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Sample records for positive inotropic response

  1. New arylsparteine derivatives as positive inotropic drugs.

    Science.gov (United States)

    Boido, Vito; Ercoli, Marcella; Tonelli, Michele; Novelli, Federica; Tasso, Bruno; Sparatore, Fabio; Cichero, Elena; Fossa, Paola; Dorigo, Paola; Froldi, Guglielmina

    2017-12-01

    Positive inotropic agents are fundamental in the treatment of heart failure; however, their arrhythmogenic liability and the increased myocardial oxygen demand strongly limit their therapeutic utility. Pursuing our study on cardiovascular activities of lupin alkaloid derivatives, several 2-(4-substituted-phenyl)-2-dehydrosparteines and 2-(4-substituted-phenyl)sparteines were prepared and tested for inotropic and chronotropic activities on isolated guinea pig atria. Four compounds (6b, 6e, 7b, and 7f) exhibited significant inotropism that, at the higher concentrations, was followed by negative inotropism or toxicity. Compound 7e (2-(4-tolyl)sparteine) exhibited a steep dose-depending inotropic activity up to the highest concentration tested (300 µM) with an E max of 116.5 ± 3.4% of basal force, proving less potent but much more active in comparison to the highest concentrations tested of digoxin and milrinone having E max of 87.5 ± 3.1% and 52.2 ± 1.1%, respectively. Finally, docking studies suggested that the relevant sparteine derivatives could target the sigma-1 receptor, whose involvement in cardiac activity is well documented.

  2. Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside.

    Science.gov (United States)

    Jaski, B E; Fifer, M A; Wright, R F; Braunwald, E; Colucci, W S

    1985-01-01

    Milrinone is a potent positive inotropic and vascular smooth muscle-relaxing agent in vitro, and therefore, it is not known to what extent each of these actions contributes to the drug's hemodynamic effects in patients with heart failure. In 11 patients with New York Heart Association class III or IV congestive heart failure, incremental intravenous doses of milrinone were administered to determine the dose-response relationships for heart rate, systemic vascular resistance, and inotropic state, the latter measured by peak positive left ventricular derivative of pressure with respect to time (dP/dt). To clarify further the role of a positive inotropic action, the relative effects of milrinone and nitroprusside on left ventricular stroke work and dP/dt were compared in each patient at doses matched to cause equivalent reductions in mean arterial pressure or systemic vascular resistance, indices of left ventricular afterload. Milrinone caused heart rate, stroke volume, and dP/dt to increase, and systemic vascular resistance to decrease in a concentration-related manner. At the two lowest milrinone doses resulting in serum concentrations of 63 +/- 4 and 156 +/- 5 ng/ml, respectively, milrinone caused significant increases in stroke volume and dP/dt, but no changes in systemic vascular resistance or heart rate. At the maximum milrinone dose administered (mean serum concentration, 427 +/- 11 ng/ml), heart rate increased from 92 +/- 4 to 99 +/- 4 bpm (P less than 0.01), mean aortic pressure fell from 82 +/- 3 to 71 +/- 3 mmHg (P less than 0.01), right atrial pressure fell from 15 +/- 2 to 7 +/- 1 mmHg (P less than 0.005), left ventricular end-diastolic pressure fell from 26 +/- 3 to 18 +/- 3 (P less than 0.005), stroke volume index increased from 20 +/- 2 to 30 +/- 2 ml/m2 (P less than 0.005), stroke work index increased from 14 +/- 2 to 21 +/- 2 g X m/m2 (P less than 0.01), and dP/dt increased from 858 +/- 54 to 1,130 +/- 108 mmHg/s (P less than 0.005). When compared

  3. Characterization of the positive and negative inotropic effects of acetylcholine in the human myocardium

    NARCIS (Netherlands)

    X.Y. Du (Xiaoyi); R.G. Schoemaker (Regien); E. Bos (Egbert); P.R. Saxena (Pramod Ranjan)

    1995-01-01

    textabstractIn the human isolated myocardium, acetylcholine (10−9 to 10−3 M) elicited a biphasic inotropic effect (a decrease in the lower and an increase in the higher concentration range) in atrial and a positive inotropic effect in ventricular trabeculae. However, under conditions of raised

  4. Studies on the positive inotropic effect of phenylephrine: a comparison with isoprenaline.

    Science.gov (United States)

    Ledda, F; Marchetti, P; Mugelli, A

    1975-05-01

    1. The effects of phenylephrine and isoprenaline on the isometric contraction of guinea-pig ventricle were compared over the whole range of their respective dose-response curves. 2. In preparations driven at 2.5 Hz the increase in contractile force induced by either isoprenaline of phenylephrine was linearly correlated to an increase in maximum velocity of force development. The relaxation time was shortened by isoprenaline but not by phenylephrine. 3. The negative inotropic effect induced by delta [N-(3,4-dimethoxyphenethyl)-N-methyl-amino]-alpha-(3,4,5-trimethoxyphenyl)alpha-isopropylvaleronitrile hydrochloride (D(600)) was reversed by isoprenaline, but little influenced by phenylephrine. 4. The study of the interval-force relationship shows that the increase in contractile force induced by phenylephrine (3 X 10(-5) M) was relatively greater at low frequencies of stimulation, and that the maximum effect was reached at the frequency of 1 Hz. 5. The positive inotropic effect of phenylephrine (10-4 M) was significantly higher at a frequency of 1 Hz than at 2.5 Hz; the effect of isoprenaline (3 x 10-8 M) was not significantly different at the two driving frequencies. 6. In preparations driven at 1 Hz the inotropic effect of the lower concentrations of phenylephrine was due to an increase in the time to peak tension without any change of the maximum velocity of force development; however an increase of this parameter became evident only after higher concentrations of the amine (10-5 M or more), associated with a progressive shortening of the time to peak. 7. A correlation between mechanical and electrophysiological effects of phenylephrine is attempted; the suggestion is advanced that the prolongation of the action potential and of the active state duration may be an important factor in the inotropic effect of phenylephrine.

  5. Characterization of the positive and negative inotropic effects of acetylcholine in the human myocardium

    OpenAIRE

    Du, Xiaoyi; Schoemaker, Regien; Bos, Egbert; Saxena, Pramod Ranjan

    1995-01-01

    textabstractIn the human isolated myocardium, acetylcholine (10−9 to 10−3 M) elicited a biphasic inotropic effect (a decrease in the lower and an increase in the higher concentration range) in atrial and a positive inotropic effect in ventricular trabeculae. However, under conditions of raised contractility achieved by exposure to noradrenaline (10−5 M), only negative inotropic effects were observed in both atria and ventricles. Atropine (10−6 M), but not propranolol (10−6 M), antagonized bot...

  6. Alteration of cardiac glycoside positive inotropic action by modulators of protein synthesis and degradation

    International Nuclear Information System (INIS)

    Nosek, T.M.; Adams, R.J.

    1986-01-01

    Numerous membrane bound and cytoplasmic proteins participate in the cardiac expression of the positive inotropic action (PIA) of digitalis glycosides including the Na,K-ATPase (NKA). Exposure of the myocardium to an inhibitor of protein synthesis (cycloheximide, CYC) or of protein degradation (leupeptin, LEU) alters the PIA of ouabain in isolated, paced guinea pig papillary muscles (PM) in opposite ways. In vivo exposure to CYC for 3 hr resulted in a 30% depression of the in vitro PIA of ouabain at 1.7μM compared to control. In vivo exposure to LEU for 1 hr resulted in a 47% enhancement of the in vitro PIA of 1.7μM ouabain. Neither drug had an apparent effect on the ouabain PIA ED50. Neither CYC nor LEU exposure to PM in vitro affect resting or developed tension or the response of skinned PM to calcium. The mechanisms of the PIA alterations by CYC or LEU do not involve a direct effect on the digitalis receptor. Exposure of isolated cardiac sarcolemma enriched in NKA to 10-100μM CYC or LEU did not affect NKA activity or 3 H-ouabain binding. Although direct physicochemical effects of CYC or LEU may be involved in the alterations of the ouabain PIA, it is possible that modulation of the cellular levels or turnover rate of short-lived proteins may affect cardiac regulation of the digitalis PIA

  7. [Alpha but not beta-adrenergic stimulation has a positive inotropic effect associated with alkalinization of intracellular pH].

    Science.gov (United States)

    Gambassi, G; Lakatta, E G; Capogrossi, M C

    1991-01-01

    There is increasing evidence that alpha-adrenoceptors also exist in the myocardium and that an increase in force of contraction may be produced by stimulation of these sites. This positive inotropism seems to be dependent either on an increased amount of Ca++ released into the cytosol with each action potential or on increased myofilament responsiveness. In contrast, beta-adrenergic stimulation reduces the sensitivity of the contractile proteins and the positive inotropic effect is due to the activation of L-type calcium channels on the sarcolemma. We used single, isolated, enzymatically dissociated, adult rat ventricular myocytes. Cells were loaded either with the ester derivative of the Ca++ probe Indo-1 or with the intracellular pH probe Snarf-1 and at the same time we measured the contractile parameters and monitored the fluorescence as an index of intracellular calcium concentration or pH value. The single cells (bicarbonate buffer continuously gassed with O2 95%, CO2 5%, Ca++ 1.5 mM, field stimulation 0.5 Hz) were exposed to phenylephrine (50 microM) and nadolol (1 microM). Alpha-adrenergic stimulation increased twitch amplitude (delta ES = 1.93 +/- 0.77, n = 8; p less than 0.05) and showed only a slight increase in Ca++ transient. On the other end, the positive inotropic effect (delta ES = 2.84 +/- 0.86, n = 4; p less than 0.02) obtained with beta-adrenergic stimulation (isoproterenol 50 nM, bicarbonate buffer, Ca++ 0.5 mM, field stimulation 0.2 Hz) was always associated with a large increase in intracellular Ca++ concentration. Isoproterenol did not change intracellular pH (delta pH = 0.006 +/- 0.006, n = 4; NS) while phenylephrine increased it significantly (delta pH = 0.055 +/- 0.011, n = 8; p less than 0.002). Moreover, there was a statistically significant correlation between delta ES and delta pH (R2 = 0.532; p less than 0.05) when phenylephrine was present. This alkalinization as well as the increased contractility was antagonized by treatment with

  8. Effects of Potassium Channel Blockers on the Negative Inotropic Responses Induced by Cromakalim and Pinacidil in Guinea Pig Atrium

    Science.gov (United States)

    1992-01-01

    RD-A2•4 875 EFFECTS OF POTASSIUM CHANNEL BLOCKERS ON THE NEGATIVE 1/1 INOTROPIC RESPONSES INDUCED BY CRONAKALIM RND PINACIDIL IN GUINEA PIG ATRIUM(U...INOTROPICTRSPONSES INDUCED BY CROMAKAUM AND PINACIDILIN GUINEA PIG ATRIUM a AUTHOR WAI-MAN LAU 7 FORMING ORG NAMES/ADDRESSES DEFENCE SCIENCE AND a...and Technology Organisaio Aot Val. Negative Inotropic Responses Victoria. Australia Induced by Cromakalim and Pinacidil in Guinea Pig Atrium Key

  9. Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation.

    Science.gov (United States)

    Sakai, Mari; Suzuki, Tokiko; Tomita, Kengo; Yamashita, Shigeyuki; Palikhe, Sailesh; Hattori, Kohshi; Yoshimura, Naoki; Matsuda, Naoyuki; Hattori, Yuichi

    2017-06-01

    Dobutamine has been used in septic shock for many years as an only inotrope, but its benefit has been questioned. We weighed the effects of dobutamine and milrinone as inotropes in mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis. CLP-induced septic mice exhibited significant cardiac inflammation, as indicated by greatly increased mRNAs of proinflammatory cytokines and robust infiltration of inflammatory cells in the ventricular myocardium. Elevations of plasma cardiac troponin-I showed cardiac injury in CLP mice. Noninvasive echocardiographic assessment of cardiac function revealed that despite preserved left ventricular function in the presence of fluid replacement, the dobutamine inotropic response was significantly impaired in CLP mice compared with sham-operated controls. By contrast, milrinone exerted inotropic effects in sham-operated and CLP mice in an equally effective manner. Surface expression levels of β 1 -adrenoceptors and α-subunits of three main G protein families in the myocardium were unaffected by CLP-induced sepsis. Plasma cAMP levels were significantly elevated in both sham-operated and CLP mice in response to milrinone but only in sham-operated controls in response to dobutamine. Of phosphodiesterase (PDE) isoforms, PDE4D, but not PDE3A, both of which are responsible for cardiac cAMP hydrolysis, was significantly upregulated in CLP mouse myocardium. We define a novel mechanism for the impaired responsiveness to dobutamine as an inotrope in sepsis, and understanding the role of PDE4D in modulating cardiac functional responsiveness in sepsis may open the potential of a PDE4D-targeted therapeutic option in septic patients with low cardiac output who have a need for inotropic support. NEW & NOTEWORTHY Advisability of the usefulness of dobutamine in septic shock management is limited. Here, we reveal that the effect of dobutamine as a positive inotrope is impaired in mice with cecal ligation and puncture-induced sepsis

  10. Synthesis and Positive Inotropic Activity of [1,2,4]Triazolo[4,3-a] Quinoxaline Derivatives Bearing Substituted Benzylpiperazine and Benzoylpiperazine Moieties

    Directory of Open Access Journals (Sweden)

    Xue-Kun Liu

    2017-02-01

    Full Text Available In an attempt to search for more potent positive inotropic agents, two series of [1,2,4]triazolo[4,3-a] quinoxaline derivatives bearing substituted benzylpiperazine and benzoylpiperazine moieties were synthesized and their positive inotropic activities evaluated by measuring left atrial stroke volume in isolated rabbit heart preparations. Several compounds showed favorable activities compared with the standard drug, milrinone. Compound 6c was the most potent agent, with an increased stroke volume of 12.53% ± 0.30% (milrinone: 2.46% ± 0.07% at 3 × 10−5 M. The chronotropic effects of compounds having considerable inotropic effects were also evaluated.

  11. Inotropic responses of the frog ventricle to adenosine triphosphate and related changes in endogenous cyclic nucleotides.

    Science.gov (United States)

    Flitney, F W; Singh, J

    1980-07-01

    1. A study has been made of a well documented but poorly understood response of the isolated frog ventricle to treatment with exogenous adenosine 5' triphosphate (ATP). Measurements of membrane potential, isometric twitch tension and levels of endogenous 3',5'-cyclic nucleotides have been made at various times during the ATP-induced response. 2. ATP elicits a characteristic triphasic response, which comprises an initial, abrupt increase in contractility, rising to a maximum within a few beats (first phase); followed by a period when the twitch amplitude falls, sometimes to below the control level (second phase); and superceded by a more slowly developing and longer-lasting increase in contractile force (third phase). The response is unaffected by atropine, propranolol or phentolamine. However, the prostaglandin synthetase inhibitor indomethacin depresses the first phase and entirely suppresses the third phase. 3. The inotropic effects of ATP are accompanied by changes in the shape of the action potential. These effects are dose-related. The duration of the action potential (D-30mV) and its positive overshoot (O) are increased during all phases of the response, for [ATP]o's up to 10(-5) M. However, at higher [ATP]o's, D-30mV and O ar both reduced during the second phase (but not the first or third phase), when isometric twitch tension is also depressed. The relationship between action potential duration and twitch tension (P) for different [ATP]o's is linear for all three phases of the response, but the slopes of the curves (delta P/delta D) are markedly different, indicating that the sensitivity of the contractile system to membrane depolarization is not constant, but varies continuously throughout the response. 4. ATP has a potent stimulatory effect on the metabolism of endogenous 3',5'-cyclic nucleotides. The time courses of the changes in adenosine 3','5-cyclic monophosphate (3',5'-cyclic AMP) and guanosine 3',5'-cyclic monophosphate (3',5'-cyclic GMP) are

  12. Istaroxime, a positive inotropic agent devoid of proarrhythmic properties in sensitive chronic atrioventricular block dogs.

    Science.gov (United States)

    Bossu, Alexandre; Kostense, Amée; Beekman, Henriette D M; Houtman, Marien J C; van der Heyden, Marcel A G; Vos, Marc A

    2018-05-10

    Current inotropic agents in heart failure therapy associate with low benefit and significant adverse effects, including ventricular arrhythmias. Istaroxime, a novel Na + /K + -transporting ATPase inhibitor, also stimulates SERCA2a activity, which would confer improved inotropic and lusitropic properties with less proarrhythmic effects. We investigated hemodynamic, electrophysiological and potential proarrhythmic and antiarrhythmic effects of istaroxime in control and chronic atrioventricular block (CAVB) dogs sensitive to drug-induced Torsades de Pointes arrhythmias (TdP). In isolated normal canine ventricular cardiomyocytes, istaroxime (0.3-10 μM) evoked no afterdepolarizations and significantly shortened action potential duration (APD) at 3 and 10 μM. Istaroxime at 3 μg/kg/min significantly increased left ventricular (LV) contractility (dP/dt + ) and relaxation (dP/dt-) respectively by 81 and 94% in anesthetized control dogs (n = 6) and by 61 and 49% in anesthetized CAVB dogs (n = 7) sensitive to dofetilide-induced TdP. While istaroxime induced no ventricular arrhythmias in control conditions, only single ectopic beats occurred in 2/7 CAVB dogs, which were preceded by increase of short-term variability of repolarization (STV) and T wave alternans in LV unipolar electrograms. Istaroxime pre-treatment (3 μg/kg/min for 60 min) did not alleviate dofetilide-induced increase in repolarization and STV, and mildly reduced incidence of TdP from 6/6 to 4/6 CAVB dogs. In six CAVB dogs with dofetilide-induced TdP, administration of istaroxime (90 μg/kg/5 min) suppressed arrhythmic episodes in two animals. Taken together, inotropic and lusitropic properties of istaroxime in CAVB dogs were devoid of significant proarrhythmic effects in sensitive CAVB dogs, and istaroxime provides a moderate antiarrhythmic efficacy in prevention and suppression of dofetilide-induced TdP. Copyright © 2018. Published by Elsevier Ltd.

  13. [Positive inotropic and lusitropic effect of RP 62719, a new class III antiarrhythmia agent].

    Science.gov (United States)

    Beregi, J P; Escande, D; Coudray, N; Chemla, D; Mestre, M; Péry, N; Lecarpentier, Y

    1994-02-01

    Antiarrhythmic drugs, especially the Class I family, exert a negative inotropic effect on the myocardium which is particularly undesirable in patients with depressed left ventricular function. Therefore, research has been directed to the development of new, more specific molecules of the Class III family. The authors studies the mechanical effects of RP 62719 on guinea pig left ventricular papillary muscle. This new molecule is a pure Class III antiarrhythmic, known to lengthen the duration of the cardiac action potential by selectively blocking the potassium current iK1 (inward rectifier K+ current). The mechanical parameters were determined during the phases of contraction and relaxation under isotonic and isometric conditions. At 0.2 and 2 microM concentrations, RP 62719 improved cardiac contraction under both isotonic and isometric conditions with an increase of about 30% of Vmax (p delta 1 (p force normalized per cross-sectional area [AF/S (p actions could provide significant therapeutic advantages especially in patients cardiac failure.

  14. Acute effect of Vagus nerve stimulation parameters on cardiac chronotropic, inotropic, and dromotropic responses

    Science.gov (United States)

    Ojeda, David; Le Rolle, Virginie; Romero-Ugalde, Hector M.; Gallet, Clément; Bonnet, Jean-Luc; Henry, Christine; Bel, Alain; Mabo, Philippe; Carrault, Guy; Hernández, Alfredo I.

    2017-11-01

    Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy and depression, and is considered as a potential therapy for other pathologies, including Heart Failure (HF) or inflammatory diseases. In the case of HF, several experimental studies on animals have shown an improvement in the cardiac function and a reverse remodeling of the cardiac cavity when VNS is applied. However, recent clinical trials have not been able to reproduce the same response in humans. One of the hypothesis to explain this lack of response is related to the way in which stimulation parameters are defined. The combined effect of VNS parameters is still poorly-known, especially in the case of VNS synchronously delivered with cardiac activity. In this paper, we propose a methodology to analyze the acute cardiovascular effects of VNS parameters individually, as well as their interactive effects. A Latin hypercube sampling method was applied to design a uniform experimental plan. Data gathered from this experimental plan was used to produce a Gaussian process regression (GPR) model in order to estimate unobserved VNS sequences. Finally, a Morris screening sensitivity analysis method was applied to each obtained GPR model. Results highlight dominant effects of pulse current, pulse width and number of pulses over frequency and delay and, more importantly, the degree of interactions between these parameters on the most important acute cardiovascular responses. In particular, high interacting effects between current and pulse width were found. Similar sensitivity profiles were observed for chronotropic, dromotropic and inotropic effects. These findings are of primary importance for the future development of closed-loop, personalized neuromodulator technologies.

  15. Cholesterol regulates contractility and inotropic response to β2-adrenoceptor agonist in the mouse atria: Involvement of Gi-protein-Akt-NO-pathway.

    Science.gov (United States)

    Odnoshivkina, Yulia G; Sytchev, Vaycheslav I; Petrov, Alexey M

    2017-06-01

    Majority of cardiac β2-adrenoceptors is located in cholesterol-rich microdomains. Here, we have investigated the underlying mechanisms by which a slight to moderate cholesterol depletion with methyl-β-cyclodextrin (MβCD, 1 and 5mM) interferes with contractility and inotropic effect of β2-adrenergic agonist (fenoterol, 50μM) in the mouse atria. Treatment with MβCD itself increased amplitude of Ca 2+ transient but did not change the contraction amplitude due to a clamping action of elevated NO. Cholesterol depletion significantly attenuated the positive inotropic response to fenoterol which is accompanied by increase in NO generation and decrease in Ca 2+ transient. Influence of 1mM MβCD on the fenoterol-driven changes in both contractility and NO level was strongly attenuated by inhibition of G i -protein (pertussis toxin), Akt (Akt 1/2 kinase inhibitor) or NO-synthase (L-NAME). After exposure to 5mM MβCD, pertussis toxin or Akt inhibitor could recover the β2-agonist effects on contractility, NO production and Ca 2+ transient, while L-NAME only reduced NO level. An adenylyl cyclase activator (forskolin, 50nM) had no influence on the MβCD-induced changes in the β2-agonist effects. Obtained results suggest that slight cholesterol depletion upregulates G i -protein/Akt/NO-synthase signaling that attenuates the positive inotropic response to β2-adrenergic stimulation without altering the Ca 2+ transient. Whilst moderate cholesterol depletion additionally could suppress the enhancement of the Ca 2+ transient amplitude caused by the β2-adrenergic agonist administration in G i -protein/Akt-dependent but NO-independent manner. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Sensitivity Analysis of Vagus Nerve Stimulation Parameters on Acute Cardiac Autonomic Responses: Chronotropic, Inotropic and Dromotropic Effects.

    Directory of Open Access Journals (Sweden)

    David Ojeda

    Full Text Available Although the therapeutic effects of Vagus Nerve Stimulation (VNS have been recognized in pre-clinical and pilot clinical studies, the effect of different stimulation configurations on the cardiovascular response is still an open question, especially in the case of VNS delivered synchronously with cardiac activity. In this paper, we propose a formal mathematical methodology to analyze the acute cardiac response to different VNS configurations, jointly considering the chronotropic, dromotropic and inotropic cardiac effects. A latin hypercube sampling method was chosen to design a uniform experimental plan, composed of 75 different VNS configurations, with different values for the main parameters (current amplitude, number of delivered pulses, pulse width, interpulse period and the delay between the detected cardiac event and VNS onset. These VNS configurations were applied to 6 healthy, anesthetized sheep, while acquiring the associated cardiovascular response. Unobserved VNS configurations were estimated using a Gaussian process regression (GPR model. In order to quantitatively analyze the effect of each parameter and their combinations on the cardiac response, the Sobol sensitivity method was applied to the obtained GPR model and inter-individual sensitivity markers were estimated using a bootstrap approach. Results highlight the dominant effect of pulse current, pulse width and number of pulses, which explain respectively 49.4%, 19.7% and 6.0% of the mean global cardiovascular variability provoked by VNS. More interestingly, results also quantify the effect of the interactions between VNS parameters. In particular, the interactions between current and pulse width provoke higher cardiac effects than the changes on the number of pulses alone (between 6 and 25% of the variability. Although the sensitivity of individual VNS parameters seems similar for chronotropic, dromotropic and inotropic responses, the interacting effects of VNS parameters

  17. Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart.

    Science.gov (United States)

    Farkas, A S; Acsai, K; Nagy, N; Tóth, A; Fülöp, F; Seprényi, G; Birinyi, P; Nánási, P P; Forster, T; Csanády, M; Papp, J G; Varró, A; Farkas, A

    2008-05-01

    The Na(+)/Ca(2+) exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na(+) concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 microM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na(+) concentrations in rabbit and rat hearts. The concentration-dependent effects of SEA0400 on I(Na/Ca) were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry. SEA0400 inhibited I(Na/Ca) with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 microM SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities. NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na(+) concentration may play an important role in the contractility response to NCX inhibition.

  18. Influence of the sarcoplasmic reticulum on the inotropic responses of the rat myocardium resulting from changes in rate and rhythm.

    Science.gov (United States)

    Mill, J G; Vassallo, D V; Leite, C M; Campagnaro, P

    1994-06-01

    1. The role of the sarcoplasmic reticulum (SR) in the inotropic responses produced by changes in stimulation rate and rhythm and resting tension was investigated in the rat myocardium. 2. Rat papillary muscles contracting isometrically (basic stimulation rate = 30/min) were superfused in vitro with normal Krebs solution and after addition of ryanodine (1 microM). Post-rest potentiation was obtained after pauses of 5, 10, 15, 30, 60 and 120 s, and the stimulation rate was changed from 6 to 90 bpm. Post-extrasystolic potentiation was induced by interpolating an extra stimulus after an interval of 413 +/- 15 ms. NiCl2 (2 mM) was used to confirm that contractions obtained after SR blockade with ryanodine were activated only by sarcolemmal calcium influx. 3. In the presence of ryanodine, the post-rest potentiation phenomenon disappears and the force-frequency relationship changes from the typical force decrease produced by rate increase to force increase. Under the effect of ryanodine, resting tension increased with the increase in stimulation rate. This behavior was enhanced by reducing extracellular KCl from 5.4 mM to 1 mM. This maneuver decreases Na(+)-K(+)-ATPase and increases intracellular Na+ activity, which reduces Ca2+ extrusion through the Na(+)-Ca2+ exchange mechanism. 4. SR participation in the post-extrasystolic potentiation phenomenon is also suggested because ryanodine treatment reversed the extrasystolic force depression into potentiation. In the presence of ryanodine, blockade of Ca2+ influx with NiCl2 (2 mM) abolished isometric contractions indicating that after SR blockade contractions are mainly dependent on sarcolemmal Ca2+ influx. 5. The results suggest that the SR is involved in the genesis of post-rest potentiation and contributes to the typical force-frequency relationship of the rat myocardium and to the post-extrasystolic potentiation phenomenon. Moreover, SR activity seems to be important for the maintenance of low resting tension in the

  19. Influence of the low thyroid state in diabetes mellitus on cardiac function and inotropic responsiveness to alpha 1-adrenoceptor stimulation: comparison with the role of hypothyroidism alone.

    Science.gov (United States)

    Beenen, O H; Pfaffendorf, M; van Zwieten, P A

    1996-10-01

    The hypothyroid state accompanying diabetes mellitus has been suggested to be partly responsible for the diabetes-induced metabolic, hemodynamic, and pharmacological cardiovascular changes. We assessed the effectivity of streptozotocin (STZ) to induce diabetes mellitus and a hypothyroid state. Furthermore, we investigated the influence of diabetes and hypothyrodism on cardiac function and the inotropic responsiveness to the alpha 1-adrenoceptor agonist cirazoline in isolated perfused hearts. Fasted or nonfasted Wistar rats were made diabetic with STZ 20, 40 or 60 mg/kg intravenously (i.v.). Another group was made hypothyroid by addition of 6-n-propyl-2-thiouracil (PTU) to their drinking water. Rats receiving PTU became hypothyroid, whereas rats receiving STZ became simultaneously diabetic and hypothyroid. Basal functional parameters obtained in isolated perfused hearts were not influenced by diabetes, whereas maximal contractility was reduced in hearts obtained from hypothyroid animals. Cardiac inotropic responses to cirazoline were increased in diabetic rats, whereas responses in hypothyroid rats were not different from those in hearts obtained from control animals. Although diabetes mellitus and hypothyroidism are associated with various similar metabolic and haemodynamic parameters, the increased inotropic response to alpha 1-adrenoceptor stimulation as observed in isolated perfused hearts of diabetic rats cannot be explained by the decrease in serum thyroxine levels.

  20. CaMKII effects on inotropic but not lusitropic force frequency responses require phospholamban

    OpenAIRE

    Wu, Yiming; Luczak, Elizabeth D; Lee, Eun-Jeong; Hidalgo, Carlos; Yang, Jinying; Gao, Zhan; Li, Jingdong; Wehrens, Xander; Granzier, Henk; Anderson, Mark E

    2012-01-01

    Increasing heart rate enhances cardiac contractility (force frequency relationship, FFR) and accelerates cardiac relaxation (frequency-dependent acceleration of relaxation, FDAR). The positive FFR together with FDAR promotes rapid filling and ejection of blood from the left ventricle (LV) at higher heart rates. Recent studies indicate that the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is involved in regulating FFR and FDAR. We used isolated perfused mouse hearts to ...

  1. Crude extract and purified components isolated from the stems of Tinospora crispa exhibit positive inotropic effects on the isolated left atrium of rats

    DEFF Research Database (Denmark)

    Praman, Siwaporn; Mulvany, Michael J.; Williams, David E.

    2013-01-01

    of 5 bioactive compounds: higenamine, salsolinol, tyramine, adenosine and uridine. Higenamine, salsolinol (at low concentration) and tyramine acted via the adrenergic receptors to increase the force of the atrial contraction, whereas a high concentration of salsolinol acted indirectly by stimulating...... an increase in the force of contraction of the electrical field stimulated left atrium. This effect was inhibited by propranolol, atenolol, ICI-118,551, phentolamine and atropine. The positive inotropic effect on the reserpenized isolated left atrium of the Tinospora crispa extract was significantly inhibited...... by propranolol, atenolol and ICI-118,551. Phentolamine, on the other hand, caused potentiation and the effect was inhibited when propranolol was also added. Higenamine caused an increase in the force of contraction of the electrical field stimulated left atrium and this effect was significantly inhibited by ICI...

  2. CaMKII effects on inotropic but not lusitropic force frequency responses require phospholamban

    Science.gov (United States)

    Wu, Yiming; Luczak, Elizabeth D; Lee, Eun-Jeong; Hidalgo, Carlos; Yang, Jinying; Gao, Zhan; Li, Jingdong; Wehrens, Xander; Granzier, Henk; Anderson, Mark E

    2014-01-01

    Increasing heart rate enhances cardiac contractility (force frequency relationship, FFR) and accelerates cardiac relaxation (frequency-dependent acceleration of relaxation, FDAR). The positive FFR together with FDAR promotes rapid filling and ejection of blood from the left ventricle (LV) at higher heart rates. Recent studies indicate that the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is involved in regulating FFR and FDAR. We used isolated perfused mouse hearts to study the mechanisms of FFR and FDAR in different genetic models, including transgenic myocardial CaMKII inhibition (AC3-I) and phosphalamban knockout (PLN−/−). When the rate was increased from 360 beats/min to 630 beats/min in wild type mouse hearts, the LV developed pressure (LVDP) and the maximum rate of increase in pressure (dP/dt max) increased by 37.6 ± 4.7% and 77.0 ± 8.1%, respectively. However, hearts from AC3-I littermates showed no increase of LVDP and a relatively modest (20.4 ± 3.9 %) increase in dP/dt max. PLN−/− hearts had a negative FFR, and myocardial AC3-I expression did not change the FFR in PLN−/− mice. PLN−/− mouse hearts did not exhibit FDAR, while PLN−/−mice with myocardial AC3-I expression showed further frequency dependent reductions in cardiac relaxation, suggesting CaMKII targets in addition to PLN were critical to myocardial relaxation. We incubated a constitutively active form of CaMKII with chemically-skinned myocardium and found that several myofilament proteins were phosphorylated by CaMKII. However, CaMKII did not affect myofilament calcium sensitivity. Our study shows that CaMKII plays an important role in modulating FFR and FDAR in murine hearts and suggest that PLN is a critical target for CaMKII effects on FFR, while CaMKII effects on FDAR partially require PLN-alternative targets. PMID:22796260

  3. Positive inotropic effects of RP 62719, a new pure class III antiarrhythmic agent, on guinea pig myocardium.

    Science.gov (United States)

    Beregi, J P; Escande, D; Coudray, N; Mery, P; Mestre, M; Chemla, D; Lecarpentier, Y

    1992-12-01

    The mechanical effects of RP 62719 [(-)1-[-2-(3,4-dihydro-2H-1- benzopyran-4-yl)ethyl]-4-(3,4-dimethoxyphenyl)-piperidine] were tested in vitro on guinea pig left ventricular papillary muscle. RP 62719 is a novel pure class III antiarrhythmic agent known to prolong the cardiac action potential duration by selectively blocking the inward rectifying K+ current. Mechanical parameters were determined from contraction and relaxation phases under isotonic and isometric conditions. At a concentration of 0.02 microM, RP 62719 did not produce significant effects on inotropy or lusitropy. At 0.2 and 2 microM, the drug improved contraction under both heavy and low loading conditions, as evidenced by a 30% increase in maximum unloaded shortening velocity (Vmax, P delta L, P force normalized per cross-sectional area (AF/s, P force derivative per mm2 (+dF/s, P force derivative per mm2 (-dF/s, P < .001). At a higher concentration (20 microM), effects of RP 62719 on inotropy and lusitropy were less marked, thus accounting for the bell-shaped form of the dose-response curve. An increase in the extracellular Ca++ concentration from 2.5 to 3.75 mM improved inotropy to a similar extent (+30-50%) as did 2 microM RP 62719. However, lusitropy and mechanical coupling between contraction and relaxation were not modified in the same proportion under RP 62719 and under 3.75 mM Ca++.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Alternagin-C (ALT-C), a disintegrin-like protein from Rhinocerophis alternatus snake venom promotes positive inotropism and chronotropism in fish heart.

    Science.gov (United States)

    Monteiro, D A; Kalinin, A L; Selistre-de-Araujo, H S; Vasconcelos, E S; Rantin, F T

    2016-02-01

    Alternagin-C (ALT-C) is a disintegrin-like protein purified from the venom of the snake, Rhinocerophis alternatus. Recent studies showed that ALT-C is able to induce vascular endothelial growth factor (VEGF) expression, endothelial cell proliferation and migration, angiogenesis and to increase myoblast viability. This peptide, therefore, can play a crucial role in tissue regeneration mechanisms. The aim of this study was to evaluate the effects of a single dose of alternagin-C (0.5 mg kg(-1), via intra-arterial) on in vitro cardiac function of the freshwater fish traíra, Hoplias malabaricus, after 7 days. ALT-C treatment increased the cardiac performance promoting: 1) significant increases in the contraction force and in the rates of contraction and relaxation with concomitant decreases in the values of time to the peak tension and time to half- and 90% relaxation; 2) improvement in the cardiac pumping capacity and maximal electrical stimulation frequency, shifting the optimum frequency curve upward and to the right; 3) increases in myocardial VEGF levels and expression of key Ca(2+)-cycling proteins such as SERCA (sarcoplasmic reticulum Ca(2+)-ATPase), PLB (phospholamban), and NCX (Na(+)/Ca(2+) exchanger); 4) abolishment of the typical negative force-frequency relationship of fish myocardium. In conclusion, this study indicates that ALT-C improves cardiac function, by increasing Ca(2+) handling efficiency leading to a positive inotropism and chronotropism. The results suggest that ALT-C may lead to better cardiac output regulation indicating its potential application in therapies for cardiac contractile dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Rational use of inotropic therapy in heart failure.

    Science.gov (United States)

    Felker, G M; O'Connor, C M

    2001-03-01

    Despite their theoretic appeal, agents that increase cardiac contractility (positive inotropes) have consistently been shown to increase mortality when given chronically to patients with heart failure. The routine use of inotropes as heart failure therapy in either the acute or the chronic setting is not supported by the available data. Some appropriate uses of inotropes are as temporary treatment of diuretic-refractory acute heart failure decompensations, or as a bridge to definitive treatment such as revascularization or cardiac transplantation. Although controversial, the use of inotropes as a palliative measure in the small subset of patients with truly end-stage heart failure may be appropriate. An understanding of the appropriate goals of therapy is important for both patients and physicians if rational decisions about the use of inotropes are to be made.

  6. Angiotensin I-converting enzyme inhibitors potentiate bradykinin's inotropic effects independently of blocking its inactivation.

    Science.gov (United States)

    Minshall, R D; Erdös, E G; Vogel, S M

    1997-08-04

    The positive inotropic effects of bradykinin (BK) and 2 analogs resistant to angiotensin I-converting enzyme (ACE) were potentiated on isolated guinea pig atrial preparations by enalaprilat. The stable BK analogs, dextran-BK and [Hyp3-Tyr(Me)8]-BK, were as active as BK. Pretreatment for 5 min with enalaprilat augmented the maximal positive inotropic effect of [Hyp3-Tyr(Me)8]-BK 2.8-fold, from 19% to 53% and that of BK from 28% to 42% over baseline; inotropic responses to dextran-BK (1 microM) were similarly increased. The activity of atrial ACE, a zinc-requiring enzyme, was completely inhibited by 8-hydroxyquinoline-5-sulfonic acid (QSA, 10 mM), which raised the maximal inotropic effect of BK to 39% above baseline. This value rose to 67% when in addition to QSA, 1 microM enalaprilat was added; enalaprilat thus, potentiated the effects of BK independently of enzyme inhibition. The positive inotropic effects to BK and its analogs decline with time in the presence of these agonists. After 10 min of exposure, the response to 1 microM [Hyp3-Tyr(Me)8]-BK decreased to about half, and after 20 min, to 0. Enalaprilat, when present in the tissue bath, prevented the decline in inotropy; even after tachyphylaxis occurred, it reversed this decrease in activity when added. The effects of 1 microM [Hyp3-Tyr(Me)8]-BK, in the absence or presence of enalaprilat, were abolished by the BK B2 receptor antagonist icatibant (0.75 microM). The results indicate that ACE inhibitors, by potentiating the BK effects and blocking BK B2-receptor desensitization, may contribute to the beneficial cardiac effects of BK independently of blocking its inactivation.

  7. In-vitro examination of the positive inotropic effect of caffeine and taurine, the two most frequent active ingredients of energy drinks.

    Science.gov (United States)

    Chaban, R; Kornberger, A; Branski, N; Buschmann, K; Stumpf, N; Beiras-Fernandez, A; Vahl, C F

    2017-08-10

    Our study aimed to evaluate changes in the contractile behavior of human myocardium after exposure to caffeine and taurine, the main active ingredients of energy drinks (EDs), and to evaluate whether taurine exhibits any inotropic effect at all in the dosages commonly used in EDs. Myocardial tissue was removed from the right atrial appendages of patients undergoing cardiac surgery and prepared to obtain specimens measuring 4 mm in length. A total of 92 specimens were exposed to electrical impulses at a frequency of 75 bpm for at least 40 min to elicit their maximum contractile force before measuring the isometric contractile force (ICF) and duration of contraction (CD). Following this, each specimen was treated with either taurine (group 1, n = 29), or caffeine (group 2, n = 31) or both (group 3, n = 32). After exposure, ICF and CD measuring were repeated. Post-treatment values were compared with pre-treatments values and indicated as percentages. Exposure to taurine did not alter the contraction behavior of the specimens. Exposure to caffeine, in contrast, led to a significant increase in ICF (118 ± 03%, p caffeine and taurine also induced a statistically significant increase in ICF (124 ± 4%, p caffeine was similar to that achieved by a combination of both caffeine and taurine (p = 0.2). The relative ICF levels achieved by administration of caffeine and a combination of taurine and caffeine, respectively, were both significantly higher (p caffeine altered the contraction behavior of the specimen significantly in our in-vitro model, taurine did not exhibit a significant effect. Adding taurine to caffeine did not significantly enhance or reduce the effect of caffeine.

  8. Cerebral effects of commonly used vasopressor-inotropes: a study in newborn piglets.

    Directory of Open Access Journals (Sweden)

    Gitte H Hahn

    Full Text Available Despite widespread use in sick infants, it is still debated whether vasopressor-inotropes have direct cerebral effects that might affect neurological outcome. We aimed to test direct cerebrovascular effects of three commonly used vasopressor-inotropes (adrenaline, dopamine and noradrenaline by comparing the responses to those of nonpharmacologically induced increases in blood pressure. We also searched for reasons for a mismatch between the response in perfusion and oxygenation.Twenty-four piglets had long and short infusions of the three vasopressor-inotropes titrated to raise mean arterial blood pressure (MAP 10 mmHg in random order. Nonpharmacological increases in MAP were induced by inflation of a balloon in the descending aorta. We measured cerebral oxygenation (near-infrared spectroscopy, perfusion (laser-Doppler, oxygen consumption (co-oximetry of arterial and superior sagittal sinus blood, and microvascular heterogeneity (side stream dark field video microscopy.Vasopressor-inotropes increased cerebral oxygenation significantly less (p≤0.01 compared to non-pharmacological MAP increases, whereas perfusion was similar. Furthermore, cerebral total hemoglobin concentration increased significantly less during vasopressor-inotrope infusions (p = 0.001. These physiologic responses were identical between the three vasopressor-inotropes (p>0.05. Furthermore, they induced a mild, although insignificant increase in cerebral metabolism and microvascular heterogeneity (p>0.05. Removal of the scalp tissue did not influence the mismatch (p>0.05.We demonstrated a moderate vasopressor-inotrope induced mismatch between cerebral perfusion and oxygenation. Scalp removal did not affect this mismatch, why vasopressor-inotropes appear to have direct cerebral actions. The statistically nonsignificant increases in cerebral metabolism and/or microvascular heterogeneity may explain the mismatch. Alternatively, it may simply reflect a vasopressor-inotrope

  9. Roselle Polyphenols Exert Potent Negative Inotropic Effects via Modulation of Intracellular Calcium Regulatory Channels in Isolated Rat Heart.

