and the corresponding clinical pharmacology strategies are summarised and depicted in a schematic diagram.

  20. Defibrotide for the treatment of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation.

    PubMed

    Corbacioglu, Selim; Kernan, Nancy; Lehmann, Leslie; Brochstein, Joel; Revta, Carolyn; Grupp, Stephan; Martin, Paul; Richardson, Paul G

    2012-06-01

    Hepatic veno-occlusive disease (VOD) is a serious complication of stem cell transplantation in children. VOD is characterized by rapid weight gain, hepatomegaly, hyperbilirubinemia and ascites. The pathogenesis of VOD is thought to involve chemotherapy and radiation-induced damage to the sinusoidal endothelium, resulting in endothelial injury, microthrombosis, subendothelial damage and cytokine activation. These processes lead to concomitant progressive hepatocellular dysfunction and subsequent fluid retention and renal impairment. Severe VOD is typically associated with multiorgan failure and high mortality. A number of possible strategies for the prevention and/or treatment of VOD in children have been investigated. The most promising agent to date is defibrotide, a novel polydeoxyribonucleotide with fibrinolytic properties but no major bleeding risk. Numerous studies, including Phase II/III trials, have shown clinical benefit in pediatric patients with the use of defibrotide treatment and prophylaxis. This review discusses VOD in children and focuses on therapeutic options, including defibrotide, in this patient population.

  1. [Study of the role of adrenergic vasoconstriction in the development of dynamic coronary obstruction in patients with stress-induced stenocardia].

    PubMed

    Kuleshova, E V; Antonova, I S; Lokhovinina, N L; Lopukhov, A A; Moroshkin, V S; Tsyrlin, V A

    1992-01-01

    The aim of the present investigation was to evaluate sympathetic vasoconstrictor influence and to define its role in the formation of coronary occlusion in patients with effort angina. The investigation covered 22 patients with Functional Class II-III stable effort angina. To detect vasoconstrictor responses on exercise and to identify their adrenergic component, pair bicycle tests were performed before and after administration of nitroglycerin and pratsiol. Repeated bicycle tests were conducted twice a day: at 10-11 a.m. and at 3-4 p.m. to study spontaneous exercise tolerance variations confirming the presence of dynamic coronary occlusion. The examinations indicated that in 18 patients the exercise resulted in functional major artery narrowing, aggravating the organic stenosis. Activation of smooth muscle alpha-adrenoreceptors is of a definite significance in the genesis of dynamic coronary occlusion in 50% of all the examinees.

  2. Parvalbumin- and vasoactive intestinal polypeptide-expressing neocortical interneurons impose differential inhibition on Martinotti cells.

    PubMed

    Walker, F; Möck, M; Feyerabend, M; Guy, J; Wagener, R J; Schubert, D; Staiger, J F; Witte, M

    2016-11-29

    Disinhibition of cortical excitatory cell gate information flow through and between cortical columns. The major contribution of Martinotti cells (MC) is providing dendritic inhibition to excitatory neurons and therefore they are a main component of disinhibitory connections. Here we show by means of optogenetics that MC in layers II/III of the mouse primary somatosensory cortex are inhibited by both parvalbumin (PV)- and vasoactive intestinal polypeptide (VIP)-expressing cells. Paired recordings revealed stronger synaptic input onto MC from PV cells than from VIP cells. Moreover, PV cell input showed frequency-independent depression, whereas VIP cell input facilitated at high frequencies. These differences in the properties of the two unitary connections enable disinhibition with distinct temporal features.

  3. Decoding the stellar fossils of the dusty Milky Way progenitors

    NASA Astrophysics Data System (ADS)

    de Bennassuti, M.; Schneider, R.; Valiante, R.; Salvadori, S.

    2014-12-01

    We investigate the metallicity distribution function (MDF) of the Galactic halo and the relative fraction of Carbon-normal and Carbon-rich stars using the semi-analytical code GAMETE. The code reconstructs the hierarchical merger tree of the Milky Way (MW) and follows the star formation history and the metal evolution in individual progenitors, including for the first time the formation and evolution of dust. We predict scaling relations between the dust, metal and gas masses for MW progenitors and compare them with observational data of galaxies at 0 <= z < 6.3. We find that the relative contribution of C-normal and C-enhanced stars to the MDF and its dependence on [Fe/H] allow to discriminate among different Pop III/II transition criteria as well as between different Initial Mass Functions (IMFs) and supernova (SN) yields for Population III stars.

  4. [Morphogenesis of connective tissue in patients with hydronephrosis caused by stricture of ureteric-pelvic segment of various etiology].

    PubMed

    Savenkov, V I

    2015-02-01

    In patients, suffering hydronephrosis stages II-III, caused by the ureteric-pelvic segment (UPS) obstruction due to inborn failures of urinary system, the collagen types I and III ratio reduction, and in acquired obstruction--its enhancement, are noted in interstitium, renal parenchyma vessels and the UPS walls. While obstruction in patients due to inborn failures in vascular basal membranes a deficiency of collagen type IV and appearance of nontypical for vascular basal membranes intersticial collagen type Il are observed. In the acquired UPS, obstruction the, enhancement of content of collagen type IV is revealed only. These disorders are mostly pronounced in patients with the disease recurrence. There was proposed diagnostic coefficient of ratio between collagens types I and III in patients, suffering hydronephrosis, caused by obstruction of various etiology. In hydronephrosis, caused by the UPS stricture, the cytokines disbalance occurs, impacting processes of collagen formation.

  5. Percutaneous mitral valve repair with MitraClip for severe functional mitral regurgitation.

    PubMed

    Yeo, Khung Keong; Ding, Zee Pin; Chua, Yeow Leng; Lim, Soo Teik; Sin, Kenny Yoong Kong; Tan, Jack Wei Chieh; Chiam, Paul Toon Lim; Hwang, Nian Chih; Koh, Tian Hai

    2013-01-01

    A 67-year-old Chinese woman with comorbidities of chronic obstructive lung disease, hypertension and prior coronary artery bypass surgery presented with severe functional mitral regurgitation (MR) and severely depressed left ventricular function. She was in New York Heart Association (NYHA) Class II-III. Due to high surgical risk, she was referred for percutaneous treatment with the MitraClip valve repair system. This procedure is typically performed via the femoral venous system and involves a transseptal puncture. A clip is delivered to grasp the regurgitant mitral valve leaflets and reduce MR. This was performed uneventfully in our patient, with reduction of MR from 4+ to 1+. She was discharged on post-procedure Day 2 and her NYHA class improved to Class I. This was the first successful MitraClip procedure performed in Asia and represents a valuable treatment option in patients with severe MR, especially those with functional MR or those at high surgical risk.

  6. National Dam Safety Program. Van Meter Dam (MO 10658), Missouri - Kansas City Basin, Saline County, Missouri. Phase I Inspection Report.

    DTIC Science & Technology

    1978-12-01

    GRADY OACW43$8- C -O07O UNCLASSIFIED NL mhh/l/m//////l IIIIIIIIIIIIIl ""IIII"IIIII IIIIIIIIII MIUOURU -VANJM5 CITlBSI VAN E DAM DTIC iA.i cou,, ..mu...I’M)es) c "r1 icfl ci n% c . OS(I’ Ic A rkifd ..14 , e thie, * -.i i’ c *rr L n ti 1 . PV 1 ,rne 147 j,. us d n preparing vafiriunc ements...bibliographies, and dote * iik. ’th . 2, he r is’ ,t ;f c " ’+ . 1.’l , , It A I., reluIr-’cl, icent the lacsifiild items on the page by the appropriate C OMP IT

  7. VizieR Online Data Catalog: Oxygen recombination lines from Cas A knots (Docenko+, 2008)

    NASA Astrophysics Data System (ADS)

    Docenko, D.; Sunyaev, R. A.

    2008-03-01

    Tables contain wavelengths and intensities or emissivities of the fine structure components of the O, Si and S ion optical and near-infrared recombination lines (RLs) in the (nlK) -> (n'l'K') resolution. Emissivities and wavelengths are given for O II-VI, Si II-III and S II-V ion {alpha}-, {beta}- and {gamma}-line components in the wavelength range between 0.3 and 5 micron and temperature range between 103 and 105K. Only low-density emissivity values are included in tables and only transitions onto levels with nl>=5 are considered. Intensities and wavelengths are given for O II-VI ion {alpha}-, {beta}- and {gamma}-line components in the same wavelength range, as computed based on the Sutherland & Dopita (1995ApJ...439..381S) model of the oxygen-rich plasma emission in supernova remnants applied to Cassiopeia A fast-moving knots. (19 data files).

  8. The influence of the call with a mobile phone on heart rate variability parameters in healthy volunteers.

    PubMed

    Andrzejak, Ryszard; Poreba, Rafal; Poreba, Malgorzata; Derkacz, Arkadiusz; Skalik, Robert; Gac, Pawel; Beck, Boguslaw; Steinmetz-Beck, Aleksandra; Pilecki, Witold

    2008-08-01

    It is possible that electromagnetic field (EMF) generated by mobile phones (MP) may have an influence on the autonomic nervous system (ANS) and modulates the function of circulatory system. The aim of the study was to estimate the influence of the call with a mobile phone on heart rate variability (HRV) in young healthy people. The time and frequency domain HRV analyses were performed to assess the changes in sympathovagal balance in a group of 32 healthy students with normal electrocardiogram (ECG) and echocardiogram at rest. The frequency domain variables were computed: ultra low frequency (ULF) power, very low frequency (VLF) power, low frequency (LF) power, high frequency (HF) power and LF/HF ratio was determined. ECG Holter monitoring was recorded in standardized conditions: from 08:00 to 09:00 in the morning in a sitting position, within 20 min periods: before the telephone call (period I), during the call with use of mobile phone (period II), and after the telephone call (period III). During 20 min call with a mobile phone time domain parameters such as standard deviation of all normal sinus RR intervals (SDNN [ms]--period I: 73.94+/-25.02, period II: 91.63+/-35.99, period III: 75.06+/-27.62; I-II: p<0.05, II-III: p<0.05) and standard deviation of the averaged normal sinus RR intervals for all 5-mm segments (SDANN [ms]--period I: 47.78+/-22.69, period II: 60.72+/-27.55, period III: 47.12+/-23.21; I-II: p<0.05, II-III: p<0.05) were significantly increased. As well as very low frequency (VLF [ms2]--period I: 456.62+/-214.13, period II: 566.84+/-216.99, period III: 477.43+/-203.94; I-II: p<0.05), low frequency (LF [ms(2)]--period I: 607.97+/-201.33, period II: 758.28+/-307.90, period III: 627.09+/-220.33; I-II: p<0.01, II-III: p<0.05) and high frequency (HF [ms(2)]--period I: 538.44+/-290.63, period II: 730.31+/-445.78, period III: 590.94+/-301.64; I-II: p<0.05) components were the highest and the LF/HF ratio (period I: 1.48+/-0.38, period II: 1

  9. [Bacteria ecology in planting-culturing system].

    PubMed

    Huang, Fenglian; Xia, Beicheng; Dai, Xin; Chen, Guizhu

    2004-06-01

    Planting-culturing system in inter-tidal zone is a new type eco-culturing model. The survey on bacteria biomass and water quality in the designed planting-culturing system in inter-tidal zone showed that the mangrove planted in the system improved water quality and made water quality to II-III type, better than the IV and V type in the control pond. Designed ponds made heterotrophic bacteria, vibrio, phosphorus bacteria and enzyme-producing bacteria populations 1-2 order lower than the control pond without mongrove planting. Correlation analyses with CORREL software showed that the biomass of these bacteria was positively related with the nitrogen and phosphorus contents in water of the system, and the correlation coefficient for heterogeneous bacteria and vibrio was up to 0.9205. Heterotrophic bacteria and vibrio could be used as the water-quality monitoring organisms.

  10. Energy approach to the problem of calculating the stresses at the initial stages of plastic deformation of crystalline substances and the appearance of structural defects

    NASA Astrophysics Data System (ADS)

    Belousov, O. K.; Palii, N. A.