    Science.gov (United States)

    Lim, Yi-Cheng; Budin, Siti Balkis; Othman, Faizah; Latip, Jalifah; Zainalabidin, Satirah

    2017-07-01

    Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 μg/ml in this study. Direct perfusion of RP in concentration-dependent manner lowered systolic function of the heart as shown by lowered LVDP and dP/dt max , suggesting a negative inotropic effect. RP also reduced heart rate (negative chronotropic action) while simultaneously increasing maximal velocity of relaxation (positive lusitropic action). Conversely, RP perfusion increased coronary pressure, an indicator for improvement in coronary blood flow. Inotropic responses elicited by pharmacological agonists for L-type Ca 2+ channel [(±)-Bay K 8644], ryanodine receptor (4-chloro-m-cresol), β-adrenergic receptor (isoproterenol) and SERCA blocker (thapsigargin) were all abolished by RP. In conclusion, RP elicits negative inotropic, negative chronotropic and positive lusitropic responses by possibly modulating calcium entry, release and reuptake in the heart. Our findings have shown the potential use of RP as a therapeutic agent to treat conditions like arrhythmia.

  10. Low-frequency blood pressure oscillations and inotrope treatment failure in premature infants.

    Science.gov (United States)

    Vesoulis, Zachary A; Hao, Jessica; McPherson, Christopher; El Ters, Nathalie M; Mathur, Amit M

    2017-07-01

    The underlying mechanism as to why some hypotensive preterm infants do not respond to inotropic medications remains unclear. For these infants, we hypothesize that impaired vasomotor function is a significant factor and is manifested through a decrease in low-frequency blood pressure variability across regulatory components of vascular tone. Infants born ≤28 wk estimated gestational age underwent prospective recording of mean arterial blood pressure for 72 h after birth. After error correction, root-mean-square spectral power was calculated for each valid 10-min data frame across each of four frequency bands ( B1 , 0.005-0.0095 Hz; B2 , 0.0095-0.02 Hz; B3 , 0.02-0.06 Hz; and B4 , 0.06-0.16) corresponding to different components of vasomotion control. Forty infants (twenty-nine normotensive control and eleven inotrope-exposed) were included with a mean ± SD estimated gestational age of 25.2 ± 1.6 wk and birth weight 790 ± 211 g. 9.7/11.8 Million (82%) data points were error-free and used for analysis. Spectral power across all frequency bands increased with time, although the magnitude was 20% less in the inotrope-exposed infants. A statistically significant increase in spectral power in response to inotrope initiation was noted across all frequency bands. Infants with robust blood pressure response to inotropes had a greater increase compared with those who had limited or no blood pressure response. In this study, hypotensive infants who require inotropes have decreased low-frequency variability at baseline compared with normotensive infants, which increases after inotrope initiation. Low-frequency spectral power does not change for those with inotrope treatment failure, suggesting dysfunctional regulation of vascular tone as a potential mechanism of treatment failure. NEW & NOTEWORTHY In this study, we examine patterns of low-frequency oscillations in blood pressure variability across regulatory components of vascular tone in normotensive and

  11. Influence of the low thyroid state in diabetes mellitus on cardiac function and inotropic responsiveness to alpha 1-adrenoceptor stimulation: comparison with the role of hypothyroidism alone

    NARCIS (Netherlands)

    Beenen, O. H.; Pfaffendorf, M.; van Zwieten, P. A.

    1996-01-01

    The hypothyroid state accompanying diabetes mellitus has been suggested to be partly responsible for the diabetes-induced metabolic, hemodynamic, and pharmacological cardiovascular changes. We assessed the effectivity of streptozotocin (STZ) to induce diabetes mellitus and a hypothyroid state.

  12. Synthesis of 14C- and 2H-labeled 1,3 dihydro-3, 3-dimethyl-5-(1,4,5,6,- tetrahydro-6-oxo-3-pyridazinyl)-2H-indol-2-one (LY195115), an orally effective positive inotrope

    International Nuclear Information System (INIS)

    Robertson, D.W.; Krushinski, J.H.; Kau, D.

    1986-01-01

    The synthesis of 14 C- and 2 H-labeled 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H-indol -2-one (LY195115), an extremely potent, orally-effective cardiotonic with inotropic and vasodilator activities is described. The 14 C-label was introduced in the antepenultimate step by reaction of a β-chloroketone precursor with Na 14 CN; acid-catalyzed hydrolysis and cyclization with hydrazine provided the tetrahydropyridazinone bearing the 14 C-label in the oxo-carbon. 1,3-Dihydro-3,3-di(methyl-d 3 ) -2H-indol-2-one was prepared by exhaustive methylation of 1-acetyl-1,3-dihydro-2H-indol-2-one with sodium hydride and iodomethane-d 3 , followed by removal of the nitrogen protecting group. This labeled material was converted in two steps to [ 2 H 6 ]-LY195115. (author)

  13. Inotropes do not increase mortality in advanced heart failure

    Directory of Open Access Journals (Sweden)

    Guglin M

    2014-05-01

    Full Text Available Maya Guglin, Marc KaufmanUniversity of South Florida, Tampa, FL, USAAbstract: Inotrope use is one of the most controversial topics in the management of heart failure. While the heart failure community utilizes them and recognizes the state of inotrope dependency, retrospective analyses and registry data have overwhelmingly suggested high mortality, which is logically to be expected given the advanced disease states of those requiring their use. Currently, there is a relative paucity of randomized control trials due to the ethical dilemma of creating control groups by withholding inotropes from patients who require them. Nonetheless, results of such trials have been mixed. Many were also performed with agents no longer in use, on patients without an indication for inotropes, or at a time before automatic cardio-defibrillators were recommended for primary prevention. Thus, their results may not be generalizable to current clinical practice. In this review, we discuss current indications for inotrope use, specifically dobutamine and milrinone, depicting their mechanisms of action, delineating their patterns of use in clinical practice, defining the state of inotrope dependency, and ultimately examining the literature to ascertain whether evidence is sufficient to support the current view that these agents increase mortality in patients with heart failure. Our conclusion is that the evidence is insufficient to link inotropes and increased mortality in low output heart failure.Keywords: inotropes, dobutamine, milrinone, heart failure

  14. Cerebral effects of commonly used vasopressor-inotropes

    DEFF Research Database (Denmark)

    Hahn, Gitte Holst; Hyttel-Sorensen, Simon; Petersen, Sandra Meinich

    2013-01-01

    Despite widespread use in sick infants, it is still debated whether vasopressor-inotropes have direct cerebral effects that might affect neurological outcome. We aimed to test direct cerebrovascular effects of three commonly used vasopressor-inotropes (adrenaline, dopamine and noradrenaline...

  15. Use of Inotropic Agents in Treatment of Systolic Heart Failure

    Directory of Open Access Journals (Sweden)

    Sohaib Tariq

    2015-12-01

    Full Text Available The most common use of inotropes is among hospitalized patients with acute decompensated heart failure, with reduced left ventricular ejection fraction and with signs of end-organ dysfunction in the setting of a low cardiac output. Inotropes can be used in patients with severe systolic heart failure awaiting heart transplant to maintain hemodynamic stability or as a bridge to decision. In cases where patients are unable to be weaned off inotropes, these agents can be used until a definite or escalated supportive therapy is planned, which can include coronary revascularization or mechanical circulatory support (intra-aortic balloon pump, extracorporeal membrane oxygenation, impella, left ventricular assist device, etc.. Use of inotropic drugs is associated with risks and adverse events. This review will discuss the use of the inotropes digoxin, dopamine, dobutamine, norepinephrine, milrinone, levosimendan, and omecamtiv mecarbil. Long-term inotropic therapy should be offered in selected patients. A detailed conversation with the patient and family shall be held, including a discussion on the risks and benefits of use of inotropes. Chronic heart failure patients awaiting heart transplants are candidates for intravenous inotropic support until the donor heart becomes available. This helps to maintain hemodynamic stability and keep the fluid status and pulmonary pressures optimized prior to the surgery. On the other hand, in patients with severe heart failure who are not candidates for advanced heart failure therapies, such as transplant and mechanical circulatory support, inotropic agents can be used for palliative therapy. Inotropes can help reduce frequency of hospitalizations and improve symptoms in these patients.

  16. Use of Inotropic Agents in Treatment of Systolic Heart Failure.

    Science.gov (United States)

    Tariq, Sohaib; Aronow, Wilbert S

    2015-12-04

    The most common use of inotropes is among hospitalized patients with acute decompensated heart failure, with reduced left ventricular ejection fraction and with signs of end-organ dysfunction in the setting of a low cardiac output. Inotropes can be used in patients with severe systolic heart failure awaiting heart transplant to maintain hemodynamic stability or as a bridge to decision. In cases where patients are unable to be weaned off inotropes, these agents can be used until a definite or escalated supportive therapy is planned, which can include coronary revascularization or mechanical circulatory support (intra-aortic balloon pump, extracorporeal membrane oxygenation, impella, left ventricular assist device, etc.). Use of inotropic drugs is associated with risks and adverse events. This review will discuss the use of the inotropes digoxin, dopamine, dobutamine, norepinephrine, milrinone, levosimendan, and omecamtiv mecarbil. Long-term inotropic therapy should be offered in selected patients. A detailed conversation with the patient and family shall be held, including a discussion on the risks and benefits of use of inotropes. Chronic heart failure patients awaiting heart transplants are candidates for intravenous inotropic support until the donor heart becomes available. This helps to maintain hemodynamic stability and keep the fluid status and pulmonary pressures optimized prior to the surgery. On the other hand, in patients with severe heart failure who are not candidates for advanced heart failure therapies, such as transplant and mechanical circulatory support, inotropic agents can be used for palliative therapy. Inotropes can help reduce frequency of hospitalizations and improve symptoms in these patients.

  17. Operative contractility: a functional concept of the inotropic state.

    Science.gov (United States)

    Curiel, Roberto; Perez-Gonzalez, Juan; Torres, Edwar; Landaeta, Ruben; Cerrolaza, Miguel

    2005-10-01

    1. Initial unsuccessful attempts to evaluate ventricular function in terms of the 'heart as a pump' led to focusing on the 'heart as a muscle' and to the concept of myocardial contractility. However, no clinically ideal index exists to assess the contractile state. The aim of the present study was to develop a mathematical model to assess cardiac contractility. 2. A tri-axial system was conceived for preload (PL), afterload (AL) and contractility, where stroke volume (SV) was represented as the volume of the tetrahedron. Based on this model, 'operative' contractility ('OperCon') was calculated from the readily measured values of PL, AL and SV. The model was tested retrospectively under a variety of different experimental and clinical conditions, in 71 studies in humans and 29 studies in dogs. A prospective echocardiographic study was performed in 143 consecutive subjects to evaluate the ability of the model to assess contractility when SV and PL were measured volumetrically (mL) or dimensionally (cm). 3. With inotropic interventions, OperCon changes were comparable to those of ejection fraction (EF), velocity of shortening (Vcf) and dP/dt-max. Only with positive inotropic interventions did elastance (Ees) show significantly larger changes. With load manipulations, OperCon showed significantly smaller changes than EF and Ees and comparable changes to Vcf and dP/dt-max. Values of OperCon were similar when AL was represented by systolic blood pressure or wall stress and when volumetric or dimensional values were used. 4. Operative contractility is a reliable, simple and versatile method to assess cardiac contractility.

  18. Negative inotropism of terpenes on guinea pig left atrium: structure-activity relationships.

    Science.gov (United States)

    Vasconcelos, Carla M L; Oliveira, Ingrid S N; Santos, José N A; Souza, Américo A; Menezes-Filho, José E R; Silva Neto, Júlio A; Lima, Tamires C; de Sousa, Damião P

    2018-06-01

    The aim of this work was to evaluate the pharmacological effect of seven structurally related terpenes on the contractility of cardiac muscle. The effect of terpenes was studied on isolated electrically driven guinea pig left atrium. From concentration-response curves for inotropic effect were determined the EC 50 and relative potency of such terpenes. Our results revealed that all terpenes, except phytol, showed ability to reduce the contractile response of guinea pig left atrium. Further, relative potency was directly related to the number of isoprene units and to the lipophilicity of the compounds. For example, sesquiterpenes farnesol and nerolidol showed higher relative potency when compared with the monoterpenes citronellol, geraniol and nerol. We can conclude that most of the evaluated terpenes showed a promising negative inotropism on the atrial muscle. Future studies are necessary to investigate their action mechanism.

  19. Synthesis and Biological Evaluation of Liguzinediol Mono- and Dual Ester Prodrugs as Promising Inotropic Agents

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    2014-11-01

    Full Text Available The potent positive inotropic effect, together with the relatively low safety risk of liguzinediol (LZDO, relative to currently available inotropic drugs, has prompted us to intensively research and develop LZDO as a potent positive inotropic agent. In this study, to obtain LZDO alternatives for oral chronic administration, a series of long-chain fatty carboxylic mono- and dual-esters of LZDO were synthesized, and preliminarily evaluated for physicochemical properties and bioconversion. Enhanced lipophilic properties and decreased solubility of the prodrugs were observed as the side chain length increased. All esters showed conspicuous chemical stability in phosphate buffer (pH 7.4. Moreover, the enzymatic hydrolysis of esters in human plasma and human liver microsomes confirmed that the majority of esters were converted to LZDO, with release profiles that varied due to the size and structure of the side chain. In vivo pharmacokinetic studies following oral administration of monopivaloyl (M5, monodecyl (M10 and monododecyl (M12 esters demonstrated the evidently extended half-lives relative to LZDO dosed alone. In particular the monopivaloyl ester M5 exhibited an optimal pharmacokinetic profile with appropriate physiochemical characteristics.

  20. Dihydropyridazinone cardiotonics: discovery of LY195115 and elucidation of structural features necessary for optimal inotropic activity

    Energy Technology Data Exchange (ETDEWEB)

    Krushinski, J.H.; Hayes, J.S.; Beedle, E.E.; Pollock, G.D.; Wilson, H.; Robertson, D.W.

    1986-03-05

    A series of 4,5-dihydro-6-aryl-3(/sup 2/H)-pyridazinones has been examined for inotropic activity. The optimal compound of the series, LY195115 (1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-/sup 2/H-indol-2-one), is one of the most potent and long-acting oral inotropes described to date. ED/sub 50/'s of LY195115, CI-914 and milrinone after i.v. administration to pentobarbital anesthetized dogs were 6.8, 46 and 37 ..mu..g/kg, respectively. ED/sub 50/'s after oral administration to conscious dogs were 25, 1000 and 500 ..mu..g/kg, respectively. For optimal positive inotropic activity and oral bioavailability in this series, the following structural features are necessary: (1) dihydropyridazinone ring with the nitrogen unsubstituted; (2) a hydrogen-bond acceptor substituent with a sigma value of ca 0.0 para to the dihydropyridazinone moiety; and (3) additional sterically undemanding lipophilic substituents adjacent to the hydrogen-bond acceptor site.

  1. Dihydropyridazinone cardiotonics: discovery of LY195115 and elucidation of structural features necessary for optimal inotropic activity

    International Nuclear Information System (INIS)

    Krushinski, J.H.; Hayes, J.S.; Beedle, E.E.; Pollock, G.D.; Wilson, H.; Robertson, D.W.

    1986-01-01

    A series of 4,5-dihydro-6-aryl-3( 2 H)-pyridazinones has been examined for inotropic activity. The optimal compound of the series, LY195115 (1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)- 2 H-indol-2-one), is one of the most potent and long-acting oral inotropes described to date. ED 50 's of LY195115, CI-914 and milrinone after i.v. administration to pentobarbital anesthetized dogs were 6.8, 46 and 37 μg/kg, respectively. ED 50 's after oral administration to conscious dogs were 25, 1000 and 500 μg/kg, respectively. For optimal positive inotropic activity and oral bioavailability in this series, the following structural features are necessary: (1) dihydropyridazinone ring with the nitrogen unsubstituted; (2) a hydrogen-bond acceptor substituent with a σ value of ca 0.0 para to the dihydropyridazinone moiety; and (3) additional sterically undemanding lipophilic substituents adjacent to the hydrogen-bond acceptor site

  2. Inotropic effect, binding properties, and calcium flux effects of the calcium channel agonist CGP 28392 in intact cultured embryonic chick ventricular cells

    International Nuclear Information System (INIS)

    Laurent, S.; Kim, D.; Smith, T.W.; Marsh, J.D.

    1985-01-01

    CGP 28392 is a recently described dihydropyridine derivative with positive inotropic properties. To study the mechanism of action of this putative calcium channel agonist, we have related the effects of CGP 28392 on contraction (measured with an optical video system) and radioactive calcium uptake to ligand-binding studies in cultured, spontaneously beating chick embryo ventricular cells. CGP 28392 produced a concentration-dependent increase in amplitude and velocity of contraction (EC 50 = 2 x 10(-7) M; maximum contractile effect = 85% of the calcium 3.6 mM response). Nifedipine produced a shift to the right of the concentration-effect curve for CGP 28392 without decreasing the maximum contractile response, suggesting competitive antagonism (pA2 = 8.3). Computer analysis of displacement of [ 3 H]nitrendipine binding to intact heart cells by unlabeled CGP 28392 indicated a K /sub D/ = 2.2 +/- 0.95 x 10(-7) M, in good agreement with the EC 50 for the inotropic effect. CGP 28392 increased the rate of radioactive calcium influx (+39% at 10 seconds) without altering beating rate, while nifedipine decreased radioactive calcium influx and antagonized the CGP 28392-induced increase in calcium influx. Our results indicate that, in intact cultured myocytes, CGP 28392 acts as a calcium channel agonist and competes for the dihydropyridine-binding site of the slow calcium channel. In contrast to calcium channel blockers, CGP 28392 increases calcium influx and enhances the contractile state

  3. The inotropic effect of the active metabolite of levosimendan, OR-1896, is mediated through inhibition of PDE3 in rat ventricular myocardium.

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    Øivind Ørstavik

    Full Text Available We recently published that the positive inotropic response (PIR to levosimendan can be fully accounted for by phosphodiesterase (PDE inhibition in both failing human heart and normal rat heart. To determine if the PIR of the active metabolite OR-1896, an important mediator of the long-term clinical effects of levosimendan, also results from PDE3 inhibition, we compared the effects of OR-1896, a representative Ca2+ sensitizer EMD57033 (EMD, levosimendan and other PDE inhibitors.Contractile force was measured in rat ventricular strips. PDE assay was conducted on rat ventricular homogenate. cAMP was measured using RII_epac FRET-based sensors.OR-1896 evoked a maximum PIR of 33 ± 10% above basal at 1 μM. This response was amplified in the presence of the PDE4 inhibitor rolipram (89 ± 14% and absent in the presence of the PDE3 inhibitors cilostamide (0.5 ± 5.3% or milrinone (3.2 ± 4.4%. The PIR was accompanied by a lusitropic response, and both were reversed by muscarinic receptor stimulation with carbachol and absent in the presence of β-AR blockade with timolol. OR-1896 inhibited PDE activity and increased cAMP levels at concentrations giving PIRs. OR-1896 did not sensitize the concentration-response relationship to extracellular Ca2+. Levosimendan, OR-1896 and EMD all increased the sensitivity to β-AR stimulation. The combination of either EMD and levosimendan or EMD and OR-1896 further sensitized the response, indicating at least two different mechanisms responsible for the sensitization. Only EMD sensitized the α1-AR response.The observed PIR to OR-1896 in rat ventricular strips is mediated through PDE3 inhibition, enhancing cAMP-mediated effects. These results further reinforce our previous finding that Ca2+ sensitization does not play a significant role in the inotropic (and lusitropic effect of levosimendan, nor of its main metabolite OR-1896.

  4. Antitussive, antispasmodic, bronchodilating and cardiac inotropic effects of the essential oil from Blepharocalyx salicifolius leaves.

    Science.gov (United States)

    Hernández, Jehison Jiménez; Ragone, María Inés; Bonazzola, Patricia; Bandoni, Arnaldo L; Consolini, Alicia E

    2018-01-10

    Blepharocalyx salicifolius (Kunth) O. Berg (Myrtaceae) is a tree native to Argentina and Uruguay that grows and is cultivated along the riverside of the Rio de la Plata. The leaves of this plant species, locally known as "anacahuita" are used in South America to prepare infusions for the empiric treatment of cough and bronchospasm, as well as diarrhoea and other intestinal disorders. Although previous phytochemical studies have been performed with the essential oil extracted from Blepharocalyx salicifolius, pharmacological evidence supporting its traditional use is still lacking. To experimentally evaluate the pharmacological properties of Blepharocalyx salicifolius based on its traditional use. The studies were performed with tincture (T-Bs) and essential oil (EO-Bs) prepared from its leaves, in isolated rat trachea, intestine and heart preparations. The ex-vivo effects of T-Bs and EO-Bs were evaluated with the agonists carbachol (CCh) and calcium chloride (Ca 2+ ) in the contractile concentration-response curves (CRC) of the isolated intestine. The muscle relaxant effect of EO-Bs was evaluated in the isolated trachea and compared with the effect achieved with papaverine as a positive control. The T-Bs and EO-Bs cardiac effects were analysed by perfusion of an isolated rat heart before a period of ischemia/reperfusion (stunning model). The antitussive effect of both T-Bs and EO-Bs was evaluated in mice exposed to ammonia using codeine as a positive control. Both T-Bs and EO-Bs induced a non-competitive inhibition of the CCh-CRC in the rat intestine, with IC 50 values of 170.3 ± 48.5µg T-Bs/mL (n = 6) and 5.9 ± 1.6µg EO-Bs/mL (n = 6), respectively. EO-Bs also inhibited non-competitively the Ca 2+ -CRC, with IC 50 value of 1.8 ± 0.3µg EO-Bs/mL (n = 8). A similar effect was obtained with the main active component of the EO-Bs 1,8-cineole. In isolated trachea, EO-Bs induced the relaxation of the CCh-contracted tissue (1.7 ± 0.2µg EO-Bs/mL, n = 11) up to a

  5. Altered contractile response due to increased beta3-adrenoceptor stimulation in diabetic cardiomyopathy: the role of nitric oxide synthase 1-derived nitric oxide.

    Science.gov (United States)

    Amour, Julien; Loyer, Xavier; Le Guen, Morgan; Mabrouk, Nejma; David, Jean-Stéphane; Camors, Emmanuel; Carusio, Nunzia; Vivien, Benoît; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno

    2007-09-01

    In the diabetic heart, the positive inotropic response to beta-adrenoceptor stimulation is altered and beta1 and beta2 adrenoceptors are down-regulated, whereas beta3 adrenoceptor is up-regulated. In heart failure, beta3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of beta3-adrenoceptor in diabetic cardiomyopathy. beta-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of beta3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline +/- SD. The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 +/- 15% vs. 160 +/- 16%; P < 0.05) and in vitro (112 +/- 5% vs. 179 +/- 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of beta3-adrenoceptor antagonist (174 +/- 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 +/- 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine [l-VNIO]; 172 +/- 13%). In diabetes, in parallel with the increase in beta3-adrenoceptor protein expression, the positive inotropic effect was partially restored by beta3-adrenoceptor antagonist (137 +/- 8%; P < 0.05), l-NAME (133 +/- 11%; P < 0.05), or l-VNIO (130 +/- 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. beta3-Adrenoceptor is involved in altered positive inotropic response to beta-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic

  6. Endogenous inotropic substance from heart tissue has digitalis-like properties

    Energy Technology Data Exchange (ETDEWEB)

    Khatter, J.C.; Agbanyo, M.; Navaratnam, S. (Univ. of Manitoba, Winnipeg (Canada))

    1991-01-01

    In the past few years, we developed an extraction procedure which we successfully used to isolate a crude fraction containing digitalis-like substance (DLS) from porcine left ventricular tissue. In this study, the crude fraction was found to cross-react with digoxin antibodies and showed immunoreactivity of 4.25 {plus minus} 0.6 ng digoxin equivalent/ml. On further purification of the crude fraction using silica gel G column chromatography, a fraction C was obtained, which was highly positive inotropic on canine trabeculae and it dose-dependently inhibited ouabain sensitive {sup 86}Rb{sup +} uptake in rate heart slices. A 50% inhibition of uptake was obtained by 25 ul of fraction C. Fraction C also inhibited canine kidney Na{sup +}, K{sup +}-ATPase dose-dependently and a 50% inhibition of this enzyme required 17 ul of fraction C. Ashing of the fraction C at 500{degree}C resulted in loss of inotropic and enzyme inhibitory activities, indicating an organic nature of the unknown digitalis-like substance.

  7. Inotropic effect of Citrus sinensis (L. Osbeck leaf extracts on the guinea pig atrium

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    Oliveira E.D.

    2005-01-01

    Full Text Available The objective of the present investigation was to determine the contractile effect of crude and acetone leaf extracts of Citrus sinensis (L. Osb. on mammalian myocardium. Crude leaf extracts have been used in folk medicine to treat neurological disorders. Some flavonoids isolated from this plant presented a positive inotropic effect on myocardium. This motivated us to test the extracts on the atria of guinea pigs of both sexes (300-500 g and surprisingly we observed inotropic depression instead of an increase in force. The maximum effect of the crude extract was 79.4 ± 8.1% of the control force amplitude (N = 5 hearts, 10 trials, 27 ± 0.1ºC, stimulus: 2 Hz, 400 V, 0.5 ms. The EC50 for crude, ethanol, acetic, aqueous, and acetone extracts was 300, 300, 600, 1000, and 140 µg/ml, respectively, with a Hill constant of 1.8, 2.0, 2.5, 2.0, and 1.4, respectively. Blockade of cholinergic, beta-adrenergic, or opioid membrane receptors with 1.5 µM atropine sulfate, 1 µM propranolol, and 10 µM naloxone, respectively, did not change the effect of the crude extract. The acetone extract abolished the Bowditch positive staircase phenomenon (N = 5 hearts, 10 trials, 27 ± 0.1ºC, suggesting a possible reduction of the calcium inward current, and also promoted the so-called Woodworth phenomenon. The effect was concentration-dependent and indicated the existence of another inhibitory contractile mechanism such as the simultaneous activation of some of the membrane potassium channels reducing the myocardial action potential duration and further decreasing the cellular calcium entry.

  8. Inotropic effects of extracts of Psidium guajava L. (guava leaves on the guinea pig atrium

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    Conde Garcia E.A.

    2003-01-01

    Full Text Available Many pharmacological effects have been ascribed to extracts of Psidium guajava L. (guava leaves. However, in spite of its widespread use in Brazilian folk medicine and a reasonable number of scientific reports about it, we could not find any study dealing with its action on the mammalian myocardium. In the present study, by measuring isometric force, we observed that the crude extract of P. guajava (water-alcohol extract obtained by macerating dry leaves depresses the guinea pig atrial contractility in a concentration-dependent fashion (N = 8 hearts, 15 trials. The compound with cardiac activity was concentrated by extraction in a Soxhlet apparatus using 17 M glacial acetic acid after removing the less polar fractions (hexane, chloroform, acetone, ethanol and methanol, suggesting that this compound is a highly polar substance. In the isolated guinea pig left atrium the acetic acid fraction (10-800 mg/l of P. guajava 1 reversibly decreased myocardial force in a concentration-dependent fashion (EC50 = 0.07g/l, N = 5 hearts, 9 trials, P<0.05, 2 increased the atrial relaxation time measured at 20% of the force amplitude up to 35% (91 ± 15 to 123 ± 30 ms, N = 3 hearts, 6 trials, P<0.05, 3 abolished the positive staircase effect (Bowditch phenomenon in a concentration-dependent fashion suggesting a decrease of the cellular inward calcium current (N = 4 hearts, 8 trials, P<0.05, and 4 its inotropic effect was abolished by cholinergic receptor blockade with 1.5 mM atropine sulfate, indicating a cholinergic involvement in the mechanism of action of the extract (N = 7 hearts, 15 trials, P<0.05. The acetic acid extract was 20 times more potent than crude extract (EC50 = 1.4 g/l. The results showed that extracts from P. guajava leaves depress myocardial inotropism.

  9. Negative inotropic and chronotropic effects on the guinea pig atrium of extracts obtained from Averrhoa carambola L. leaves

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    Vasconcelos C.M.L.

    2005-01-01

    Full Text Available It has been reported that star fruit can lead to a fatal outcome in uremic patients. The intoxication syndrome consists of hiccups, mental confusion, dizziness, and vomiting. On the other hand, folk medicine uses teas and infusions of carambola leaves to treat headache, vomiting, cough, insomnia, and diabetes. This motivated us to determine if Averrhoa carambola can act on the contractility and automaticity of the guinea pig heart. We measured the atrial isometric force in stimulated left atria and determined the chronotropic changes in spontaneously beating right atria. The carambola leaf extracts (1.5 mg/ml abolished the contractile force in a concentration-dependent manner. Among the crude, methanolic, ethanolic, aqueous, and acetic extracts, the aqueous one was the most potent (EC50 = 520 ± 94 µg/ml; flavonoids and tannins are the main constituents; Na+ and K+ contents in 1.0 mg/ml of aqueous extract were 0.12 ± 0.016 and 1.19 ± 0.15 mM, respectively. The aqueous extract abolished the positive Bowditch staircase phenomenon and reduced the inotropic response to CaCl2 (0.17-8.22 mM, events that are dependent on the cellular Ca2+ inward current. The adrenergic, muscarinic or opioid membrane receptors do not seem to participate in the mechanism of action of the cardioactive substance(s. In spontaneously beating atria, the aqueous extract promoted a negative chronotropic effect that was antagonized by 0.1 µM isoproterenol bitartrate. With this agonist, the EC50 of the aqueous extract increased from 133 ± 58 to 650 ± 100 µg/ml. These data regarding the effect of A. carambola on guinea pig atrial contractility and automaticity indicate an L-type Ca2+ channel blockade.

  10. Negative inotropic and chronotropic effects on the guinea pig atrium of extracts obtained from Averrhoa carambola L. leaves.

    Science.gov (United States)

    Vasconcelos, C M L; Araújo, M S; Silva, B A; Conde-Garcia, E A

    2005-07-01

    It has been reported that star fruit can lead to a fatal outcome in uremic patients. The intoxication syndrome consists of hiccups, mental confusion, dizziness, and vomiting. On the other hand, folk medicine uses teas and infusions of carambola leaves to treat headache, vomiting, cough, insomnia, and diabetes. This motivated us to determine if Averrhoa carambola can act on the contractility and automaticity of the guinea pig heart. We measured the atrial isometric force in stimulated left atria and determined the chronotropic changes in spontaneously beating right atria. The carambola leaf extracts (1.5 mg/ml) abolished the contractile force in a concentration-dependent manner. Among the crude, methanolic, ethanolic, aqueous, and acetic extracts, the aqueous one was the most potent (EC50 = 520 +/- 94 microg/ml; flavonoids and tannins are the main constituents; Na+ and K+ contents in 1.0 mg/ml of aqueous extract were 0.12 +/- 0.016 and 1.19 +/- 0.15 mM, respectively). The aqueous extract abolished the positive Bowditch staircase phenomenon and reduced the inotropic response to CaCl2 (0.17-8.22 mM), events that are dependent on the cellular Ca2+ inward current. The adrenergic, muscarinic or opioid membrane receptors do not seem to participate in the mechanism of action of the cardioactive substance(s). In spontaneously beating atria, the aqueous extract promoted a negative chronotropic effect that was antagonized by 0.1 microM isoproterenol bitartrate. With this agonist, the EC50 of the aqueous extract increased from 133 +/- 58 to 650 +/- 100 microg/ml. These data regarding the effect of A. carambola on guinea pig atrial contractility and automaticity indicate an L-type Ca2+ channel blockade.

  11. Anti-ischemic effects of inotropic agents in experimental right ventricular infarction.

    NARCIS (Netherlands)

    Hein, M.; Roehl, A.B.; Baumert, J.H.; Scherer, K.; Steendijk, P.; Rossaint, R.

    2009-01-01

    BACKGROUND: Right ventricular (RV) function is an important determinant of survival after myocardial infarction. The efficacy of reperfusion therapy might be increased by the cardioprotective action of inotropic agents, which are used for symptomatic therapy in situations with compromised

  12. Inotropes for Preterm Infants: 50 Years on Are We Any Wiser?

    Directory of Open Access Journals (Sweden)

    Aisling A. Garvey

    2018-04-01

    Full Text Available For almost half a century, inotropes have been administered to preterm infants with the ultimate goal of increasing their blood pressure. A number of trials, the majority of which focused on dopamine administration, have demonstrated increased blood pressure following inotrope administration in preterm infants and have led to continued use of inotropes in our neonatal units. We have also seen an increase in the number of potential agents available to the clinician. However, we now know that hypotension is a much broader concept than blood pressure alone, and our aim should instead be focused on improving end organ perfusion, specifically cerebral perfusion. Only a limited number of studies have incorporated the organ-relevant hemodynamic changes and long-term outcomes when assessing inotropic effects in neonates, the majority of which are observational studies or have a small sample size. In addition, important considerations, including the developing/maturing adrenergic receptors, polymorphisms of these receptors, and other differences in the pharmacokinetics and pharmacodynamics of preterm infants, are only recently being recognized. Certainly, there remains huge variation in practice. The lack of well-conducted randomized controlled trials addressing these relevant outcomes, along with the difficulty executing such RCTs, leaves us with more questions than answers. This review provides an overview of the various inotropic agents currently being used in the care of preterm infants, with a particular focus on their organ/cerebral hemodynamic effects both during and after transition.

  13. Structural aspects of inotropic bipyridine binding. Crystal structure determination to 1.9 A of the human serum transthyretin-milrinone complex.

    Science.gov (United States)

    Wojtczak, A; Luft, J R; Cody, V

    1993-03-25

    The crystal structure of human transthyretin (TTR) complexed with milrinone (2-methyl-5-cyano-3,4'-bipyridin-6(1H)-one), a positive inotropic cardiac agent, has been refined to R = 17.4% for 8-1.9-A resolution data. This report provides the first detailed description of protein interactions for an inotropic bipyridine agent which is an effective thyroid hormone binding competitor to transthyretin. Milrinone is bound along the 2-fold axis in the binding site with its substituted pyridone ring located deep within the channel of the two identical binding domains of the TTR tetramer. In this orientation the 5-cyano group occupies the same site as the 3'-iodine in the TTR complex with 3,3'-diiodothyronine (Wojtczak, A., Luft, J., and Cody, V. (1992) J. Biol. Chem. 267, 353-357), which is 3.5 A deeper in the channel than thyroxine (Blake, C. C. F., and Oately, S. J., (1977) Nature 268, 115-120). These structural results confirm computer modeling studies of milrinone structural homology with thyroxine and its TTR binding interactions and explain the effectiveness of milrinone competition for thyroxine binding to TTR. To understand the weaker binding affinity of the parent inotropic drug, amrinone (5-amino-3,4'-bipyridin-6(1H)-one), modeling studies of its TTR binding were carried out which indicate that the 5-amino group cannot participate in strong interactions with TTR and the lack of the 2-methyl further weakens amrinone binding.

  14. F layer positive response to a geomagnetic storm - June 1972

    International Nuclear Information System (INIS)

    Miller, N.J.; Grebowsky, J.M.; Mayr, H.G.; Harris, I.; Tulunay, Y.K.

    1979-01-01

    A circulation model of neutral thermosphere-ionosphere coupling is used to interpret in situ spacecraft measurements taken during a topside mid-latitude ionospheric storm. The data are measurements of electron density taken along the circular polar orbit of Ariel 4 at 550 km during the geomagnetically disturbed period June 17--18, 1972. We infer that collisional momentum transfer from the disturbed neutral thermosphere to the ionosphere was the dominant midday process generating the positive F layer storm phase in the summer hemisphere. In the winter hemisphere the positive storm phase drifted poleward in apparent response to magnetospheric E x B drifts. A summer F layer positive phase developed at the sudden commencement and again during the geomagnetic main phase; a winter F layer positive phase developed only during the geomagnetic main phase. The observed seasonal differences in both the onsets and the magnitudes of the positive phases are attributed to the interhemispheric asymmetry in thermospheric dynamics

  15. Home inotropic therapy in advanced heart failure: cost analysis and clinical outcomes.

    Science.gov (United States)

    Harjai, K J; Mehra, M R; Ventura, H O; Lapeyre, Y M; Murgo, J P; Stapleton, D D; Smart, F W

    1997-11-05

    This study was conducted to assess cost savings and clinical outcomes associated with the use of home i.v. inotropic therapy in patients with advanced (New York Heart Association [NYHA] class IV) heart failure. Retrospective analysis. Tertiary care referral center. Twenty-four patients (13 men, 11 women; age, 61+/-12 years) with left ventricular ejection fraction home i.v. inotropic therapy for at least 4 consecutive weeks between May 1994 and April 1996. Inotropic agents used included dobutamine (n=20; dose, 5.0+/-2.2 microg/kg/min) or milrinone (n=7; dose, 0.53+/-0.05 microg/kg/min). Cost of care and clinical outcomes (hospital admissions, length of hospital stay, NYHA functional class) were compared during the period of inotropic therapy (study period) and the immediate preceding period of equal duration (control period). In comparison to the control period, the study period (3.9+/-2.7 months) was associated with a 16% reduction in cost, amounting to a calculated savings of $5,700 per patient or $1,465 per patient per month. Concomitantly, a decrease in the number of hospital admissions from 2.7+/-2.6 to 1.3+/-1.3 (p=0.056) and length of hospital stay from 20.9+/-12.7 to 5.5+/-5.4 days (p=0.0004) was observed with improvement in NYHA functional class from 4.0+/-0.0 to 2.7+/-0.9 (phome i.v. inotropic therapy. Home i.v. inotropic therapy reduces hospital admissions, length of stay, and cost of care and improves functional class in patients with advanced (NYHA class IV) heart failure.

  16. Vantage sensitivity: individual differences in response to positive experiences.

    Science.gov (United States)

    Pluess, Michael; Belsky, Jay

    2013-07-01

    The notion that some people are more vulnerable to adversity as a function of inherent risk characteristics is widely embraced in most fields of psychology. This is reflected in the popularity of the diathesis-stress framework, which has received a vast amount of empirical support over the years. Much less effort has been directed toward the investigation of endogenous factors associated with variability in response to positive influences. One reason for the failure to investigate individual differences in response to positive experiences as a function of endogenous factors may be the absence of adequate theoretical frameworks. According to the differential-susceptibility hypothesis, individuals generally vary in their developmental plasticity regardless of whether they are exposed to negative or positive influences--a notion derived from evolutionary reasoning. On the basis of this now well-supported proposition, we advance herein the new concept of vantage sensitivity, reflecting variation in response to exclusively positive experiences as a function of individual endogenous characteristics. After distinguishing vantage sensitivity from theoretically related concepts of differential-susceptibility and resilience, we review some recent empirical evidence for vantage sensitivity featuring behavioral, physiological, and genetic factors as moderators of a wide range of positive experiences ranging from family environment and psychotherapy to educational intervention. Thereafter, we discuss genetic and environmental factors contributing to individual differences in vantage sensitivity, potential mechanisms underlying vantage sensitivity, and practical implications. 2013 APA, all rights reserved

  17. PDE3, but not PDE4, reduces β1- and β2-adrenoceptor-mediated inotropic and lusitropic effects in failing ventricle from metoprolol-treated patients

    Science.gov (United States)

    Molenaar, Peter; Christ, Torsten; Hussain, Rizwan I; Engel, Andreas; Berk, Emanuel; Gillette, Katherine T; Chen, Lu; Galindo-Tovar, Alejandro; Krobert, Kurt A; Ravens, Ursula; Levy, Finn Olav; Kaumann, Alberto J

    2013-01-01

    Background and Purpose PDE3 and/or PDE4 control ventricular effects of catecholamines in several species but their relative effects in failing human ventricle are unknown. We investigated whether the PDE3-selective inhibitor cilostamide (0.3–1 μM) or PDE4 inhibitor rolipram (1–10 μM) modified the positive inotropic and lusitropic effects of catecholamines in human failing myocardium. Experimental Approach Right and left ventricular trabeculae from freshly explanted hearts of 5 non-β-blocker-treated and 15 metoprolol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through β1 adrenoceptors (β2 adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β2 adrenoceptors (β1 adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of PDE inhibitors. Catecholamine potencies were estimated from –logEC50s. Key Results Cilostamide did not significantly potentiate the inotropic effects of the catecholamines in non-β-blocker-treated patients. Cilostamide caused greater potentiation (P = 0.037) of the positive inotropic effects of (-)-adrenaline (0.78 ± 0.12 log units) than (-)-noradrenaline (0.47 ± 0.12 log units) in metoprolol-treated patients. Lusitropic effects of the catecholamines were also potentiated by cilostamide. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline on right and left ventricular trabeculae from metoprolol-treated patients. Conclusions and Implications Metoprolol induces a control by PDE3 of ventricular effects mediated through both β1 and β2 adrenoceptors, thereby further reducing sympathetic cardiostimulation in patients with terminal heart failure. Concurrent therapy with a PDE3 blocker and metoprolol could conceivably facilitate cardiostimulation evoked by adrenaline through β2 adrenoceptors. PDE4 does not appear to reduce inotropic and lusitropic effects of

  18. SR Ca2+-leak and disordered excitation-contraction coupling as the basis for arrhythmogenic and negative inotropic effects of acute ethanol exposure.