    2016-09-01

    The critical shear stress and its temperature dependence are calculated for 12 simple substances with different structures and types of bonding. The shear stress for stage II-III of deformation of single crystals (τII-III) and σ0, y, i.e., the Hall-Petch relation extrapolated to an infinitely large grain size, are estimated. The energy of formation of lattice defects (vacancies) is calculated using a proposed expression. The results of calculation of the elastic shear energy of a matrix and regions with a high elastic anisotropy are used to estimate the role of elastic anisotropy in lattice stability and fracture. The calculated and experimental results agree satisfactorily with each other.

  11. Cariprazine: First Global Approval.

    PubMed

    McCormack, Paul L

    2015-11-01

    Cariprazine (Vraylar) is an oral atypical antipsychotic originated by Gedeon Richter. It is a potent dopamine D3 and D2 receptor partial agonist, which preferentially binds to the D3 receptor. Cariprazine also has partial agonist activity at serotonin 5-HT1A receptors. In September 2015, cariprazine received its first global approval in the USA for the treatment of schizophrenia and for the acute treatment of manic or mixed episodes associated with bipolar I disorder. It is also in development in a variety of countries for the treatment of schizophrenia with predominant negative symptoms (phase III), as adjunctive therapy for major depressive disorder (phase II/III) and for the treatment of bipolar depression (phase II). This article summarizes the milestones in the development of cariprazine leading to this first approval for schizophrenia and manic or mixed episodes associated with bipolar I disorder.

  12. Endometrial carcinoma in women 40 year old or younger: a case report and literature review.

    PubMed

    Gerli, S; Spanò, F; Di Renzo, G C

    2014-01-01

    Endometrial cancer is the most frequent gynecologic cancer. Although it mainly occurs in menopausal women, it can hit younger patients as well. Only few cases of affected women under the age of 30 are reported. A case of a 23-year-old patient with endometrioid carcinoma grade II-III is presented. Hysterectomy is considered the standard treatment and it could represent a problem for those young women who desire to preserve fertility. A conservative management can be offered to these patients when the tumor is well differentiated and advanced stage is excluded. Several studies are available in literature about fertility sparing approach. Progestin treatment, combined or not with hysteroscopic ablation seem to be the most validated conservative management. Anyhow this treatment is not free risk, because it is not always effective and disease progression during or after treatment is possible. Then a strict evaluation and selection of patients before starting treatment is mandatory.

  13. [Child abuse in Tlaxcala: a case-control study].

    PubMed

    Herrada-Huidobro, A; Nazar-Beutelspacher, A; Cassaball-Núñez, M; Vega-Ramos, R; Nava-Cruz, C B

    1992-01-01

    A longitudinal, retrospective and descriptive study about child abuse was carried out in the Hospitals of the Tlaxcala Secretariat of Health, Mexico. The information was obtained from hospitalized children's charts between January first and November 30, 1991. The charts included were those belonging to zero to 14 year old children with injuries, poisoning, and II-III degrees of malnutrition. Four child-abuse criteria were established: physical, sexual, non organic malnutrition and mixed (physical and non organic malnutrition). Two control groups were defined. Different patterns were observed between accidental and non accidental injuries, malnutrition and poisoning among the case and the control groups. The study provides useful information for the integral diagnosis of child abuse in hospitalized children.

  14. Statistical inference for response adaptive randomization procedures with adjusted optimal allocation proportions.

    PubMed

    Zhu, Hongjian

    2016-12-12

    Seamless phase II/III clinical trials have attracted increasing attention recently. They mainly use Bayesian response adaptive randomization (RAR) designs. There has been little research into seamless clinical trials using frequentist RAR designs because of the difficulty in performing valid statistical inference following this procedure. The well-designed frequentist RAR designs can target theoretically optimal allocation proportions, and they have explicit asymptotic results. In this paper, we study the asymptotic properties of frequentist RAR designs with adjusted target allocation proportions, and investigate statistical inference for this procedure. The properties of the proposed design provide an important theoretical foundation for advanced seamless clinical trials. Our numerical studies demonstrate that the design is ethical and efficient.

  15. Causes and Corrections for Propeller-Excited Airborne Noise on a Naval Auxiliary Oiler.

    DTIC Science & Technology

    1983-11-01

    i1 t 1i’t i~i I, I, 1t ii . 1 :- ill stll , - pIF 1110141it’ri tilt’tit) tt’stt tl itt the *itln formssilrr f l io tittf doi’ po t’ .I11, 1 J 1 ". ,t...34AD-A135 731 CAUSES AND CORRECTIONS FOR PROPELLER-EXCITED AIRBORNE 1 /|, NOISE ON A NAVAL AU..(U) DAVID W TAYLOR NAVAL SHIP RESEARCH AND DEVELOPMENT...CENTER BET.. UNCtASSIFIED M B WILSON ET AL. NOV 83 DTNSRDC-83/097 F/G 20/ 1 NL EEEIIIIIIEEEhmhhmhIIhIIhu EhEEEIIhIIIII EEEEEIIIII L *G~B ’ ’~ I.112. 0

  16. [Clinical and morphologic characteristics of lung cancer in miners of Krivoy Rog iron-ore region and of uranium mines of Zhovti Vody].

    PubMed

    Bednaryk, O M; Filipchenko, L L; Pan'kova, A O; Kryvosheĭ, L O; Slinchenko, M Z

    2004-01-01

    Clinical and morphological features of cancer were observed in two groups of miners (of Krivoy Rog iron-ore and Zholty Vody uranium mines), working in hazardous labour conditions. In both of groups the disease course had typical features for lung cancer. Roentgenologic changes were observed, central cancer of left and right lung was revealed by bronchoscopy method. In all the cases lung cancer was morphologically proved and classified as squamous. Rapid progression of the disease and late medical aid appealability cause the patients consulted with their doctors only at the stage of II-III, sometimes III of the disease and it makes a distinction of lung cancer in miners of iron-ore and uranium mines. In order to prevent such a late diagnostics all the miners should be referred to the group of risk on lung cancer.

  17. A novel mutation 3090 G>A of the mitochondrial 16S ribosomal RNA associated with myopathy.

    PubMed

    Coulbault, L; Deslandes, B; Herlicoviez, D; Read, M H; Leporrier, N; Schaeffer, S; Mouadil, A; Lombès, A; Chapon, F; Jauzac, P; Allouche, S

    2007-10-26

    We describe a young woman who presented with a progressive myopathy since the age of 9. Spectrophotometric analysis of the respiratory chain in muscle tissue revealed combined and profound complex I, III, II+III, and IV deficiency ranging from 60% to 95% associated with morphological and histochemical abnormalities of the muscle. An exhaustive screening of mitochondrial transfer and ribosomal RNAs showed a novel G>A substitution at nucleotide position 3090 which was detected only in urine sediment and muscle of the patient and was not found in her mother's blood cells and urine sample. We suggest that this novel de novo mutation in the 16S ribosomal RNA, a nucleotide which is highly conserved in different species, would impair mitochondrial protein synthesis and would cause a severe myopathy.

  18. F-16 Simulator for Man-in-the-Loop Testing of Aircraft Control Systems (SIMTACS).

    DTIC Science & Technology

    1987-12-01

    AD-4199 675 F-16 SIMULA TR FOR MAN-JN-THE- JO TTI M? OF AIRCR"F7 L/2 CONTROL M IS (SjMTAC~ )(U) AHOFQC IN T OFT0 UNCLASSIFIED DE 8 A FJ7CTI 3NCKO7O...OF GNI. 4 HLS 󈧨 - Il1.8 IIIIi .25 1.4 1.6 MICROCOPY RESOLUTION T ES r CHART --- .- u,...,n..nmmnmmna,.,mn mmi ihh’nunan immii u N: 9 It ILL 0...belief in my ability to accomplish this task. Acce slon For t NTIS3 FA&I ti :’ ’,. u " ii jj... W\\i U t At .. .. ..) Page Preface

  19. VizieR Online Data Catalog: MYStIX candidate protostars (Romine+, 2016)

    NASA Astrophysics Data System (ADS)

    Romine, G.; Feigelson, E. D.; Getman, K. V.; Kuhn, M. A.; Povich, M. S.

    2017-04-01

    The present study seeks protostars from the Massive Young Star-forming complex in Infrared and X-ray (MYStIX) survey catalogs. We combine objects with protostellar infrared SEDs and 4.5um excesses with X-ray sources exhibiting ultrahard spectra denoting very heavy obscuration. These criteria filter away nearly all of the older Class II-III stars and contaminant populations, but give very incomplete samples. The result is a list of 1109 protostellar candidates in 14 star-forming regions. See sections 1 and 2 for further explanations. The reliability of the catalog is strengthened because a large majority (86%) are found to be associated with dense cores seen in Herschel 500um maps that trace cold dust emission. However, the candidate list requires more detailed study for confirmation and cannot be viewed as an unbiased view of star formation in the clouds. (3 data files).

  20. Enhanced Vision for All-Weather Operations Under NextGen

    NASA Technical Reports Server (NTRS)

    Bailey, Randall E.; Kramer, Lynda J.; Williams, Steven P.; Bailey, Randall E.; Kramer, Lynda J.; Williams, Steven P.

    2010-01-01

    Recent research in Synthetic/Enhanced Vision technology is analyzed with respect to existing Category II/III performance and certification guidance. The goal is to start the development of performance-based vision systems technology requirements to support future all-weather operations and the NextGen goal of Equivalent Visual Operations. This work shows that existing criteria to operate in Category III weather and visibility are not directly applicable since, unlike today, the primary reference for maneuvering the airplane is based on what the pilot sees visually through the "vision system." New criteria are consequently needed. Several possible criteria are discussed, but more importantly, the factors associated with landing system performance using automatic and manual landings are delineated.

  1. Multilocular hydrocephalus: ultrasound studies of origin and development.

    PubMed

    Prats, J M; López-Heredia, J; Gener, B; Freijo, M M; Garaizar, C

    2001-02-01

    Multilocular hydrocephalus is a complication of neonatal hydrocephalus. Its main feature is the presence of multiple cysts inside the ventricles, which requires a specific therapeutic approach. The case of a preterm infant with intracranial hemorrhage grade II-III and central nervous system infection is reported. The cysts developed at the subependymal layer in the posterior area of the patient's thalamus. Their growth and development were charted by ultrasound imaging for several weeks. These types of cysts may grow to occupy the totality of the lateral ventricles, isolating the temporal horns. Of all the reviewed pathogenic mechanisms, we support the hypothesis of an inflammatory vasculitis at the subependymal level, with the subsequent infarct giving rise to the cysts. The osmotic pressure within the cavities, rather than intraventricular fluid, would account for the enlargement of the cysts.

  2. Five-color band ultraviolet photometry of fourteen close binaries

    NASA Technical Reports Server (NTRS)

    Kondo, Y.; Mccluskey, G. E.; Wu, C.-C.

    1981-01-01

    Photometric observations obtained with the Astronomical Netherlands Satellite in five ultraviolet wavelength regions for 14 close binaries are presented. Strong excess far-ultraviolet flux is detected in four objects. The binaries TT Hya, RX Cas, and SX Cas exhibit a pronounced excess of far-ultraviolet flux, which is thought to be the result of mass transfer phenomena in these systems. Observations of the binary R Ara show very peculair variations; its far ultraviolet flux at 1550 A brightened by 0.4 mag between phases 0.7 and 0.8, while its near ultraviolet flux at 3300 A decreased by 0.5 mag over this same half-day interval. The A0 II-III component in the system RZ Sct is seen to dominate the ultraviolet spectrum.