    Science.gov (United States)

    Mustroph, Julian; Wagemann, Olivia; Lebek, Simon; Tarnowski, Daniel; Ackermann, Jasmin; Drzymalski, Marzena; Pabel, Steffen; Schmid, Christof; Wagner, Stefan; Sossalla, Samuel; Maier, Lars S; Neef, Stefan

    2018-03-01

    Ethanol has acute negative inotropic and arrhythmogenic effects. The underlying mechanisms, however, are largely unknown. Sarcoplasmic reticulum Ca 2+ -leak is an important mechanism for reduced contractility and arrhythmias. Ca 2+ -leak can be induced by oxidative stress and Ca 2+ /Calmodulin-dependent protein kinase II (CaMKII). Therefore, we investigated the influence of acute ethanol exposure on excitation-contraction coupling in atrial and ventricular cardiomyocytes. Isolated human atrial and murine atrial or ventricular cardiomyocytes were preincubated for 30 min and then superfused with control solution or solution containing ethanol. Ethanol had acute negative inotropic and positive lusitropic effects in human atrial muscle strips and murine ventricular cardiomyocytes. Accordingly, Ca 2+ -imaging indicated lower Ca 2+ -transient amplitudes and increased SERCA2a activity, while myofilament Ca 2+ -sensitivity was reduced. SR Ca 2+ -leak was assessed by measuring Ca 2+ -sparks. Ethanol induced severe SR Ca 2+ -leak in human atrial cardiomyocytes (calculated leak: 4.60 ± 0.45 mF/F 0 vs 1.86 ± 0.26 in control, n ≥ 80). This effect was dose-dependent, while spontaneous arrhythmogenic Ca 2+ -waves increased ~5-fold, as investigated in murine cardiomyocytes. Delayed afterdepolarizations, which can result from increased SR Ca 2+ -leak, were significantly increased by ethanol. Measurements using the reactive oxygen species (ROS) sensor CM-H 2 DCFDA showed increased ROS-stress in ethanol treated cells. ROS-scavenging with N-acetylcysteine prevented negative inotropic and positive lusitropic effects in human muscle strips. Ethanol-induced Ca 2+ -leak was abolished in mice with knockout of NOX2 (the main source for ROS in cardiomyocytes). Importantly, mice with oxidation-resistant CaMKII (Met281/282Val mutation) were protected from ethanol-induced Ca 2+ -leak. We show for the first time that ethanol acutely induces strong SR Ca 2+ -leak, also altering

  19. Subliminal mere exposure and explicit and implicit positive affective responses.

    Science.gov (United States)

    Hicks, Joshua A; King, Laura A

    2011-06-01

    Research suggests that repeated subliminal exposure to environmental stimuli enhances positive affective responses. To date, this research has primarily concentrated on the effects of repeated exposure on explicit measures of positive affect (PA). However, recent research suggests that repeated subliminal presentations may increase implicit PA as well. The present study tested this hypothesis. Participants were either subliminally primed with repeated presentations of the same stimuli or only exposed to each stimulus one time. Results confirmed predictions showing that repeated exposure to the same stimuli increased both explicit and implicit PA. Implications for the role of explicit and implicit PA in attitudinal judgements are discussed.

  20. Adaptation response of Arabidopsis thaliana to random positioning

    Science.gov (United States)

    Kittang, A.-I.; Winge, P.; van Loon, J. J. W. A.; Bones, A. M.; Iversen, T.-H.

    2013-10-01

    Arabidopsis thaliana seedlings were exposed on a Random Positioning Machine (RPM) under light conditions for 16 h and the samples were analysed using microarray techniques as part of a preparation for a space experiment on the International Space Station (ISS). The results demonstrated a moderate to low regulation of 55 genes (genes). Genes encoding proteins associated with the chaperone system (e.g. heat shock proteins, HSPs) and enzymes in the flavonoid biosynthesis were induced. Most of the repressed genes were associated with light and sugar responses. Significant up-regulation of selected HSP genes was found by quantitative Real-Time PCR in 1 week old plants after the RPM exposure both in light and darkness. Higher quantity of DPBA (diphenylboric acid 2-amino-ethyl ester) staining was observed in the whole root and in the root elongation zone of the seedlings exposed on the RPM by use of fluorescent microscopy, indicating higher flavonoid content. The regulated genes and an increase of flavonoids are related to several stresses, but increased occurrence of HSPs and flavonoids are also representative for normal growth (e.g. gravitropism). The response could be a direct stress response or an integrated response of the two signal pathways of light and gravity resulting in an overall light response.

  1. Positive interaction of social comparison and personal responsibility for outcomes.

    Science.gov (United States)

    Grygolec, Jaroslaw; Coricelli, Giorgio; Rustichini, Aldo

    2012-01-01

    We formulate and test a model that allows sharp separation between two different ways in which environment affects evaluation of outcomes, by comparing social vs. private and personal responsibility vs. chance. In the experiment, subjects chose between two lotteries, one low-risk and one high-risk. They could then observe the outcomes. By varying the environment between private (they could observe the outcome of the chosen lottery and the outcome of the lottery they had not chosen) and social (they could observe the outcome of the lottery chosen by another subject) we can differentiate the response and brain activity following the feedback in social and private settings. The evidence suggests that envy and pride are significant motives driving decisions and outcomes evaluation, stronger than private emotions like regret and rejoice, with ventral striatum playing a key role. When we focus on the outcome evaluation stage we demonstrate that BOLD signal in ventral striatum is increasing in the difference between obtained and counterfactual payoffs. For a given difference in payoffs, striatal responses are more pronounced in social than in private environment. Moreover, a positive interaction (complementarity) between social comparison and personal responsibility is reflected in the pattern of activity in the ventral striatum. At decision stage we observe getting ahead of the Joneses effect in ventral striatum with subjective value of risk larger in social than in private environment.

  2. Asymmetric positive feedback loops reliably control biological responses.

    Science.gov (United States)

    Ratushny, Alexander V; Saleem, Ramsey A; Sitko, Katherine; Ramsey, Stephen A; Aitchison, John D

    2012-04-24

    Positive feedback is a common mechanism enabling biological systems to respond to stimuli in a switch-like manner. Such systems are often characterized by the requisite formation of a heterodimer where only one of the pair is subject to feedback. This ASymmetric Self-UpREgulation (ASSURE) motif is central to many biological systems, including cholesterol homeostasis (LXRα/RXRα), adipocyte differentiation (PPARγ/RXRα), development and differentiation (RAR/RXR), myogenesis (MyoD/E12) and cellular antiviral defense (IRF3/IRF7). To understand why this motif is so prevalent, we examined its properties in an evolutionarily conserved transcriptional regulatory network in yeast (Oaf1p/Pip2p). We demonstrate that the asymmetry in positive feedback confers a competitive advantage and allows the system to robustly increase its responsiveness while precisely tuning the response to a consistent level in the presence of varying stimuli. This study reveals evolutionary advantages for the ASSURE motif, and mechanisms for control, that are relevant to pharmacologic intervention and synthetic biology applications.

  3. Nonlinearities in the response of beam position monitors

    International Nuclear Information System (INIS)

    Assmann, R.; Dehning, B.; Matheson, J.; Prochnow, J.

    2000-01-01

    At the LEP e + /e - collider at CERN, Geneva, a Spectrometer is used to determine the beam energy with a relative accuracy of 10 -4 .The Spectrometer measures the change in bending angle in a dipole magnet, the beam trajectory being obtained using beam position monitors (BPMs), which must have an accuracy close to 1 μm in order to achieve the desired precision. The BPMs used feature an aluminum block with an elliptical aperture and capacitive pickup electrodes. The response depends on the electrode geometry and also on the shape of the monitor aperture. In addition, the size of the beam itself contributes if the beam is off-center. The beam size varies according to the beta and dispersion functions at the Spectrometer, so that each BPM may exhibit a systematic shift of the measured beam position. We have investigated the implications of such shifts on the performance of the Spectrometer. We present analytical results, a computer model of the BPM response, and comparison with measurements. The model suggests strategies such as beam-based alignment to minimize the systematic effects arising from the BPMs

  4. Response of Autonomic Nervous System to Body Positions:

    Science.gov (United States)

    Xu, Aiguo; Gonnella, G.; Federici, A.; Stramaglia, S.; Simone, F.; Zenzola, A.; Santostasi, R.

    Two mathematical methods, the Fourier and wavelet transforms, were used to study the short term cardiovascular control system. Time series, picked from electrocardiogram and arterial blood pressure lasting 6 minutes, were analyzed in supine position (SUP), during the first (HD1) and the second parts (HD2) of 90° head down tilt, and during recovery (REC). The wavelet transform was performed using the Haar function of period T=2j (j=1,2,...,6) to obtain wavelet coefficients. Power spectra components were analyzed within three bands, VLF (0.003-0.04), LF (0.04-0.15) and HF (0.15-0.4) with the frequency unit cycle/interval. Wavelet transform demonstrated a higher discrimination among all analyzed periods than the Fourier transform. For the Fourier analysis, the LF of R-R intervals and VLF of systolic blood pressure show more evident difference for different body positions. For the wavelet analysis, the systolic blood pressures show much more evident differences than the R-R intervals. This study suggests a difference in the response of the vessels and the heart to different body positions. The partial dissociation between VLF and LF results is a physiologically relevant finding of this work.

  5. Brain response to prosodic boundary cues depends on boundary position

    Directory of Open Access Journals (Sweden)

    Julia eHolzgrefe

    2013-07-01

    Full Text Available Prosodic information is crucial for spoken language comprehension and especially for syntactic parsing, because prosodic cues guide the hearer’s syntactic analysis. The time course and mechanisms of this interplay of prosody and syntax are not yet well understood. In particular, there is an ongoing debate whether local prosodic cues are taken into account automatically or whether they are processed in relation to the global prosodic context in which they appear. The present study explores whether the perception of a prosodic boundary is affected by its position within an utterance. In an event-related potential (ERP study we tested if the brain response evoked by the prosodic boundary differs when the boundary occurs early in a list of three names connected by conjunctions (i.e., after the first name as compared to later in the utterance (i.e., after the second name. A closure positive shift (CPS — marking the processing of a prosodic phrase boundary — was elicited only for stimuli with a late boundary, but not for stimuli with an early boundary. This result is further evidence for an immediate integration of prosodic information into the parsing of an utterance. In addition, it shows that the processing of prosodic boundary cues depends on the previously processed information from the preceding prosodic context.

  6. The mode of inotropic action of ciguatoxin on guinea-pig cardiac muscle.

    Science.gov (United States)

    Seino, A.; Kobayashi, M.; Momose, K.; Yasumoto, T.; Ohizumi, Y.

    1988-01-01

    1. Ciguatoxin (CTX) caused a dose-dependent increase in the contractile force of the guinea-pig isolated left atria at concentrations ranging from 0.1 to 10 ng ml-1 with the ED50 value of 0.5 ng ml-1. 2. In the atria, tetrodotoxin (5 x 10(-7) M) inhibited markedly the inotropic action of CTX. The inotropic effect of CTX at low concentrations was abolished by practolol (10(-5) M) and reserpine (2 mg kg-1 daily, for 3 days), whereas that of CTX at high concentrations was partially inhibited by both drugs. 3. In single atrial cells, CTX (3 ng ml-1) produced a marked increase in the amplitude of longitudinal contractions. 4. CTX (3 ng ml-1) caused marked prolongation in the falling phase of action potentials of atrial strips without affecting the maximum rate of rise of action potentials and membrane resting potentials. The effect of CTX on action potentials was abolished by tetrodotoxin (10(-6) M). 5. The whole-cell patch-clamp experiments on myocytes revealed that CTX (20 ng ml-1) shifted the current-voltage curve of Na inward currents by 40 mV in the negative direction. CTX caused a small sustained Na inward current even at resting membrane potentials. 6. These results suggest that the inotropic action of lower concentrations of CTX is primarily due to an indirect action via noradrenaline release, whereas that of higher concentrations is caused not only by an indirect action but also by a direct action on voltage-dependent Na channels of cardiac muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3207997

  7. Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

    Science.gov (United States)

    Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz

    2015-01-01

    Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

  8. Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

    Directory of Open Access Journals (Sweden)

    Leslie Shanks

    Full Text Available Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals.Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367 in the VL group compared to 7.9% (200/2526 in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively.The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

  9. Responsive Social Positioning Behaviors for Semi-Autonomous Telepresence Robots

    NARCIS (Netherlands)

    Vroon, Jered Hendrik

    2017-01-01

    Social interaction with a mobile robot requires the establishment of appropriate social positioning behaviors. Previous work has focused mostly on general and static rules that can be applied to robotics, such as proxemics. How can we deal effectively and efficiently with the dynamic positioning

  10. Aqueous leaf extract of Averrhoa carambola L. (Oxalidaceae reduces both the inotropic effect of BAY K 8644 on the guinea pig atrium and the calcium current on GH3cells

    Directory of Open Access Journals (Sweden)

    Carla M. L. Vasconcelos

    Full Text Available It was previously showed that aqueous leaf extract (AqEx of Averrhoa carambola depresses the guinea pig atrial inotropism. Therefore, experiments were carried out on guinea pig left atrium and on pituitary GH3 cells in order to evaluate the effect of AqEx on the cellular calcium influx. The atrium was mounted in an organ chamber (5 mL, Tyrode, 27 ± 0.1 ºC, 95 % O2, 5 % CO2, stretched to 10 mN, and paced at 2 Hz (0.5 ms, 400 V and GH3 cells were submitted to a whole cell voltage clamp configuration. In the atrium, the AqEx (1500 µg/mL shifted to the right the concentration-effect curve of the positive inotropic effect produced by (± BAY K 8644, an L-type calcium channel agonist. The AqEx increased EC50 (concentration required to promote 50% of the maximum effect of the inotropic effect of BAY K 8644 from 7.8 ± 0.38 to 115.1 ± 0.44 nM (N = 3; p < 0.05. In GH3 cells assayed with 500 µg/mL of AqEx, the L-type calcium inward current declined 30 % (from 282 to 190 pA. Nevertheless, the extract did not change the voltage correspondent to the peak current. These data suggest that, at least in part, the negative inotropic effect of AqEx on the guinea pig atrium is due to a reduction of the L-type calcium current.

  11. People newly in love are more responsive to positive feedback.

    Science.gov (United States)

    Brown, Cassandra L; Beninger, Richard J

    2012-06-01

    Passionate love is associated with increased activity in dopamine-rich regions of the brain. Increased dopamine in these regions is associated with a greater tendency to learn from reward in trial-and-error learning tasks. This study examined the prediction that individuals who were newly in love would be better at responding to reward (positive feedback). In test trials, people who were newly in love selected positive outcomes significantly more often than their single (not in love) counterparts but were no better at the task overall. This suggests that people who are newly in love show a bias toward responding to positive feedback, which may reflect a general bias towards reward-seeking.

  12. Market segmentation and positioning: matching creativity with fiscal responsibility.

    Science.gov (United States)

    Kiener, M E

    1989-01-01

    This paper describes an approach to continuing professional education (CPE) program development in nursing within a university environment that utilizes the concepts of market segmentation and positioning. Use of these strategies enables the academic CPE enterprise to move beyond traditional needs assessment practices to create more successful and better-managed CPE programs.

  13. Positive and negative emotional responses to work-related trauma ...

    African Journals Online (AJOL)

    Data were gathered via the Professional Quality of Life Scale: Compassion Satisfaction and Fatigue Subscales – Revision IV (ProQOL – R-IV) and the Silencing Response Scale and were analysed according to descriptive statistics and correlation coefficients. Findings suggest a high risk for compassion fatigue, a moderate ...

  14. Analytical expression for position sensitivity of linear response beam position monitor having inter-electrode cross talk

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Mukesh, E-mail: mukeshk@rrcat.gov.in [Beam Diagnostics Section, Indus Operations, Beam Dynamics & Diagnostics Division, Raja Ramanna Centre for Advanced Technology, Indore, 452013 MP (India); Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400 094 (India); Ojha, A.; Garg, A.D.; Puntambekar, T.A. [Beam Diagnostics Section, Indus Operations, Beam Dynamics & Diagnostics Division, Raja Ramanna Centre for Advanced Technology, Indore, 452013 MP (India); Senecha, V.K. [Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400 094 (India); Ion Source Lab., Proton Linac & Superconducting Cavities Division, Raja Ramanna Centre for Advanced Technology, Indore, 452013 MP (India)

    2017-02-01

    According to the quasi electrostatic model of linear response capacitive beam position monitor (BPM), the position sensitivity of the device depends only on the aperture of the device and it is independent of processing frequency and load impedance. In practice, however, due to the inter-electrode capacitive coupling (cross talk), the actual position sensitivity of the device decreases with increasing frequency and load impedance. We have taken into account the inter-electrode capacitance to derive and propose a new analytical expression for the position sensitivity as a function of frequency and load impedance. The sensitivity of a linear response shoe-box type BPM has been obtained through simulation using CST Studio Suite to verify and confirm the validity of the new analytical equation. Good agreement between the simulation results and the new analytical expression suggest that this method can be exploited for proper designing of BPM.

  15. Overexpression of cyclic adenosine monophosphate effluent protein MRP4 induces an altered response to β-adrenergic stimulation in the senescent rat heart.

    Science.gov (United States)

    Carillion, Aude; Feldman, Sarah; Jiang, Cheng; Atassi, Fabrice; Na, Na; Mougenot, Nathalie; Besse, Sophie; Hulot, Jean-Sébastien; Riou, Bruno; Amour, Julien

    2015-02-01

    In the senescent heart, the positive inotropic response to β-adrenoceptor stimulation is reduced, partly by dysregulation of β1- and β3-adrenoceptors. The multidrug resistance protein 4 (MRP4) takes part in the control of intracellular cyclic adenosine monophosphate concentration by controlling its efflux but the role of MRP4 in the β-adrenergic dysfunction of the senescent heart remains unknown. The β-adrenergic responses to isoproterenol were investigated in vivo (stress echocardiography) and in vitro (isolated cardiomyocyte by Ionoptix with sarcomere shortening and calcium transient) in young (3 months old) and senescent (24 months old) rats pretreated or not with MK571, a specific MRP4 inhibitor. MRP4 was quantified in left ventricular homogenates by Western blotting. Data are mean ± SD expressed as percent of baseline value. The positive inotropic effect of isoproterenol was reduced in senescent rats in vivo (left ventricular shortening fraction 120 ± 16% vs. 158 ± 20%, P < 0.001, n = 16 rats) and in vitro (sarcomere shortening 129 ± 37% vs. 148 ± 35%, P = 0.004, n = 41 or 43 cells) as compared to young rats. MRP4 expression increased 3.6-fold in senescent compared to young rat myocardium (P = 0.012, n = 8 rats per group). In senescent rats, inhibition of MRP4 by MK571 restored the positive inotropic effect of isoproterenol in vivo (143 ± 11%, n = 8 rats). In vitro in senescent cardiomyocytes pretreated with MK571, both sarcomere shortening (161 ± 45% vs. 129 ± 37%, P = 0.007, n = 41 cells per group) and calcium transient amplitude (132 ± 25% vs. 113 ± 27%, P = 0.007) increased significantly. MRP4 overexpression contributes to the reduction of the positive inotropic response to β-adrenoceptor stimulation in the senescent heart.

  16. Tyrosine 370 phosphorylation of ATM positively regulates DNA damage response

    Science.gov (United States)

    Lee, Hong-Jen; Lan, Li; Peng, Guang; Chang, Wei-Chao; Hsu, Ming-Chuan; Wang, Ying-Nai; Cheng, Chien-Chia; Wei, Leizhen; Nakajima, Satoshi; Chang, Shih-Shin; Liao, Hsin-Wei; Chen, Chung-Hsuan; Lavin, Martin; Ang, K Kian; Lin, Shiaw-Yih; Hung, Mien-Chie

    2015-01-01

    Ataxia telangiectasia mutated (ATM) mediates DNA damage response by controling irradiation-induced foci formation, cell cycle checkpoint, and apoptosis. However, how upstream signaling regulates ATM is not completely understood. Here, we show that upon irradiation stimulation, ATM associates with and is phosphorylated by epidermal growth factor receptor (EGFR) at Tyr370 (Y370) at the site of DNA double-strand breaks. Depletion of endogenous EGFR impairs ATM-mediated foci formation, homologous recombination, and DNA repair. Moreover, pretreatment with an EGFR kinase inhibitor, gefitinib, blocks EGFR and ATM association, hinders CHK2 activation and subsequent foci formation, and increases radiosensitivity. Thus, we reveal a critical mechanism by which EGFR directly regulates ATM activation in DNA damage response, and our results suggest that the status of ATM Y370 phosphorylation has the potential to serve as a biomarker to stratify patients for either radiotherapy alone or in combination with EGFR inhibition. PMID:25601159

  17. Positive response of Indian summer rainfall to Middle East dust

    KAUST Repository

    Jin, Qinjian

    2014-06-02

    Using observational and reanalyses data, we investigated the impact of dust aerosols over the Middle East and the Arabian Sea (AS) on the Indian summer monsoon (ISM) rainfall. Satellite and aerosol reanalysis data show extremely heavy aerosol loading, mainly mineral dust, over the Middle East and AS during the ISM season. Multivariate empirical orthogonal function analyses suggest an aerosol-monsoon connection. This connection may be attributed to dust-induced atmospheric heating centered over the Iranian Plateau (IP), which enhances the meridional thermal contrast and strengthens the ISM circulation and rainfall. The enhanced circulation further transports more dust to the AS and IP, heating the atmosphere (positive feedback). The aerosols over the AS and the Arabian Peninsula have a significant correlation with rainfall over central and eastern India about 2 weeks later. This finding highlights the nonlocal radiative effect of dust on the ISM circulation and rainfall and may improve ISM rainfall forecasts. © 2014. American Geophysical Union. All Rights Reserved.

  18. Positive response of Indian summer rainfall to Middle East dust

    KAUST Repository

    Jin, Qinjian; Wei, Jiangfeng; Yang, Zong-Liang

    2014-01-01

    Using observational and reanalyses data, we investigated the impact of dust aerosols over the Middle East and the Arabian Sea (AS) on the Indian summer monsoon (ISM) rainfall. Satellite and aerosol reanalysis data show extremely heavy aerosol loading, mainly mineral dust, over the Middle East and AS during the ISM season. Multivariate empirical orthogonal function analyses suggest an aerosol-monsoon connection. This connection may be attributed to dust-induced atmospheric heating centered over the Iranian Plateau (IP), which enhances the meridional thermal contrast and strengthens the ISM circulation and rainfall. The enhanced circulation further transports more dust to the AS and IP, heating the atmosphere (positive feedback). The aerosols over the AS and the Arabian Peninsula have a significant correlation with rainfall over central and eastern India about 2 weeks later. This finding highlights the nonlocal radiative effect of dust on the ISM circulation and rainfall and may improve ISM rainfall forecasts. © 2014. American Geophysical Union. All Rights Reserved.

  19. Effects of cardiac resynchronization therapy in patients with inotrope-dependent class IV end-stage heart failure

    Directory of Open Access Journals (Sweden)

    Ikutaro Nakajima

    2013-12-01

    Conclusion: CRT did not result in significant reverse remodeling in patients with inotrope-dependent class IV end-stage HF. However, it contributed to dramatically improve the cardiovascular outcomes at least in the short-term period in some patients.

  20. What good are positive emotions for treatment? Trait positive emotionality predicts response to Cognitive Behavioral Therapy for anxiety.

    Science.gov (United States)

    Taylor, Charles T; Knapp, Sarah E; Bomyea, Jessica A; Ramsawh, Holly J; Paulus, Martin P; Stein, Murray B

    2017-06-01

    Cognitive behavioral therapy (CBT) is empirically supported for the treatment of anxiety disorders; however, not all individuals achieve recovery following CBT. Positive emotions serve a number of functions that theoretically should facilitate response to CBT - they promote flexible patterns of information processing and assimilation of new information, encourage approach-oriented behavior, and speed physiological recovery from negative emotions. We conducted a secondary analysis of an existing clinical trial dataset to test the a priori hypothesis that individual differences in trait positive emotions would predict CBT response for anxiety. Participants meeting diagnostic criteria for panic disorder (n = 28) or generalized anxiety disorder (n = 31) completed 10 weekly individual CBT sessions. Trait positive emotionality was assessed at pre-treatment, and severity of anxiety symptoms and associated impairment was assessed throughout treatment. Participants who reported a greater propensity to experience positive emotions at pre-treatment displayed the largest reduction in anxiety symptoms as well as fewer symptoms following treatment. Positive emotions remained a robust predictor of change in symptoms when controlling for baseline depression severity. Initial evidence supports the predictive value of trait positive emotions as a prognostic indicator for CBT outcome in a GAD and PD sample. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. RETRACTED ARTICLE: Happiness as alchemy: Positive mood leads to self-serving responses to social comparisons

    OpenAIRE

    Johnson, Camille S.; Stapel, Diederik A.

    2011-01-01

    People in a positive mood process information in ways that reinforce and maintain this positive mood. The current studies examine how positive mood influences responses to social comparisons and demonstrates that people in a positive mood interpret ambiguous information about comparison others in self-benefitting ways. Specifically, four experiments demonstrate that compared to negative mood or neutral mood participants, participants in a positive mood engage in effortful re-interpretations o...

  2. Physiological Response to Static Muscle Contractions in Standing and Supine Positions

    DEFF Research Database (Denmark)

    Pedersen, Jens Meldgaard; Andersen, T. Bull

    2013-01-01

    The purpose of this study was to investigate the physiological responses to static muscle contractions in the standing position and the supine position. Eight subjects performed static contractions of the ankle extensors in both positions. Blood pressure (SBP and DBP), heart rate (HR...

  3. A Psychometric Evaluation of the Dutch Version of the Responses to Positive Affect Questionnaire

    Directory of Open Access Journals (Sweden)

    Filip Raes

    2010-12-01

    Full Text Available In 698 respondents selected from the community, the authors examined the psychometric properties of the Dutch version of the Responses to Positive Affect questionnaire (RPA; Feldman, Joormann, & Johnson, 2008 which measures ruminative and dampening thoughts in response to positive affect. In a first sample ('n' = 170, exploratory factor analyses largely replicated the 3-factor model obtained by Feldman et al. (2008 with the following factors: Dampening, Self-focused positive rumination, and Emotion-focused positive rumination. The 3-factor model revealed in the first sample was confirmed using confirmatory factor analyses in a second independent sample of 528 respondents. All subscales showed adequate internal consistency and evidence of convergent and incremental validity with concurrent measures of depressive rumination, depressive symptoms, trait hypomania, and positive and negative affect. Results underscore the value of assessing responses to positive as well as negative affect in the study of mood disorders.

  4. Inotropic effects of extracts of Psidium guajava L. (guava) leaves on the guinea pig atrium.

    Science.gov (United States)

    Conde Garcia, E A; Nascimento, V T; Santiago Santos, A B

    2003-05-01

    Many pharmacological effects have been ascribed to extracts of Psidium guajava L. (guava) leaves. However, in spite of its widespread use in Brazilian folk medicine and a reasonable number of scientific reports about it, we could not find any study dealing with its action on the mammalian myocardium. In the present study, by measuring isometric force, we observed that the crude extract of P. guajava (water-alcohol extract obtained by macerating dry leaves) depresses the guinea pig atrial contractility in a concentration-dependent fashion (N = 8 hearts, 15 trials). The compound with cardiac activity was concentrated by extraction in a Soxhlet apparatus using 17 M glacial acetic acid after removing the less polar fractions (hexane, chloroform, acetone, ethanol and methanol), suggesting that this compound is a highly polar substance. In the isolated guinea pig left atrium the acetic acid fraction (10-800 mg/l) of P. guajava 1) reversibly decreased myocardial force in a concentration-dependent fashion (EC50 = 0.07g/l, N = 5 hearts, 9 trials, Pleaves depress myocardial inotropism.

  5. Response to pediatric physical therapy in infants with positional preference and skull deformation

    NARCIS (Netherlands)

    Wijk, R.M. van; Pelsma, M.; Groothuis-Oudshoorn, C.G.; IJzerman, M.J.; Vlimmeren, L.A. van; Boere-Boonekamp, M.M.

    2014-01-01

    BACKGROUND: Pediatric physical therapy seems to reduce skull deformation in infants with positional preference. However, not all infants show improvement. OBJECTIVE: The study objective was to determine which infant and parent characteristics were related to responses to pediatric physical therapy

  6. Reduced local immune response with continuous positive airway pressure during one-lung ventilation for oesophagectomy

    NARCIS (Netherlands)

    Verhage, R. J. J.; Boone, J.; Rijkers, G. T.; Cromheecke, G. J.; Kroese, A. C.; Weijs, T. J.; Borel Rinkes, I. H. M.; van Hillegersberg, R.

    2014-01-01

    Background. Transthoracic oesophagectomy requires prolonged one-lung ventilation causing systemic and local inflammatory responses. Application of continuous positive airway pressure (CPAP) to the collapsed lung potentially reduces pulmonary damage, hypoxia, and consequent inflammation. This

  7. Predictors of inotrope use in patients undergoing concomitant coronary artery bypass graft (CABG and aortic valve replacement (AVR surgeries at separation from cardiopulmonary bypass (CPB

    Directory of Open Access Journals (Sweden)

    Nelson William B

    2009-06-01

    Full Text Available Abstract Background Left ventricular dysfunction is common after coronary artery bypass graft and valve replacement surgeries and is often treated with inotropic drugs to maintain adequate hemodynamic status. In this study, we aimed to identify the demographic, clinical, laboratory, echocardiographic and hemodynamic factors that are associated with use of inotropic drugs in patients undergoing concomitant coronary artery bypass graft and aortic valve replacement surgery. Methods The study included 97 patients who had undergone concomitant coronary artery bypass graft and aortic valve replacement at Regions Hospital, University of Minnesota Medical School from January 2006 to December 2008. All data were collected retrospectively after reviewing electronic medical records. Inotropic support was defined as the use of dopamine [greater than or equal to] 5 ug/kg/min; any dose of epinephrine, norepinephrine, dobutamine, and milrinone at the separation from cardiopulmonary bypass. Results Inotropic support was used in a total of 50 patients (52% at the separation from cardiopulmonary bypass. Average age of the patients requiring inotropic support was 72.2 +/- 8.8 years. The study identified four significant, independent predictors of inotrope use: (1 Cardiac index [less than or equal to]2.5 L/min/m2, (2 LVEDP [greater than or equal to] 20 mm Hg, (3 LVEF [less than or equal to]40%, and (4 CKD stage 3 to 5. Conclusion We identified four independent risk factors for postoperative use of inotropic support in patients undergoing concomitant coronary artery bypass graft and arotic valve replacement surgery at the separation from cardiopulmonary bypass. The study results will be helpful to prospectively identify patients who will likely to require inotropic support at the separation from cardiopulmonary bypass.

  8. Renal Function and Outcomes With Use of Left Ventricular Assist Device Implantation and Inotropes in End-Stage Heart Failure: A Retrospective Single Center Study.

    Science.gov (United States)

    Verma, Sean; Bassily, Emmanuel; Leighton, Shane; Mhaskar, Rahul; Sunjic, Igor; Martin, Angel; Rihana, Nancy; Jarmi, Tambi; Bassil, Claude

    2017-07-01

    Left ventricular assist device (LVAD) and inotrope therapy serve as a bridge to transplant (BTT) or as destination therapy in patients who are not heart transplant candidates. End-stage heart failure patients often have impaired renal function, and renal outcomes after LVAD therapy versus inotrope therapy have not been evaluated. In this study, 169 patients with continuous flow LVAD therapy and 20 patients with continuous intravenous inotrope therapy were analyzed. The two groups were evaluated at baseline and at 3 and 6 months after LVAD or inotrope therapy was started. The incidence of acute kidney injury (AKI), need for renal replacement therapy (RRT), BTT rate, and mortality for 6 months following LVAD or inotrope therapy were studied. Results between the groups were compared using Mann-Whitney U test and Chi-square with continuity correction or Fischer's exact at the significance level of 0.05. Mean glomerular filtration rate (GFR) was not statistically different between the two groups, with P = 0.471, 0.429, and 0.847 at baseline, 3 and 6 months, respectively. The incidence of AKI, RRT, and BTT was not statistically different. Mortality was less in the inotrope group (P < 0.001). Intravenous inotrope therapy in end-stage heart failure patients is non-inferior for mortality, incidence of AKI, need for RRT, and renal function for 6-month follow-up when compared to LVAD therapy. Further studies are needed to compare the effectiveness of inotropes versus LVAD implantation on renal function and outcomes over a longer time period.

  9. The schizophrenia risk gene ZNF804A influences the antipsychotic response of positive schizophrenia symptoms

    OpenAIRE

    Mössner, R; Schumacher, A; Wagner, M; Lennertz, L; Steinbrecher, A; Quednow, Boris B; Rujescu, D; Rietschel, M; Maier, W

    2012-01-01

    Genetic factors determining the response to antipsychotic treatment in schizophrenia are poorly understood. A new schizophrenia susceptibility gene, the zinc-finger gene ZNF804A, has recently been identified. To assess the pharmacogenetic importance of this gene, we treated 144 schizophrenia patients and assessed the response of positive and negative symptoms by PANSS. Patients homozygous for the ZNF804A risk allele for schizophrenia (rs1344706 AA) showed poorer improvement of positive sympto...

  10. Dimorphous expressions of positive emotion: displays of both care and aggression in response to cute stimuli.

    Science.gov (United States)

    Aragón, Oriana R; Clark, Margaret S; Dyer, Rebecca L; Bargh, John A

    2015-03-01

    Extremely positive experiences, and positive appraisals thereof, produce intense positive emotions that often generate both positive expressions (e.g., smiles) and expressions normatively reserved for negative emotions (e.g., tears). We developed a definition of these dimorphous expressions and tested the proposal that their function is to regulate emotions. We showed that individuals who express emotions in this dimorphous manner do so as a general response across a variety of emotionally provoking situations, which suggests that these expressions are responses to intense positive emotion rather than unique to one particular situation. We used cute stimuli (an elicitor of positive emotion) to demonstrate both the existence of these dimorphous expressions and to provide preliminary evidence of their function as regulators of emotion. © The Author(s) 2015.

  11. Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

    Science.gov (United States)

    Yang, Hongfei; Li, Juan

    2016-01-01

    The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

  12. Involvement of beta 3-adrenoceptor in altered beta-adrenergic response in senescent heart: role of nitric oxide synthase 1-derived nitric oxide.

    Science.gov (United States)

    Birenbaum, Aurélie; Tesse, Angela; Loyer, Xavier; Michelet, Pierre; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno; Amour, Julien

    2008-12-01

    In senescent heart, beta-adrenergic response is altered in parallel with beta1- and beta2-adrenoceptor down-regulation. A negative inotropic effect of beta3-adrenoceptor could be involved. In this study, the authors tested the hypothesis that beta3-adrenoceptor plays a role in beta-adrenergic dysfunction in senescent heart. beta-Adrenergic responses were investigated in vivo (echocardiography-dobutamine, electron paramagnetic resonance) and in vitro (isolated left ventricular papillary muscle, electron paramagnetic resonance) in young adult (3-month-old) and senescent (24-month-old) rats. Nitric oxide synthase (NOS) immunolabeling (confocal microscopy), nitric oxide production (electron paramagnetic resonance) and beta-adrenoceptor Western blots were performed in vitro. Data are mean percentages of baseline +/- SD. An impaired positive inotropic effect (isoproterenol) was confirmed in senescent hearts in vivo (117 +/- 23 vs. 162 +/- 16%; P < 0.05) and in vitro (127 +/- 10 vs. 179 +/- 15%; P < 0.05). In the young adult group, the positive inotropic effect was not significantly modified by the nonselective NOS inhibitor N-nitro-L-arginine methylester (L-NAME; 183 +/- 19%), the selective NOS1 inhibitor vinyl-L-N-5(1-imino-3-butenyl)-L-ornithine (L-VNIO; 172 +/- 13%), or the selective NOS2 inhibitor 1400W (183 +/- 19%). In the senescent group, in parallel with beta3-adrenoceptor up-regulation and increased nitric oxide production, the positive inotropic effect was partially restored by L-NAME (151 +/- 8%; P < 0.05) and L-VNIO (149 +/- 7%; P < 0.05) but not by 1400W (132 +/- 11%; not significant). The positive inotropic effect induced by dibutyryl-cyclic adenosine monophosphate was decreased in the senescent group with the specific beta3-adrenoceptor agonist BRL 37344 (167 +/- 10 vs. 142 +/- 10%; P < 0.05). NOS1 and NOS2 were significantly up-regulated in the senescent rat. In senescent cardiomyopathy, beta3-adrenoceptor overexpression plays an important role in the

  13. Applying the Nominal Response Model within a Longitudinal Framework to Construct the Positive Family Relationships Scale

    Science.gov (United States)

    Preston, Kathleen Suzanne Johnson; Parral, Skye N.; Gottfried, Allen W.; Oliver, Pamella H.; Gottfried, Adele Eskeles; Ibrahim, Sirena M.; Delany, Danielle

    2015-01-01

    A psychometric analysis was conducted using the nominal response model under the item response theory framework to construct the Positive Family Relationships scale. Using data from the Fullerton Longitudinal Study, this scale was constructed within a long-term longitudinal framework spanning middle childhood through adolescence. Items tapping…

  14. Analysis of the negative inotropic effect of acetylcholine on frog atrial fibres.

    Science.gov (United States)

    Nargeot, J; Garnier, D; Rougier, O

    1981-03-01

    Voltage-clamp experiments have been performed on frog atrial preparations in order to study the mechanism of the inotropic effect of acetylcholine (ACh) at various concentrations. The amplitude of the slow inward current (Is) is reduced even at low ACh concentrations; such low concentrations have little or no effect on potassium permeability. Dose-effect relationships for Is inhibition (Is/Is max) by ACh show a half amplitude dose (K0.5 around 8 X 10(-8) M ACh. The reduction of Is is attributed largely to a decrease of the maximal conductance of the slow channel (gs). Steady-state activation and inactivation parameters are not affected by ACh. Experiments in a Na-free solution (Na replaced by Li ions) or in a Ca-free solution (with EGTA) indicate that the "slow sodium current" is more sensitive to ACh than the "slow Ca current", although these two currents both seem to flow through the slow channel. The decrease of the phasic component of contraction observed in the presence of ACh is very well correlated with the decrease of Is (K0.5 = 8 X 10(-8) M ACh), while the increase of the tonic tension may be related to the outward potassium current induced by high concentrations of ACh. The significant difference between the half amplitude dose (K0.5) observed in the dose effect curves with ACh for Is inhibition (K0.5 = 8 X 10(-8) M) and for ACh-induced extra-current (K0.5 - 10(-6) M) may indicate the presence of two muscarinic receptors.

  15. Response and binding elements for ligand-dependent positive transcription factors integrate positive and negative regulation of gene expression

    International Nuclear Information System (INIS)

    Rosenfeld, M.G.; Glass, C.K.; Adler, S.; Crenshaw, E.B. III; He, X.; Lira, S.A.; Elsholtz, H.P.; Mangalam, H.J.; Holloway, J.M.; Nelson, C.; Albert, V.R.; Ingraham, H.A.

    1988-01-01

    Accurate, regulated initiation of mRNA transcription by RNA polymerase II is dependent on the actions of a variety of positive and negative trans-acting factors that bind cis-acting promoter and enhancer elements. These transcription factors may exert their actions in a tissue-specific manner or function under control of plasma membrane or intracellular ligand-dependent receptors. A major goal in the authors' laboratory has been to identify the molecular mechanisms responsible for the serial activation of hormone-encoding genes in the pituitary during development and the positive and negative regulation of their transcription. The anterior pituitary gland contains phenotypically distinct cell types, each of which expresses unique trophic hormones: adrenocorticotropic hormone, thyroid-stimulating hormone, prolactin, growth hormone, and follicle-stimulating hormone/luteinizing hormone. The structurally related prolactin and growth hormone genes are expressed in lactotrophs and somatotrophs, respectively, with their expression virtually limited to the pituitary gland. The reported transient coexpression of these two structurally related neuroendocrine genes raises the possibility that the prolactin and growth hormone genes are developmentally controlled by a common factor(s)

  16. Effects of upright and supine position on cardiac rest and exercise response in aortic regurgitation.

    Science.gov (United States)

    Shen, W F; Roubin, G S; Fletcher, P J; Choong, C Y; Hutton, B F; Harris, P J; Kelly, D T

    1985-02-01

    The effects of upright and supine position on cardiac response to exercise were assessed by radionuclide ventriculography in 15 patients with moderate to severe aortic regurgitation (AR) and in 10 control subjects. In patients with AR, heart rate was higher during upright exercise, but systolic and diastolic blood pressure and left ventricular (LV) output were similar during both forms of exercise. LV stroke volume and end-diastolic volume were not altered during supine exercise. LV end-systolic volume increased and ejection fraction decreased during supine exercise, but both were unchanged during upright exercise. Of 15 patients, 5 in the upright and 12 in the supine position had an abnormal LV ejection fraction response to exercise (p less than 0.01). Right ventricular ejection fraction increased and regurgitant index decreased with both forms of exercise and was not significantly different between the 2 positions. Thus, posture is important in determining LV response to exercise in patients with moderate to severe AR.