  3. Airland Battle and the Division Artillery Counterfire Dilemma,

    DTIC Science & Technology

    1987-11-30

    ITRRY STUDIESUN A I F J iI36 l NOEhhEE|IIhimI----- i----i---i I’llIIIII 4.’ ....~ - - - -- S -U S.t -. -". ’. . -’.. -’- - -- - ’. _- _ - _ r...celegating part of the counter fire mission to an F .’- a~. . he abilit to mass fires required numerous field artillery D Ar.g’orld A~ar 11, a corps could...envisioned by the -V tle De ense Doctrine. Furthermore, the AirLand Ihattle is not ,itniply a brigade 3 S f ig h t n o r r e a . Cl a i ,i T h r’ t

  4. Imaging of the stroke-related changes in the vascular system of the mouse brain with the use of extended focus optical coherence microscopy

    NASA Astrophysics Data System (ADS)

    Tamborski, Szymon; Lyu, Hong Chou; Bukowska, Danuta; Dolezyczek, Hubert; Wilczynski, Grzegorz; Szlag, Daniel; Lasser, Theo; Wojtkowski, Maciej; Szkulmowski, Maciej

    2016-03-01

    We used Optical Coherence Microscopy (OCM) to monitor structural and functional changes due to ischemic stroke in small animals brains in vivo. To obtain lateral resolution of 2.2 μm over the range of 600 μm we used extended focus configuration of OCM instrument involving Bessel beam. It provided access to detailed 3D information about the changes in brain vascular system up to the level of capillaries across I and II/III layers of neocortex. We used photothrombotic stroke model involving photoactive application of rose bengal to assure minimal invasiveness of the procedure and precise localization of the clot distribution center. We present the comparative analysis involving structural and angiographic maps of the stroke-affected brain enabling in-depth insight to the process of development of the disorder.

  5. Structural and microstructural investigation of CdxZn1-xIn2S4 photocatalyst for solar hydrogen production

    NASA Astrophysics Data System (ADS)

    Indrea, E.; Silipaş, D. T.; Bǎnicǎ, R.; Nyari, Terezia; Suciu, Ramona-Crina

    2012-02-01

    A novel low temperature hydrothermal synthesis of II-III2-VI4 (II = Zn, Cd; III = In; VI = S) mixed ternary chalcogenide semiconductors as visible photocatalysts for solar hydrogen production was performed. In this work, an X-ray diffraction based structural and microstructural study of chalcogenide semiconductors type CdxZn1-xIn2S4 (0 ≤ x ≤ 1) is reported. The investigated powder samples were synthesized by a hydrothermal technique, using a Teflon lined closed autoclave with self-generated pressure, at 180°C for 20 hours. Rietveld method based on pseudo-Voigt profile fitting function was applied to perform a simultaneous refinement of X-ray diffraction patterns concerning both material structure and microstructure. The Rietveld refinement of the X-ray diffraction data has been done using the MATCH, MAUD and PowderCel softwares.

  6. Cholinergic and noradrenergic triggers' in soman induced convulsions

    SciTech Connect

    Shipley, M.T.; Zimmer, L.; Ennis, M.; Etri, M.

    1993-05-13

    Considerable evidence suggests that soman induced seizure's are initiated in the piriform cortex (PC). Consistent with this, PC is the most frequent site of neuropathology in soman treated rats and other species. Previous studies in this laboratory have shown that convulsive doses of soman cause the rapid induction of the immediate early gene protein product, Fos, in piriform cortex (PC). Fos is known to be expressed when neurons undergo sustained excitatory activity. Following soman, Fos is selectively expressed by neurons in layers II Ill of PC. These neurons are known to send excitatory projections to the hippocampus and to thalamus and neocortex. Thus, we have suggested that soman may initially cause seizure activity in layer II-III PC neurons; this seizure activity could then spread to the hippocampus and neocortex. Consistent with this hypothesis, we have observed that Fos is expressed in hippocampus, thalamus and neocortex subsequent to its expression in PC.

  7. Phase I-II clinical trial of Californium-252. Treatment of stage IB carcinoma of the cervix

    SciTech Connect

    Maruyama, Y.; VanNagell, J.R.; Yoneda, J.; Donaldson, E.; Gallion, H.; Rowley, K.; Kryscio, R.; Beach, J.L.

    1987-04-15

    Intracavitary Californium-252 combined with whole-pelvis photon radiotherapy was tested as the sole form of treatment for 22 patients with Stage IB carcinoma of the cervix. Californium-252 (Cf) is a fast neutron-emitting radioisotope currently being tested in trials of neutron brachytherapy (NT). The outcomes of the treated group of patients were traced for local tumor control, survival, patterns of failure, and complications. The Cf intracavitary therapy combined with whole-pelvis photon radiotherapy resulted in 95% 2-year and 91% 5-year actuarial survival. There were 9% Grade II-III complications by the Stockholm scale and 4% local failures. These results were obtained in an early clinical trial with a group of largely poor-risk patients with tumors of mean diameter of 4.3 cm.

  8. Application of J-Integral in the Case of a Single Crack in Cantilever Beam

    NASA Astrophysics Data System (ADS)

    Mladensky, Angel S.; Rizov, Victor I.

    2012-12-01

    Mixed mode II/III crack investigation in cantilever bilayered unidirectional fiber reinforced composite beam is reported. The crack is situated between the layers. The two crack arms have different widths. Formula for the strain energy release rate is obtained by the linear elastic fracture mechanics methods using the magnitude of the applied forces, geometrical characteristics of the cross-section, and the elastic moduli of the layers. An equivalent shear modulus of the un-cracked beam portion is used. Several diagrams illustrating the results of parametrical analysis of the strain energy release rate are presented. The paper is a part of a research in the field of fracture behaviour of composite beams.

  9. Atypical Squamous Cells of Undetermined Significance: Bethesda Classification and Association with Human Papillomavirus

    PubMed Central

    Barcelos, Ana Cristina Macêdo; Michelin, Márcia Antoniazi; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2011-01-01

    Introduction. To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. Methods. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed. Results. Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031). Conclusions. ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN. PMID:21760701

  10. Improving efficiency and reducing costs: Design of an adaptive, seamless, and enriched pragmatic efficacy trial of an online asthma management program.

    PubMed

    Lu, Mei; Ownby, Dennis R; Zoratti, Edward; Roblin, Douglas; Johnson, Dayna; Johnson, Christine Cole; Joseph, Christine L M

    2014-05-01

    Clinical trials are critical for medical decision-making, however, under the current paradigm, clinical trials are fraught with problems including low enrollment and high cost. Promising alternatives to increase trial efficiency and reduce costs include the use of (1) electronic initiatives that permit electronic remote data capture (EDC) for direct data collection at a site (2), electronic medical records (EMR) for patient identification and data collection, and (3) adaptive, enrichment designs with pragmatic approaches. We describe the design of a seamless, multi-site randomized Phase II/III trial to evaluate an asthma management intervention in urban adolescents with asthma. Patients are randomized, asked to access four online sessions of the intervention or control asthma management program, and are then followed for one year. The primary efficacy endpoint is self-reported asthma control as measured by the Asthma Control Test (ACT). Comparative effectiveness parametric approaches are utilized to conduct the trial in a real world setting with reduced costs. Escalated electronic initiatives are implemented for patient identification, assent, enrollment and tracking. Patient enrollment takes place during primary care visits. A centralized database with EDC is used for CRF data collection with integration of EMR data. This Phase II/III trial plans to have a total sample size of 500 patients with an interim look at the completion of Phase II (n=250), The interim analyses include an assessment of the intervention effect, marker(s) identification and the feasibility study of EMR data as the trial CRF data collection. Patient enrollment has begun and is ongoing.

  11. Misuse of antimicrobials and selection of methicillin-resistant Staphylococcus pseudintermedius strains in breeding kennels: genetic characterization of bacteria after a two-year interval.

    PubMed

    Rota, A; Milani, C; Corrò, M; Drigo, I; Börjesson, S

    2013-02-01

    Methicillin-resistant Staphylococcus pseudintermedius (MRSP) strains have been isolated from dogs with increasing frequency; prolonged or excessive use of antimicrobials is associated with the selection of MRSP, and misuse of antimicrobials is frequent in breeding kennels. This study was carried out in two breeding kennels (A and B) in which we had isolated MRSP in 2008: the aim was to assess colonization of previously positive bitches and of other bitches sharing the same environment and to assess the genetic profile of both the old and the new strains [spa typing, staphylococcal cassette chromosome mec (SCCmec) typing and Pulsed-field Gel Electrophoresis (PFGE)]. Six animals from Kennel A (two from 2008) and eight from Kennel B (one from 2008) were tested: 16 MRSP strains were isolated only from bitches housed in Kennel B. Old and new isolates were mecA positive, resulted spa type t02 and carried SSCmec II-III. PGFE showed that all isolates were related and belonged to the main clone lineage dominating in Europe, ST71-J-t02-II-III. Kennels A and B differ in the use of antimicrobials, which has been reduced over time in Kennel A, while has remained excessive in Kennel B, where many agents belonging to different classes (third-generation cephalosporins, fluoroquinolones, macrolids) are administered to dogs, without veterinary supervision, especially around parturition. Misuse of antimicrobials is the key factor for the selection of MRSP strains in healthy dogs and for their persistence over time. Dog breeders should be aware that infections caused by multiresistant bacteria have very limited therapeutical options and represent a huge challenge for animal health.

  12. Depression and body mass index, differences by education: Evidence from a population-based study of adult women in the U.S. Buffalo-Niagara region.

    PubMed

    Kranjac, Ashley Wendell; Nie, Jing; Trevisan, Maurizio; Freudenheim, Jo L

    The relationship between obesity and depression is well described. However, the evidence linking depression and body mass index (BMI) across the broad range of body size is less consistent. We examined the association between depressive symptoms and BMI in a sample of adult women in the Buffalo-Niagara region between 1997 and 2001. Using logistic regression, we investigated whether increased weight status beyond normal-weight was associated with a higher prevalence of depressive symptoms, and if educational attainment modified the association between obesity and depression. There was a trend for increased weight status to be associated with higher depressive symptoms (obese II/III, OR 1.57, 95% CI 1.03-2.41), whereas higher education was associated with lower odds of depressive symptoms, in an adjusted model including BMI (more than 12 but less than 16 years, OR 0.70, 95% CI 0.49-0.98; 16 or more years of education, OR 0.61, 95% CI 0.40-0.93). The association of being obese I with depressive symptoms was different for more educated (OR 2.15, 95% CI 1.27-3.62) compared to less educated women (OR 0.90, 95% CI 0.50-1.62); the sample was larger for the more educated women and reached statistical significance. There were no differences in the association for obese II/III women in strata of education. There was evidence of risk-difference heterogeneity (0.88, 95% CI 0.84-0.93). In this population-based sample of women in western New York state, increased weight was negligibly associated with depressive symptoms. The association of being obese I with depressive symptoms was different for more compared to less educated women. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  13. Accelerated dendritic development of rat cortical pyramidal cells and interneurons after biolistic transfection with BDNF and NT4/5.

    PubMed

    Wirth, Marcus J; Brun, Annika; Grabert, Jochen; Patz, Silke; Wahle, Petra

    2003-12-01

    Neurotrophins are candidate molecules for regulating dendritogenesis. We report here on dendritic growth of rat visual cortex pyramidal and interneurons overexpressing 'brain-derived neurotrophic factor' BDNF and 'neurotrophin 4/5' NT4/5. Neurons in organotypic cultures were transfected with plasmids encoding either 'enhanced green fluorescent protein' EGFP, BDNF/EGFP or NT4/5/EGFP either at the day of birth with analysis at 5 days in vitro, or at 5 days in vitro with analysis at 10 days in vitro. In pyramidal neurons, both TrkB ligands increased dendritic length and number of segments without affecting maximum branch order and number of primary dendrites. In the early time window, only infragranular neurons were responsive. Neurons in layers II/III became responsive to NT4/5, but not BDNF, during the later time window. BDNF and NT4/5 transfectants at 10 days in vitro had still significantly shorter dendrites than adult pyramidal neurons, suggesting a massive growth spurt after 10 days in vitro. However, segment numbers were already in the range of adult neurons. Although this suggested a role for BDNF, long-term activity-deprived, and thus BDNF-deprived, pyramidal cells developed a dendritic complexity not different from neurons in active cultures except for higher spine densities on neurons of layers II/III and VI. Neutralization of endogenous NT4/5 causes shorter and less branched dendrites at 10 days in vitro suggesting an essential role for NT4/5. Neutralization of BDNF had no effect. Transfected multipolar interneurons became identifiable during the second time window. Both TrkB ligands significantly increased number of segments and branch order towards the adult state with little effects on dendritic length. The results suggested that early in development BDNF and NT4/5 probably accelerate dendritogenesis in an autocrine fashion. In particular, branch formation was advanced towards the adult pattern in pyramidal cells and interneurons.