  17. [Clinical features and therapeutic response of our anti-SRP positive patients with myositis].

    Science.gov (United States)

    Botos, Balázs; Nagy-Vincze, Melinda; Dankó, Katalin

    2017-09-01

    Idiopathic inflammatory myopathies are a group of clinically heterogeneous diseases, which have been classified by myositis specific antibodies recently. The anti-SRP positive subset of this group is characterized by more severe clinical prognosis than other myositis specific antibody positive types. Our goal was to compare 16 anti-SRP positive patients in the Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen with 16 antibody negative ones. Muscle strength validated in both groups by the manual muscle test proved to be significantly decreased both before and after therapy (χ 2 = 0.006 and 0.019) in the anti-SRP positive group. Muscle-specific inflammatory laboratory parameters showed significant difference only in case of LDH-levels after therapy. Both groups showed good clinical response to first line steroid treatment, yet the significantly higher rate of second line administration suggests worse therapeutic response of the antibody positive group. Based on these facts we determined poor clinical prognosis and therapeutic response of the anti-SRP positive group. Orv Hetil. 2017; 158(35): 1382-1389.

  18. On the duality between interaction responses and mutual positions in flocking and schooling.

    Science.gov (United States)

    Perna, Andrea; Grégoire, Guillaume; Mann, Richard P

    2014-01-01

    Recent research in animal behaviour has contributed to determine how alignment, turning responses, and changes of speed mediate flocking and schooling interactions in different animal species. Here, we propose a complementary approach to the analysis of flocking phenomena, based on the idea that animals occupy preferential, anysotropic positions with respect to their neighbours, and devote a large amount of their interaction responses to maintaining their mutual positions. We test our approach by deriving the apparent alignment and attraction responses from simulated trajectories of animals moving side by side, or one in front of the other. We show that the anisotropic positioning of individuals, in combination with noise, is sufficient to reproduce several aspects of the movement responses observed in real animal groups. This anisotropy at the level of interactions should be considered explicitly in future models of flocking and schooling. By making a distinction between interaction responses involved in maintaining a preferred flock configuration, and interaction responses directed at changing it, our work provides a frame to discriminate movement interactions that signal directional conflict from interactions underlying consensual group motion.

  19. Positive solutions for a nonlocal boundary-value problem with vector-valued response

    Directory of Open Access Journals (Sweden)

    Andrzej Nowakowski

    2002-05-01

    Full Text Available Using variational methods, we study the existence of positive solutions for a nonlocal boundary-value problem with vector-valued response. We develop duality and variational principles for this problem and present a numerical version which enables the approximation of solutions and gives a measure of a duality gap between primal and dual functional for approximate solutions for this problem.

  20. Increasing Humidity Blocks Continuous Positive Airflow-induced Apnea Responses in Rats

    Directory of Open Access Journals (Sweden)

    Ching-Ting Tan

    2010-07-01

    Conclusion: Laryngeal cold dry air stimulation triggered an apneic response, which could be eliminated by humidification but not by the heating of air. These results suggest that using continuous positive airway pressure (CPAP with humidified air decreases CPAP-induced apnea.

  1. Online manual movement adjustments in response to target position changes and apparent target motion

    NARCIS (Netherlands)

    Oostwoud Wijdenes, L.; Brenner, E.; Smeets, J.B.J.

    2014-01-01

    This study set out to determine whether the fastest online hand movement corrections are only responses to changing judgments of the targets' position or whether they are also influenced by the apparent target motion. Introducing a gap between when a target disappears and when it reappears at a new

  2. Suspicion of Motives Predicts Minorities' Responses to Positive Feedback in Interracial Interactions.

    Science.gov (United States)

    Major, Brenda; Kunstman, Jonathan W; Malta, Brenna D; Sawyer, Pamela J; Townsend, Sarah S M; Mendes, Wendy Berry

    2016-01-01

    Strong social and legal norms in the United States discourage the overt expression of bias against ethnic and racial minorities, increasing the attributional ambiguity of Whites' positive behavior to ethnic minorities. Minorities who suspect that Whites' positive overtures toward minorities are motivated more by their fear of appearing racist than by egalitarian attitudes may regard positive feedback they receive from Whites as disingenuous. This may lead them to react to such feedback with feelings of uncertainty and threat. Three studies examined how suspicion of motives relates to ethnic minorities' responses to receiving positive feedback from a White peer or same-ethnicity peer (Experiment 1), to receiving feedback from a White peer that was positive or negative (Experiment 2), and to receiving positive feedback from a White peer who did or did not know their ethnicity (Experiment 3). As predicted, the more suspicious Latinas were of Whites' motives for behaving positively toward minorities in general, the more they regarded positive feedback from a White peer who knew their ethnicity as disingenuous and the more they reacted with cardiovascular reactivity characteristic of threat/avoidance, increased feelings of stress, heightened uncertainty, and decreased self-esteem. We discuss the implications for intergroup interactions of perceptions of Whites' motives for nonprejudiced behavior.

  3. Suspicion of Motives Predicts Minorities’ Responses to Positive Feedback in Interracial Interactions

    Science.gov (United States)

    Major, Brenda; Kunstman, Jonathan W.; Malta, Brenna D.; Sawyer, Pamela J.; Townsend, Sarah S. M.; Mendes, Wendy Berry

    2015-01-01

    Strong social and legal norms in the United States discourage the overt expression of bias against ethnic and racial minorities, increasing the attributional ambiguity of Whites’ positive behavior to ethnic minorities. Minorities who suspect that Whites’ positive overtures toward minorities are motivated more by their fear of appearing racist than by egalitarian attitudes may regard positive feedback they receive from Whites as disingenuous. This may lead them to react to such feedback with feelings of uncertainty and threat. Three studies examined how suspicion of motives relates to ethnic minorities’ responses to receiving positive feedback from a White peer or same-ethnicity peer (Experiment 1), to receiving feedback from a White peer that was positive or negative (Experiment 2), and to receiving positive feedback from a White peer who did or did not know their ethnicity (Experiment 3). As predicted, the more suspicious Latinas were of Whites’ motives for behaving positively toward minorities in general, the more they regarded positive feedback from a White peer who knew their ethnicity as disingenuous and the more they reacted with cardiovascular reactivity characteristic of threat/avoidance, increased feelings of stress, heightened uncertainty, and decreased self-esteem. We discuss the implications for intergroup interactions of perceptions of Whites’ motives for nonprejudiced behavior. PMID:26688594

  4. Amygdala responses to unpleasant pictures are influenced by task demands and positive affect trait

    Directory of Open Access Journals (Sweden)

    Tiago Arruda Sanchez

    2015-03-01

    Full Text Available The role of attention in emotional processing is still the subject of debate. Recent studies have found that high positive affect in approach motivation narrows attention. Furthermore, the positive affect trait has been suggested as an important component for determining human variability in threat reactivity. We employed fMRI to investigate whether different states of attention control would modulate amygdala responses to highly unpleasant pictures relative to neutral and whether this modulation would be influenced by the positive affect trait. Participants (n=22, 12 male were scanned while viewing neutral (people or unpleasant pictures (mutilated bodies flanked by two peripheral bars. They were instructed to (a judge the picture content as unpleasant or neutral or (b to judge the difference in orientation between the bars in an easy condition (0º or 90º orientation difference or (c in a hard condition (0º or 6º orientation difference. Whole brain analysis revealed a task main effect of brain areas related to the experimental manipulation of attentional control, including the amygdala, dorsolateral prefrontal cortex and posterior parietal cortex. ROI analysis showed an inverse correlation (r = -0.51, p < 0.01 between left amygdala activation and positive affect level when participants viewed unpleasant stimuli and judged bar orientation in the easy condition. This result suggests that subjects with high positive affect exhibit lower amygdala reactivity to distracting unpleasant pictures. In conclusion, the current study suggests that positive affect modulates attention effect on unpleasant pictures, therefore attenuating emotional responses.

  5. The position response of a large-volume segmented germanium detector

    International Nuclear Information System (INIS)

    Descovich, M.; Nolan, P.J.; Boston, A.J.; Dobson, J.; Gros, S.; Cresswell, J.R.; Simpson, J.; Lazarus, I.; Regan, P.H.; Valiente-Dobon, J.J.; Sellin, P.; Pearson, C.J.

    2005-01-01

    The position response of a large-volume segmented coaxial germanium detector is reported. The detector has 24-fold segmentation on its outer contact. The output from each contact was sampled with fast digital signal processing electronics in order to determine the position of the γ-ray interaction from the signal pulse shape. The interaction position was reconstructed in a polar coordinate system by combining the radial information, contained in the rise-time of the pulse leading edge, with the azimuthal information, obtained from the magnitude of the transient charge signals induced on the neighbouring segments. With this method, a position resolution of 3-7mm is achieved in both the radial and the azimuthal directions

  6. The position response of a large-volume segmented germanium detector

    Energy Technology Data Exchange (ETDEWEB)

    Descovich, M. [Oliver Lodge Laboratory, Physics Department, University of Liverpool, Liverpool L69 7ZE (United Kingdom)]. E-mail: mdescovich@lbl.gov; Nolan, P.J. [Oliver Lodge Laboratory, Physics Department, University of Liverpool, Liverpool L69 7ZE (United Kingdom); Boston, A.J. [Oliver Lodge Laboratory, Physics Department, University of Liverpool, Liverpool L69 7ZE (United Kingdom); Dobson, J. [Oliver Lodge Laboratory, Physics Department, University of Liverpool, Liverpool L69 7ZE (United Kingdom); Gros, S. [Oliver Lodge Laboratory, Physics Department, University of Liverpool, Liverpool L69 7ZE (United Kingdom); Cresswell, J.R. [Oliver Lodge Laboratory, Physics Department, University of Liverpool, Liverpool L69 7ZE (United Kingdom); Simpson, J. [CCLRC Daresbury Laboratory, Daresbury, Warrington, Cheshire WA4 4AD (United Kingdom); Lazarus, I. [CCLRC Daresbury Laboratory, Daresbury, Warrington, Cheshire WA4 4AD (United Kingdom); Regan, P.H. [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Valiente-Dobon, J.J. [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Sellin, P. [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Pearson, C.J. [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom)

    2005-11-21

    The position response of a large-volume segmented coaxial germanium detector is reported. The detector has 24-fold segmentation on its outer contact. The output from each contact was sampled with fast digital signal processing electronics in order to determine the position of the {gamma}-ray interaction from the signal pulse shape. The interaction position was reconstructed in a polar coordinate system by combining the radial information, contained in the rise-time of the pulse leading edge, with the azimuthal information, obtained from the magnitude of the transient charge signals induced on the neighbouring segments. With this method, a position resolution of 3-7mm is achieved in both the radial and the azimuthal directions.

  7. Prefrontal serotonin transporter availability is positively associated with the cortisol awakening response

    DEFF Research Database (Denmark)

    Frokjaer, Vibe Gedsoe; Erritzoe, David; Holst, Klaus Kähler

    2013-01-01

    higher cortisol responses when exposed to psychosocial stressors relative to high expressing 5-HTTLPR variants. However, it is not clear how the relation between SERT and cortisol output is reflected in the adult brain. We investigated the relation between cortisol response to awakening (CAR) and SERT...... binding in brain regions considered relevant to modify the cortisol awakening response. Methods: thirty-two healthy volunteers underwent in vivo SERT imaging with [11C]DASB-Positron Emission Tomography (PET), genotyping, and performed home-sampling of saliva to assess CAR. Results: CAR, defined...... between CAR and prefrontal SERT binding as tested by an interaction analysis (genotype×CAR). Conclusion: prefrontal SERT binding is positively associated with cortisol response to awakening. We speculate that in mentally healthy individuals prefrontal serotonergic neurotransmission may exert an inhibitory...

  8. The effect of transport time, season and position on the truck on stress response in rabbits

    OpenAIRE

    Liste, M.G; María, G. A.; García-Belenguer, S.; Chacón, G.; Gazzola, P.; Villarroel, M.

    2008-01-01

    The present study analyzed the effect of transport time, season and position on the truck on physiological stress response of commercial rabbits in Aragón (Spain). A total of 156 animals were sampled in a 2x2x3 factorial design testing two transport times: short, 1 hour (1hT) and long, 7 hours (7hT), in two different seasons: hot, during summer (HT) and cold during winter (CT), and three different positions on the truck: upper, middle or lower decks in multi-floor cages on rolling stands (MFR...

  9. Understanding Positive Play: An Exploration of Playing Experiences and Responsible Gambling Practices.

    Science.gov (United States)

    Wood, Richard T A; Griffiths, Mark D

    2015-12-01

    This study is one of the first to explore in detail the behaviors, attitudes and motivations of players that show no signs of at-risk or problem gambling behavior (so-called 'positive players'). Via an online survey, 1484 positive players were compared with 209 problem players identified using the Lie/Bet screen. The study identified two distinct groups of positive players defined according to their motivations to play and their engagement with responsible gambling (RG) practices. Those positive players that played most frequently employed the most personal RG strategies. Reasons that positive players gave for gambling were focused on leisure (e.g., playing for fun, being entertained, and/or winning a prize). By contrast, problem gamblers were much more focused upon modifying mood states (e.g., excitement, relaxation, depression and playing when bored or upset). The present study also suggests that online gambling is not, by default, inherently riskier than gambling in more traditional ways, as online gambling was the most popular media by which positive players gambled. Furthermore, most positive players reported that it was easier to stick to their limits when playing the National Lottery online compared to traditional retail purchasing of tickets. Problem players were significantly more likely than positive players to gamble with family and friends, suggesting that, contrary to a popular RG message, social play may not be inherently safer than gambling alone. It is proposed that players (generally) may identify more with the term 'positive play' than the term 'RG' which is frequently interpreted as being aimed at people with gambling problems, rather than all players.

  10. Human infant faces provoke implicit positive affective responses in parents and non-parents alike.

    Science.gov (United States)

    Senese, Vincenzo Paolo; De Falco, Simona; Bornstein, Marc H; Caria, Andrea; Buffolino, Simona; Venuti, Paola

    2013-01-01

    Human infants' complete dependence on adult caregiving suggests that mechanisms associated with adult responsiveness to infant cues might be deeply embedded in the brain. Behavioural and neuroimaging research has produced converging evidence for adults' positive disposition to infant cues, but these studies have not investigated directly the valence of adults' reactions, how they are moderated by biological and social factors, and if they relate to child caregiving. This study examines implicit affective responses of 90 adults toward faces of human and non-human (cats and dogs) infants and adults. Implicit reactions were assessed with Single Category Implicit Association Tests, and reports of childrearing behaviours were assessed by the Parental Style Questionnaire. The results showed that human infant faces represent highly biologically relevant stimuli that capture attention and are implicitly associated with positive emotions. This reaction holds independent of gender and parenthood status and is associated with ideal parenting behaviors.

  11. Twice the negativity bias and half the positivity offset: Evaluative responses to emotional information in depression.

    Science.gov (United States)

    Gollan, Jackie K; Hoxha, Denada; Hunnicutt-Ferguson, Kallio; Norris, Catherine J; Rosebrock, Laina; Sankin, Lindsey; Cacioppo, John

    2016-09-01

    Humans have the dual capacity to assign a slightly pleasant valence to neutral stimuli (the positivity offset) to encourage approach behaviors, as well as to assign a higher negative valence to unpleasant images relative to the positive valence to equally arousing and extreme pleasant images (the negativity bias) to facilitate defensive strategies. We conducted an experimental psychopathology study to examine the extent to which the negativity bias and the positivity offset differ in participants with and without major depression.. Forty-one depressed and thirty-six healthy participants were evaluated using a structured clinical interview for DSM-IV Axis I disorders, questionnaires, and a computerized task designed to measure implicit affective responses to unpleasant, neutral, and pleasant stimuli. The negativity bias was significantly higher and the positivity offset was significantly lower in depressed relative to healthy participants.. Entry criteria enrolling medication-free participants with minimal DSM-IV comorbidity may limit generalizability of the findings. This study advances our understanding of the positive and negative valence systems in depression, highlighting the irregularities in the positive valence system.. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Range position and climate sensitivity: The structure of among-population demographic responses to climatic variation

    Science.gov (United States)

    Amburgey, Staci M.; Miller, David A. W.; Grant, Evan H. Campbell; Rittenhouse, Tracy A. G.; Benard, Michael F.; Richardson, Jonathan L.; Urban, Mark C.; Hughson, Ward; Brand, Adrianne B,; Davis, Christopher J.; Hardin, Carmen R.; Paton, Peter W. C.; Raithel, Christopher J.; Relyea, Rick A.; Scott, A. Floyd; Skelly, David K.; Skidds, Dennis E.; Smith, Charles K.; Werner, Earl E.

    2018-01-01

    Species’ distributions will respond to climate change based on the relationship between local demographic processes and climate and how this relationship varies based on range position. A rarely tested demographic prediction is that populations at the extremes of a species’ climate envelope (e.g., populations in areas with the highest mean annual temperature) will be most sensitive to local shifts in climate (i.e., warming). We tested this prediction using a dynamic species distribution model linking demographic rates to variation in temperature and precipitation for wood frogs (Lithobates sylvaticus) in North America. Using long-term monitoring data from 746 populations in 27 study areas, we determined how climatic variation affected population growth rates and how these relationships varied with respect to long-term climate. Some models supported the predicted pattern, with negative effects of extreme summer temperatures in hotter areas and positive effects on recruitment for summer water availability in drier areas. We also found evidence of interacting temperature and precipitation influencing population size, such as extreme heat having less of a negative effect in wetter areas. Other results were contrary to predictions, such as positive effects of summer water availability in wetter parts of the range and positive responses to winter warming especially in milder areas. In general, we found wood frogs were more sensitive to changes in temperature or temperature interacting with precipitation than to changes in precipitation alone. Our results suggest that sensitivity to changes in climate cannot be predicted simply by knowing locations within the species’ climate envelope. Many climate processes did not affect population growth rates in the predicted direction based on range position. Processes such as species-interactions, local adaptation, and interactions with the physical landscape likely affect the responses we observed. Our work highlights the

  13. Cardiovascular responses to the change from the left lateral to the upright position in pregnant hypertensives.

    Science.gov (United States)

    Dyer, R A; Anthony, J; Ledeboer, Q; James, M F

    2004-03-01

    To evaluate by non-invasive means, the autonomically mediated changes in heart rate and blood pressure in response to postural change in pregnancy. Ninety-one patients were studied, of whom 17 were non-pregnant controls, 21 were normotensive parturients, 22 had non-proteinuric hypertension, and 31 were pre-eclamptics. In all patients the heart rate and blood pressure response to the change from the left lateral to the erect position was measured non-invasively, during the third trimester in the pregnant groups. The change from the left lateral to the erect position induced significantly greater mean changes (increases) in systolic blood pressure in the normotensive pregnant (PC) women than all other groups (Pchanges when comparing the PC, NP and H groups. The PE group exhibited a significantly greater increase in heart rate on adopting the erect position than all other groups. Pre-eclamptics exhibit smaller changes in blood pressure than normotensive pregnant patients and non-proteinuric hypertensives on standing, while producing an exaggerated heart rate response, indicating altered autonomic compensatory mechanisms in these patients.

  14. Reductions in Children's Vicariously Learnt Avoidance and Heart Rate Responses Using Positive Modeling.

    Science.gov (United States)

    Reynolds, Gemma; Field, Andy P; Askew, Chris

    2016-03-23

    Recent research has indicated that vicarious learning can lead to increases in children's fear beliefs and avoidance preferences for stimuli and that these fear responses can subsequently be reversed using positive modeling (counterconditioning). The current study investigated children's vicariously acquired avoidance behavior, physiological responses (heart rate), and attentional bias for stimuli and whether these could also be reduced via counterconditioning. Ninety-six (49 boys, 47 girls) 7- to 11-year-olds received vicarious fear learning for novel stimuli and were then randomly assigned to a counterconditioning, extinction, or control group. Fear beliefs and avoidance preferences were measured pre- and post-learning, whereas avoidance behavior, heart rate, and attentional bias were all measured post-learning. Control group children showed increases in fear beliefs and avoidance preferences for animals seen in vicarious fear learning trials. In addition, significantly greater avoidance behavior, heart rate responding, and attentional bias were observed for these animals compared to a control animal. In contrast, vicariously acquired avoidance preferences of children in the counterconditioning group were significantly reduced post-positive modeling, and these children also did not show the heightened heart rate responding to fear-paired animals. Children in the extinction group demonstrated comparable responses to the control group; thus the extinction procedure showed no effect on any fear measures. The findings suggest that counterconditioning with positive modelling can be used as an effective early intervention to reduce the behavioral and physiological effects of vicarious fear learning in childhood.

  15. Infant pupil diameter changes in response to others' positive and negative emotions.

    Directory of Open Access Journals (Sweden)

    Elena Geangu

    Full Text Available It has been suggested that infants resonate emotionally to others' positive and negative affect displays, and that these responses become stronger towards emotions with negative valence around the age of 12-months. In this study we measured 6- and 12-month-old infants' changes in pupil diameter when presented with the image and sound of peers experiencing happiness, distress and an emotionally neutral state. For all participants the perception of another's distress triggered larger pupil diameters. Perceiving other's happiness also induced larger pupil diameters but for shorter time intervals. Importantly, we also found evidence for an asymmetry in autonomous arousal towards positive versus negative emotional displays. Larger pupil sizes for another's distress compared to another's happiness were recorded shortly after stimulus onset for the older infants, and in a later time window for the 6-month-olds. These findings suggest that arousal responses for negative as well as for positive emotions are present in the second half of the first postnatal year. Importantly, an asymmetry with stronger responses for negative emotions seems to be already present at this age.

  16. Linearization of Positional Response Curve of a Fiber-optic Displacement Sensor

    Science.gov (United States)

    Babaev, O. G.; Matyunin, S. A.; Paranin, V. D.

    2018-01-01

    Currently, the creation of optical measuring instruments and sensors for measuring linear displacement is one of the most relevant problems in the area of instrumentation. Fiber-optic contactless sensors based on the magneto-optical effect are of special interest. They are essentially contactless, non-electrical and have a closed optical channel not subject to contamination. The main problem of this type of sensors is the non-linearity of their positional response curve due to the hyperbolic nature of the magnetic field intensity variation induced by moving the magnetic source mounted on the controlled object relative to the sensing element. This paper discusses an algorithmic method of linearizing the positional response curve of fiber-optic displacement sensors in any selected range of the displacements to be measured. The method is divided into two stages: 1 - definition of the calibration function, 2 - measurement and linearization of the positional response curve (including its temperature stabilization). The algorithm under consideration significantly reduces the number of points of the calibration function, which is essential for the calibration of temperature dependence, due to the use of the points that randomly deviate from the grid points with uniform spacing. Subsequent interpolation of the deviating points and piecewise linear-plane approximation of the calibration function reduces the microcontroller storage capacity for storing the calibration function and the time required to process the measurement results. The paper also presents experimental results of testing real samples of fiber-optic displacement sensors.

  17. Amygdala responses to unpleasant pictures are influenced by task demands and positive affect trait.

    Science.gov (United States)

    Sanchez, Tiago A; Mocaiber, Izabela; Erthal, Fatima S; Joffily, Mateus; Volchan, Eliane; Pereira, Mirtes G; de Araujo, Draulio B; Oliveira, Leticia

    2015-01-01

    The role of attention in emotional processing is still the subject of debate. Recent studies have found that high positive affect in approach motivation narrows attention. Furthermore, the positive affect trait has been suggested as an important component for determining human variability in threat reactivity. We employed functional magnetic resonance imaging to investigate whether different states of attention control would modulate amygdala responses to highly unpleasant pictures relative to neutral and whether this modulation would be influenced by the positive affect trait. Participants (n = 22, 12 male) were scanned while viewing neutral (people) or unpleasant pictures (mutilated bodies) flanked by two peripheral bars. They were instructed to (a) judge the picture content as unpleasant or neutral or (b) to judge the difference in orientation between the bars in an easy condition (0 or 90(∘) orientation difference) or (c) in a hard condition (0 or 6(∘) orientation difference). Whole brain analysis revealed a task main effect of brain areas related to the experimental manipulation of attentional control, including the amygdala, dorsolateral prefrontal cortex, and posterior parietal cortex. Region of interest analysis showed an inverse correlation (r = -0.51, p pictures. In conclusion, the current study suggests that positive affect modulates attention effect on unpleasant pictures, therefore attenuating emotional responses.

  18. Social responsibility of business and government as the basic scientific and practical position of regional studies

    Directory of Open Access Journals (Sweden)

    Efim Mikhaylovich Kozakov

    2012-03-01

    Full Text Available This paper describes social responsibility in regional studies as a base of scientific and practical position has an interdisciplinary character and is a key in economic theory topic, referred to as «behavioral economics». The strategic aspect of social behavior should eventually become a daily norm at all levels of administration and corporate governance in all spheres of human activity. Tactical objective of regional and municipal authorities is development and implementation of research-based socially responsible policy. The level of social responsibility cannot be measured using a single universal (integral indicator. The idea that «The economics has as much science inside, as much as it has mathematics», as formulated in the XIX century, in the beginning of the XXI century should be rephrased the following way: «The economics has as much science inside, as much as it has humanity».

  19. Listening to motivational music while walking elicits more positive affective response in patients with cystic fibrosis.

    Science.gov (United States)

    Calik-Kutukcu, Ebru; Saglam, Melda; Vardar-Yagli, Naciye; Cakmak, Aslihan; Inal-Ince, Deniz; Bozdemir-Ozel, Cemile; Sonbahar-Ulu, Hazal; Arikan, Hulya; Yalcin, Ebru; Karakaya, Jale

    2016-05-01

    The purpose of this study was to investigate the effects of motivational and relaxation music on affective responses during exercise in patients with cystic fibrosis (CF). Thirty-seven patients with CF performed the 6-min walk test (6MWT) under three experimental conditions: listening to no music, relaxation music, and motivational music. 6-min distance × body weight product (6MWORK) was calculated for each trial. Patients' affective responses during exercise was evaluated with Feeling Scale (FS). The motivational qualities of music were evaluated with the Brunel Music Rating Inventory-2 (BMRI-2). 6MWORK was significantly lower while listening to relaxation music compared to 6MWORK without music (p motivational music than 6MWT with relaxation music (p motivational music can lead to positive affective response during exercise and increase the enjoyment of patients from exercises in CF. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Engaging in an experiential processing mode increases positive emotional response during recall of pleasant autobiographical memories.

    Science.gov (United States)

    Gadeikis, Darius; Bos, Nikita; Schweizer, Susanne; Murphy, Fionnuala; Dunn, Barnaby

    2017-05-01

    It is important to identify effective emotion regulation strategies to increase positive emotion experience in the general population and in clinical conditions characterized by anhedonia. There are indications that engaging in experiential processing (direct awareness of sensory and bodily experience) bolsters positive emotion experience but this has not been extensively tested during memory recall. To further test this notion, 99 community participants recalled two positive autobiographical memories. Prior to the second recall, participants either underwent an experiential, analytical, or distraction induction (n = 33 per condition). Subjective happiness and sadness ratings and heart rate variability (HRV) response were measured during each recall. Greater spontaneous use of experiential processing during the first memory was associated with greater happiness experience, but was unrelated to HRV and sadness experience. Inducing experiential processing increased happiness experience relative to both the analytical and distraction conditions (but had no impact on sadness experience). There was a significant difference in HRV between conditions. The experiential condition led to a trend-significant increase, and the other conditions a non-significant decrease, in HRV from the first to the second memory. These results suggest that engaging in experiential processing is an effective way to up-regulate positive emotion experience during positive memory recall. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Differences between negative inotropic and vasodilator effects of calcium antagonists acting on extra- and intracellular calcium movements in rat and guinea-pig cardiac preparations

    NARCIS (Netherlands)

    Hugtenburg, J. G.; Mathy, M. J.; Boddeke, H. W.; Beckeringh, J. J.; van Zwieten, P. A.

    1989-01-01

    In order to get more insight into the utilization of calcium in the mammalian heart and the influence of calcium antagonists on this process we have evaluated the negative inotropic and vasodilator effect of nifedipine, diltiazem, verapamil, bepridil and lidoflazine as well as of the intracellularly

  2. [Brazilian teenagers and beer advertising: relationship between exposure, positive response, and alcohol consumption].

    Science.gov (United States)

    Vendrame, Alan; Pinsky, Ilana; Faria, Roberta; Silva, Rebeca

    2009-02-01

    Brazilian teenagers report problematic patterns of alcohol consumption. Alcohol advertising strategies are one of the main factors influencing adolescents' alcohol consumption. The aim of this study was to evaluate the relationship between positive responses to TV beer commercials, exposure, and alcohol consumption. Thirty-two recent TV commercials were shown to 133 high school students from public schools in São Bernardo do Campo, São Paulo State, Brazil. The subjects recorded how well they liked the ads and how often they had already watched each commercial. The teenagers also reported their alcohol consumption rates. The ten commercials analyzed in this article were the five most popular and the five least popular. The analysis showed that subjects had already seen the five most popular ads, but not the five least popular. In addition, the five most popular ads received higher scores from teenagers that reported having consumed beer during the previous month. The study found a positive relationship between enjoying beer advertising and exposure to beer ads, as well as between alcohol consumption and positive responses to alcohol commercials.

  3. Inotropic and chronotropic effects of crude extract and its butanol fraction of dry fruit of aegle marmelos linn. in isolated working rat heart

    International Nuclear Information System (INIS)

    Rahman, A.U.

    2016-01-01

    The fruit of Aegle marmelos Linn. is a most edible part of the tree, ripe, unripe and dry fruit is recommended for wide variety of disorders. Lack of pharmacological evaluation limits the use to nutritional value. Dry and ripe fruit of A. marmelos was investigated as crude extract and its butanol fraction in isolated working male Wistar rat heart. Aortic out flow, coronary effluent, cardiac output, dP/dt(max), dP/dt(min), systolic and diastolic pressure, heart rate, and aortic pressure were measured. Preload and after load was kept constant. These parameters are relevant to cardiac physiology and pathological conditions. All the concentrations of crude extract caused concentration-dependent effects. The crude extract decreased coronary effluent at 100.0 and 300.0 mg/mL, increased the dP/dt(max) at 300.0 mg/mL, systolic pressure and aortic pressure were observed maximum at 100.0 mg/mL. Whereas, aortic out flow, dP/dt(min) diastolic pressure and cardiac output and heart rate remained unaffected. The butanol fraction increased the aortic outflow, dP/dt(max), aortic pressure at 10.0 and 30.0 mg/mL maximally. Whereas, dP/dt(min), diastolic pressure and cardiac output remained unaffected. Coronary effluent at 1.0, 10.0, and 30.0 mg/mL and heart rate at 10.0 and 30.0 mg/mL were decreased maximally. It seems that the bioactive compound got concentrated in butanol fraction according to polarity of the solvent. The crude extract and butanol fraction were found to be positive inotropic whereas, butanol fraction showed negative chronotropic effect as well. (author)

  4. Female song rates in response to simulated intruder are positively related to reproductive success.

    Directory of Open Access Journals (Sweden)

    Kristal E Cain

    2015-10-01

    Full Text Available Bird song is well studied in males as a sexually selected behavior. However, although song is also common among females, it is infrequently examined and poorly understood. Research suggests that song is often used as a resource defense behavior and is important in female-female competition for limited resources, e.g. mates and territories. If so, song should be positively related to fitness and related to other resource defense behaviors, but this possibility has rarely been explored. Here we examine fitness estimates in relation to spontaneous song rates and song rates in response to a simulated intruder (playback, in the superb fairy-wren (Malurus cyaneus, a cooperatively breeding songbird. We also determine how song rates relate to other territorial defense behaviors. Song rate in response to playback, but not spontaneous song rate, was positively related to nest success and the number of fledglings produced by successful females. Further, response song rate was also correlated with other territorial defense behaviors (latency to respond and flights. This evidence supports the hypothesis that female song may be used in the context of female-female competition to improve access to limited reproductive resources, and suggests that song may provide direct fitness benefits.

  5. DNA demethylases target promoter transposable elements to positively regulate stress responsive genes in Arabidopsis.

    Science.gov (United States)

    Le, Tuan-Ngoc; Schumann, Ulrike; Smith, Neil A; Tiwari, Sameer; Au, Phil Chi Khang; Zhu, Qian-Hao; Taylor, Jennifer M; Kazan, Kemal; Llewellyn, Danny J; Zhang, Ren; Dennis, Elizabeth S; Wang, Ming-Bo

    2014-09-17

    DNA demethylases regulate DNA methylation levels in eukaryotes. Arabidopsis encodes four DNA demethylases, DEMETER (DME), REPRESSOR OF SILENCING 1 (ROS1), DEMETER-LIKE 2 (DML2), and DML3. While DME is involved in maternal specific gene expression during seed development, the biological function of the remaining DNA demethylases remains unclear. We show that ROS1, DML2, and DML3 play a role in fungal disease resistance in Arabidopsis. A triple DNA demethylase mutant, rdd (ros1 dml2 dml3), shows increased susceptibility to the fungal pathogen Fusarium oxysporum. We identify 348 genes differentially expressed in rdd relative to wild type, and a significant proportion of these genes are downregulated in rdd and have functions in stress response, suggesting that DNA demethylases maintain or positively regulate the expression of stress response genes required for F. oxysporum resistance. The rdd-downregulated stress response genes are enriched for short transposable element sequences in their promoters. Many of these transposable elements and their surrounding sequences show localized DNA methylation changes in rdd, and a general reduction in CHH methylation, suggesting that RNA-directed DNA methylation (RdDM), responsible for CHH methylation, may participate in DNA demethylase-mediated regulation of stress response genes. Many of the rdd-downregulated stress response genes are downregulated in the RdDM mutants nrpd1 and nrpe1, and the RdDM mutants nrpe1 and ago4 show enhanced susceptibility to F. oxysporum infection. Our results suggest that a primary function of DNA demethylases in plants is to regulate the expression of stress response genes by targeting promoter transposable element sequences.

  6. Timing and position response of a block detector for fast neutron time-of-flight imaging

    Energy Technology Data Exchange (ETDEWEB)

    Laubach, M.A., E-mail: mlaubach@utk.edu [Department of Nuclear Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Hayward, J.P., E-mail: jhayward@utk.edu [Department of Nuclear Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Oak Ridge National Laboratory, 1 Bethel Valley Rd., Oak Ridge, TN 37831 (United States); Zhang, X., E-mail: xzhang39@utk.edu [Department of Nuclear Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Cates, J.W., E-mail: jcates7@vols.utk.edu [Department of Nuclear Engineering, University of Tennessee, Knoxville, TN 37996 (United States)

    2014-11-01

    Our research effort seeks to improve the spatial and timing performance of a block detector made of a pixilated plastic scintillator (EJ-200), first demonstrated as part of Oak Ridge National Laboratory's Advanced Portable Neutron Imaging System. Improvement of the position and time response is necessary to achieve better resolution and contrast in the images of shielded special nuclear material. Time-of-flight is used to differentiate between gamma and different sources of neutrons (e.g., transmission and fission neutrons). Factors limiting the timing and position performance of the neutron detector have been revealed through simulations and measurements. Simulations have suggested that the degradation in the ability to resolve pixels in the neutron detector is due to those interactions occurring near the light guide. The energy deposition within the neutron detector is shown to affect position performance and imaging efficiency. This examination details how energy cuts improve the position performance and degrade the imaging efficiency. Measurements have shown the neutron detector to have a timing resolution of σ=238 ps. The majority of this timing uncertainty is from the depth-of-interaction (DOI) of the neutron which is confirmed by simulations and analytical calculations.

  7. The role of storm scale, position and movement in controlling urban flood response

    Directory of Open Access Journals (Sweden)

    M.-C. ten Veldhuis

    2018-01-01

    Full Text Available The impact of spatial and temporal variability of rainfall on hydrological response remains poorly understood, in particular in urban catchments due to their strong variability in land use, a high degree of imperviousness and the presence of stormwater infrastructure. In this study, we analyze the effect of storm scale, position and movement in relation to basin scale and flow-path network structure on urban hydrological response. A catalog of 279 peak events was extracted from a high-quality observational dataset covering 15 years of flow observations and radar rainfall data for five (semiurbanized basins ranging from 7.0 to 111.1 km2 in size. Results showed that the largest peak flows in the event catalog were associated with storm core scales exceeding basin scale, for all except the largest basin. Spatial scale of flood-producing storm events in the smaller basins fell into two groups: storms of large spatial scales exceeding basin size or small, concentrated events, with storm core much smaller than basin size. For the majority of events, spatial rainfall variability was strongly smoothed by the flow-path network, increasingly so for larger basin size. Correlation analysis showed that position of the storm in relation to the flow-path network was significantly correlated with peak flow in the smallest and in the two more urbanized basins. Analysis of storm movement relative to the flow-path network showed that direction of storm movement, upstream or downstream relative to the flow-path network, had little influence on hydrological response. Slow-moving storms tend to be associated with higher peak flows and longer lag times. Unexpectedly, position of the storm relative to impervious cover within the basins had little effect on flow peaks. These findings show the importance of observation-based analysis in validating and improving our understanding of interactions between the spatial distribution of rainfall and catchment variability.

  8. The role of storm scale, position and movement in controlling urban flood response

    Science.gov (United States)

    ten Veldhuis, Marie-claire; Zhou, Zhengzheng; Yang, Long; Liu, Shuguang; Smith, James

    2018-01-01

    The impact of spatial and temporal variability of rainfall on hydrological response remains poorly understood, in particular in urban catchments due to their strong variability in land use, a high degree of imperviousness and the presence of stormwater infrastructure. In this study, we analyze the effect of storm scale, position and movement in relation to basin scale and flow-path network structure on urban hydrological response. A catalog of 279 peak events was extracted from a high-quality observational dataset covering 15 years of flow observations and radar rainfall data for five (semi)urbanized basins ranging from 7.0 to 111.1 km2 in size. Results showed that the largest peak flows in the event catalog were associated with storm core scales exceeding basin scale, for all except the largest basin. Spatial scale of flood-producing storm events in the smaller basins fell into two groups: storms of large spatial scales exceeding basin size or small, concentrated events, with storm core much smaller than basin size. For the majority of events, spatial rainfall variability was strongly smoothed by the flow-path network, increasingly so for larger basin size. Correlation analysis showed that position of the storm in relation to the flow-path network was significantly correlated with peak flow in the smallest and in the two more urbanized basins. Analysis of storm movement relative to the flow-path network showed that direction of storm movement, upstream or downstream relative to the flow-path network, had little influence on hydrological response. Slow-moving storms tend to be associated with higher peak flows and longer lag times. Unexpectedly, position of the storm relative to impervious cover within the basins had little effect on flow peaks. These findings show the importance of observation-based analysis in validating and improving our understanding of interactions between the spatial distribution of rainfall and catchment variability.

  9. The Implicit Positive and Negative Affect Test: Validity and Relationship with Cardiovascular Stress-Responses.

    Science.gov (United States)

    van der Ploeg, Melanie M; Brosschot, Jos F; Thayer, Julian F; Verkuil, Bart

    2016-01-01

    Self-report, i.e., explicit, measures of affect cannot fully explain the cardiovascular (CV) responses to stressors. Measuring affect beyond self-report, i.e., using implicit measures, could add to our understanding of stress-related CV activity. The Implicit Positive and Negative Affect Test (IPANAT) was administered in two studies to test its ecological validity and relation with CV responses and self-report measures of affect. In Study 1 students (N = 34) viewed four film clips inducing anger, happiness, fear, or no emotion, and completed the IPANAT and the Positive And Negative Affect Scale at baseline and after each clip. Implicit negative affect (INA) was higher and implicit positive affect (IPA) was lower after the anger inducing clip and vice versa after the happiness inducing clip. In Study 2 students performed a stressful math task with (n = 14) or without anger harassment (n = 15) and completed the IPANAT and a Visual Analog Scale as an explicit measure afterwards. Systolic (SBP), diastolic (DBP) blood pressure, heart rate (HR), heart rate variability (HRV), and total peripheral resistance (TPR) were recorded throughout. SBP and DBP were higher and TPR was lower in the harassment condition during the task with a prolonged effect on SBP and DBP during recovery. As expected, explicit negative affect (ENA) was higher and explicit positive affect (EPA) lower after harassment, but ENA and EPA were not related to CV activity. Although neither INA nor IPA differed between the tasks, during both tasks higher INA was related to higher SBP, lower HRV and lower TPR and to slower recovery of DBP after both tasks. Low IPA was related to slower recovery of SBP and DBP after the tasks. Implicit affect was not related to recovery of HR, HRV, and TPR. In conclusion, the IPANAT seems to respond to film clip-induced negative and positive affect and was related to CV activity during and after stressful tasks. These findings support the theory that implicitly measured affect

  10. Tilt angles and positive response of head-up tilt test in children with orthostatic intolerance.

    Science.gov (United States)

    Lin, Jing; Wang, Yuli; Ochs, Todd; Tang, Chaoshu; Du, Junbao; Jin, Hongfang

    2015-01-01

    This study aimed at examining three tilt angle-based positive responses and the time to positive response in a head-up tilt test for children with orthostatic intolerance, and the psychological fear experienced at the three angles during head-up tilt test. A total of 174 children, including 76 boys and 98 girls, aged from 4 to 18 years old (mean 11.3±2.8 years old), with unexplained syncope, were randomly divided into three groups, to undergo head-up tilt test at the angles of 60°, 70° and 80°, respectively. The diagnostic rates and times were analysed, and Wong-Baker face pain rating scale was used to access the children's psychological fear. There were no significant differences in diagnostic rates of postural orthostatic tachycardia syndrome and vasovagal syncope at different tilt angles during the head-up tilt test (p>0.05). There was a significant difference, however, in the psychological fear at different tilt angles utilising the Kruskal-Wallis test (χ2=36.398, ptest (ptest for vasovagal syncope or for postural orthostatic tachycardia syndrome. Hence, it is suggested that a tilt angle of 60° and head-up tilt test time of 45 minutes should be suitable for children with vasovagal syncope.

  11. Ideophones in Japanese modulate the P2 and late positive complex responses.

    Directory of Open Access Journals (Sweden)

    Gwilym eLockwood

    2015-07-01

    Full Text Available Sound-symbolism, or the direct link between sound and meaning, is typologically and behaviorally attested across languages. However, neuroimaging research has mostly focused on artificial non-words or individual segments, which do not represent sound-symbolism in natural language. We used EEG to compare Japanese ideophones, which are phonologically distinctive sound-symbolic lexical words, and arbitrary adverbs during a sentence reading task. Ideophones elicit a larger visual P2 response and a sustained late positive complex in comparison to arbitrary adverbs. These results and previous literature suggest that the larger P2 may indicate the integration of sound and sensory information by association in response to the distinctive phonology of ideophones. The late positive complex may reflect the facilitated lexical retrieval of ideophones in comparison to arbitrary words. This account provides new evidence that ideophones exhibit similar cross-modal correspondences to those which have been proposed for non-words and individual sounds, and that these effects are detectable in natural language.

  12. Cue-induced positive motivational implicit response in young adults with Internet gaming addiction.

    Science.gov (United States)

    Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Cheng-Sheng; Tang, Tze-Chun; Huang, Tzu-Hui; Ko, Chih-Hung

    2011-12-30

    This study evaluated the positive motivational implicit response to Internet gaming cues (i.e., screenshots of popular online games) to identify potential mechanisms of dyscontrolled Internet use in young adults with Internet gaming addiction (IGA). The final analysis included 64 young adults with IGA and 71 control subjects. The subjects completed the implicit association task to test their reaction to congruent pairing (Internet gaming screenshot paired with liked words) and incongruent pairing (Internet gaming screenshot paired with disliked words). The results demonstrated that, compared to the control group, the IGA group reacted faster to congruent pairing. It suggests that the IGA group had a positive motivational implicit response to screenshots of online games. Implicit cognition is an important mechanism of dyscontrolled substance use, such as alcohol dependence. This result suggests that implicit cognition might also be associated with dyscontrolled online gaming. The findings also demonstrate the important role of implicit cognition in dyscontrolled Internet use in young adults with IGA. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Frequency-dependence of the slow force response.

    Science.gov (United States)

    von Lewinski, Dirk; Zhu, Danan; Khafaga, Mounir; Kockskamper, Jens; Maier, Lars S; Hasenfuss, Gerd; Pieske, Burkert

    2008-05-01

    Stretch induces biphasic inotropic effects in mammalian myocardium. A delayed component (slow force response, SFR) has been demonstrated in various species, however, experimental conditions varied and the underlying mechanisms are controversial. The physiological relevance of the SFR is poorly understood. Experiments were performed in ventricular muscle strips from failing human hearts and non-failing rabbit hearts. Upon stretch, twitch force was assessed at basal conditions (1 Hz, 37 degrees C) and after changing stimulation frequency with and without blockade of the Na+/H+-exchanger-1 (NHE1) or reverse-mode Na+/Ca2+-exchange (NCX). Action potential duration (APD) was assessed using floating electrodes. Low stimulation rates (0.2 Hz) potentiated and higher stimulation rates (2 and 3 Hz) reduced the SFR. The extent of SFR inhibition by NHE1 or NCX inhibition was not affected by stimulation rate. APD decreased at 0.2 Hz but was not altered at higher stimulation rates. The data demonstrate frequency-dependence of the SFR with greater positive inotropic effects at lower stimulation rates. Subcellular mechanisms underlying the SFR are not fundamentally affected by stimulation rate. The SFR may have more pronounced physiological effects at lower heart rates.

  14. Effects of exercise position on the ventilatory responses to exercise in chronic heart failure.

    Science.gov (United States)

    Armour, W; Clark, A L; McCann, G P; Hillis, W S

    1998-09-01

    Patients with heart failure frequently complain of orthopnoea. The objective was to assess the ventilatory response of patients with chronic heart failure during erect and supine exercise. Maximal incremental exercise testing with metabolic gas exchange measurements in erect and supine positions conducted in random order. Tertiary referral centre for cardiology. Nine patients with heart failure (aged 61.9+/-6.1 years) and 10 age matched controls (63.8+/-4.6). Metabolic gas exchange measurements. The slope of the relation between ventilation and carbon dioxide production. Ratings of perceived breathlessness during exercise. Oxygen consumption (VO2) and ventilation were higher during erect exercise at each stage in each group. Peak VO2 was [mean (SD)] 17.12 ml/kg/min (4.07) erect vs 12.92 (3.61) supine in the patients (P<0.01) and 22.62 (5.03) erect-supine vs 19.16 (3.78) erect (P<0.01) in the controls. Ratings of perceived exertion were higher in the patients at each stage, but unaffected by posture. There was no difference in the slope of the relation between ventilation and carbon dioxide production between erect and supine exercise 36.39 (6.12) erect vs 38.42 (8.89) supine for patients; 30.05 (4.52) vs 28.80 (3.96) for controls. In this group of patients during exercise, there was no change in the perception of breathlessness, nor the ventilatory response to carbon dioxide production with change in posture, although peak ventilation was greater in the erect position. The sensation of breathlessness may be related to the appropriateness of the ventilatory response to exertion rather than to the absolute ventilation.

  15. Nurse-Administered, Gut-Directed Hypnotherapy in IBS: Efficacy and Factors Predicting a Positive Response.

    Science.gov (United States)

    Lövdahl, Jenny; Ringström, Gisela; Agerforz, Pia; Törnblom, Hans; Simrén, Magnus

    2015-07-01

    Hypnotherapy is an effective treatment in irritable bowel syndrome (IBS). It is often delivered by a psychotherapist and is costly and time consuming. Nurse-administered hypnotherapy could increase availability and reduce costs. In this study the authors evaluate the effectiveness of nurse-administered, gut-directed hypnotherapy and identify factors predicting treatment outcome. Eighty-five patients were included in the study. Participants received hypnotherapy by a nurse once/week for 12 weeks. Patients reported marked improvement in gastrointestinal (GI) and extra-colonic symptoms after treatment, as well as a reduction in GI-specific anxiety, general anxiety, and depression. Fifty-eight percent were responders after the 12 weeks treatment period, and of these 82% had a favorable clinical response already at week 6. Women were more likely than men to respond favorably to the treatment. Nurse-administered hypnotherapy is an effective treatment for IBS. Being female and reporting a favorable response to treatment by week 6 predicted a positive treatment response at the end of the 12 weeks treatment period.

  16. Emergency Preparedness and Response in the School Setting--The Role of the School Nurse. Position Statement

    Science.gov (United States)

    Tuck, Christine M.; Haynie, Kathey; Davis, Catherine

    2014-01-01

    It is the position of the National Association of School Nurses (NASN) that the registered professional school nurse (hereinafter referred to as school nurse) provides leadership in all phases of emergency preparedness and response. School nurses are a vital part of the school team responsible for developing emergency response procedures for the…

  17. Measuring Responsible Gambling amongst Players: Development of the Positive Play Scale.

    Science.gov (United States)

    Wood, Richard T A; Wohl, Michael J A; Tabri, Nassim; Philander, Kahlil

    2017-01-01

    The modern gambling industry has, by-in-large, assumed a duty of care to minimize the risks associated with gambling, which has manifested in responsible gambling (RG) programming (e.g., educating players about the odds of success). The current study fills a void in gambling operators, regulators, and researchers ability to measure RG beliefs and behavior in their player-base, with the development and validation of the Positive Play Scale (PPS). In Study 1, we reviewed the literature and consulted 30 players as well as 10 RG experts to help generate a definition of RG beliefs and behavior that helped guide item generation. In Study 2, regular players ( N = 1,551) of a Canadian provincial gambling operator completed a positive play survey. Four components from a principal components analysis (PCA) were extracted: Honesty and Control, Pre-commitment, Personal Responsibility, and Gambling Literacy. The PPS subscales were either not associated with gambling frequency or had small-to-moderate negative relationships with frequency of play for games most often associated with disordered gambling (e.g., electronic games). In Study 3 ( N = 413), the factor structure of the PPS was confirmed and refined in a new sample of players. Moreover, a 1-month follow-up session demonstrated that the PPS has high test-retest reliability. The PPS is the first validated scale that reliably assesses the extent to which a consumer base has positive beliefs about gambling and gambles in a positive manner. The PPS can be used by the gambling industry to objectively assess the efficacy of their RG strategy, pinpoint specific areas for future focus, as well as examine the utility of new RG initiatives that aim to promote healthy patterns of gambling consumption. Furthermore, by examining the PPS scores for different player segments (e.g., sex, age, games played) it becomes possible to tailor RG strategy to the needs of specific players. In this way, RG strategy can be optimized by focusing

  18. Recommendations to improve the positive and negative syndrome scale (PANSS) based on item response theory.

    Science.gov (United States)

    Levine, Stephen Z; Rabinowitz, Jonathan; Rizopoulos, Dimitris

    2011-08-15

    The adequacy of the Positive and Negative Syndrome Scale (PANSS) items in measuring symptom severity in schizophrenia was examined using Item Response Theory (IRT). Baseline PANSS assessments were analyzed from two multi-center clinical trials of antipsychotic medication in chronic schizophrenia (n=1872). Generally, the results showed that the PANSS (a) item ratings discriminated symptom severity best for the negative symptoms; (b) has an excess of "Severe" and "Extremely severe" rating options; and (c) assessments are more reliable at medium than very low or high levels of symptom severity. Analysis also showed that the detection of statistically and non-statistically significant differences in treatment were highly similar for the original and IRT-modified PANSS. In clinical trials of chronic schizophrenia, the PANSS appears to require the following modifications: fewer rating options, adjustment of 'Lack of judgment and insight', and improved severe symptom assessment. 2011 Elsevier Ltd. All rights reserved.

  19. Positive responses of belowground C dynamics to nitrogen enrichment in China.

    Science.gov (United States)

    Deng, Lei; Peng, Changhui; Zhu, Guangyu; Chen, Lei; Liu, Yulin; Shangguan, Zhouping

    2018-03-01

    Determining how nitrogen (N) impacts ecosystem carbon (C) cycling is critical to using C sequestration to offset anthropogenic CO 2 emissions. The N deposition rate in China is higher than the global average; however, many results of N enrichment experiments in China have not been included in global syntheses. In this study, we assembled a large dataset that comprised 124 published studies concerning N addition experiments, including 570 observations at 127 sites across China, to quantify the responses of belowground C dynamics to N enrichment in terrestrial ecosystems in China by a meta-analysis. The results showed that overall soil organic C, dissolved organic C (DOC) and soil microbial biomass C (MBC) increased by 1.8, 7.4, and 8.8%, respectively (Penrichment; belowground biomass and litter increased by 14.6 and 24.4%, respectively (Penrichment promoted C inputs into the soil mainly by increasing litter and belowground biomass inputs. Additionally, N enrichment increased C output by increasing soil respiration. Land use type and N addition level had different impacts on the soil C pool and on soil respiration. DOC, MBC, and litter exhibited more positive responses to N deposition in cooler and more arid regions than in other regions. The meta-analysis indicated that N enrichment had a positive impact on belowground C cycles in China. Climate played a greater role than did N deposition level in affecting processes of ecosystem C cycling. Moreover, belowground C cycle processes are determined by complicated interactions among land use type, N enrichment, and climate. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Rice homeobox transcription factor HOX1a positively regulates gibberellin responses by directly suppressing EL1.

    Science.gov (United States)

    Wen, Bi-Qing; Xing, Mei-Qing; Zhang, Hua; Dai, Cheng; Xue, Hong-Wei

    2011-11-01

    Homeobox transcription factors are involved in various aspects of plant development, including maintenance of the biosynthesis and signaling pathways of different hormones. However, few direct targets of homeobox proteins have been identified. We here show that overexpression of rice homeobox gene HOX1a resulted in enhanced gibberellin (GA) response, indicating a positive effect of HOX1a in GA signaling. HOX1a is induced by GA and encodes a homeobox transcription factor with transcription repression activity. In addition, HOX1a suppresses the transcription of early flowering1 (EL1), a negative regulator of GA signaling, and further electrophoretic mobility shift assay and chromatin immunoprecipitation analysis revealed that HOX1a directly bound to the promoter region of EL1 to suppress its expression and stimulate GA signaling. These results demonstrate that HOX1a functions as a positive regulator of GA signaling by suppressing EL1, providing informative hints on the study of GA signaling. © 2011 Institute of Botany, Chinese Academy of Sciences.

  1. [Connection between the evaluation of positive or negative valence and verbal responses to a lexical decision making task].

    Science.gov (United States)

    Brouillet, Thibaut; Syssau, Arielle

    2005-12-01

    Evaluation of the positive or negative valence of a stimulus is an activity that is part of any emotional experience that has been mostly studied using the affective priming paradigm. When the prime and the target have the same valence (e.g. positive prime and positive target), the target response is facilitated as a function of opposing valence conditions (e.g. negative prime and positive target). These studies show that this evaluation is automatic but depends on the nature of the task's implied response because the priming effects are only observed for positive responses, not for negative responses. This result was explained in automatic judgmental tendency model put forth by Abelson and Rosenberg (1958) and Klauer and Stern (1992). In this model, affective priming assumes there is an overlap between both responses, the first response taking precedence as a function of the prime-target valence, and the second response one that is required by the task. We are assuming that another type of response was not foreseen under this model. In fact, upon activating the valence for each of the prime-target elements, two preliminary responses would be activated before the response on the prime-target valence relationship. These responses are directly linked to the prime and target evaluation independently of the prime-target relationship. This hypothesis can be linked to the larger hypothesis whereby the evaluative process is related to two distinct motivational systems corresponding to approach and avoidance behaviour responses (Lang, Bradley, & Cuthbert, 1990; Neuman & Strack, 2000; Cacciopo, Piester & Bernston, 1993). In this study, we use the hypothesis that when a word leads to a positive valence evaluation, this favours a positive verbal response and inversely, a negative valence word favours a negative response. We are testing this hypothesis outside the affective priming paradigm to study to what extent evaluating a word, even when it is not primed, activates both

  2. History of childhood adversity is positively associated with ventral striatal dopamine responses to amphetamine.

    Science.gov (United States)

    Oswald, Lynn M; Wand, Gary S; Kuwabara, Hiroto; Wong, Dean F; Zhu, Shijun; Brasic, James R

    2014-06-01

    Childhood exposure to severe or chronic trauma is an important risk factor for the later development of adult mental health problems, such as substance abuse. Even in nonclinical samples of healthy adults, persons with a history of significant childhood adversity seem to experience greater psychological distress than those without this history. Evidence from rodent studies suggests that early life stress may impair dopamine function in ways that increase risks for drug abuse. However, the degree to which these findings translate to other species remains unclear. This study was conducted to examine associations between childhood adversity and dopamine and subjective responses to amphetamine in humans. Following intake assessment, 28 healthy male and female adults, aged 18-29 years, underwent two consecutive 90-min positron emission tomography studies with high specific activity [(11)C]raclopride. The first scan was preceded by intravenous saline; the second by amphetamine (AMPH 0.3 mg/kg). Consistent with prior literature, findings showed positive associations between childhood trauma and current levels of perceived stress. Moreover, greater number of traumatic events and higher levels of perceived stress were each associated with higher ventral striatal dopamine responses to AMPH. Findings of mediation analyses further showed that a portion of the relationship between childhood trauma and dopamine release may be mediated by perceived stress. Overall, results are consistent with preclinical findings suggesting that early trauma may lead to enhanced sensitivity to psychostimulants and that this mechanism may underlie increased vulnerability for drug abuse.

  3. Assessment of inotropic and vasodilating effects of milrinone lactate in patients with dilated cardiomyopathy and severe heart failure

    Directory of Open Access Journals (Sweden)

    Edson Antonio Bregagnollo

    1999-02-01

    Full Text Available OBJECTIVE: To assess the hemodynamic and vasodilating effects of milrinone lactate (ML in patients with dilated cardiomyopathy (DCM and New York Heart Association (NYHA class III and IV heart failure. METHODS: Twenty patients with DCM and NYHA class III and IV heart failure were studied. The hemodynamic and vasodilating effects of ML, administered intravenously, were evaluated. The following variables were compared before and during drug infusion: cardiac output (CO and cardiac index (CI; pulmonary capillary wedge pressure (PCWP; mean aortic pressure (MAP; mean pulmonary artery pressure (MPAP; mean right atrial pressure (MRAP; left ventricular systolic and end-diastolic pressures (LVSP and LVEDP, respectively; peak rate of left ventricular pressure rise (dP/dt; systemic vascular resistance (SVR; pulmonary vascular resistance (PVR; and heart rate (HR. RESULTS: All patients showed a significant improvement of the analysed parameters of cardiac performance with an increase of CO and CI; a significant improvement in myocardial contractility (dP/dt and reduction of the LVEDP; PCWP; PAP; MAP; MRAP; SVR; PVR. Were observed no significant increase in HR occurred. CONCLUSION: Milrinone lactate is an inotropic dilating drug that, when administered intravenously, has beneficial effects on cardiac performance and myocardial contractility. It also promotes reduction of SVR and PVR in patients with DCM and NYHA class III and IV of heart failure.

  4. How and When Retailers’ Sustainability Efforts Translate into Positive Consumer Responses: The Interplay Between Personal and Social Factors

    NARCIS (Netherlands)

    Hofenk, D.; Birgelen, M.J.H. van; Bloemer, J.M.M.; Semeijn, J.

    2017-01-01

    This study aims to address how (through which mechanisms) and when (under which conditions) retailers’ sustainability efforts translate into positive consumer responses. Hypotheses are developed and tested through a scenario-based experiment among 672 consumers. Retailers’ assortment sustainability

  5. Carotid blood flow distribution, haemodynamics and inotropic responses following calcitonin gene-related peptide in the pig

    NARCIS (Netherlands)

    E.M. van Gelderen (E.); X.Y. Du (Xiaoyi); R.G. Schoemaker (Regien); P.R. Saxena (Pramod Ranjan)

    1995-01-01

    textabstractThe sensory neuropeptide, calcitonin gene-related peptide (α-CGRP), has been implicated in the pathogenesis of migraine headache. The present study aimed to evaluate the effects of intracarotid infusions of human α-CGRP (10, 30 and 100 pmol/kg · min; n = 8), as compared to that of saline

  6. β-Catenin acts in a position-independent regeneration response in the simple eumetazoan Hydra.

    Science.gov (United States)

    Gufler, S; Artes, B; Bielen, H; Krainer, I; Eder, M-K; Falschlunger, J; Bollmann, A; Ostermann, T; Valovka, T; Hartl, M; Bister, K; Technau, U; Hobmayer, B

    2018-01-15

    Wnt/β-Catenin signaling plays crucial roles in regenerative processes in eumetazoans. It also acts in regeneration and axial patterning in the simple freshwater polyp Hydra, whose morphallactic regenerative capacity is unparalleled in the animal kingdom. Previous studies have identified β-catenin as an early response gene activated within the first 30min in Hydra head regeneration. Here, we have studied the role of β-Catenin in more detail. First, we show that nuclear β-Catenin signaling is required for head and foot regeneration. Loss of nuclear β-Catenin function blocks head and foot regeneration. Transgenic Hydra tissue, in which β-Catenin is over-expressed, regenerates more heads and feet. In addition, we have identified a set of putative β-Catenin target genes by transcriptional profiling, and these genes exhibit distinct expression patterns in the hypostome, in the tentacles, or in an apical gradient in the body column. All of them are transcriptionally up-regulated in the tips of early head and foot regenerates. In foot regenerates, this is a transient response, and expression starts to disappear after 12-36h. ChIP experiments using an anti-HydraTcf antibody show Tcf binding at promoters of these targets. We propose that gene regulatory β-Catenin activity in the pre-patterning phase is generally required as an early regeneration response. When regenerates are blocked with iCRT14, initial local transcriptional activation of β-catenin and the target genes occurs, and all these genes remain upregulated at the site of both head and foot regeneration for the following 2-3 days. This indicates that the initial regulatory network is followed by position-specific programs that inactivate fractions of this network in order to proceed to differentiation of head or foot structures. brachyury1 (hybra1) has previously been described as early response gene in head and foot regeneration. The HyBra1 protein, however, appears in head regenerating tips not earlier

  7. Slight hypercalcemia is not associated with positive responses in the Comet Assay in male rat liver.

    Science.gov (United States)

    Thiel, Anette; Hamel, Annie; Schaefer, Katrien; Cardoso, Renato; Beilstein, Paul

    2017-08-01

    Maintenance of physiological levels of intracellular and extracellular calcium is essential for life. Increased intracellular calcium levels are involved in cell death (apoptosis and necrosis) and are associated with positive responses in the Comet assay in vitro. In addition, high calcium and vitamin D intakes were reported to induce apoptosis in adipose tissue in obese mice and to increase DNA-migration in the Comet assay. To investigate increased serum concentration of calcium as a potential confounding factor in the regulatory Comet assay in vivo, we induced mild hypercalcemia in male Wistar rats by 3-day continuous intravenous infusion of calcium gluconate and performed the Comet assay in the liver in line with regulatory guidelines. The results of the study showed that mild increases in serum calcium concentration (up to 1.4 times above the concurrent control) and increased urinary calcium concentration (up to 27.8 times above the concurrent control) results in clinical signs like mild tremor, faster respiration rate and decreased activity in a few animals. However, under the conditions of the study, no increase in the %Tail DNA in the Comet assay and no indication of liver damage as determined by histopathological means were observed. Thus, mild increases in plasma calcium did not lead to positive results in a genotoxicity assessment by the Comet assay in the rat liver. This result is important as it confirms the reliability of this assay for regulatory evaluation of safety. Copyright © 2017 DSM Nutritional Products AG. Published by Elsevier B.V. All rights reserved.

  8. Theory and Practice of Positive Feminist Therapy: A Culturally Responsive Approach to Divorce Therapy with Chinese Women

    Science.gov (United States)

    Tzou, Jean Yuh-Jin; Kim, Eunha; Waldheim, Kim

    2012-01-01

    Positive Feminist Therapy (PFT) is a strength-based culturally responsive therapy model specifically designed for helping Chinese women facing marital conflicts and divorce, integrating Empowerment Feminist Therapy, systems theory, and positive psychology. To help clients become change agents, PFT uses clients' existing strengths to develop…

  9. cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction

    Energy Technology Data Exchange (ETDEWEB)

    Son, Jieun; Lee, Jong-Ho; Kim, Ha-Neui; Ha, Hyunil, E-mail: hyunil74@hotmail.com; Lee, Zang Hee, E-mail: zang1959@snu.ac.kr

    2010-07-23

    Research highlights: {yields} CREB is highly expressed in advanced breast cancer cells. {yields} Tumor-related factors such as TGF-{beta} further elevate CREB expression. {yields} CREB upregulation stimulates metastatic potential of breast cancer cells. {yields} CREB signaling is required for breast cancer-induced bone destruction. -- Abstract: cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cells and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-{beta}. Using wild-type CREB and a dominant-negative form (K-CREB), we found that CREB signaling positively regulated the proliferation, migration, and invasion of MDA-MB-231 cells. In addition, K-CREB prevented MDA-MB-231 cell-induced osteolytic lesions in a mouse model of cancer metastasis. Furthermore, CREB signaling in cancer cells regulated the gene expression of PTHrP, MMPs, and OPG, which are closely involved in cancer metastasis and bone destruction. These results indicate that breast cancer cells acquire CREB overexpression during their development and that this CREB upregulation plays an important role in multiple steps of breast cancer bone metastasis.

  10. The processing of unexpected positive response outcomes in the mediofrontal cortex.

    Science.gov (United States)

    Ferdinand, Nicola K; Mecklinger, Axel; Kray, Jutta; Gehring, William J

    2012-08-29

    The human mediofrontal cortex, especially the anterior cingulate cortex, is commonly assumed to contribute to higher cognitive functions like performance monitoring. How exactly this is achieved is currently the subject of lively debate but there is evidence that an event's valence and its expectancy play important roles. One prominent theory, the reinforcement learning theory by Holroyd and colleagues (2002, 2008), assigns a special role to feedback valence, while the prediction of response-outcome (PRO) model by Alexander and Brown (2010, 2011) claims that the mediofrontal cortex is sensitive to unexpected events regardless of their valence. However, paradigms examining this issue have included confounds that fail to separate valence and expectancy. In the present study, we tested the two competing theories of performance monitoring by using an experimental task that separates valence and unexpectedness of performance feedback. The feedback-related negativity of the event-related potential, which is commonly assumed to be a reflection of mediofrontal cortex activity, was elicited not only by unexpected negative feedback, but also by unexpected positive feedback. This implies that the mediofrontal cortex is sensitive to the unexpectedness of events in general rather than their valence and by this supports the PRO model.

  11. Positive response of a recurrent keloid scar to topical methyl aminolevulinate-photodynamic therapy.

    Science.gov (United States)

    Nie, Zhuxiang; Bayat, Ardeshir; Behzad, Farhad; Rhodes, Lesley E

    2010-12-01

    A 36-year-old Caucasian female of Iranian origin presented with a persistently raised dermal lesion under her chin, confirmed histologically to be a keloid scar. There was a 4-year history of a negative response to a range of conventional treatments including topical silicone gel sheets, steroid creams, steroid injections and surgical excision. In view of treatment failure and an in vitro study indicating a positive effect of photodynamic therapy (PDT)on keloid fibroblasts, we treated our patient's lesion with five sessions of methyl aminolevulinate photodynamic therapy (MAL-PDT) over a period of 5 months. Following this treatment regime, her keloid scar had considerably reduced in size and become flattened.The surface of the keloid also became smooth, with attenuation in erythema at the margin as well as an improvement in the colour of the scar, which was better matched to the surrounding skin. There was no recurrence at 1-year follow-up and this treatment resulted in an overall acceptable cosmetic outcome. This case report presents PDT as a potential treatment option for persistent keloid lesions unresponsive to conventional scar modulation therapies and suggests a need for further research in this area.

  12. Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality.

    Science.gov (United States)

    Tarvasmäki, Tuukka; Lassus, Johan; Varpula, Marjut; Sionis, Alessandro; Sund, Reijo; Køber, Lars; Spinar, Jindrich; Parissis, John; Banaszewski, Marek; Silva Cardoso, Jose; Carubelli, Valentina; Di Somma, Salvatore; Mebazaa, Alexandre; Harjola, Veli-Pekka

    2016-07-04

    Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS. The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling. Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined

  13. Existence, Multiplicity, and Stability of Positive Solutions of a Predator-Prey Model with Dinosaur Functional Response

    Directory of Open Access Journals (Sweden)

    Xiaozhou Feng

    2017-01-01

    Full Text Available We investigate the property of positive solutions of a predator-prey model with Dinosaur functional response under Dirichlet boundary conditions. Firstly, using the comparison principle and fixed point index theory, the sufficient conditions and necessary conditions on coexistence of positive solutions of a predator-prey model with Dinosaur functional response are established. Secondly, by virtue of bifurcation theory, perturbation theory of eigenvalues, and the fixed point index theory, we establish the bifurcation of positive solutions of the model and obtain the stability and multiplicity of the positive solution under certain conditions. Furthermore, the local uniqueness result is studied when b and d are small enough. Finally, we investigate the multiplicity, uniqueness, and stability of positive solutions when k>0 is sufficiently large.

  14. [The relationship of empathic-affective responses toward others' positive affect with prosocial behaviors and aggressive behaviors].

    Science.gov (United States)

    Sakurai, Shigeo; Hayama, Daichi; Suzuki, Takashi; Kurazumi, Tomoe; Hagiwara, Toshihiko; Suzuki, Miyuki; Ohuchi, Akiko; Chizuko, Oikawa

    2011-06-01

    The purposes of this study were to develop and validate the Empathic-Affective Response Scale, and to examine the relationship of empathic-affective responses with prosocial behaviors and aggressive behaviors. Undergraduate students (N = 443) participated in a questionnaire study. The results of factor analysis indicated that empathic-affective responses involved three factors: (a) sharing and good feeling toward others' positive affect, (b) sharing of negative affect and (c) sympathy toward others' negative affect. Correlations with other empathy-related scales and internal consistency suggested that this scale has satisfactory validity and reliability. Cluster analysis revealed that participants were clustered into four groups: high-empathic group, low-empathic group, insufficient positive affective response group and insufficient negative affective response group. Additional analysis showed the frequency of prosocial behaviors in high-empathic group was highest in all groups. On the other hand, the frequency of aggressive behaviors in both insufficient positive affective response group and low-empathic group were higher than others' groups. The results indicated that empathic-affective responses toward positive affect are also very important to predict prosocial behaviors and aggressive behaviors.

  15. C'mon get happy: reduced magnitude and duration of response during a positive-affect induction in depression.

    Science.gov (United States)

    Horner, Michelle S; Siegle, Greg J; Schwartz, Robert M; Price, Rebecca B; Haggerty, Agnes E; Collier, Amanda; Friedman, Edward S

    2014-11-01

    Depression involves decreased positive affect. Whether this is due to a failure to achieve or maintain positive emotion in response to discrete stimuli is unclear. Understanding the nature of decreased positive affect could help to address how to intervene in the phenomenon, for example, how to structure interventions using positive and rewarding stimuli in depression. Thus, we examined the time course of affect following exposure to positive stimuli in depressed and healthy individuals. Seventy-one adults with major depressive disorder and thirty-four never-depressed controls read a self-generated highly positive script and continuously rated their affect for 7 min. Both groups quickly achieved increased positive affect, however, compared to controls, depressed participants did not achieve the same level of positive affect, did not maintain their positive affect, spent less time rating their affect as happy, and demonstrated larger drops in mood. These data indicate that depressed and nondepressed individuals can generate positive reactions to happy scripts, but depressed individuals cannot achieve or sustain equivalent levels of positive affect. Interventions for depression might fruitfully focus on increasing depressed individuals' ability to maintain initial engagement with positive stimuli over a sustained period of time. © 2014 Wiley Periodicals, Inc.

  16. Responses to positive affect, life satisfaction and self-esteem: A cross-lagged panel analysis during middle adolescence.

    Science.gov (United States)

    Gomez-Baya, Diego; Mendoza, Ramon; Gaspar, Tania; Gomes, Paulo

    2018-05-11

    During middle adolescence, elevated stress and a greater presence of psychological disorders have been documented. The research has paid little attention to the regulation of positive affective states. Fredrickson's broaden-and-build theory suggests that cultivating positive emotions helps to build resources that boost well-being. The current research aimed to examine the longitudinal associations between responses to positive affect (emotion-focused positive rumination, self-focused positive rumination, and dampening) and psychological adjustment (self-esteem and life satisfaction) during middle adolescence. A longitudinal study with two waves separated by one year was conducted, assessing 977 adolescents (M = 13.81, SD = 0.79; 51.5% boys) with self-report measures. A cross-lagged panel analysis was performed by including within the same model the relationships between all of the variables in the two assessment points. The results indicated cross-lagged positive relationships of self-focused positive rumination with both self-esteem and life satisfaction, while dampening showed a negative cross-lagged relationship with self-esteem. Moreover, higher self-esteem predicted more emotion-focused positive rumination, and more dampening predicted lower life satisfaction. Thus, the use of adaptive responses to positive affect and a better psychological adjustment were found to be prospectively interrelated at the one-year follow-up during middle adolescence. The discussion argues for the need to implement programmes to promote more adaptive responses to positive affect to enhance psychological adjustment in the adolescent transition to adulthood. © 2018 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  17. Is the lateral jack-knife position responsible for cases of transient neurapraxia?

    Science.gov (United States)

    Molinares, Diana Margarita; Davis, Timothy T; Fung, Daniel A; Liu, John Chung-Liang; Clark, Stephen; Daily, David; Mok, James M

    2016-01-01

    The lateral jack-knife position is often used during transpsoas surgery to improve access to the spine. Postoperative neurological signs and symptoms are very common after such procedures, and the mechanism is not adequately understood. The objective of this study is to assess if the lateral jack-knife position alone can cause neurapraxia. This study compares neurological status at baseline and after positioning in the 25° right lateral jack-knife (RLJK) and the right lateral decubitus (RLD) position. Fifty healthy volunteers, ages 21 to 35, were randomly assigned to one of 2 groups: Group A (RLD) and Group B (RLJK). Motor and sensory testing was performed prior to positioning. Subjects were placed in the RLD or RLJK position, according to group assignment, for 60 minutes. Motor testing was performed immediately after this 60-minute period and again 60 minutes thereafter. Sensory testing was performed immediately after the 60-minute period and every 15 minutes thereafter, for a total of 5 times. Motor testing was performed by a physical therapist who was blinded to group assignment. A follow-up call was made 7 days after the positioning sessions. Motor deficits were observed in the nondependent lower limb in 100% of the subjects in Group B, and no motor deficits were seen in Group A. Statistically significant differences (p knife positioning for 60 minutes results in neurapraxia of the nondependent lower extremity. Our results support the hypothesis that jack-knife positioning alone can cause postoperative neurological symptoms.

  18. Primary immunization-like response without hepatitis following transfusion of HBeAg-positive blood

    DEFF Research Database (Denmark)

    Gluud, C; Aldershvile, J; Kryger, P

    1983-01-01

    An accidental transfusion of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive whole blood was given to a 19-yr-old male, bleeding after tonsillectomy. Serum obtained from the patient before the transfusion revealed no hepatitis B antigens or antibodies. After...... the transfusion the patient became HBsAg-positive, cleared this antigen and developed antibodies to both HBsAg and HBeAg. The transfusion blood was positive for total antibody and IgM antibody to hepatitis B core antigen (HBcAg). The patient's blood became positive for these antibodies after the transfusion...

  19. Nasal Oxytocin Treatment Biases Dogs’ Visual Attention and Emotional Response toward Positive Human Facial Expressions

    Directory of Open Access Journals (Sweden)

    Sanni Somppi

    2017-10-01

    Full Text Available The neuropeptide oxytocin plays a critical role in social behavior and emotion regulation in mammals. The aim of this study was to explore how nasal oxytocin administration affects gazing behavior during emotional perception in domestic dogs. Looking patterns of dogs, as a measure of voluntary attention, were recorded during the viewing of human facial expression photographs. The pupil diameters of dogs were also measured as a physiological index of emotional arousal. In a placebo-controlled within-subjects experimental design, 43 dogs, after having received either oxytocin or placebo (saline nasal spray treatment, were presented with pictures of unfamiliar male human faces displaying either a happy or an angry expression. We found that, depending on the facial expression, the dogs’ gaze patterns were affected selectively by oxytocin treatment. After receiving oxytocin, dogs fixated less often on the eye regions of angry faces and revisited (glanced back at more often the eye regions of smiling (happy faces than after the placebo treatment. Furthermore, following the oxytocin treatment dogs fixated and revisited the eyes of happy faces significantly more often than the eyes of angry faces. The analysis of dogs’ pupil diameters during viewing of human facial expressions indicated that oxytocin may also have a modulatory effect on dogs’ emotional arousal. While subjects’ pupil sizes were significantly larger when viewing angry faces than happy faces in the control (placebo treatment condition, oxytocin treatment not only eliminated this effect but caused an opposite pupil response. Overall, these findings suggest that nasal oxytocin administration selectively changes the allocation of attention and emotional arousal in domestic dogs. Oxytocin has the potential to decrease vigilance toward threatening social stimuli and increase the salience of positive social stimuli thus making eye gaze of friendly human faces more salient for dogs. Our

  20. Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy.

    Science.gov (United States)

    Tietze, Julia K; Angelova, Daniela; Heppt, Markus V; Ruzicka, Thomas; Berking, Carola

    2017-07-01

    The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T-cell populations has been studied extensively, but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56 dim and CD56 bright NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry. In 15 (47%) patients, an abnormal low amount of NK cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for CD56 dim NK cells, whereas the baseline levels of CD56 bright NK cells were either normal or abnormally high. The relative and absolute amounts of NK cells and of CD56 dim and CD56 bright NK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD56 dim NK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD56 bright NK cells was unaffected by treatment. The baseline levels of NK cells were correlated with the number of metastatic organs. Their proportion increased, whereas the expression of NKG2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of NK cells and CD56 dim NK cells as well as normal baseline levels of CD56 bright NK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of CD56 dim NK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD56 bright NK cells were significantly correlated with longer survival as compared to patients with high baseline levels. In conclusion, analysis of the amounts of total NK cells

  1. Addressing False Positives in Early Reading Assessment Using Intervention Response Data

    Science.gov (United States)

    McAlenney, Athena Lentini; Coyne, Michael D.

    2015-01-01

    The current study examined a solution to high false positive reading risk classification rates in early kindergarten by investigating a method of identifying students with possible false positive risk classifications and returning them to general classroom instruction. Researchers assessed kindergarten students (N = 105) identified as at risk who…

  2. Counterbalancing Regulation in Response Memory of a Positively Autoregulated Two-Component System.

    Science.gov (United States)

    Gao, Rong; Godfrey, Katherine A; Sufian, Mahir A; Stock, Ann M

    2017-09-15

    Fluctuations in nutrient availability often result in recurrent exposures to the same stimulus conditions. The ability to memorize the past event and use the "memory" to make adjustments to current behaviors can lead to a more efficient adaptation to the recurring stimulus. A short-term phenotypic memory can be conferred via carryover of the response proteins to facilitate the recurrent response, but the additional accumulation of response proteins can lead to a deviation from response homeostasis. We used the Escherichia coli PhoB/PhoR two-component system (TCS) as a model system to study how cells cope with the recurrence of environmental phosphate (Pi) starvation conditions. We discovered that "memory" of prior Pi starvation can exert distinct effects through two regulatory pathways, the TCS signaling pathway and the stress response pathway. Although carryover of TCS proteins can lead to higher initial levels of transcription factor PhoB and a faster initial response in prestarved cells than in cells not starved, the response enhancement can be overcome by an earlier and greater repression of promoter activity in prestarved cells due to the memory of the stress response. The repression counterbalances the carryover of the response proteins, leading to a homeostatic response whether or not cells are prestimulated. A computational model based on sigma factor competition was developed to understand the memory of stress response and to predict the homeostasis of other PhoB-regulated response proteins. Our insight into the history-dependent PhoBR response may provide a general understanding of how TCSs respond to recurring stimuli and adapt to fluctuating environmental conditions. IMPORTANCE Bacterial cells in their natural environments experience scenarios that are far more complex than are typically replicated in laboratory experiments. The architectures of signaling systems and the integration of multiple adaptive pathways have evolved to deal with such complexity

  3. Counterbalancing Regulation in Response Memory of a Positively Autoregulated Two-Component System

    Science.gov (United States)

    Gao, Rong; Godfrey, Katherine A.; Sufian, Mahir A.

    2017-01-01

    ABSTRACT Fluctuations in nutrient availability often result in recurrent exposures to the same stimulus conditions. The ability to memorize the past event and use the “memory” to make adjustments to current behaviors can lead to a more efficient adaptation to the recurring stimulus. A short-term phenotypic memory can be conferred via carryover of the response proteins to facilitate the recurrent response, but the additional accumulation of response proteins can lead to a deviation from response homeostasis. We used the Escherichia coli PhoB/PhoR two-component system (TCS) as a model system to study how cells cope with the recurrence of environmental phosphate (Pi) starvation conditions. We discovered that “memory” of prior Pi starvation can exert distinct effects through two regulatory pathways, the TCS signaling pathway and the stress response pathway. Although carryover of TCS proteins can lead to higher initial levels of transcription factor PhoB and a faster initial response in prestarved cells than in cells not starved, the response enhancement can be overcome by an earlier and greater repression of promoter activity in prestarved cells due to the memory of the stress response. The repression counterbalances the carryover of the response proteins, leading to a homeostatic response whether or not cells are prestimulated. A computational model based on sigma factor competition was developed to understand the memory of stress response and to predict the homeostasis of other PhoB-regulated response proteins. Our insight into the history-dependent PhoBR response may provide a general understanding of how TCSs respond to recurring stimuli and adapt to fluctuating environmental conditions. IMPORTANCE Bacterial cells in their natural environments experience scenarios that are far more complex than are typically replicated in laboratory experiments. The architectures of signaling systems and the integration of multiple adaptive pathways have evolved to deal

  4. Patients' Positive and Negative Responses to Reading Mental Health Clinical Notes Online.

    Science.gov (United States)

    Denneson, Lauren M; Chen, Jason I; Pisciotta, Maura; Tuepker, Anais; Dobscha, Steven K

    2018-05-01

    This study describes responses to OpenNotes, clinical notes available online, among patients receiving mental health care and explores whether responses vary by patient demographic or clinical characteristics. Survey data from 178 veterans receiving mental health treatment at a large Veterans Affairs medical center included patient-reported health self-efficacy, health knowledge, alliance with clinicians, and negative emotional responses after reading OpenNotes. Health care data were extracted from the patient care database. Reading OpenNotes helped many participants feel in control of their health care (49%) and have more trust in clinicians (45%), although a few (8%) frequently felt upset after reading their notes. In multivariate models, posttraumatic stress disorder was associated with increased patient-clinician alliance (p=.046) but also with negative emotional responses (p<.01). Patients receiving mental health care frequently reported benefits from reading OpenNotes, yet some experienced negative responses.