  14. The origin of oil in the Cretaceous succession from the South Pars Oil Layer of the Persian Gulf

    NASA Astrophysics Data System (ADS)

    Rahmani, Omeid; Aali, Jafar; Junin, Radzuan; Mohseni, Hassan; Padmanabhan, Eswaran; Azdarpour, Amin; Zarza, Sahar; Moayyed, Mohsen; Ghazanfari, Parviz

    2013-07-01

    The origin of the oil in Barremian-Hauterivian and Albian age source rock samples from two oil wells (SPO-2 and SPO-3) in the South Pars oil field has been investigated by analyzing the quantity of total organic carbon (TOC) and thermal maturity of organic matter (OM). The source rocks were found in the interval 1,000-1,044 m for the Kazhdumi Formation (Albian) and 1,157-1,230 m for the Gadvan Formation (Barremian-Hauterivian). Elemental analysis was carried out on 36 samples from the source rock candidates (Gadvan and Kazhdumi formations) of the Cretaceous succession of the South Pars Oil Layer (SPOL). This analysis indicated that the OM of the Barremian-Hauterivian and Albian samples in the SPOL was composed of kerogen Types II and II-III, respectively. The average TOC of analyzed samples is less than 1 wt%, suggesting that the Cretaceous source rocks are poor hydrocarbon (HC) producers. Thermal maturity and Ro values revealed that more than 90 % of oil samples are immature. The source of the analyzed samples taken from Gadvan and Kazhdumi formations most likely contained a content high in mixed plant and marine algal OM deposited under oxic to suboxic bottom water conditions. The Pristane/nC17 versus Phytane/nC18 diagram showed Type II-III kerogen of mixture environments for source rock samples from the SPOL. Burial history modeling indicates that at the end of the Cretaceous time, pre-Permian sediments remained immature in the Qatar Arch. Therefore, lateral migration of HC from the nearby Cretaceous source rock kitchens toward the north and south of the Qatar Arch is the most probable origin for the significant oils in the SPOL.

  15. Human epidermal growth factor receptor 2/neu protein expression in meningiomas: An immunohistochemical study

    PubMed Central

    Telugu, Ramesh Babu; Chowhan, Amit Kumar; Rukmangadha, Nandyala; Patnayak, Rashmi; Phaneendra, Bobbidi Venkata; Prasad, Bodapati Chandra Mowliswara; Reddy, Mandyam Kumaraswamy

    2016-01-01

    Background: Meningiomas are common slow-growing primary central nervous system tumors that arise from the meningothelial cells of the arachnoid and spinal cord. Human epidermal growth factor receptor 2 (HER2) or HER2/neu (also known as c-erbB2) is a 185-kD transmembrane glycoprotein with tyrosine kinase activity expressed in meningiomas and various other tumors. It can be used in targeted therapy for HER2/neu positive meningiomas. Aim: To correlate the expression of HER2/neu protein in meningiomas with gender, location, histological subtypes, and grade. Materials and Methods: It was 3½ years prospective (March 2010–October 2011) and retrospective (May 2008–February 2010) study of histopathologically diagnosed intracranial and intraspinal meningiomas. Clinical details of all the cases were noted from the computerized hospital information system. Immunohistochemistry for HER2/neu protein was performed along with scoring. Statistical analysis was done using Chi-square test to look for any association of HER2/neu with gender, location, grade, and various histological subtypes of meningiomas at 5% level of significance. Results: A total of 100 cases of meningiomas were found during the study period. Of which, 80 were Grade I, 18 were Grade II, and 2 were Grade III meningiomas as per the World Health Organization 2007 criteria. The female-male ratio was 1.9:1 and the mean age was 47.8 years. HER2/neu protein was expressed in 75% of Grade I and 72.2% of Grade II and none of Grade III meningiomas. About 72.7% brain invasive meningiomas showed HER2/neu immunopositivity. Conclusion: HER2/neu protein was expressed in 73% of meningiomas. Statistically significant difference of HER2/neu expression was not seen between females and males of Grade I and Grade II/III meningiomas, intracranial and spinal tumors, Grade I and Grade II/III cases, and various histological subtypes of meningiomas. PMID:27695231

  16. Human epidermal growth factor receptor 2/neu protein expression in meningiomas: An immunohistochemical study.

    PubMed

    Telugu, Ramesh Babu; Chowhan, Amit Kumar; Rukmangadha, Nandyala; Patnayak, Rashmi; Phaneendra, Bobbidi Venkata; Prasad, Bodapati Chandra Mowliswara; Reddy, Mandyam Kumaraswamy

    2016-01-01

    Meningiomas are common slow-growing primary central nervous system tumors that arise from the meningothelial cells of the arachnoid and spinal cord. Human epidermal growth factor receptor 2 (HER2) or HER2/neu (also known as c-erbB2) is a 185-kD transmembrane glycoprotein with tyrosine kinase activity expressed in meningiomas and various other tumors. It can be used in targeted therapy for HER2/neu positive meningiomas. To correlate the expression of HER2/neu protein in meningiomas with gender, location, histological subtypes, and grade. It was 3½ years prospective (March 2010-October 2011) and retrospective (May 2008-February 2010) study of histopathologically diagnosed intracranial and intraspinal meningiomas. Clinical details of all the cases were noted from the computerized hospital information system. Immunohistochemistry for HER2/neu protein was performed along with scoring. Statistical analysis was done using Chi-square test to look for any association of HER2/neu with gender, location, grade, and various histological subtypes of meningiomas at 5% level of significance. A total of 100 cases of meningiomas were found during the study period. Of which, 80 were Grade I, 18 were Grade II, and 2 were Grade III meningiomas as per the World Health Organization 2007 criteria. The female-male ratio was 1.9:1 and the mean age was 47.8 years. HER2/neu protein was expressed in 75% of Grade I and 72.2% of Grade II and none of Grade III meningiomas. About 72.7% brain invasive meningiomas showed HER2/neu immunopositivity. HER2/neu protein was expressed in 73% of meningiomas. Statistically significant difference of HER2/neu expression was not seen between females and males of Grade I and Grade II/III meningiomas, intracranial and spinal tumors, Grade I and Grade II/III cases, and various histological subtypes of meningiomas.