  5. Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals.

    Science.gov (United States)

    Massari, V J; Dickerson, L W; Gray, A L; Lauenstein, J M; Blinder, K J; Newsome, J T; Rodak, D J; Fleming, T J; Gatti, P J; Gillis, R A

    1998-08-17

    Recent physiological evidence indicates that vagal postganglionic control of left ventricular contractility is mediated by neurons found in a ventricular epicardial fat pad ganglion. In the dog this region has been referred to as the cranial medial ventricular (CMV) ganglion [J.L. Ardell, Structure and function of mammalian intrinsic cardiac neurons, in: J.A. Armour, J.L. Ardell (Eds.). Neurocardiology, Oxford Univ. Press, New York, 1994, pp. 95-114; B.X. Yuan, J.L. Ardell, D.A. Hopkins, A.M. Losier, J.A. Armour, Gross and microscopic anatomy of the canine intrinsic cardiac nervous system, Anat. Rec., 239 (1994) 75-87]. Since activation of the vagal neuronal input to the CMV ganglion reduces left ventricular contractility without influencing cardiac rate or AV conduction, this ganglion contains a functionally selective pool of negative inotropic parasympathetic postganglionic neurons. In the present report we have defined the light microscopic distribution of preganglionic negative inotropic neurons in the CNS which are retrogradely labeled from the CMV ganglion. Some tissues were also processed for the simultaneous immunocytochemical visualization of tyrosine hydroxylase (TH: a marker for catecholaminergic neurons) and examined with both light microscopic and electron microscopic methods. Histochemically visualized neurons were observed in a long slender column in the ventrolateral nucleus ambiguus (NA-VL). The greatest number of retrogradely labeled neurons were observed just rostral to the level of the area postrema. TH perikarya and dendrites were commonly observed interspersed with vagal motoneurons in the NA-VL. TH nerve terminals formed axo-dendritic synapses upon negative inotropic vagal motoneurons, however the origin of these terminals remains to be determined. We conclude that synaptic interactions exist which would permit the parasympathetic preganglionic vagal control of left ventricular contractility to be modulated monosynaptically by

  6. Transforming the Structure of the Military: Combat Decisions -- Rank, Responsibility, or Frontline Position?

    National Research Council Canada - National Science Library

    West, Bing

    2007-01-01

    ...-centric operations allow commanders to operate effectively from the front lines. Many have assumed that new information technologies lift the fog of war and therefore allow commanders to operate with clear vision from rear positions...

  7. Differential Effects of Positive versus Negative Self-Involving Counselor Responses.

    Science.gov (United States)

    Remer, Pam; And Others

    1983-01-01

    Investigated the effects of positive and negative counselor disclosure using typescripts of hypothetical counseling interviews. Results indicated impact of condition was mixed, with each having some desirable effects. (PAS)

  8. Biomarkers of Environmental Enteropathy are Positively Associated with Immune Responses to an Oral Cholera Vaccine in Bangladeshi Children.

    Directory of Open Access Journals (Sweden)

    Muhammad Ikhtear Uddin

    2016-11-01

    Full Text Available Environmental enteropathy (EE is a poorly understood condition that refers to chronic alterations in intestinal permeability, absorption, and inflammation, which mainly affects young children in resource-limited settings. Recently, EE has been linked to suboptimal oral vaccine responses in children, although immunological mechanisms are poorly defined. The objective of this study was to determine host factors associated with immune responses to an oral cholera vaccine (OCV. We measured antibody and memory T cell immune responses to cholera antigens, micronutrient markers in blood, and EE markers in blood and stool from 40 Bangladeshi children aged 3-14 years who received two doses of OCV given 14 days apart. EE markers included stool myeloperoxidase (MPO and alpha anti-trypsin (AAT, and plasma endotoxin core antibody (EndoCab, intestinal fatty acid binding protein (i-FABP, and soluble CD14 (sCD14. We used multiple linear regression analysis with LASSO regularization to identify host factors, including EE markers, micronutrient (nutritional status, age, and HAZ score, predictive for each response of interest. We found stool MPO to be positively associated with IgG antibody responses to the B subunit of cholera toxin (P = 0.03 and IgA responses to LPS (P = 0.02; plasma sCD14 to be positively associated with LPS IgG responses (P = 0.07; plasma i-FABP to be positively associated with LPS IgG responses (P = 0.01 and with memory T cell responses specific to cholera toxin (P = 0.01; stool AAT to be negatively associated with IL-10 (regulatory T cell responses specific to cholera toxin (P = 0.02, and plasma EndoCab to be negatively associated with cholera toxin-specific memory T cell responses (P = 0.02. In summary, in a cohort of children 3-14 years old, we demonstrated that the majority of biomarkers of environmental enteropathy were positively associated with immune responses after vaccination with an OCV.

  9. When compliments fail to flatter: American individualism and responses to positive stereotypes.

    Science.gov (United States)

    Siy, John Oliver; Cheryan, Sapna

    2013-01-01

    Five studies show that being the target of a positive stereotype is a negative interpersonal experience for those from individualistic cultures because positive stereotypes interfere with their desire to be seen as individuals separate from their groups. U.S.-born Asian Americans and women who heard a positive stereotype about their group in an intergroup interaction (e.g., "Asians are good at math," "women are nurturing") derogated their partner and experienced greater negative emotions than those who heard no stereotype. Negative reactions were mediated by a sense of being depersonalized, or "lumped together" with others in one's group, by the positive stereotype (Studies 1-3). Cross-cultural differences (Study 4) and an experimental manipulation of cultural self-construal (Study 5) demonstrated that those with an independent self-construal reacted more negatively to positive stereotypes than those with an interdependent self-construal. By bringing together research on stereotypes from the target's perspective with research on culture, this work demonstrates how cultural self-construals inform the way people interpret and respond to being the target of positive stereotypes.

  10. Human amygdala response to dynamic facial expressions of positive and negative surprise.

    Science.gov (United States)

    Vrticka, Pascal; Lordier, Lara; Bediou, Benoît; Sander, David

    2014-02-01

    Although brain imaging evidence accumulates to suggest that the amygdala plays a key role in the processing of novel stimuli, only little is known about its role in processing expressed novelty conveyed by surprised faces, and even less about possible interactive encoding of novelty and valence. Those investigations that have already probed human amygdala involvement in the processing of surprised facial expressions either used static pictures displaying negative surprise (as contained in fear) or "neutral" surprise, and manipulated valence by contextually priming or subjectively associating static surprise with either negative or positive information. Therefore, it still remains unresolved how the human amygdala differentially processes dynamic surprised facial expressions displaying either positive or negative surprise. Here, we created new artificial dynamic 3-dimensional facial expressions conveying surprise with an intrinsic positive (wonderment) or negative (fear) connotation, but also intrinsic positive (joy) or negative (anxiety) emotions not containing any surprise, in addition to neutral facial displays either containing ("typical surprise" expression) or not containing ("neutral") surprise. Results showed heightened amygdala activity to faces containing positive (vs. negative) surprise, which may either correspond to a specific wonderment effect as such, or to the computation of a negative expected value prediction error. Findings are discussed in the light of data obtained from a closely matched nonsocial lottery task, which revealed overlapping activity within the left amygdala to unexpected positive outcomes. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  11. Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T

    NARCIS (Netherlands)

    Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; Van der Zwaag, W.

    External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and

  12. Frequency response variation of two offshore wind park transformers with different tap changer positions

    DEFF Research Database (Denmark)

    Arana Aristi, Iván; Holbøll, Joachim; Sørensen, T

    2010-01-01

    This paper presents the results of several sweep frequency response analysis (SFRA) measurements performed on two identical offshore wind farm transformers. A comparison is made between the transformers based on different recommended measurements and procedures, different measurement systems...

  13. Dual channel photoplethysmography studies of cardio-vascular response to the body position changes

    Science.gov (United States)

    Erts, R.; Kukulis, I.; Spigulis, J.; Kere, L.

    2005-08-01

    The dual-channel photoplethysmography studies of physiological responses during 3-stage orthostatic test were performed. Clear differences in heartbeat rate, pulse wave transit time and blood pressure variations of healthy volunteers and diabetic patients have been observed.

  14. Attachment style impacts behavior and early oculomotor response to positive, but not negative, pictures.

    Science.gov (United States)

    Silva, Catarina; Chaminade, Thierry; David, Da Fonseca; Santos, Andreia; Esteves, Francisco; Soares, Isabel; Deruelle, Christine

    2015-06-01

    The present study investigated whether oculomotor behavior is influenced by attachment styles. The Relationship Scales Questionnaire was used to assess attachment styles of forty-eight voluntary university students and to classify them into attachment groups (secure, preoccupied, fearful, and dismissing). Eye-tracking was recorded while participants engaged in a 3-seconds free visual exploration of stimuli presenting either a positive or a negative picture together with a neutral picture, all depicting social interactions. The task consisted in identifying whether the two pictures depicted the same emotion. Results showed that the processing of negative pictures was impermeable to attachment style, while the processing of positive pictures was significantly influenced by individual differences in insecure attachment. The groups highly avoidant regarding to attachment (dismissing and fearful) showed reduced accuracy, suggesting a higher threshold for recognizing positive emotions compared to the secure group. The groups with higher attachment anxiety (preoccupied and fearful) showed differences in automatic capture of attention, in particular an increased delay preceding the first fixation to a picture of positive emotional valence. Despite lenient statistical thresholds induced by the limited sample size of some groups (p < 0.05 uncorrected for multiple comparisons), the current findings suggest that the processing of positive emotions is affected by attachment styles. These results are discussed within a broader evolutionary framework. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  15. Comparison of Tuberculin Skin Test result and interferon gamma response to human PPD in BCG scar positive and negative children.

    Science.gov (United States)

    Sayyahfar, Shirin; Karimi, Abdollah; Fahimzad, Alireza; Shamshiri, Ahmad Reza

    2014-03-01

    The aim of this study is to compare Tuberculin Skin Test (TST) result and interferon gamma response to human PPD (purified protein derivative), in scar positive and scar negative BCG-vaccinated children. Between August 2007 and May 2008 a total of 236 children aged 1-168 months (mean 21 months) admitted to Mofid Children's Hospital, Tehran, Iran, were enrolled in a cross-sectional study. Each patient was examined for BCG vaccine scar and tested with TST and human PPD-based Interferon Gamma Release Assay (IGRA). Two hundred and twenty one cases out of 236 (44% female, 1-168 months, mean age 21 months) were scar positive of whom 95% TST result was negative. Human PPD-based IGRA was positive in 110 (49.8%), negative in 85 (38.4 %) and indeterminate in 26 (11.8%) of scar positive patients. Fifteen children (40% female, 1-156 months; mean age 42 months) were scar negative. All the scar negative cases were TST negative. Human PPD-based IGRA was positive in 10 (66.7%), negative in 4 (26.7%) and indeterminate in 1 (6.7%) of scar negative patients. Immune responsiveness to human PPD antigens in scar positive and negative children may not correspond with results of the Tuberculin Skin Test. Copyright © 2013 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  16. Simulation of Transient Response of Ir-TES for Position-Sensitive TES with Waveform Domain Multiplexing

    Science.gov (United States)

    Minamikawa, Y.; Sato, H.; Mori, F.; Damayanthi, R. M. T.; Takahashi, H.; Ohno, M.

    2008-04-01

    We are developing a new x-ray microcalorimeter based on a superconducting transition edge sensor (TES) as an imaging sensor. Our measurement shows unique waveforms which we consider as an expression of thermal nonuniformity of TES films. This arises from the different thermal responses, so that response signal shapes would vary according to the position of the incident x-ray. This position dependency deteriorate the measured energy resolution, but with appropriate waveform analysis, this would be useful for imaging device. For more inspection, we have developed a simulation code which enables a dynamic simulation to obtain a transient response of the TES by finite differential method. Temperature and electric current distributions are calculated. As a result, we successfully obtained waveform signals. The calculated signal waveforms have similar characteristics to the measured signals. This simulation visualized the transition state of the device and will help to design better detector.

  17. What a Difference a Label Makes: Positioning and Response in an Afterschool Tutoring Program

    Science.gov (United States)

    McCloskey, Erin; Cann, Colette N.

    2013-01-01

    In this qualitative case study, we used the framework of positioning to show how college-age tutors and their middle school tutees interact in an afterschool tutoring setting with regard to ability. The authors show how educational tracking and understandings of disability permeated tutoring spaces and influence tutors' instructional decisions.…

  18. Mechanically Evoked Torque and Electromyographic Responses During Passive Elbow Extension in Upper Limb Tension Test Position

    Science.gov (United States)

    2001-10-25

    axis during passive elbow extension. A padded shoulder block was placed superior to the subject’s acromioclavicular joint to stabilize the shoulder...girdle position. A pressure sensor was used between the padded shoulder block and the acromioclavicular joint to monitor and standardize the pressure

  19. Externalizing shame responses in children: The role of fragile positive self-esteem

    NARCIS (Netherlands)

    Thomaes, Sander

    2007-01-01

    When faced with shame, children can either respond in submissive ways to withdraw from their environment or in externalizing ways to oppose their environment. This study tested the hypothesis that fragile-positive views of self predispose children to respond in externalizing ways to shame

  20. Externalizing shame responses in children: The role of fragile-positive self-esteem

    NARCIS (Netherlands)

    Thomaes, S.; Stegge, G.T.M.; Olthof, T.

    2007-01-01

    When faced with shame, children can either respond in submissive ways to withdraw from their environment or in externalizing ways to oppose their environment. This study tested the hypothesis that fragile-positive views of self predispose children to respond in externalizing ways to shame

  1. Low Estrogen Receptor (ER)-Positive Breast Cancer and Neoadjuvant Systemic Chemotherapy: Is Response Similar to Typical ER-Positive or ER-Negative Disease?

    Science.gov (United States)

    Landmann, Alessandra; Farrugia, Daniel J; Zhu, Li; Diego, Emilia J; Johnson, Ronald R; Soran, Atilla; Dabbs, David J; Clark, Beth Z; Puhalla, Shannon L; Jankowitz, Rachel C; Brufsky, Adam M; Ahrendt, Gretchen M; McAuliffe, Priscilla F; Bhargava, Rohit

    2018-05-08

    Pathologic complete response (pCR) rate after neoadjuvant chemotherapy was compared between 141 estrogen receptor (ER)-negative (43%), 41 low ER+ (13%), 47 moderate ER+ (14%), and 98 high ER+ (30%) tumors. Human epidermal growth factor receptor 2-positive cases, cases without semiquantitative ER score, and patients treated with neoadjuvant endocrine therapy alone were excluded. The pCR rate of low ER+ tumors was similar to the pCR rate of ER- tumors (37% and 26% for low ER and ER- respectively, P = .1722) but significantly different from the pCR rate of moderately ER+ (11%, P = .0049) and high ER+ tumors (4%, P < .0001). Patients with pCR had an excellent prognosis regardless of the ER status. In patients with residual disease (no pCR), the recurrence and death rate were higher in ER- and low ER+ cases compared with moderate and high ER+ cases. Low ER+ breast cancers are biologically similar to ER- tumors. Semiquantitative ER H-score is an important determinant of response to neoadjuvant chemotherapy.

  2. Red light-induced shift of the fluence-response curve for first positive curvature of maize [Zea mays] coleoptiles

    International Nuclear Information System (INIS)

    Hofmann, E.; Schäfer, E.

    1987-01-01

    The fluence-response curve for first positive phototropic curvture of dark-grown maize coleoptiles is shifted to ten-fold higher fluences if the coieoptiles are irradiated with red light 2 h prior to the phototropic induction with blue light. Fluence-response curves for this red-induced shift were obtained with unilateral red irradiations 2 h prior to inductive blue pulses of different fluences. They differ significantly depending on whether the red light was given from the same side as or the opposite side to the respective inductive blue pulse, thus demonstrating that the red light effect is a local response of the coleoptile. The fluence-response curves for an inductive blue pulse in the ascending part were compared with those for an inductive blue pulse in the descending part of the fluence-response curve for blue light induced phototropism. They are quite different in threshold of red light sensitivity and shape for irradiations from both the same and the opposite sides. This offers evidence for the hypothesis that at least two different photosystems are involved in phototropism, and that they are modulated differently by a red light preirradiation. All these fluence-response curves indicate that it is possible to increase the response in the coleoptile, if the red light preirradiation is given opposite to the inductive blue pulse. This is supported by blue light fluence-response curves obtained after a weak unilateral red preirradiation. (author)

  3. Biological pacemakers in canines exhibit positive chronotropic response to emotional arousal

    NARCIS (Netherlands)

    Shlapakova, Iryna N.; Nearing, Bruce D.; Lau, David H.; Boink, Gerard J. J.; Danilo, Peter; Kryukova, Yelena; Robinson, Richard B.; Cohen, Ira S.; Rosen, Michael R.; Verrier, Richard L.

    2010-01-01

    Biological pacemakers based on the HCN2 channel isoform respond to beta-adrenergic and muscarinic stimulation, suggesting a capacity to respond to autonomic input. The purpose of this study was to investigate autonomic response to emotional arousal in canines implanted with murine HCN2-based

  4. Teaching and Assessing Ethics and Social Responsibility in Undergraduate Science: A Position Paper

    Science.gov (United States)

    Schultz, Madeleine

    2014-01-01

    Institutional graduate capabilities and discipline threshold learning outcomes require science students to demonstrate ethical conduct and social responsibility. However, the teaching and assessment of these concepts are not straightforward. Australian chemistry academics participated in a workshop in 2013 to discuss and develop teaching and…

  5. Subjective Response to Foot-Fall Noise, Including Localization of the Source Position

    DEFF Research Database (Denmark)

    Brunskog, Jonas; Hwang, Ha Dong; Jeong, Cheol-Ho

    2011-01-01

    annoyance, using simulated binaural room impulse responses, with sources being a moving point source or a nonmoving surface source, and rooms being a room with a reverberation time of 0.5 s or an anechoic room. The paper concludes that no strong effect of the source localization on the annoyance can...

  6. The cardioprotective and inotropic components of the postconditioning effects of GLP-1 and GLP-1(9-36)a in an isolated rat heart

    DEFF Research Database (Denmark)

    Ossum, Alvilde; van Deurs, Ulla; Engstrøm, Thomas

    2009-01-01

    GLP-1 and its metabolite GLP-1(9-36)a have been shown to exert cardiotropic effects, and were demonstrated to be cardioprotective agents in isolated, postischemic rat or mouse hearts. An agent's total effect on myocardial performance in a postconditioning paradigm is a sum of its myocyte-preservi......GLP-1 and its metabolite GLP-1(9-36)a have been shown to exert cardiotropic effects, and were demonstrated to be cardioprotective agents in isolated, postischemic rat or mouse hearts. An agent's total effect on myocardial performance in a postconditioning paradigm is a sum of its myocyte...... protocol, as exemplified by use of GLP-1 and GLP-1(9-36)a following a global ischemia in isolated rat hearts. Peptides were administered during the first 15min of 120min reperfusion. GLP-1 0.3nM reduced infarct size from 23.2+/-2.4% to 14.1+/-2.3% of area-at-risk (n=15, P=0.0223), an effect abolished......, rather than any true inotropic effect. In contrast, GLP-1(9-36)a did not reduce infarct size significantly, but acted as a strong negative inotrope in postischemic hearts, causing a contractility deficit (LVDP 58.8%, P=0.0004; RPP 58.2%, P=0.0007; dP/dt(max)=58.2%, P=0.0012), quantifiable by an analysis...

  7. Asymmetrical Responses of Ecosystem Processes to Positive Versus Negative Precipitation Extremes: a Replicated Regression Experimental Approach

    Science.gov (United States)

    Felton, A. J.; Smith, M. D.

    2016-12-01

    Heightened climatic variability due to atmospheric warming is forecast to increase the frequency and severity of climate extremes. In particular, changes to interannual variability in precipitation, characterized by increases in extreme wet and dry years, are likely to impact virtually all terrestrial ecosystem processes. However, to date experimental approaches have yet to explicitly test how ecosystem processes respond to multiple levels of climatic extremity, limiting our understanding of how ecosystems will respond to forecast increases in the magnitude of climate extremes. Here we report the results of a replicated regression experimental approach, in which we imposed 9 and 11 levels of growing season precipitation amount and extremity in mesic grassland during 2015 and 2016, respectively. Each level corresponded to a specific percentile of the long-term record, which produced a large gradient of soil moisture conditions that ranged from extreme wet to extreme dry. In both 2015 and 2016, asymptotic responses to water availability were observed for soil respiration. This asymmetry was driven in part by transitions between soil moisture versus temperature constraints on respiration as conditions became increasingly dry versus increasingly wet. In 2015, aboveground net primary production (ANPP) exhibited asymmetric responses to precipitation that largely mirrored those of soil respiration. In total, our results suggest that in this mesic ecosystem, these two carbon cycle processes were more sensitive to extreme drought than to extreme wet years. Future work will assess ANPP responses for 2016, soil nutrient supply and physiological responses of the dominant plant species. Future efforts are needed to compare our findings across a diverse array of ecosystem types, and in particular how the timing and magnitude of precipitation events may modify the response of ecosystem processes to increasing magnitudes of precipitation extremes.

  8. Body Composition Response to Lower Body Positive Pressure Training in Obese Children

    OpenAIRE

    Basant H. El-Refay; Nabeel T. Faiad

    2014-01-01

    Background: The high prevalence of obesity in Egypt has a great impact on the health care system, economic and social situation. Evidence suggests that even a moderate amount of weight loss can be useful. Aim of the study: To analyze the effects of lower body positive pressure supported treadmill training, conducted with hypocaloric diet, on body composition of obese children. Methods: Thirty children aged between 8 and 14 years, were randomly assigned into two groups: intervention group (15 ...

  9. The joyful, yet balanced, amygdala: moderated responses to positive but not negative stimuli in trait happiness

    OpenAIRE

    Cunningham, William A.; Kirkland, Tabitha

    2013-01-01

    Although much is known about the neural dynamics of maladaptive affective styles, the mechanisms of happiness and well-being are less clear. One possibility is that the neural processes of trait happiness are the opposite of those involved in depression/anxiety: ‘rose-colored glasses’ cause happy people to focus on positive cues while remaining oblivious to threats. Specifically, because negative affective styles have been associated with increased amygdala activation to negative stimuli, it ...

  10. Response of Autonomic Nervous System to Body Positions: Fourier and Wavelet Analysis

    OpenAIRE

    Xu, Aiguo; Gonnella, G.; Federici, A.; Stramaglia, S.; Simone, F.; Zenzola, A.; Santostasi, R.

    2003-01-01

    Two mathematical methods, the Fourier and wavelet transforms, were used to study the short term cardiovascular control system. Time series, picked from electrocardiogram and arterial blood pressure lasting 6 minutes, were analyzed in supine position (SUP), during the first (HD1), and the second parts (HD2) of $90^{\\circ}$ head down tilt and during recovery (REC). The wavelet transform was performed using the Haar function of period $T=2^j$ ($% j=1$,2,$... $,6) to obtain wavelet coefficients. ...

  11. The Holy See on sexual and reproductive health rights: conservative in position, dynamic in response.

    Science.gov (United States)

    Coates, Amy L; Hill, Peter S; Rushton, Simon; Balen, Julie

    2014-11-01

    The Holy See has engaged extensively in United Nations negotiations on issues concerning sexual and reproductive health rights as they have emerged and evolved in a dynamic global agenda over the past two decades. A meta-narrative review of the mission's official statements was conducted to examine the positions, discourses and tensions across the broad range of agendas. The Holy See represents a fundamentally conservative and stable position on a range of sexual and reproductive health rights concerns. However, the mission has been dynamic in the ways in which it has forwarded its arguments, increasingly relying upon secularised technical claims and empirical evidence; strategically interpreting human rights norms in ways consistent with its own position; and framing sexuality and reproduction in the context of "the family". Seen in the broader context of a "religious resurgence" in international relations, and in light of the fact that the Holy See has frequently sought to form alliances with conservative State and non-State actors, these findings make an important contribution to understanding the slow progress as well as the potential obstacles that lie ahead in the battle to realise sexual and reproductive health rights in a changing global political environment. Copyright © 2014 Reproductive Health Matters. Published by Elsevier Ltd. All rights reserved.

  12. Magnetosphere and ionosphere response to a positive-negative pulse pair of solar wind dynamic pressure

    Science.gov (United States)

    Tian, A.; Degeling, A. W.

    2017-12-01

    Simulations and observations had shown that single positive/negative solar wind dynamic pressure pulse would excite geomagnetic impulsive events along with ionosphere and/or magnetosphere vortices which are connected by field aligned currents(FACs). In this work, a large scale ( 9min) magnetic hole event in solar wind provided us with the opportunity to study the effects of positive-negative pulse pair (△p/p 1) on the magnetosphere and ionosphere. During the magnetic hole event, two traveling convection vortices (TCVs, anti-sunward) first in anticlockwise then in clockwise rotation were detected by geomagnetic stations located along the 10:30MLT meridian. At the same time, another pair of ionospheric vortices azimuthally seen up to 3 MLT first in clockwise then in counter-clockwise rotation were also appeared in the afternoon sector( 14MLT) and centered at 75 MLAT without obvious tailward propagation feature. The duskside vortices were also confirmed in SuperDARN radar data. We simulated the process of magnetosphere struck by a positive-negative pulse pair and it shows that a pair of reversed flow vortices in the magnetosphere equatorial plane appeared which may provide FACs for the vortices observed in ionosphere. Dawn dusk asymmetry of the vortices as well as the global geomagnetism perturbation characteristics were also discussed.

  13. Mucolipin 1 positively regulates TLR7 responses in dendritic cells by facilitating RNA transportation to lysosomes.

    Science.gov (United States)

    Li, Xiaobing; Saitoh, Shin-Ichiroh; Shibata, Takuma; Tanimura, Natsuko; Fukui, Ryutaro; Miyake, Kensuke

    2015-02-01

    Toll-like receptor 7 (TLR7) and TLR9 sense microbial single-stranded RNA (ssRNA) and ssDNA in endolysosomes. Nucleic acid (NA)-sensing in endolysosomes is thought to be important for avoiding TLR7/9 responses to self-derived NAs. Aberrant self-derived NA transportation to endolysosomes predisposes to autoimmune diseases. To restrict NA-sensing in endolysosomes, TLR7/9 trafficking is tightly controlled by a multiple transmembrane protein Unc93B1. In contrast to TLR7/9 trafficking, little is known about a mechanism underlying NA transportation. We here show that Mucolipin 1 (Mcoln1), a member of the transient receptor potential (TRP) cation channel gene family, has an important role in ssRNA trafficking into lysosomes. Mcoln1(-/-) dendritic cells (DCs) showed impaired TLR7 responses to ssRNA. A mucolipin agonist specifically enhanced TLR7 responses to ssRNAs. The channel activity of Mcoln1 is activated by a phospholipid phosphatidylinositol (3,5) bisphosphate (PtdIns(3,5)P2), which is generated by a class III lipid kinase PIKfyve. A PIKfyve inhibitor completely inhibited TLR7 responses to ssRNA in DCs. Confocal analyses showed that ssRNA transportation to lysosomes in DCs was impaired by PIKfyve inhibitor as well as by the lack of Mcoln1. Transportation of TLR9 ligands was also impaired by the PIKfyve inhibitor. These results demonstrate that the PtdIns(3,5)P2-Mcoln1 axis has an important role in ssRNA transportation into lysosomes in DCs. © The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Body mass is positively associated with neural response to sweet taste, but not alcohol, among drinkers.

    Science.gov (United States)

    Gardiner, Casey K; YorkWilliams, Sophie L; Bryan, Angela D; Hutchison, Kent E

    2017-07-28

    Obesity is a large and growing public health concern, presenting enormous economic and health costs to individuals and society. A burgeoning literature demonstrates that overweight and obese individuals display different neural processing of rewarding stimuli, including caloric substances, as compared to healthy weight individuals. However, much extant research on the neurobiology of obesity has focused on addiction models, without highlighting potentially separable neural underpinnings of caloric intake versus substance use. The present research explores these differences by examining neural response to alcoholic beverages and a sweet non-alcoholic beverage, among a sample of individuals with varying weight status and patterns of alcohol use and misuse. Participants received tastes of a sweet beverage (litchi juice) and alcoholic beverages during fMRI scanning. When controlling for alcohol use, elevated weight status was associated with increased activation in response to sweet taste in regions including the cingulate cortex, hippocampus, precuneus, and fusiform gyrus. However, weight status was not associated with neural response to alcoholic beverages. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans.

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    Won Hee Jung

    2010-11-01

    Full Text Available The fungal pathogen Cryptococcus neoformans is a major cause of illness in immunocompromised individuals such as AIDS patients. The ability of the fungus to acquire nutrients during proliferation in host tissue and the ability to elaborate a polysaccharide capsule are critical determinants of disease outcome. We previously showed that the GATA factor, Cir1, is a major regulator both of the iron uptake functions needed for growth in host tissue and the key virulence factors such as capsule, melanin and growth at 37°C. We are interested in further defining the mechanisms of iron acquisition from inorganic and host-derived iron sources with the goal of understanding the nutritional adaptation of C. neoformans to the host environment. In this study, we investigated the roles of the HAP3 and HAPX genes in iron utilization and virulence. As in other fungi, the C. neoformans Hap proteins negatively influence the expression of genes encoding respiratory and TCA cycle functions under low-iron conditions. However, we also found that HapX plays both positive and negative roles in the regulation of gene expression, including a positive regulatory role in siderophore transporter expression. In addition, HapX also positively regulated the expression of the CIR1 transcript. This situation is in contrast to the negative regulation by HapX of genes encoding GATA iron regulatory factors in Aspergillus nidulans and Schizosaccharomyces pombe. Although both hapX and hap3 mutants were defective in heme utilization in culture, only HapX made a contribution to virulence, and loss of HapX in a strain lacking the high-affinity iron uptake system did not cause further attenuation of disease. Therefore, HapX appears to have a minimal role during infection of mammalian hosts and instead may be an important regulator of environmental iron uptake functions. Overall, these results indicated that C. neoformans employs multiple strategies for iron acquisition during infection.

  16. Energy distribution extraction of negative charges responsible for positive bias temperature instability

    International Nuclear Information System (INIS)

    Ren Shang-Qing; Yang Hong; Wang Wen-Wu; Tang Bo; Tang Zhao-Yun; Wang Xiao-Lei; Xu Hao; Luo Wei-Chun; Zhao Chao; Yan Jiang; Chen Da-Peng; Ye Tian-Chun

    2015-01-01

    A new method is proposed to extract the energy distribution of negative charges, which results from electron trapping by traps in the gate stack of nMOSFET during positive bias temperature instability (PBTI) stress based on the recovery measurement. In our case, the extracted energy distribution of negative charges shows an obvious dependence on energy, and the energy level of the largest energy density of negative charges is 0.01 eV above the conduction band of silicon. The charge energy distribution below that energy level shows strong dependence on the stress voltage. (paper)

  17. Analysis of the positive ionospheric response to a moderate geomagnetic storm using a global numerical model

    Directory of Open Access Journals (Sweden)

    A. A. Namgaladze

    2000-04-01

    Full Text Available Current theories of F-layer storms are discussed using numerical simulations with the Upper Atmosphere Model, a global self-consistent, time dependent numerical model of the thermosphere-ionosphere-plasmasphere-magnetosphere system including electrodynamical coupling effects. A case study of a moderate geomagnetic storm at low solar activity during the northern winter solstice exemplifies the complex storm phenomena. The study focuses on positive ionospheric storm effects in relation to thermospheric disturbances in general and thermospheric composition changes in particular. It investigates the dynamical effects of both neutral meridional winds and electric fields caused by the disturbance dynamo effect. The penetration of short-time electric fields of magnetospheric origin during storm intensification phases is shown for the first time in this model study. Comparisons of the calculated thermospheric composition changes with satellite observations of AE-C and ESRO-4 during storm time show a good agreement. The empirical MSISE90 model, however, is less consistent with the simulations. It does not show the equatorward propagation of the disturbances and predicts that they have a gentler latitudinal gradient. Both theoretical and experimental data reveal that although the ratio of [O]/[N2] at high latitudes decreases significantly during the magnetic storm compared with the quiet time level, at mid to low latitudes it does not increase (at fixed altitudes above the quiet reference level. Meanwhile, the ionospheric storm is positive there. We conclude that the positive phase of the ionospheric storm is mainly due to uplifting of ionospheric F2-region plasma at mid latitudes and its equatorward movement at low latitudes along geomagnetic field lines caused by large-scale neutral wind circulation and the passage of travelling atmospheric disturbances (TADs. The calculated zonal electric field disturbances also help to create the positive ionospheric

  18. Analysis of the positive ionospheric response to a moderate geomagnetic storm using a global numerical model

    Directory of Open Access Journals (Sweden)

    A. A. Namgaladze

    Full Text Available Current theories of F-layer storms are discussed using numerical simulations with the Upper Atmosphere Model, a global self-consistent, time dependent numerical model of the thermosphere-ionosphere-plasmasphere-magnetosphere system including electrodynamical coupling effects. A case study of a moderate geomagnetic storm at low solar activity during the northern winter solstice exemplifies the complex storm phenomena. The study focuses on positive ionospheric storm effects in relation to thermospheric disturbances in general and thermospheric composition changes in particular. It investigates the dynamical effects of both neutral meridional winds and electric fields caused by the disturbance dynamo effect. The penetration of short-time electric fields of magnetospheric origin during storm intensification phases is shown for the first time in this model study. Comparisons of the calculated thermospheric composition changes with satellite observations of AE-C and ESRO-4 during storm time show a good agreement. The empirical MSISE90 model, however, is less consistent with the simulations. It does not show the equatorward propagation of the disturbances and predicts that they have a gentler latitudinal gradient. Both theoretical and experimental data reveal that although the ratio of [O]/[N2] at high latitudes decreases significantly during the magnetic storm compared with the quiet time level, at mid to low latitudes it does not increase (at fixed altitudes above the quiet reference level. Meanwhile, the ionospheric storm is positive there. We conclude that the positive phase of the ionospheric storm is mainly due to uplifting of ionospheric F2-region plasma at mid latitudes and its equatorward movement at low latitudes along geomagnetic field lines caused by large-scale neutral wind circulation and the passage of travelling atmospheric disturbances (TADs. The calculated zonal electric field disturbances also help

  19. Association of positive responses to suicide screening questions with hospital admission and repeated emergency department visits in children and adolescents.

    Science.gov (United States)

    Ballard, Elizabeth D; Horowitz, Lisa M; Jobes, David A; Wagner, Barry M; Pao, Maryland; Teach, Stephen J

    2013-10-01

    Although validated suicide screening tools exist for use among children and adolescents presenting to emergency departments (EDs), the associations between screening positive for suicide risk and immediate psychiatric hospital admission or subsequent ED use, stratified by age, have not been examined. This is a retrospective cohort study of a consecutive case series of patients aged 8 to 18 years presenting with psychiatric chief complaints during a 9-month period to a single urban tertiary care pediatric ED. Eligible patients were administered a subset of questions from the Risk of Suicide Questionnaire. Outcomes included the odds of psychiatric hospitalization at the index visit and repeated ED visits for psychiatric complaints within the following year, stratified by age. Of the 568 patients presenting during the study period, responses to suicide screening questions were available for 442 patients (78%). A total of 159 (36%) of 442 were hospitalized and 130 (29%) of 442 had 1 or more ED visits within the following year. The proportion of patients providing positive responses to 1 or more suicide screening questions did not differ between patients aged 8 to 12 years and those aged 13 to 18 years (77/154 [50%] vs 137/288 [48%], P = 0.63). A positive response to 1 or more of the questions was significantly associated with increased odds of psychiatric hospitalization in the older age group [adjusted odds ratio, 3.82; 95% confidence interval, 2.24-6.54) and with repeated visits to the ED in the younger age group (adjusted odds ratio, 3.55 95% confidence interval, 1.68-7.50). Positive responses to suicide screening questions were associated with acute psychiatric hospitalization and repeated ED visits. Suicide screening in a pediatric ED may identify children and adolescents with increased need of psychiatric resources.

  20. Prosocial attitudes and empathic behavior in emotional positive versus negative situations: brain response (ERPs) and source localization (LORETA) analysis.

    Science.gov (United States)

    Balconi, Michela; Canavesio, Ylenia

    2013-03-01

    The present research firstly investigated the neural correlates (ERPs, event-related potentials) of attitudes to engage in prosocial-helping behaviors, and secondly, it analyzed the relation between these brain-based potentials and personal profile (high vs. low empathic profile). It was considered the subjects' behavior in response to specific emotional situations (positive vs. negative) in case it was required a possible prosocial intervention. Thirty-one subjects were invited to empathize with the emotional contexts (videotapes that reproduced two person's exchanges) and to decide whether to intervene or not to support these persons. BEES questionnaire for empathic behavior was submitted to the subjects after the experimental session. ERP acquisition and LORETA source analysis revealed a negative ongoing deflection (N200 effect) more prefrontally distributed (dorsolateral prefrontal cortex) in response to prosocial intervention options mainly for negative and positive contexts. Moreover, a significant positive correlation was found between high-empathic profiles, intervention behaviors (higher frequency of interventions) and N200 amplitude (higher peak). These results highlight the role of emotions in prosocial behavior, since the N200 effect was considered a marker of the emotional significance of the interpersonal situation. Secondly, the empathic trait may explain the prosocial decisional processes: Higher empathic trait contributes to induce subject's intervention behavior which in turn appears to be directly related to the cortical responsiveness within the prefrontal areas.

  1. Elongator Plays a Positive Role in Exogenous NAD-Induced Defense Responses in Arabidopsis.

    Science.gov (United States)

    An, Chuanfu; Ding, Yezhang; Zhang, Xudong; Wang, Chenggang; Mou, Zhonglin

    2016-05-01

    Extracellular NAD is emerging as an important signal molecule in animal cells, but its role in plants has not been well-established. Although it has been shown that exogenous NAD(+) activates defense responses in Arabidopsis, components in the exogenous NAD(+)-activated defense pathway remain to be fully discovered. In a genetic screen for mutants insensitive to exogenous NAD(+) (ien), we isolated a mutant named ien2. Map-based cloning revealed that IEN2 encodes ELONGATA3 (ELO3)/AtELP3, a subunit of the Arabidopsis Elongator complex, which functions in multiple biological processes, including histone modification, DNA (de)methylation, and transfer RNA modification. Mutations in the ELO3/AtELP3 gene compromise exogenous NAD(+)-induced expression of pathogenesis-related (PR) genes and resistance to the bacterial pathogen Pseudomonas syringae pv. maculicola ES4326, and transgenic expression of the coding region of ELO3/AtELP3 in elo3/Atelp3 restores NAD(+) responsiveness to the mutant plants, demonstrating that ELO3/AtELP3 is required for exogenous NAD(+)-induced defense responses. Furthermore, mutations in genes encoding the other five Arabidopsis Elongator subunits (ELO2/AtELP1, AtELP2, ELO1/AtELP4, AtELP5, and AtELP6) also compromise exogenous NAD(+)-induced PR gene expression and resistance to P. syringae pv. maculicola ES4326. These results indicate that the Elongator complex functions as a whole in exogenous NAD(+)-activated defense signaling in Arabidopsis.

  2. The position of a standard optical computer mouse affects cardiorespiratory responses during the operation of a computer under time constraints.

    Science.gov (United States)

    Sako, Shunji; Sugiura, Hiromichi; Tanoue, Hironori; Kojima, Makoto; Kono, Mitsunobu; Inaba, Ryoichi

    2014-08-01

    This study investigated the association between task-induced stress and fatigue by examining the cardiovascular responses of subjects using different mouse positions while operating a computer under time constraints. The study was participated by 16 young, healthy men and examined the use of optical mouse devices affixed to laptop computers. Two mouse positions were investigated: (1) the distal position (DP), in which the subjects place their forearms on the desk accompanied by the abduction and flexion of their shoulder joints, and (2) the proximal position (PP), in which the subjects place only their wrists on the desk without using an armrest. The subjects continued each task for 16 min. We assessed differences in several characteristics according to mouse position, including expired gas values, autonomic nerve activities (based on cardiorespiratory responses), operating efficiencies (based on word counts), and fatigue levels (based on the visual analog scale - VAS). Oxygen consumption (VO(2)), the ratio of inspiration time to respiration time (T(i)/T(total)), respiratory rate (RR), minute ventilation (VE), and the ratio of expiration to inspiration (Te/T(i)) were significantly lower when the participants were performing the task in the DP than those obtained in the PP. Tidal volume (VT), carbon dioxide output rates (VCO(2)/VE), and oxygen extraction fractions (VO(2)/VE) were significantly higher for the DP than they were for the PP. No significant difference in VAS was observed between the positions; however, as the task progressed, autonomic nerve activities were lower and operating efficiencies were significantly higher for the DP than they were for the PP. Our results suggest that the DP has fewer effects on cardiorespiratory functions, causes lower levels of sympathetic nerve activity and mental stress, and produces a higher total workload than the PP. This suggests that the DP is preferable to the PP when operating a computer.