  17. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    SciTech Connect

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  18. A Novel Form of Compensation in the Tg2576 Amyloid Mouse Model of Alzheimer's Disease.

    PubMed

    Somogyi, Attila; Katonai, Zoltán; Alpár, Alán; Wolf, Ervin

    2016-01-01

    One century after its first description, pathology of Alzheimer's disease (AD) is still poorly understood. Amyloid-related dendritic atrophy and membrane alterations of susceptible brain neurons in AD, and in animal models of AD are widely recognized. However, little effort has been made to study the potential effects of combined morphological and membrane alterations on signal transfer and synaptic integration in neurons that build up affected neural networks in AD. In this study spatial reconstructions and electrophysiological measurements of layer II/III pyramidal neurons of the somatosensory cortex from wild-type (WT) and transgenic (TG) human amyloid precursor protein (hAPP) overexpressing Tg2576 mice were used to build faithful segmental cable models of these neurons. Local synaptic activities were simulated in various points of the dendritic arbors and properties of subthreshold dendritic impulse propagation and predictors of synaptic input pattern recognition ability were quantified and compared in modeled WT and TG neurons. Despite the widespread dendritic degeneration and membrane alterations in mutant mouse neurons, surprisingly little, or no change was detected in steady-state and 50 Hz sinusoidal voltage transfers, current transfers, and local and propagation delays of PSPs traveling along dendrites of TG neurons. Synaptic input pattern recognition ability was also predicted to be unaltered in TG neurons in two different soma-dendritic membrane models investigated. Our simulations predict the way how subthreshold dendritic signaling and pattern recognition are preserved in TG neurons: amyloid-related membrane alterations compensate for the pathological effects that dendritic atrophy has on subthreshold dendritic signal transfer and integration in layer II/III somatosensory neurons of this hAPP mouse model for AD. Since neither propagation of single PSPs nor integration of multiple PSPs (pattern recognition) changes in TG neurons, we conclude that AD

  19. Peptide fragments of the dihydropyridine receptor can modulate cardiac ryanodine receptor channel activity and sarcoplasmic reticulum Ca2+ release.

    PubMed Central

    Dulhunty, Angela F; Curtis, Suzanne M; Cengia, Louise; Sakowska, Magdalena; Casarotto, Marco G

    2004-01-01

    We show that peptide fragments of the dihydropyridine receptor II-III loop alter cardiac RyR (ryanodine receptor) channel activity in a cytoplasmic Ca2+-dependent manner. The peptides were AC (Thr-793-Ala-812 of the cardiac dihydropyridine receptor), AS (Thr-671-Leu-690 of the skeletal dihydropyridine receptor), and a modified AS peptide [AS(D-R18)], with an extended helical structure. The peptides added to the cytoplasmic side of channels in lipid bilayers at > or = 10 nM activated channels when the cytoplasmic [Ca2+] was 100 nM, but either inhibited or did not affect channel activity when the cytoplasmic [Ca2+] was 10 or 100 microM. Both activation and inhibition were independent of bilayer potential. Activation by AS, but not by AC or AS(D-R18), was reduced at peptide concentrations >1 mM in a voltage-dependent manner (at +40 mV). In control experiments, channels were not activated by the scrambled AS sequence (ASS) or skeletal II-III loop peptide (NB). Resting Ca2+ release from cardiac sarcoplasmic reticulum was not altered by peptide AC, but Ca2+-induced Ca2+ release was depressed. Resting and Ca2+-induced Ca2+ release were enhanced by both the native and modified AS peptides. NMR revealed (i) that the structure of peptide AS(D-R18) is not influenced by [Ca2+] and (ii) that peptide AC adopts a helical structure, particularly in the region containing positively charged residues. This is the first report of specific functional interactions between dihydropyridine receptor A region peptides and cardiac RyR ion channels in lipid bilayers. PMID:14678014

  20. Prognostic Influence of Preoperative Fibrinogen to Albumin Ratio for Breast Cancer

    PubMed Central

    Chung, Jung Kee; Roh, Eun Youn; Kim, Jongjin; Oh, Sohee; Kim, Young A; Rhu, Jiyoung; Kim, Suzy

    2017-01-01

    Purpose Elevated serum concentration of fibrinogen and decreased serum concentration of albumin have been reported to be markers of elevated systemic inflammation. We attempted to investigate the prognostic influence of preoperative fibrinogen to albumin ratio (FAR) for breast cancer. Methods Data from 793 consecutive primary breast cancer patients were retrospectively analyzed. Serum levels of fibrinogen and albumin were tested before curative surgery. Subjects were grouped into two groups according to the cutoff value determined by performing the receiver operating characteristic curve analysis: the high FAR group (FAR>7.1) and the low FAR group (FAR≤7.1). Overall survival was assessed using the Kaplan-Meier estimator. Independent prognostic significance was analyzed using the Cox proportional hazards model. Results The high FAR group had a worse prognosis compared to the low FAR group (log-rank test, p<0.001). The prognostic effect of FAR was more significant than that of single markers such as fibrinogen (log-rank test, p=0.001) or albumin (log-rank test, p=0.001). The prognostic effect of FAR was prominent in the stage II/III subgroup (log-rank test, p<0.001) and luminal A-like subtype (log-rank test, p<0.001). FAR was identified as a significant independent factor on both univariate (hazard ratio [HR], 2.722; 95% confidence interval [CI], 1.659–4.468; p<0.001) and multivariate analysis (HR, 2.622; 95% CI, 1.455–4.724; p=0.001). Conclusion Preoperative FAR was a strong independent prognostic factor in breast cancer. Its prognostic effect was more prominent in the stage II/III subgroup and in the luminal A-like subtype. Therefore, preoperative FAR can be utilized as a useful prognosticator for breast cancer patients. Further studies are needed to validate its applications in clinical settings.