  3. The position of a standard optical computer mouse affects cardiorespiratory responses during the operation of a computer under time constraints

    Directory of Open Access Journals (Sweden)

    Shunji Sako

    2014-08-01

    Full Text Available Objectives: This study investigated the association between task-induced stress and fatigue by examining the cardiovascular responses of subjects using different mouse positions while operating a computer under time constraints. Material and Methods: The study was participated by 16 young, healthy men and examined the use of optical mouse devices affixed to laptop computers. Two mouse positions were investigated: (1 the distal position (DP, in which the subjects place their forearms on the desk accompanied by the abduction and flexion of their shoulder joints, and (2 the proximal position (PP, in which the subjects place only their wrists on the desk without using an armrest. The subjects continued each task for 16 min. We assessed differences in several characteristics according to mouse position, including expired gas values, autonomic nerve activities (based on cardiorespiratory responses, operating efficiencies (based on word counts, and fatigue levels (based on the visual analog scale – VAS. Results: Oxygen consumption (VO2, the ratio of inspiration time to respiration time (Ti/Ttotal, respiratory rate (RR, minute ventilation (VE, and the ratio of expiration to inspiration (Te/Ti were significantly lower when the participants were performing the task in the DP than those obtained in the PP. Tidal volume (VT, carbon dioxide output rates (VCO2/VE, and oxygen extraction fractions (VO2/VE were significantly higher for the DP than they were for the PP. No significant difference in VAS was observed between the positions; however, as the task progressed, autonomic nerve activities were lower and operating efficiencies were significantly higher for the DP than they were for the PP. Conclusions: Our results suggest that the DP has fewer effects on cardiorespiratory functions, causes lower levels of sympathetic nerve activity and mental stress, and produces a higher total workload than the PP. This suggests that the DP is preferable to the PP when

  4. FIN5 positively regulates far-red light responses in Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Cho, D.S.; Hong, S.H.; Nam, H.G.; Soh, M.S.

    2003-01-01

    We report the characterization of a semi-dominant mutation fin5-1 (far-red insensitive 5-1) of Arabidopsis, which was isolated from genetic screening of phytochrome A (phyA) signaling components. Plants with the fin5-1 mutation exhibited a long hypocotyl phenotype when grown under far-red (FR) light, but not under red light. Physiological analyses implied that FIN5 might be differentially involved in diverse responses that are regulated by phyA under continuous FR light. Anthocyanin accumulation, gravitropic response of hypocotyl growth, and FR light-preconditioned blocking of greening were also impaired in the fin5-1 mutant, whereas photoperiodic floral induction was not, if at all, significantly affected. Moreover, light-regulated expression of the CHS, PORA and PsbS genes was attenuated in fin5-1 mutant plants, while the light-induced expression of CAB was normal. The mutation exhibited semi-dominance regarding control of hypocotyl growth in FR light. We suggest that FIN5 defines a novel branch in the network of phyA signaling in Arabidopsis. (author)

  5. A 12-week resistance training program elicits positive changes in hemodynamic responses in the elderly

    Directory of Open Access Journals (Sweden)

    Cinthya Campos Salazar

    2009-03-01

    Full Text Available The aim of the study was to determine the effect of a resistance training program in hemodynamic responses and adaptations in 60 yr. old elderly. Volunteers were 60 healthy-elderly who underwent a training program 3 times/wk. for 12 wk. Participants were randomly assigned to either a control group, an exercise group who trained at 30% intensity of 5 maximal repetitions (5RM (30% of 5RM or an exercise group at an intensity of 70% (70% of 5RM. Hemodynamic variables measured were mean arterial pressure (MAP, calculated before and immediately after the training session, and rate pressure product (RPP, estimated once a month and before and after finishing the program. Results indicated that resistance exercise training at 30% and 70% of 5RM, with a total exercise work of 872.7 and 890.9 kg did not elicited cardiovascular risks for the elderly. A 12-wk resistance exercise training reduced the cardiovascular strain as shown by the RPP (~16% and the MAP (~9%, with no adverse effects throughout the program. Unfortunately, all the hemodynamic benefits were reverted 6 days following completion of the program. In conclusion, a healthy elderly population must perform resistance training exercises to significantly reduce the cardiovascular stress. We suggest to conduct further research that looks into different exercise intensities in longer program duration and to determine the mechanisms responsible for the deleterious effects of the detraining by using physiological, biochemical and biomechanical variables.

  6. AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA

    Directory of Open Access Journals (Sweden)

    Yuki Nakaya

    2017-07-01

    Full Text Available Cytosolic DNAs derived from retrotransposons serve as pathogen-associated molecular patterns for pattern recognition receptors (PRRs that stimulate the induction of interferons (IFNs and other cytokines, leading to autoimmune disease. Cyclic GMP-AMP synthase is one PRR that senses retrotransposon DNA, activating type I IFN responses through the stimulator of IFN genes (STING. Absent in melanoma 2 (AIM2-like receptors (ALRs have also been implicated in these pathways. Here we show that the mouse ALR IFI205 senses cytosolic retrotransposon DNA independently of cyclic GMP-AMP production. AIM2 antagonizes IFI205-mediated IFN induction activity by sequestering it from STING. We also found that the complement of genes located in the ALR locus in C57BL/6 and AIM2 knockout mice are different and unique, which has implications for interpretation of the sensing of pathogens in different mouse strains. Our data suggest that members of the ALR family are critical to the host IFN response to endogenous DNA.

  7. Do you want some spiritual support? Different rates of positive response to chaplains' versus nurses' offer.

    Science.gov (United States)

    Martinuz, Marco; Dürst, Anne-Véronique; Faouzi, Mohamed; Pétremand, Daniel; Reichel, Virginie; Ortega, Barbara; Waeber, Gérard; Vollenweider, Peter

    2013-01-01

    Access to spiritual support appears to be important in the hospital setting. The offer of spiritual support can be done by different providers such as doctors, nurses or chaplains. Who should initiate or coordinate this spiritual care. This study addresses the following questions: 1) How many patients accept spiritual proposition? 2) What is the better mode of proposition? The study's objectives are the assessment and comparison of the rates of acceptance to an offer of spiritual support made by nurses and chaplains. Two hundred twenty-three consecutive hospitalized patients hospitalized received a proposal of spiritual support and were randomly assigned to one of two conditions. Results revealed that 85.8% of patients accepted the offer in the chaplains' group and 38.5% in the nurses' group. Acceptance of the offer of spiritual support was positively associated with the proposal being made by the chaplains by the frequency of meditation and age, and negatively related to physical well-being.

  8. STUDENTS POSITIVE RESPONSE THROUGH THINK PAIR SHARE STRATEGY ON ENGLISH SPEAKING SKILLS

    Directory of Open Access Journals (Sweden)

    Iin Baroroh Ma’arif

    2017-12-01

    Full Text Available Harmonious communication has an important role in teaching and learning process, especially in encouraging the success of teaching and learning process in the classroom. This research was conducted to know the student's response to the implementation of Think Pair Share strategy in Speaking course. This strategy emphasizes how students are more active in communicating using English in the classroom. The purpose of this research is 1 how the implementation of Think Pair Share strategy in class; 2 how students respond to the Think Pair Share strategy in the classroom; The design of this study is descriptive-qualitative to answer these questions. In this study, researchers themselves are the main instrument. In collecting data, researchers used observation sheets, and field notes.

  9. Overexpression of GbWRKY1 positively regulates the Pi starvation response by alteration of auxin sensitivity in Arabidopsis.

    Science.gov (United States)

    Xu, Li; Jin, Li; Long, Lu; Liu, Linlin; He, Xin; Gao, Wei; Zhu, Longfu; Zhang, Xianlong

    2012-12-01

    Overexpression of a cotton defense-related gene GbWRKY1 in Arabidopsis resulted in modification of the root system by enhanced auxin sensitivity to positively regulate the Pi starvation response. GbWRKY1 was a cloned WRKY transcription factor from Gossypium barbadense, which was firstly identified as a defense-related gene and showed moderate similarity with AtWRKY75 from Arabidopsis thaliana. Overexpression of GbWRKY1 in Arabidopsis resulted in attenuated Pi starvation stress symptoms, including reduced accumulation of anthocyanin and impaired density of lateral roots (LR) in low Pi stress. The study also indicated that overexpression of GbWRKY1 caused plants constitutively exhibited Pi starvation response including increased development of LR, relatively high level of total P and Pi, high expression level of some high-affinity Pi transporters and phosphatases as well as enhanced accumulation of acid phosphatases activity during Pi-sufficient. It was speculated that GbWRKY1 may act as a positive regulator in the Pi starvation response as well as AtWRKY75. GbWRKY1 probably involves in the modulation of Pi homeostasis and participates in the Pi allocation and remobilization but do not accumulate more Pi in Pi-deficient condition, which was different from the fact that AtWRKY75 influenced the Pi status of the plant during Pi deprivation by increasing root surface area and accumulation of more Pi. Otherwise, further study suggested that the overexpression plants were more sensitive to auxin than wild-type and GbWRKY1 may partly influence the LPR1-dependent (low phosphate response 1) Pi starvation signaling pathway and was putatively independent of SUMO E3 ligase SIZ1 and PHR1 (phosphate starvation response 1) in response to Pi starvation.

  10. Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T.

    Science.gov (United States)

    Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; van der Zwaag, Wietske

    2018-02-20

    External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI. © 2018 Wiley Periodicals, Inc.

  11. AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA.

    Science.gov (United States)

    Nakaya, Yuki; Lilue, Jingtao; Stavrou, Spyridon; Moran, Eileen A; Ross, Susan R

    2017-07-05

    Cytosolic DNAs derived from retrotransposons serve as pathogen-associated molecular patterns for pattern recognition receptors (PRRs) that stimulate the induction of interferons (IFNs) and other cytokines, leading to autoimmune disease. Cyclic GMP-AMP synthase is one PRR that senses retrotransposon DNA, activating type I IFN responses through the stimulator of IFN genes (STING). Absent in melanoma 2 (AIM2)-like receptors (ALRs) have also been implicated in these pathways. Here we show that the mouse ALR IFI205 senses cytosolic retrotransposon DNA independently of cyclic GMP-AMP production. AIM2 antagonizes IFI205-mediated IFN induction activity by sequestering it from STING. We also found that the complement of genes located in the ALR locus in C57BL/6 and AIM2 knockout mice are different and unique, which has implications for interpretation of the sensing of pathogens in different mouse strains. Our data suggest that members of the ALR family are critical to the host IFN response to endogenous DNA. IMPORTANCE Autoimmune diseases like Aicardi-Goutières syndrome and lupus erythematosus arise when cells of the immune system become activated and attack host cells and tissues. We found that DNA generated by endogenous retroviruses and retroelements in inbred mice and mouse cells is recognized by several host proteins found in macrophages that are members of the ALR family and that these proteins both suppress and activate the pathways leading to the generation of cytokines and IFNs. We also show that there is great genetic diversity between different inbred mouse strains in the ALR genes, which might contribute to differential susceptibility to autoimmunity. Understanding how immune cells become activated is important to the control of disease. Copyright © 2017 Nakaya et al.

  12. Vibratory response of a mirror support/positioning system for the Advanced Photon Source project at Argonne National Laboratory

    International Nuclear Information System (INIS)

    Basdogan, I.; Shu, Deming; Kuzay, T.M.; Royston, T.J.; Shabana, A.A.

    1996-01-01

    The vibratory response of a typical mirror support/positioning system used at the experimental station of the Advanced Photon Source (APS) project at Argonne National Laboratory is investigated. Positioning precision and stability are especially critical when the supported mirror directs a high-intensity beam aimed at a distant target. Stability may be compromised by low level, low frequency seismic and facility-originated vibrations traveling through the ground and/or vibrations caused by flow-structure interactions in the mirror cooling system. The example case system has five positioning degrees of freedom through the use of precision actuators and rotary and linear bearings. These linkage devices result in complex, multi-dimensional vibratory behavior that is a function of the range of positioning configurations. A rigorous multibody dynamical approach is used for the development of the system equations. Initial results of the study, including estimates of natural frequencies and mode shapes, as well as limited parametric design studies, are presented. While the results reported here are for a particular system, the developed vibratory analysis approach is applicable to the wide range of high-precision optical positioning systems encountered at the APS and at other comparable facilities

  13. Primate body temperature and sleep responses to lower body positive pressure

    Science.gov (United States)

    Edgar, D. M.; Fuller, C. A.

    1984-01-01

    Cephalic fluid shifts, induced by lower body positive pressure (LBPP) are known to influence various physiological systems (i.e., cardiovascular and renal). In earlier experiments, an apparent change in the arousal state of primates in such LBPP conditions was observed. This study was designed to examine the effects of LBPP on arousal state and body temperature level which is normally correlated with sleep. Chair-restrained male squirrel monkeys were exposed to 40 mmHg LBPP for 90-100 minutes between the daytime hours of 13:00-15:00. Each monkey was placed in a specially modified restraint chair to which they were highly trained. Deep body temperature (DBT) was collected from 10 animals. Sleep parameters were obtained from six animals chronically implanted for sleep recording. A video camera was used to observe each animal's apparent state of arousal. LBPP resulted in an approximate 0.9 C decrease in DBT. During video observation, some animals appeared drowsy during LBPP; however, sleep recording revealed no significant changes in the state of arousal. Thus, LBPP is capable of inducing a mild hyperthermia. Further, the mechanisms underlying the observed lowering of body temperature appear to be independent of arousal state.

  14. Real-time Position Based Population Data Analysis and Visualization Using Heatmap for Hazard Emergency Response

    Science.gov (United States)

    Ding, R.; He, T.

    2017-12-01

    With the increased popularity in mobile applications and services, there has been a growing demand for more advanced mobile technologies that utilize real-time Location Based Services (LBS) data to support natural hazard response efforts. Compared to traditional sources like the census bureau that often can only provide historical and static data, an LBS service can provide more current data to drive a real-time natural hazard response system to more accurately process and assess issues such as population density in areas impacted by a hazard. However, manually preparing or preprocessing the data to suit the needs of the particular application would be time-consuming. This research aims to implement a population heatmap visual analytics system based on real-time data for natural disaster emergency management. System comprised of a three-layered architecture, including data collection, data processing, and visual analysis layers. Real-time, location-based data meeting certain polymerization conditions are collected from multiple sources across the Internet, then processed and stored in a cloud-based data store. Parallel computing is utilized to provide fast and accurate access to the pre-processed population data based on criteria such as the disaster event and to generate a location-based population heatmap as well as other types of visual digital outputs using auxiliary analysis tools. At present, a prototype system, which geographically covers the entire region of China and combines population heat map based on data from the Earthquake Catalogs database has been developed. It Preliminary results indicate that the generation of dynamic population density heatmaps based on the prototype system has effectively supported rapid earthquake emergency rescue and evacuation efforts as well as helping responders and decision makers to evaluate and assess earthquake damage. Correlation analyses that were conducted revealed that the aggregation and movement of people

  15. Crude extract and purified components isolated from the stems of Tinospora crispa exhibit positive inotropic effects on the isolated left atrium of rats

    DEFF Research Database (Denmark)

    Praman, Siwaporn; Mulvany, Michael J.; Williams, David E.

    2013-01-01

    -butanol soluble material was concentrated and dried under reduced pressure and lyophilized to obtain a crude powder (Tinospora crispa extract). The active components of Tinospora crispa extract were separated by column chromatography and preparative HPLC. The effects and mechanisms of the n-butanol extract...

  16. Na+/Ca2+ exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart

    OpenAIRE

    Farkas, A S; Acsai, K; Nagy, N; Tóth, A; Fülöp, F; Seprényi, G; Birinyi, P; Nánási, P P; Forster, T; Csanády, M; Papp, J G; Varró, A; Farkas, A

    2008-01-01

    Background and purpose: The Na+/Ca2+ exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na+ concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 μM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na+ concentrations in rabbit and rat hearts.

  17. Regulation of BAZ1A and nucleosome positioning in the nucleus accumbens in response to cocaine.

    Science.gov (United States)

    Sun, HaoSheng; Damez-Werno, Diane M; Scobie, Kimberly N; Shao, Ning-Yi; Dias, Caroline; Rabkin, Jacqui; Wright, Katherine N; Mouzon, Ezekiell; Kabbaj, Mohamed; Neve, Rachael; Turecki, Gustavo; Shen, Li; Nestler, Eric J

    2017-06-14

    Chromatin regulation, in particular ATP-dependent chromatin remodelers, have previously been shown to be important in the regulation of reward-related behaviors in animal models of mental illnesses. Here we demonstrate that BAZ1A, an accessory subunit of the ISWI family of chromatin remodeling complexes, is downregulated in the nucleus accumbens (NAc) of mice exposed repeatedly to cocaine and of cocaine-addicted humans. Viral-mediated overexpression of BAZ1A in mouse NAc reduces cocaine reward as assessed by conditioned place preference (CPP), but increases cocaine-induced locomotor activation. Furthermore, we investigate nucleosome repositioning genome-wide by conducting chromatin immunoprecipitation (ChIP)-sequencing for total H3 in NAc of control mice and after repeated cocaine administration, and find extensive nucleosome occupancy and shift changes across the genome in response to cocaine exposure. These findings implicate BAZ1A in molecular and behavioral plasticity to cocaine and offer new insight into the pathophysiology of cocaine addiction. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Response of the 'patient dose calibrator' chamber for incident positions and sizes of X-ray fields

    International Nuclear Information System (INIS)

    Oliveira, Cassio M.; Abrantes, Marcos Eugenio S.; Ferreira, Flavia C. Bastos; Lacerda, Marco A. de Souza; Alonso, Thessa C.; Silva, Teogenes A. da; Oliveira, Paulo Marcio C.

    2009-01-01

    The evaluation of patient doses is an important tool for optimizing radiodiagnostic medical procedures with conventional X-ray equipment and for improving the quality of the radiographic image. The Patient Dose Calibrator (PDC) chamber is a dosimetric instrument that is used in the evaluation of the air kerma-area product (P KA ) quantity aiming the reduction of patient doses. The objective this work was to study the P KA variation caused by different field incident positions and sizes of the X-ray beam on the PDC chamber. Results showed that the PDC chamber has repeatability lower than 0.6%, beam position dependence of 3% and linearity response within ± 6%; these characteristics are to be taken into account during evaluation of the radiological protection conditions of conventional x-ray equipment. (author)

  19. Ocular surface squamous neoplasia in HIV-positive and HIV-negative patients and response to 5-fluorouracil in Angola

    Directory of Open Access Journals (Sweden)

    Nutt RJ

    2014-12-01

    Full Text Available Robert J Nutt,1 John L Clements,2 William H Dean3 1Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK; 2Boa Vista Eye Clinic, Benguela, Angola; 3Bristol Eye Hospital, Bristol, UK Background: Ocular surface squamous neoplasia (OSSN is becoming increasingly prevalent and aggressive in Sub-Saharan Africa. It is a phenomenon linked with human immunodeficiency virus (HIV infection, although association rates in Angola are currently unknown. A topical treatment that is effective in HIV-positive and HIV-negative individuals may be preferable to surgery in some contexts. We aimed to estimate the proportion of OSSN associated with HIV in Angola and to report on the success of topical 5-fluorouracil as a primary treatment in HIV-positive and HIV-negative patients.Methods: Photographs of OSSNs taken at presentation and following treatment with 5-fluorouracil in patients presenting to Boa Vista Eye Clinic, Angola, between October 2011 and July 2013 were grouped into HIV-positive and HIV-negative groups and analyzed to compare presenting features and treatment response. Eighty-one OSSNs were analyzed for clinical features and 24 met the inclusion criteria for analysis of treatment response.Results: Eighty-two patients presented with OSSN between October 2011 and July 2013. Twenty-one (26% were HIV-positive and typically had OSSNs that exhibited more pathological features than those in HIV-negative patients. Twenty-four (29% patients met the inclusion criteria for analysis of treatment response; of these, 26 (91% OSSNs in both groups displayed at least partial resolution after one treatment course. In the HIV-positive group, five of eight patients displayed complete resolution, two showed partial resolution, and one failed. In the HIV-negative group, five of 16 showed complete resolution, ten of 16 had partial resolution, and one failed.Conclusion: Individuals presenting with OSSN in Angola are more likely to have HIV infection compared

  20. Neoadjuvant chemotherapy with trastuzumab in HER2-positive breast cancer: pathologic complete response rate, predictive and prognostic factors

    Directory of Open Access Journals (Sweden)

    I.P.C. Buzatto

    Full Text Available The purpose of this study was to retrospectively review the pathologic complete response (pCR rate from patients (n=86 with stage II and III HER2-positive breast cancer treated with neoadjuvant chemotherapy at our institution from 2008 to 2013 and to determine possible predictive and prognostic factors. Immunohistochemistry for hormone receptors and Ki-67 was carried out. Clinical and pathological features were analyzed as predictive factors of response to therapy. For survival analysis, we used Kaplan-Meier curves to estimate 5-year survival rates and the log-rank test to compare the curves. The addition of trastuzumab to neoadjuvant chemotherapy significantly improved pCR rate from 4.8 to 46.8%, regardless of the number of preoperative trastuzumab cycles (P=0.0012. Stage II patients achieved a higher response rate compared to stage III (P=0.03. The disease-free and overall survivals were not significantly different between the group of patients that received trastuzumab in the neoadjuvant setting (56.3 and 70% at 5 years, respectively and the group that initiated it post-operatively (75.8 and 88.7% at 5 years, respectively. Axillary pCR post neoadjuvant chemotherapy with trastuzumab was associated with reduced risk of recurrence (HR=0.34; P=0.03 and death (HR=0.21; P=0.02. In conclusion, we confirmed that trastuzumab improves pCR rates and verified that this improvement occurs even with less than four cycles of the drug. Hormone receptors and Ki-67 expressions were not predictive of response in this subset of patients. Axillary pCR clearly denotes prognosis after neoadjuvant target therapy and should be considered to be a marker of resistance, providing an opportunity to investigate new strategies for HER2-positive treatment.

  1. Monte Carlo modelling of a-Si EPID response: The effect of spectral variations with field size and position

    International Nuclear Information System (INIS)

    Parent, Laure; Seco, Joao; Evans, Phil M.; Fielding, Andrew; Dance, David R.

    2006-01-01

    This study focused on predicting the electronic portal imaging device (EPID) image of intensity modulated radiation treatment (IMRT) fields in the absence of attenuation material in the beam with Monte Carlo methods. As IMRT treatments consist of a series of segments of various sizes that are not always delivered on the central axis, large spectral variations may be observed between the segments. The effect of these spectral variations on the EPID response was studied with fields of various sizes and off-axis positions. A detailed description of the EPID was implemented in a Monte Carlo model. The EPID model was validated by comparing the EPID output factors for field sizes between 1x1 and 26x26 cm 2 at the isocenter. The Monte Carlo simulations agreed with the measurements to within 1.5%. The Monte Carlo model succeeded in predicting the EPID response at the center of the fields of various sizes and offsets to within 1% of the measurements. Large variations (up to 29%) of the EPID response were observed between the various offsets. The EPID response increased with field size and with field offset for most cases. The Monte Carlo model was then used to predict the image of a simple test IMRT field delivered on the beam axis and with an offset. A variation of EPID response up to 28% was found between the on- and off-axis delivery. Finally, two clinical IMRT fields were simulated and compared to the measurements. For all IMRT fields, simulations and measurements agreed within 3%--0.2 cm for 98% of the pixels. The spectral variations were quantified by extracting from the spectra at the center of the fields the total photon yield (Y total ), the photon yield below 1 MeV (Y low ), and the percentage of photons below 1 MeV (P low ). For the studied cases, a correlation was shown between the EPID response variation and Y total , Y low , and P low

  2. CCR6-dependent positioning of memory B cells is essential for their ability to mount a recall response to antigen.

    Science.gov (United States)

    Elgueta, Raul; Marks, Ellen; Nowak, Elizabeth; Menezes, Shinelle; Benson, Micah; Raman, Vanitha S; Ortiz, Carla; O'Connell, Samuel; Hess, Henry; Lord, Graham M; Noelle, Randolph

    2015-01-15

    Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to ensure successful cognate interactions. Although cognate interactions between T cells and memory B cells (B(mem)) are essential for the secondary humoral immune responses, the chemokine response patterns of B(mem) cells are largely unknown. In contrast to naive B cells, this study shows that Ag-specific B(mem) cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. Although CCR6 appears be nonessential for the initial clonal expansion and maintenance of B(mem), CCR6 is essential for the ability of B(mem) to respond to a recall response to their cognate Ag. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient B(mem) was revealed by immunohistological analysis with an altered distribution of CCR6-deficient B(mem) from the marginal and perifollicular to the follicular/germinal center area. Copyright © 2015 by The American Association of Immunologists, Inc.

  3. CCR6-dependent positioning of memory B cells is essential for their ability to mount a recall response to antigen

    Science.gov (United States)

    Elgueta, Raul; Marks, Ellen; Nowak, Elizabeth; Menezes, Shinelle; Benson, Micah; Raman, Vanitha S.; Ortiz, Carla; O’Connell, Samuel; Hess, Henry; Lord, Graham M.; Noelle, Randolph

    2014-01-01

    Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to insure successful cognate interactions. While cognate interactions between T cells and memory B cells (Bmem)5 are essential for the secondary humoral immune responses, the chemokine response patterns of Bmem cells are largely unknown. In contrast to naïve B cells, this study shows that antigen-specific Bmem cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. While CCR6 appears be non-essential for the initial clonal expansion and maintenance of Bmem, CCR6 is essential for the ability of Bmem to respond to a recall response to their cognate antigen. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone-marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient Bmem was revealed by immunohistological analysis with an altered distribution of CCR6-deficient Bmem from the marginal and perifollicular to the follicular/germinal center area. PMID:25505290

  4. ETHYLENE RESPONSE FACTOR 96 positively regulates Arabidopsis resistance to necrotrophic pathogens by direct binding to GCC elements of jasmonate - and ethylene-responsive defence genes.

    Science.gov (United States)

    Catinot, Jérémy; Huang, Jing-Bo; Huang, Pin-Yao; Tseng, Min-Yuan; Chen, Ying-Lan; Gu, Shin-Yuan; Lo, Wan-Sheng; Wang, Long-Chi; Chen, Yet-Ran; Zimmerli, Laurent

    2015-12-01

    The ERF (ethylene responsive factor) family is composed of transcription factors (TFs) that are critical for appropriate Arabidopsis thaliana responses to biotic and abiotic stresses. Here we identified and characterized a member of the ERF TF group IX, namely ERF96, that when overexpressed enhances Arabidopsis resistance to necrotrophic pathogens such as the fungus Botrytis cinerea and the bacterium Pectobacterium carotovorum. ERF96 is jasmonate (JA) and ethylene (ET) responsive and ERF96 transcripts accumulation was abolished in JA-insensitive coi1-16 and in ET-insensitive ein2-1 mutants. Protoplast transactivation and electrophoresis mobility shift analyses revealed that ERF96 is an activator of transcription that binds to GCC elements. In addition, ERF96 mainly localized to the nucleus. Microarray analysis coupled to chromatin immunoprecipitation-PCR of Arabidopsis overexpressing ERF96 revealed that ERF96 enhances the expression of the JA/ET defence genes PDF1.2a, PR-3 and PR-4 as well as the TF ORA59 by direct binding to GCC elements present in their promoters. While ERF96-RNAi plants demonstrated wild-type resistance to necrotrophic pathogens, basal PDF1.2 expression levels were reduced in ERF96-silenced plants. This work revealed ERF96 as a key player of the ERF network that positively regulates the Arabidopsis resistance response to necrotrophic pathogens. © 2015 John Wiley & Sons Ltd.

  5. Tomato NAC transcription factor SlSRN1 positively regulates defense response against biotic stress but negatively regulates abiotic stress response.

    Directory of Open Access Journals (Sweden)

    Bo Liu

    Full Text Available Biotic and abiotic stresses are major unfavorable factors that affect crop productivity worldwide. NAC proteins comprise a large family of transcription factors that play important roles in plant growth and development as well as in responses to biotic and abiotic stresses. In a virus-induced gene silencing-based screening to identify genes that are involved in defense response against Botrytis cinerea, we identified a tomato NAC gene SlSRN1 (Solanum lycopersicum Stress-related NAC1. SlSRN1 is a plasma membrane-localized protein with transactivation activity in yeast. Expression of SlSRN1 was significantly induced by infection with B. cinerea or Pseudomonas syringae pv. tomato (Pst DC3000, leading to 6-8 folds higher than that in the mock-inoculated plants. Expression of SlSRN1 was also induced by salicylic acid, jasmonic acid and 1-amino cyclopropane-1-carboxylic acid and by drought stress. Silencing of SlSRN1 resulted in increased severity of diseases caused by B. cinerea and Pst DC3000. However, silencing of SlSRN1 resulted in increased tolerance against oxidative and drought stresses. Furthermore, silencing of SlSRN1 accelerated accumulation of reactive oxygen species but attenuated expression of defense genes after infection by B. cinerea. Our results demonstrate that SlSRN1 is a positive regulator of defense response against B. cinerea and Pst DC3000 but is a negative regulator for oxidative and drought stress response in tomato.

  6. Postpartum depressive symptoms moderate the link between mothers’ neural response to positive faces in reward and social regions and observed caregiving

    Science.gov (United States)

    Guo, Chaohui; Moses-Kolko, Eydie L; Phillips, Mary L; Stepp, Stephanie D; Hipwell, Alison E

    2017-01-01

    Abstract Postpartum depression may disrupt socio-affective neural circuitry and compromise provision of positive parenting. Although work has evaluated how parental response to negative stimuli is related to caregiving, research is needed to examine how depressive symptoms during the postpartum period may be related to neural response to positive stimuli, especially positive faces, given depression’s association with biased processing of positive faces. The current study examined the association between neural response to adult happy faces and observations of maternal caregiving and the moderating role of postpartum depression, in a sample of 18- to 22-year old mothers (n = 70) assessed at 17 weeks (s.d. = 4.7 weeks) postpartum. Positive caregiving was associated with greater precuneus and occipital response to positive faces among mothers with lower depressive symptoms, but not for those with higher symptoms. For mothers with higher depressive symptoms, greater ventral and dorsal striatal response to positive faces was associated with more positive caregiving, whereas the opposite pattern emerged for mothers with lower symptoms. There was no association between negative caregiving and neural response to positive faces or negative faces. Processing of positive stimuli may be an important prognostic target in mothers with depressive symptoms, given its link with healthy caregiving behaviors. PMID:29048603

  7. Ranking low, feeling high: How hierarchical position and experienced power promote prosocial behavior in response to procedural justice.

    Science.gov (United States)

    van Dijke, Marius; De Cremer, David; Langendijk, Gerben; Anderson, Cameron

    2018-02-01

    Research shows that power can lead to prosocial behavior by facilitating the behavioral expression of dispositional prosocial motivation. However, it is not clear how power may facilitate responses to contextual factors that promote prosocial motivation. Integrating fairness heuristic theory and the situated focus theory of power, we argue that in particular, organization members in lower (vs. higher) hierarchical positions who simultaneously experience a high (vs. low) sense of power respond with prosocial behavior to 1 important antecedent of prosocial motivation, that is, the enactment of procedural justice. The results from a multisource survey among employees and their leaders from various organizations (Study 1) and an experiment using a public goods dilemma (Study 2) support this prediction. Three subsequent experiments (Studies 3-5) show that this effect is mediated by perceptions of authority trustworthiness. Taken together, this research (a) helps resolve the debate regarding whether power promotes or undermines prosocial behavior, (b) demonstrates that hierarchical position and the sense of power can have very different effects on processes that are vital to the functioning of an organization, and (c) helps solve ambiguity regarding the roles of hierarchical position and power in fairness heuristic theory. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  8. TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy.

    Science.gov (United States)

    Vlahakis, Ariadne; Graef, Martin; Nunnari, Jodi; Powers, Ted

    2014-07-22

    The highly conserved Target of Rapamycin (TOR) kinase is a central regulator of cell growth and metabolism in response to nutrient availability. TOR functions in two structurally and functionally distinct complexes, TOR Complex 1 (TORC1) and TOR Complex 2 (TORC2). Through TORC1, TOR negatively regulates autophagy, a conserved process that functions in quality control and cellular homeostasis and, in this capacity, is part of an adaptive nutrient deprivation response. Here we demonstrate that during amino acid starvation TOR also operates independently as a positive regulator of autophagy through the conserved TORC2 and its downstream target protein kinase, Ypk1. Under these conditions, TORC2-Ypk1 signaling negatively regulates the Ca(2+)/calmodulin-dependent phosphatase, calcineurin, to enable the activation of the amino acid-sensing eIF2α kinase, Gcn2, and to promote autophagy. Our work reveals that the TORC2 pathway regulates autophagy in an opposing manner to TORC1 to provide a tunable response to cellular metabolic status.

  9. Identification of the yeast gene encoding the tRNA m1G methyltransferase responsible for modification at position 9.

    Science.gov (United States)

    Jackman, Jane E; Montange, Rebecca K; Malik, Harmit S; Phizicky, Eric M

    2003-05-01

    Methylation of tRNA at the N-1 position of guanosine to form m(1)G occurs widely in nature. It occurs at position 37 in tRNAs from all three kingdoms, and the methyltransferase that catalyzes this reaction is known from previous work of others to be critically important for cell growth in Escherichia coli and the yeast Saccharomyces cerevisiae. m(1)G is also widely found at position 9 in eukaryotic tRNAs, but the corresponding methyltransferase was unknown. We have used a biochemical genomics approach with a collection of purified yeast GST-ORF fusion proteins to show that m(1)G(9) formation of yeast tRNA(Gly) is associated with ORF YOL093w, named TRM10. Extracts lacking Trm10p have undetectable levels of m(1)G(9) methyltransferase activity but retain normal m(1)G(37) methyltransferase activity. Yeast Trm10p purified from E. coli quantitatively modifies the G(9) position of tRNA(Gly) in an S-adenosylmethionine-dependent fashion. Trm10p is responsible in vivo for most if not all m(1)G(9) modification of tRNAs, based on two results: tRNA(Gly) purified from a trm10-Delta/trm10-Delta strain is lacking detectable m(1)G; and a primer extension block occurring at m(1)G(9) is removed in trm10-Delta/trm10-Delta-derived tRNAs for all 9 m(1)G(9)-containing species that were testable by this method. There is no obvious growth defect of trm10-Delta/trm10-Delta strains. Trm10p bears no detectable resemblance to the yeast m(1)G(37) methyltransferase, Trm5p, or its orthologs. Trm10p homologs are found widely in eukaryotes and many archaea, with multiple homologs in several metazoans, including at least three in humans.

  10. EFFECTS OF STRAIN, CAGE DENSITY AND POSITION ON IMMUNE RESPONSE TO VACCINES AND BLOOD PARAMETERS IN LAYER PULLETS

    Directory of Open Access Journals (Sweden)

    Z. BOZKURT

    2009-05-01

    Full Text Available Two thousand 1-day-old layer chicks were used in the study from Lohman Brown, Isa Brown, Lohman White and Bowans White breeds. The chicks were placed in the at 3 cage densities (211.8, 274.5 and 370.6 cm2 per bird and on 3 positions (as top, middle and bottom tiers. All birds were kept under standard management policy and a commercial vaccination program was practiced. Total specific antibody titres to Infectious Brochitis Virus (IBV, Infectious Bursal Desease Virus (IBDV, Newcastle Disease Virus (NDV and Egg Drop Syndrome Virus (EDSV vaccines at the ages of 5, 10 and 20 weeks were serologically determined by ELISA. Cellmediated immune response was also evaluated. In commercial white egg laying strains specific antibody titres to IBV, IBDV, NDV and EDSV vaccines were greater than in Brown egg layer strains. Keeping in cage created more stress in Brown egg laying chicks than those in white egg laying chicks. As cage density increased, the ratio of heterophils to lymphocytes (H/L ratio slightly increased. Cage position had no influence on the titres of antibodies to IBV and IBDV vaccines but the position of cage in pullets where chicks were stocked, from top to bottom, NDV and EDSV antibody titre decreased and percentage of heterophils, H/L ratio and basophil rates were low. These findings suggest that cage-related stress could be decreased, resistance to diseases and finally well-being of hens may be improved if hens are kept under proper position and density within cage systems with respect to their physiological and behavioral characteristics that controlled by genes.

  11. Positive exercise thallium-201 test responses in patients with less than 50% maximal coronary stenosis: angiographic and clinical predictors

    International Nuclear Information System (INIS)

    Brown, K.A.; Osbakken, M.; Boucher, C.A.; Strauss, H.W.; Pohost, G.M.; Okada, R.D.

    1985-01-01

    The incidence and causes of abnormal thallium-201 (TI-201) myocardial perfusion studies in the absence of significant coronary artery disease were examined. The study group consisted of 100 consecutive patients undergoing exercise TI-201 testing and coronary angiography who were found to have maximal coronary artery diameter narrowing of less than 50%. Maximal coronary stenosis ranged from 0 to 40%. The independent and relative influences of patient clinical, exercise and angiographic data were assessed by logistic regression analysis. Significant predictors of a positive stress TI-201 test result were: (1) percent maximal coronary stenosis (p less than 0.0005), (2) propranolol use (p less than 0.01), (3) interaction of propranolol use and percent maximal stenosis (p less than 0.005), and (4) stress-induced chest pain (p . 0.05). No other patient variable had a significant influence. Positive TI-201 test results were more common in patients with 21 to 40% maximal stenosis (59%) than in patients with 0 to 20% maximal stenosis (27%) (p less than 0.01). Among patients with 21 to 40% stenosis, a positive test response was more common when 85% of maximal predicted heart rate was achieved (75%) than when it was not (40%) (p less than 0.05). Of 16 nonapical perfusion defects seen in patients with 21 to 40% maximal stenosis, 14 were in the territory that corresponded with such a coronary stenosis. Patients taking propranolol were more likely to have a positive TI-201 test result (45%) than patients not taking propranolol (22%) (p less than 0.05)

  12. Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans.

    Directory of Open Access Journals (Sweden)

    Blandine Patillon

    Full Text Available VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2 is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK. This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8, and PRSS8 with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect.

  13. Evaluation of the x-ray response of a position-sensitive microstrip detector with an integrated readout chip

    International Nuclear Information System (INIS)

    Rossington, C.; Jaklevic, J.; Haber, C.; Spieler, H.; Reid, J.

    1990-08-01

    The performance of an SVX silicon microstrip detector and its compatible integrated readout chip have been evaluated in response to Rh Kα x-rays (average energy 20.5 keV). The energy and spatial discrimination capabilities, efficient data management and fast readout rates make it an attractive alternative to the CCD and PDA detectors now being offered for x-ray position sensitive diffraction and EXAFS work. The SVX system was designed for high energy physics applications and thus further development of the existing system is required to optimize it for use in practical x-ray experiments. For optimum energy resolution the system noise must be decreased to its previously demonstrated low levels of 2 keV FWHM at 60 keV or less, and the data handling rate of the computer must be increased. New readout chips are now available that offer the potential of better performance. 15 refs., 7 figs

  14. Individual differences in response to positive and negative stimuli: endocannabinoid-based insight on approach and avoidance behaviors

    Directory of Open Access Journals (Sweden)

    Daniela eLaricchiuta

    2014-12-01

    Full Text Available Approach and avoidance behaviors - the primary responses to the environmental stimuli of danger, novelty and reward - are associated with the brain structures that mediate cognitive functionality, reward sensitivity and emotional expression. Individual differences in approach and avoidance behaviors are modulated by the functioning of amygdaloid-hypothalamic-striatal and striatal-cerebellar networks implicated in action and reaction to salient stimuli. The nodes of these networks are strongly interconnected and by acting on them the endocannabinoid and dopaminergic systems increase the intensity of appetitive or defensive motivation. This review analyzes the approach and avoidance behaviors in humans and rodents, addresses neurobiological and neurochemical aspects of these behaviors, and proposes a possible synaptic plasticity mechanism, related to endocannabinoid-dependent long-term potentiation and depression that allows responding to salient positive and negative stimuli.

  15. Factors that predict a positive response on gonadotropin-releasing hormone stimulation test for diagnosing central precocious puberty in girls

    Directory of Open Access Journals (Sweden)

    Junghwan Suh

    2013-12-01

    Full Text Available PurposeThe rapid increase in the incidence of precocious puberty in Korea has clinical and social significance. Gonadotropin-releasing hormone (GnRH stimulation test is required to diagnose central precocious puberty (CPP, however this test is expensive and time-consuming. This study aimed to identify factors that can predict a positive response to the GnRH stimulation test.MethodsClinical and laboratory parameters, including basal serum luteinizing hormone (LH, follicle-stimulating hormone (FSH, and estradiol (E2, were measured in 540 girls with clinical signs of CPP.ResultsTwo hundred twenty-nine of 540 girls with suspected CPP had a peak serum LH level higher than 5 IU/L (the CPP group. The CPP group had advanced bone age (P<0.001, accelerated yearly growth rate (P<0.001, increased basal levels of LH (P=0.02, FSH (P<0.001, E2 (P=0.001, and insulin-like growth factor-I levels (P<0.001 compared to the non-CPP group. In contrast, body weight (P<0.001 and body mass index (P<0.001 were lower in the CPP group. Although basal LH was significantly elevated in the CPP group compared to the non-CPP group, there was considerable overlap between the 2 groups. Cutoff values of basal LH (0.22 IU/L detected CPP with 87.8% sensitivity and 20.9% specificity.ConclusionNo single parameter can predict a positive response on the GnRH stimulation test with both high sensitivity and specificity. Therefore, multiple factors should be considered in evaluation of sexual precocity when deciding the timing of the GnRH stimulation test.

  16. No differences in ventral striatum responsivity between adolescents with a positive family history of alcoholism and controls.

    Science.gov (United States)

    Müller, Kathrin U; Gan, Gabriela; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Lawrence, Claire; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomáš; Pausova, Zdenka; Rietschel, Marcella; Ströhle, Andreas; Struve, Maren; Schumann, Gunter; Smolka, Michael N

    2015-05-01

    Individuals with alcohol-dependent parents show an elevated risk of developing alcohol-related problems themselves. Modulations of the mesolimbic reward circuit have been postulated as a pre-existing marker of alcoholism. We tested whether a positive family history of alcoholism is correlated with ventral striatum functionality during a reward task. All participants performed a modified version of the monetary incentive delay task while their brain responses were measured with functional magnetic resonance imaging. We compared 206 healthy adolescents (aged 13-15) who had any first- or second-degree relative with alcoholism to 206 matched controls with no biological relative with alcoholism. Reward anticipation as well as feedback of win recruited the ventral striatum in all participants, but adolescents with a positive family history of alcoholism did not differ from their matched peers. Also we did not find any correlation between family history density and reward anticipation or feedback of win. This finding of no differences did not change when we analyzed a subsample of 77 adolescents with at least one parent with alcohol use disorder and their matched controls. Because this result is in line with another study reporting no differences between children with alcohol-dependent parents and controls at young age, but contrasts with studies of older individuals, one might conclude that at younger age the effect of family history has not yet exerted its influence on the still developing mesolimbic reward circuit. © 2014 Society for the Study of Addiction.

  17. Arabidopsis calcium-dependent protein kinase AtCPK1 plays a positive role in salt/drought-stress response.

    Science.gov (United States)

    Huang, Kui; Peng, Lu; Liu, Yingying; Yao, Rundong; Liu, Zhibin; Li, Xufeng; Yang, Yi; Wang, Jianmei

    2018-03-25

    The calcium-dependent protein kinases (CDPKs) play vital roles in plant response to various environmental stimuli. Here, we investigated the function of Arabidopsis AtCPK1 in response to salt and drought stress. The loss-of-function cpk1 mutant displayed hypersensitive to salt and drought stress, whereas overexpressing AtCPK1 in Arabidopsis plants significantly enhanced the resistance to salt or drought stress. The reduced or elevated tolerance of cpk1 mutant and AtCPK1-overexpressing lines was confirmed by the changes of proline, malondialdehyde (MDA) and H 2 O 2 . Real-time PCR analysis revealed that the expression of several stress-inducible genes (RD29A, COR15A, ZAT10, APX2) down-regulated in cpk1 mutant and up-regulated in AtCPK1-overexpressing plants. These results are likely to indicate that AtCPK1 positively regulates salt and drought stress in Arabidopsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections.

    Directory of Open Access Journals (Sweden)

    Nadine T Nehme

    2011-03-01

    Full Text Available Two NF-kappaB signaling pathways, Toll and immune deficiency (imd, are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense.In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus, we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response.Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.

  19. Preservation of the positive lusitropic effect of beta-adrenoceptors stimulation in diabetic cardiomyopathy.

    Science.gov (United States)

    Amour, Julien; Loyer, Xavier; Michelet, Pierre; Birenbaum, Aurélie; Riou, Bruno; Heymes, Christophe

    2008-10-01

    In diabetic cardiomyopathy, diastolic dysfunction results in part from sarcoplasmic reticulum abnormalities affecting both phospholamban and sarcoplasmic reticulum Ca2+ uptake (SERCA2a). Consequently, the positive lusitropic effect of beta-adrenoceptors stimulation could be altered, and beta3-adrenoceptor over-expression may play a role, as previously demonstrated with an altered positive inotropic effect. In this study, we tested the hypothesis that the beta-adrenergic positive lusitropic effect is altered in diabetic cardiomyopathy, and that beta3-adrenoceptor over-expression is involved. beta-adrenergic responses were investigated in vivo (dobutamine-echocardiography) and in vitro (papillary muscle preparation) in healthy and diabetic rats killed 4 (4W) and 12 (12W) wk after IV streptozotocin injection. The effect of beta3-adrenoceptor pathway inhibition by S-cyanopindolol (selective beta3-adrenoceptor antagonist) or by NG-nitro-L-arginine-methyl-ester (nonselective nitric oxide synthase inhibitor) on the lusitropic response to isoproterenol (nonselective beta-adrenoceptors agonist) was studied in vitro. Western blots were performed to quantify the protein expressions of beta1- and beta3-adrenoceptors, phospholamban, and SERCA2a. Data are presented as mean percentages of baseline+/-sd. Despite the increased phospholamban/SERCA2a protein ratio and documented diastolic dysfunction, the positive lusitropic effect of beta-adrenoceptors stimulation was preserved in vivo (dobutamine) and in vitro (isoproterenol) in 4W and 12W diabetic, compared with healthy, rats. The beta3-adrenoceptor was up-regulated whereas beta1-adrenoceptor was down-regulated in 4W and 12W diabetic, compared with healthy, rats. Nevertheless, S-cyanopindolol or NG-nitro-L-arginine-methyl-ester had no lusitropic effect. The positive lusitropic effect of beta-adrenoceptor stimulation was preserved in diabetic cardiomyopathy. beta3-adrenoceptor over-expression does not seem to affect this process.

  20. Visual spatial attention enhances the amplitude of positive and negative fMRI responses to visual stimulation in an eccentricity-dependent manner

    Science.gov (United States)

    Bressler, David W.; Fortenbaugh, Francesca C.; Robertson, Lynn C.; Silver, Michael A.

    2013-01-01

    Endogenous visual spatial attention improves perception and enhances neural responses to visual stimuli at attended locations. Although many aspects of visual processing differ significantly between central and peripheral vision, little is known regarding the neural substrates of the eccentricity dependence of spatial attention effects. We measured amplitudes of positive and negative fMRI responses to visual stimuli as a function of eccentricity in a large number of topographically-organized cortical areas. Responses to each stimulus were obtained when the stimulus was attended and when spatial attention was directed to a stimulus in the opposite visual hemifield. Attending to the stimulus increased both positive and negative response amplitudes in all cortical areas we studied: V1, V2, V3, hV4, VO1, LO1, LO2, V3A/B, IPS0, TO1, and TO2. However, the eccentricity dependence of these effects differed considerably across cortical areas. In early visual, ventral, and lateral occipital cortex, attentional enhancement of positive responses was greater for central compared to peripheral eccentricities. The opposite pattern was observed in dorsal stream areas IPS0 and putative MT homolog TO1, where attentional enhancement of positive responses was greater in the periphery. Both the magnitude and the eccentricity dependence of attentional modulation of negative fMRI responses closely mirrored that of positive responses across cortical areas. PMID:23562388

  1. Negative and positive participant responses to the composite international diagnostic interview - Results of the Netherlands Mental Health Survey and Incidence Study

    NARCIS (Netherlands)

    Graaf, R. de; Have, M.L. ten; Dorsselaer, S.A.F.M. van; Schoemaker, C.G.; Vollebergh, W.A.M.

    2004-01-01

    Little is known about the emotional responses of participants in community surveys to standardised psychiatric interviews like the Composite International Diagnostic Interview (CIDI). This study investigates the proportion of subjects responding negatively or positively to the CIDI, and identifies

  2. Measurements and simulations on position dependencies in the response of single PWO crystals and a prototype for the PANDA EMC

    International Nuclear Information System (INIS)

    Bremer, Daniel Andreas

    2013-01-01

    The PANDA experiment, which will be located at the future Facility for Antiproton and Ion Research, aims at the study of strong interaction within the charm sector via antiproton- proton collisions. An essential component of the PANDA detector to achieve the ambitious physics goals is the Electromagnetic Calorimeter (EMC). Reason for this is particularly its high detection efficiency for photons and electrons over a large dynamic range, since most of the expected physics channels are accompanied by secondary photons. The EMC is based on second generation lead tungstate scintillator crystals and thus features a very compact design and improved performance. To guarantee a homogeneous and precise energy and momentum response, an exact knowledge on the incident particle position is mandatory. In the scope of this work, non-uniformities in the light yield of single lead tungstate crystals with tapered geometry are investigated. This effect was studied with the SLitrani simulation package in comparison to a series of dedicated experimental setups. The so called precision setup allowed for a comparative measurement of the response to cosmic muons and low energetic photons. Furthermore, an analogous beam measurement was performed with 80 MeV protons. Both, simulation and experiments agree that, in case of the PANDA crystal geometry types, the obtained light yield increases quadratically with the distance of the location of the energy deposition inside the crystal to the photo sensor. A clear correlation of the observed amount of non-uniformity to the mean tapering angle of the individual crystal geometry type could be determined. Furthermore, no significant difference in non-uniformity was observed for the three different particle species. Therefore, the observed non-uniformities can be regarded as independent of the exact mechanism of the energy deposition. Hence, the main effect governing the obtained non-uniformities is the interplay of the focussing caused by the high

  3. Activity Profiles and Physiological Responses of Representative Tag Football Players in Relation to Playing Position and Physical Fitness

    Science.gov (United States)

    2015-01-01

    This study determined the physical fitness, match-activity profiles and physiological responses of representative tag football players and examined the relationship between physical fitness and the match-activity profile. Microtechnology devices and heart rate (HR) chest straps were used to determine the match-activity profiles of sixteen tag football players for five matches during the 2014 Australian National Championships. The relationships between lower body muscular power, straight line running speed and Yo-Yo intermittent recovery test level 2 (Yo-Yo IR2) and the match-activity profile were examined using Pearson’s correlation coefficients. Outside players had greater lower body muscular power (ES = 0.98) and straight line running speed (ES = 1.03–1.18) than inside players, and also covered greater very high-speed running (VHSR) distance/min (ES = 0.67) and reached higher peak running speeds (ES = 0.95) during matches. Inside and outside players performed a similar number of repeated high-intensity effort (RHIE) bouts and reported similar mean and maximum efforts per RHIE bout. However, there were differences between playing positions for mean and maximal RHIE effort durations (ES = 0.69–1.15) and mean RHIE bout recovery (ES = 0.56). Inside and outside players also reported small to moderate differences (ES = 0.43–0.80) for times spent in each HR zone. There were a number of moderate to very large correlations between physical fitness measures and match-activity profile variables. This study found lower body muscular power, straight line running speed and Yo-Yo IR2 to be related to the match-activities of representative tag football players, although differences between inside and outside players suggest that athlete testing and training practices should be modified for different playing positions. PMID:26642320

  4. A highly restricted T-cell receptor dominates the CD8+ T-cell response to parvovirus B19 infection in HLA-A*2402-positive individuals

    DEFF Research Database (Denmark)

    Kasprowicz, V; Isa, Adiba; Jeffery, K

    2006-01-01

    Six of seven HLA-A*2402-positive individuals with acute parvovirus B19 infections made vigorous CD8-positive cytotoxic T-cell (CTL) responses to the viral epitope FYTPLADQF. All responders showed highly focused T-cell receptor (TCR) usage, using almost exclusively BV5.1. The BV5.1 TCR dominated...

  5. Restoring the salivary cortisol awakening response through nasal continuous positive airway pressure therapy in obstructive sleep apnea.

    Science.gov (United States)

    Ghiciuc, Cristina Mihaela; Dima Cozma, Lucia Corina; Bercea, Raluca Mihaela; Lupusoru, Catalina Elena; Mihaescu, Traian; Szalontay, Andreea; Gianfreda, Angela; Patacchioli, Francesca Romana

    2013-10-01

    Partial and largely conflicting data are currently available on the interplay between obstructive sleep apnea (OSA) and hypothalamus-pituitary-adrenal axis (HPA) activity in adult obese men. This study was performed to evaluate the daily trajectories of salivary cortisol, specifically with respect to the salivary cortisol awakening response (CAR), a common method used to assess HPA axis activity. The main findings of this study were that adult male obese subjects who were newly diagnosed with severe OSA showed the following: (1) a flattening of the CAR; (2) levels of cortisol at awakening that were lower than those of the controls; and (3) maintenance of the physiological circadian activity of the HPA axis, with the highest hormone concentrations produced in the morning and the lowest in the evening. This study was also designed to investigate the effects of 3 and 6 mos of treatment with continuous airways positive pressure (CPAP). CPAP use resulted in a significant recovery of the sleep patterns disrupted by OSA; moreover, mild neuropsychological signs of depression and anxiety in severe OSA patients were concomitantly progressively improved by CPAP treatment. Furthermore, this study reports that 3 and 6 mos of CPAP therapy restored the presence of CAR and was able to significantly reduce the difference in the morning cortisol levels between the OSA and control groups. In conclusion, we report here that compared with obese nonapneic matched controls, OSA patients present a dysregulation of HPA axis activity, as shown by the flattening of the diurnal pattern of cortisol production in response to repeated challenge due to hypoxia and sleep fragmentation. This dysregulation was especially detectable in the first hour after awakening and restored after 3 and 6 mos of treatment with CPAP.

  6. [Influence of nasal continuous positive airway pressure on response to exercise in patients with obstructive sleep apnea syndrome].

    Science.gov (United States)

    Przybyłowski, Tadeusz; Bielicki, Piotr; Kumor, Marta; Hildebrand, Katarzyna; Maskey-Warzechowska, Marta; Wiwała, Joanna; Kościuch, Justyna; Korczyński, Piotr; Chazan, Ryszarda

    2006-01-01

    Obstructive sleep apnea syndrome (OSAS) patients are at risk of cardiovascular complications. The aim of this study was to assess the effect of treatment with continuous positive airway pressure (CPAP) on the response to symptom limited exercise test. twenty nine OSAS patients (1 F, 28 M), mean age 50.7+/-9.7 yrs with body mass index of 32.6+/-4.5 kg/m2 participated in the study. OSAS was diagnosed by overnight polysomnography. Incremental cardiopulmonary exercise test (CPET) on a treadmill was performed twice: before and after 2-3 weeks of regular treatment with CPAP. mean apnea + hypopnea index (AHI) before therapy was 57.6+/-12 h(-1). CPAP treatment did not change peak oxygen consumption (VO2max) (38.3+/-9.0 vs. 38.9+/-6.9 mlO2/kg/min, p=ns) or peak heart rate (153.4+/-21 min- vs. 155.5+/-22 min(-1), p=ns). There were no significant changes in ventilation or gas exchange variables. However, a decrease in peak systolic blood pressure from 194.5+/-24 mmHg to 186.7+/-27.9 mmHg (prate (at 1st minute and minutes 3 - 6) and mean arterial pressure (MAP) (minutes 4-7) with CPAP treatment was observed. Significant correlations between VO2max and AHI (r=-0,38, p<0,05); MAP at peak exercise and: AHI, mean oxygen saturation (SaO2) during sleep, minutes of sleep with SaO2<90% (T90); MAP at recovery (minutes 3-8) and T90 before CPAP treatment were also noted. OSAS patients are not limited on exercise. Treatment with nasal CPAP attenuates circulatory response to incremental exercise on a treadmill.

  7. Differing responses in right and left ventricular filling, loading and volumes during positive end-expiratory pressure

    International Nuclear Information System (INIS)

    Schulman, D.S.; Biondi, J.W.; Matthay, R.A.; Zaret, B.L.; Soufer, R.

    1989-01-01

    Using a combined hemodynamic and radionuclide technique, 20 patients with varied ventricular function were evaluated during positive end-expiratory pressure (PEEP) application. Left ventricular (LV) and right ventricular (RV) ejection fractions and cardiac output were measured, and ventricular volumes were derived. Seven patients (group 1) who had an increase in LV end-diastolic volume with PEEP and 13 patients (group 2) who had the more typical response, a decrease in LV end-diastolic volume with PEEP, were identified. Compared with group 2, group 1 patients had a higher incidence of coronary artery disease (5 of 7 vs 1 of 13, p less than 0.005) and lower cardiac output (3.9 +/- 1.6 vs 9.1 +/- 3.2 liters/min, p less than 0.005), LV ejection fraction (27 +/- 13 vs 51 +/- 21%, p less than 0.05), RV ejection fraction (15 +/- 6 vs 32 +/- 8%, p less than 0.005) and peak filling rate (1.32 +/- 0.43 vs 3.51 +/- 1.70 end-diastolic volumes/s, p less than 0.05). LV and RV volumes increased and peak filling rate decreased with PEEP in group 1, whereas in group 2 LV volume decreased and RV volume and peak filling rate remained unchanged. Using stepwise regression analysis, the change in LV volume with PEEP was related directly to baseline systemic vascular resistance and inversely to baseline blood pressure. Similarly, the change in peak filling rate with PEEP was inversely related to the change in RV end-diastolic volume. Thus, the hemodynamic response to PEEP is heterogeneous and may be related to LV ischemia

  8. Responses and mechanisms of positive electron affinity molecules in the N2 mode of the thermionic ionization detector and the electron-capture detector

    International Nuclear Information System (INIS)

    Jones, C.S.

    1989-01-01

    Very little knowledge has been acquired in the past on the mechanistic pathway by which molecules respond in the N 2 mode of the thermionic ionization detector. An attempt is made here to elucidate the response mechanism of the detector. The basic response mechanisms are known for the electron capture detector, and an attempt is made to identify the certain mechanism by which selected molecules respond. The resonance electron capture rate constant has been believed to be temperature independent, and investigations of the temperature dependence of electron capture responses are presented. Mechanisms for the N 2 mode of the thermionic ionization detector have been proposed by examining the detector response to positive electron affinity molecules and by measurement of the ions produced by the detector. Electron capture mechanisms for selected molecules have been proposed by examining their temperature dependent responses in the electron capture detector and negative ion mass spectra of the samples. In studies of the resonance electron capture rate constant, the relative responses of selected positive electron affinity molecules and their temperature dependent responses were investigated. Positive electron affinity did not guarantee large responses in the N 2 mode thermionic ionization detector. High mass ions were measured following ionization of samples in the detector. Responses in the electron capture detector varied with temperature and electron affinity

  9. Long-term sub second-response monitoring of gaseous ammonia in ambient air by positive inhaling ion mobility spectrometry.

    Science.gov (United States)

    Huang, Wei; Wang, Weiguo; Chen, Chuang; Li, Mei; Peng, Liying; Li, Hang; Liu, Jiwei; Hou, Keyong; Li, Haiyang

    2017-12-01

    A real-time dynamic measurements of ammonia (NH 3 ) is crucial for understanding the atmospheric nucleation process. A novel method was developed for on line monitoring at the sub-second time scale for the gaseous ammonia in ambient air for months, based on a positive inhaling ion mobility spectrometry (IMS) with a 63 Ni ion source. The selective detection of NH 3 was achieved using a high resolution IMS with an optimization of the drift tube temperature above 150°C. This method improved the peak-to-peak resolution significantly, thus avoided the interferences of the adjacent peaks to the quantitative analysis of NH 3 . The time resolution of the IMS was less than 0.1s at a data averaging of 10 times. The limit of detection (LOD) achieved at sub-ppb level while a linear response of peak intensity versus concentration of NH 3 in the range of 10-60ppb and 60-400ppb were obtained. The relative standard deviations (RSD), the confidence level and the errors were 1.06%, 95% and ± 0.21ppb by measuring 100ppb NH 3 for 100 times. The effect of ambient humidity could be greatly reduced by using the drift temperature of over 150°C. At last, the application of measuring the NH 3 concentration evolutions of Dalian city was performed from June 19 to December 3 in 2015. The results illustrated a potential method of using IMS for a real-time measuring atmospheric NH 3 at an unprecedented accuracy and sensitivity with long-term stability. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Gender related differences in response to "in favor of myself" wellness program to enhance positive self & body image among adolescents.

    Science.gov (United States)

    Golan, Moria; Hagay, Noa; Tamir, Snait

    2014-01-01

    Physical, neurological and psychological changes are often experienced differently by male and female adolescents. Positive self-esteem, emotional well-being, school achievements, and family connectedness are considered as protective factors against health-compromising behaviors. This study examines the gender differences in respect to the effect of a school-based interactive wellness program--"In Favor of Myself"--on self-image, body image, eating attitudes and behaviors of young adolescents. Two hundred and ten adolescents (mean age 13.5) participated in the intervention group, 55% were girls and 45% boys. Program consisted of eight 90-minutes structured sessions integrated into a regular school coping skills curriculum. The program focused on self-esteem, self-image, body image, media literacy and cognitive dissonance. The overall impact of the program and the study protocol were previously published. Overall, there are gender related differences in respect to body image and self-image in young adolescents in response to "In Favor of Myself". Compared to boys, girls reported at baseline higher self-esteem, being more contingent by appearance, and their self-image was more influenced by popularity, appearance, interpersonal communication and admired people. Furthermore girls presented greater gap between current body figure and perceived ideal figure. Not only were girls more dissatisfied with their body, but they were more active in attempts to become and/or remain "thin". At program termination, gender × time effect was detected in reduction of self-worth contingent by others, change in importance given to achievements at schools, parents' perceptions, as well as the impact of comparisons to friends and family members on self-image. Girls exhibited more gains than boys from 'In Favor of Myself' which raise the questions about how effective would be the program when delivered in mixed gender groups vs. mono-gender groups.

  11. Gender related differences in response to "in favor of myself" wellness program to enhance positive self & body image among adolescents.

    Directory of Open Access Journals (Sweden)

    Moria Golan

    Full Text Available BACKGROUND: Physical, neurological and psychological changes are often experienced differently by male and female adolescents. Positive self-esteem, emotional well-being, school achievements, and family connectedness are considered as protective factors against health-compromising behaviors. This study examines the gender differences in respect to the effect of a school-based interactive wellness program--"In Favor of Myself"--on self-image, body image, eating attitudes and behaviors of young adolescents. METHODS: Two hundred and ten adolescents (mean age 13.5 participated in the intervention group, 55% were girls and 45% boys. Program consisted of eight 90-minutes structured sessions integrated into a regular school coping skills curriculum. The program focused on self-esteem, self-image, body image, media literacy and cognitive dissonance. The overall impact of the program and the study protocol were previously published. RESULTS: Overall, there are gender related differences in respect to body image and self-image in young adolescents in response to "In Favor of Myself". Compared to boys, girls reported at baseline higher self-esteem, being more contingent by appearance, and their self-image was more influenced by popularity, appearance, interpersonal communication and admired people. Furthermore girls presented greater gap between current body figure and perceived ideal figure. Not only were girls more dissatisfied with their body, but they were more active in attempts to become and/or remain "thin". At program termination, gender × time effect was detected in reduction of self-worth contingent by others, change in importance given to achievements at schools, parents' perceptions, as well as the impact of comparisons to friends and family members on self-image. CONCLUSIONS: Girls exhibited more gains than boys from 'In Favor of Myself' which raise the questions about how effective would be the program when delivered in mixed gender groups

  12. Exploratory Cost-Effectiveness Analysis of Response-Guided Neoadjuvant Chemotherapy for Hormone Positive Breast Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Anna Miquel-Cases

    Full Text Available Guiding response to neoadjuvant chemotherapy (guided-NACT allows for an adaptative treatment approach likely to improve breast cancer survival. In this study, our primary aim is to explore the expected cost-effectiveness of guided-NACT using as a case study the first randomized controlled trial that demonstrated effectiveness (GeparTrio trial.As effectiveness was shown in hormone-receptor positive (HR+ early breast cancers (EBC, our decision model compared the health-economic outcomes of treating a cohort of such women with guided-NACT to conventional-NACT using clinical input data from the GeparTrio trial. The expected cost-effectiveness and the uncertainty around this estimate were estimated via probabilistic cost-effectiveness analysis (CEA, from a Dutch societal perspective over a 5-year time-horizon.Our exploratory CEA predicted that guided-NACT as proposed by the GeparTrio, costs additional €110, but results in 0.014 QALYs gained per patient. This scenario of guided-NACT was considered cost-effective at any willingness to pay per additional QALY. At the prevailing Dutch willingness to pay threshold (€80.000/QALY cost-effectiveness was expected with 78% certainty.This exploratory CEA indicated that guided-NACT (as proposed by the GeparTrio trial is likely cost-effective in treating HR+ EBC women. While prospective validation of the GeparTrio findings is advisable from a clinical perspective, early CEAs can be used to prioritize further research from a broader health economic perspective, by identifying which parameters contribute most to current decision uncertainty. Furthermore, their use can be extended to explore the expected cost-effectiveness of alternative guided-NACT scenarios that combine the use of promising imaging techniques together with personalized treatments.

  13. Bilateral electromyogram response latency following platform perturbation in unilateral transtibial prosthesis users: influence of weight distribution and limb position.

    Science.gov (United States)

    Rusaw, David; Hagberg, Kerstin; Nolan, Lee; Ramstrand, Nerrolyn

    2013-01-01

    Appropriate muscular response following an external perturbation is essential in preventing falls. Transtibial prosthesis users lack a foot-ankle complex and associated sensorimotor structures on the side with the prosthesis. The effect of this lack on rapid responses of the lower limb to external surface perturbations is unknown. The aim of the present study was to compare electromyogram (EMG) response latencies of otherwise healthy, unilateral, transtibial prosthesis users (n = 23, mean +/- standard deviation [SD] age = 48 +/- 14 yr) and a matched control group (n = 23, mean +/- SD age = 48 +/- 13 yr) following sudden support-surface rotations in the pitch plane (toes-up and toes-down). Perturbations were elicited in various weight-bearing and limb-perturbed conditions. The results indicated that transtibial prosthesis users have delayed responses of multiple muscles of the lower limb following perturbation, both in the intact and residual limbs. Weight-bearing had no influence on the response latency in the residual limb, but did on the intact limb. Which limb received the perturbation was found to influence the muscular response, with the intact limb showing a significantly delayed response when the perturbation was received only on the side with a prosthesis. These delayed responses may represent an increased risk of falling for individuals who use transtibial prostheses.

  14. Interim staff position on environmental qualification of safety-related electrical equipment: including staff responses to public comments. Regulatory report

    International Nuclear Information System (INIS)

    Szukiewicz, A.J.

    1981-07-01

    This document provides the NRC staff positions regarding selected areas of environmental qualification of safety-related electrical equipment, in the resolution of Unresolved Safety Issue A-24, 'Qualification of Class IE Safety-Related Equipment.' The positions herein are applicable to plants that are or will be in the construction permit (CP) or operating license (OL) review process and that are required to satisfy the requirements set forth in either the 1971 or the 1974 version of IEEE-323 standard

  15. Positive Response Distortion by Police Officer Applicants: Association of Paulhus Deception Scales with MMPI-2 and Inwald Personality Inventory Validity Scales

    Science.gov (United States)

    Detrick, Paul; Chibnall, John T.

    2008-01-01

    Interpretation of positive response distortion (socially desirable responding) in employment evaluations is an important validity issue. This study of police officer applicants examined the construct validity of the Paulhus Deception Scales (PDS)--Moralistic Bias (MB; exaggerated adjustment/agreeableness) and Egoistic Bias (EB; exaggerated…

  16. Definitive radiotherapy for head-and-neck cancer with radiographically positive retropharyngeal nodes: Incomplete radiographic response does not necessarily indicate failure

    International Nuclear Information System (INIS)

    Liauw, Stanley L.; Mancuso, Anthony A.; Morris, Christopher G. M.S.; Amdur, Robert J.; Mendenhall, William M.

    2006-01-01

    Purpose: Our aim was to report the control rate of radiographically positive retropharyngeal (RP) nodes with radiation therapy (RT) and to correlate posttreatment imaging with clinical outcome. Methods and Materials: Sixteen patients treated with definitive RT for head-and-neck cancer had radiographically positive RP nodes (size >1 cm in largest axial dimension, or presence of focal enhancement, lucency, or calcification), and both pre-RT and post-RT image sets available for review. An additional 21 patients with unconfirmed radiographically positive RP nodes had post-RT imaging, which consisted of computed tomography (CT) at a median of 4 weeks after completing RT. Patients with positive post-RT RP nodes underwent observation with serial imaging. Results: Of 16 patients with pre-RT and post-RT images available for review, 9 (56%) had a radiographic complete response, and of 21 patients with unconfirmed positive RP nodes with post-RT images available for review, 14 (67%) had a radiographic complete response. In all, 14 patients with incomplete response on post-RT imaging experienced control of their disease with no further therapy, and no RP node or neck failures were noted during a median follow-up of 2.8 years. Six patients with positive post-RT RP nodes had serial imaging available for review, and none demonstrated radiographic progression of disease. Conclusions: Radiographic response at 4 weeks may not accurately reflect long-term locoregional control, as RP nodes may continue to resolve over time. The highest index of suspicion should be reserved for patients with progressive changes in size, focal lucency, or focal enhancement on serial imaging after RT

  17. Distributed transition-edge sensors for linearized position response in a phonon-mediated X-ray imaging spectrometer

    Science.gov (United States)

    Cabrera, Blas; Brink, Paul L.; Leman, Steven W.; Castle, Joseph P.; Tomada, Astrid; Young, Betty A.; Martínez-Galarce, Dennis S.; Stern, Robert A.; Deiker, Steve; Irwin, Kent D.

    2004-03-01

    For future solar X-ray satellite missions, we are developing a phonon-mediated macro-pixel composed of a Ge crystal absorber with four superconducting transition-edge sensors (TES) distributed on the backside. The X-rays are absorbed on the opposite side and the energy is converted into phonons, which are absorbed into the four TES sensors. By connecting together parallel elements into four channels, fractional total energy absorbed between two of the sensors provides x-position information and the other two provide y-position information. We determine the optimal distribution for the TES sub-elements to obtain linear position information while minimizing the degradation of energy resolution.

  18. Positive regulation of humoral and innate immune responses induced by inactivated Avian Influenza Virus vaccine in broiler chickens.

    Science.gov (United States)

    Abdallah, Fatma; Hassanin, Ola

    2015-12-01

    Avian Influenza (AI) vaccines are widely used for mammals and birds in a trial to eliminate the Avian Influenza virus (AIV) infection from the world. However and up till now the virus is still existed via modulation of its antigenic structure to evade the pressure of host immune responses. For a complete understanding of the immune responses following AI vaccination in chickens, the modulations of the chickens humoral immune responses and interferon-alpha signaling pathway, as a fundamental part of the innate immune responses, were investigated. In our study, we measured the humoral immune response using hemagglutination-inhibition (HI) and enzyme-linked immunosorbent assay (ELISA) tests. In addition, chicken interferon-alpha pathway components was measured at RNA levels using Quantitative Real-time PCR (qRT-PCR) following one dose of inactivated H5N1 influenza vaccine at 14 days of age. In this study, the protective levels of humoral antibody responses were observed at 14, 21 and 28 days following immunization with inactivated (Re-1/H5N1) AI vaccine. In the chicken spleen cells, up regulation in the chicken interferon-alpha pathway components (MX1 & IRF7) was existed as early as 48 h post vaccination and remained until 28 days post vaccination at the endogenous state. However, after the recall with ex-vivo stimulation, the up regulation was more pronounced in the transcriptional factor (IRF7) compared to the antiviral gene (MX1) at 28 days post vaccination. So far, from our results it appears that the inactivated H5N1 vaccine can trigger the chicken interferon-alpha signaling pathway as well as it can elicit protective humoral antibody responses.

  19. Preparation of 14c- amd 180-labeled 2-[2-methoxy-4-(methylsulfinyl)phenyl]-1H-imidazo[4,5-c]-pyridine hydrochloride (LY175326), a cardiotonic with inotropic and vasodilator activities

    International Nuclear Information System (INIS)

    Kau, Don; Krushinski, J.H.; Robertson, D.W.

    1985-01-01

    Two different forms of 14 C-labeled 2-methoxy-4-(methyl-thio)benzoic acid were prepared and employed in the synthesis of 14 C-labeled 2-:2-methoxy-4-(methylsulfinyl)phenyl:-1H-imidazo-[4,5-c]pyridine hydrochloride (LY175326), a cardiotonic with inotropic and vasodilator activities that is currently in clinical trials. The synthetic procedures described in this report allowed the introduction of the 14 C-label in the antepenultimate step. Additionally, an 18 0-labeled form of LY175326 was synthesized to facilitate kinetic analysis of the formation of its sulfide and sulfone metabolites. (author)

  20. Positioning and number of nutritional levels in dose-response trials to estimate the optimal-level and the adjustment of the models

    Directory of Open Access Journals (Sweden)

    Fernando Augusto de Souza

    2014-07-01

    Full Text Available The aim of this research was to evaluate the influence of the number and position of nutrient levels used in dose-response trials in the estimation of the optimal-level (OL and the goodness of fit on the models: quadratic polynomial (QP, exponential (EXP, linear response plateau (LRP and quadratic response plateau (QRP. It was used data from dose-response trials realized in FCAV-Unesp Jaboticabal considering the homogeneity of variances and normal distribution. The fit of the models were evaluated considered the following statistics: adjusted coefficient of determination (R²adj, coefficient of variation (CV and the sum of the squares of deviations (SSD.It was verified in QP and EXP models that small changes on the placement and distribution of the levels caused great changes in the estimation of the OL. The LRP model was deeply influenced by the absence or presence of the level between the response and stabilization phases (change in the straight to plateau. The QRP needed more levels on the response phase and the last level on stabilization phase to estimate correctly the plateau. It was concluded that the OL and the adjust of the models are dependent on the positioning and the number of the levels and the specific characteristics of each model, but levels defined near to the true requirement and not so spaced are better to estimate the OL.

  1. Response of Preterm Infants to 2 Noninvasive Ventilatory Support Systems: Nasal CPAP and Nasal Intermittent Positive-Pressure Ventilation.

    Science.gov (United States)

    Silveira, Carmen Salum Thomé; Leonardi, Kamila Maia; Melo, Ana Paula Carvalho Freire; Zaia, José Eduardo; Brunherotti, Marisa Afonso Andrade

    2015-12-01

    Noninvasive ventilation (NIV) in preterm infants is currently applied using intermittent positive pressure (2 positive-pressure levels) or in a conventional manner (one pressure level). However, there are no studies in the literature comparing the chances of failure of these NIV methods. The aim of this study was to evaluate the occurrence of failure of 2 noninvasive ventilatory support systems in preterm neonates over a period of 48 h. A randomized, prospective, clinical study was conducted on 80 newborns (gestational age CPAP and 40 infants with nasal intermittent positive-pressure ventilation (NIPPV). The occurrence of apnea, progression of respiratory distress, nose bleeding, and agitation was defined as ventilation failure. The need for intubation and re-intubation after failure was also observed. There were no significant differences in birth characteristics between groups. Ventilatory support failure was observed in 25 (62.5%) newborns treated with nasal CPAP and in 12 (30%) newborns treated with NIPPV, indicating an association between NIV failure and the absence of intermittent positive pressure (odds ratio [OR] 1.22, P CPAP failure. After failure, 25% (OR 0.33) of the newborns receiving nasal CPAP and 12.5% (OR 0.14) receiving NIPPV required invasive mechanical ventilation. Ventilatory support failure was significantly more frequent when nasal CPAP was used. Copyright © 2015 by Daedalus Enterprises.

  2. Survival is associated with complete response on MRI after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer

    NARCIS (Netherlands)

    Loo, Claudette E; Rigter, Lisanne S; Pengel, Kenneth E; Wesseling, Jelle; Rodenhuis, Sjoerd; Peeters, Marie-Jeanne T F D Vrancken; Sikorska, Karolina; Gilhuijs, Kenneth G A

    2016-01-01

    BACKGROUND: Pathological complete remission (pCR) of estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer is rarely achieved after neoadjuvant chemotherapy (NAC). In addition, the prognostic value of pCR for this breast cancer subtype is limited. We

  3. Is response to anti-hepatitis C virus treatment predictive of mortality in hepatitis C virus/HIV-positive patients?

    DEFF Research Database (Denmark)

    Peters, Lars; Raben, Dorthe

    2017-01-01

    BACKGROUND: Long-term clinical outcomes after hepatitis C virus (HCV) treatment of HIV/HCV patients are not well described. We aimed to compare the risk of all-cause and liver-related death (LRD) according to HCV treatment response in HIV/HCV patients in the multicohort study Collaboration...... of Observational HIV Epidemiological Research in Europe. METHODS: All patients who had started pegylated interferon + ribavirin (baseline) and followed for at least 72 weeks after baseline were included. Patients were categorized into three response groups depending on treatment duration and HCV-RNA measured...... in the window 24-72 weeks after baseline. Patients who received at least 24 weeks of therapy were defined as responders if their last HCV-RNA measured between 24 and 72 weeks after baseline was negative, and having 'unknown response' if HCV-RNA was unknown. Nonresponders were treated for less than 24 weeks...

  4. AtRAV and AtbZIP transcription factors positively regulate ABA responses: Overexpression in cotton enhances drought stress adaptation

    Science.gov (United States)

    Drought tolerance is an important trait being pursued by the agbiotech industry. Abscisic acid (ABA) is a stress hormone that mediates a multitude of processes in growth and development, water use efficiency, and gene expression during seed development and in response to environmental stresses. Ar...

  5. The Position of Member States in (Autonomous) Institutional Decision-Making : Implications for the Establishment of Responsibility

    NARCIS (Netherlands)

    Ryngaert, Cedric; Barros, Sofia

    2014-01-01

    The international legal personality and autonomy of international organizations constitute the main vantage point from which responsibility issues in an institutional context are addressed in legal scholarship. In such an exercise, what is often missed is an explanation of how both concepts impact

  6. Destination branding by residents : The role of perceived responsibility in positive and negative word-of-mouth

    NARCIS (Netherlands)

    Jeuring, Jelmer; Haartsen, Tialda

    2017-01-01

    The importance of residents’ communication about their home region as tourist destination is increasingly acknowledged in the place branding process. However, the extent to which residents feel responsible for communicating Destination Images (DIs), and how these attributions affect word-of-mouth

  7. Preoperative apolipoprotein CI levels correlate positively with the proinflammatory response in patients experiencing endotoxemia following elective cardiac surgery

    NARCIS (Netherlands)

    Schippers, E.F.; Berbée, J.F.P.; Disseldorp, I.M. van; Versteegh, M.I.M.; Havekes, L.M.; Rensen, P.C.N.; Dissel, J.T. van

    2008-01-01

    Objective: Experimental models show that apolipoprotein CI (apoCI) binds and enhances the inflammatory response to endotoxin. We studied in patients undergoing cardiopulmonary bypass surgery (CPB) and experiencing endotoxemia during reperfusion whether plasma apoCI levels correlate with the

  8. Developing Training Programs to Enhance Positive Attitude toward the ASEAN Community and Self-responsibility For Students in the 6th Grade Naku Distric Kalasin

    Directory of Open Access Journals (Sweden)

    Siriporn Chooarerom

    2016-09-01

    Full Text Available The purposes of this study were to ; 1 Study the status and problem of an through attitude the ASEAN community for grade 6 students. 2 Develop training programs to enhance their positive attitude towards the ASEAN community and self-responsibility for grade 6 students. 3 Experiment training program to enhance their positive attitude towards the ASEAN community and self-responsibility for grade 6 students. The samples of this study were 21 students. They were selected though cluster random sampling method. The research instruments used in the study were the Training programs to enhance their positive attitude towards the ASEAN community and self-responsibility. Surveys of problems from the event ASEAN week. Lenarning ASEAN. Measuring a positive attitude towards the ASEAN community scale with discriminating power ranging 0.375 – 0.793 and Measuring self-responsibility scale with discriminating power ranging 0.411 – 0.893 and a reliability of 0.973. The statistics used for analyzing the collected data were mean, standard deviation, and One-way repeated measure MANOVA The study showed that 1 Study of the attitude of the ASEAN community condition survey found that teachers have trouble understanding, Interested to attend the event and have admired and awareness in preparation the ASEAN community, the levels are minimal. The students realized in preparation, understanding about . Attention to participation and appreciation the ASEAN community, the levels are minimal 2 Training programs to enhance their positive attitude toward the ASEAN community and self-responsibility for grade 6 students was created by. Activities focus on the students involved and take action. Remove group activities used in the event. Stage one consists of two steps leading to the involvement step 3 step 4 step by step analysis and application of the five-stage process and evaluation. By 5 experts have evaluated the overall level more appropriate. 3 Students attend their

  9. Systemic Epstein-Barr Virus-positive T-Cell Lymphoproliferative Disease of Childhood With Good Response to Steroid Therapy.

    Science.gov (United States)

    Kim, Do-Hoon; Kim, Myungshin; Kim, Yonggoo; Han, Kyungja; Han, Eunhee; Lee, Jae Wook; Chung, Nack-Gyun; Cho, Bin

    2017-11-01

    Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood is a rare disease and has a very fulminant clinical course with high mortality. A 21-month-old female patient was referred to our hospital with a 1 week history of fever and was subsequently diagnosed with systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease of childhood. After starting treatment with dexamethasone, she showed early defervescence and improvement of laboratory parameters, and has remained disease-free after stopping steroid treatment, although longer follow-up is necessary. Our report underscores the possibility that this disease entity may be heterogenous in terms of prognosis.

  10. Exposure to blue wavelength light modulates anterior cingulate cortex activation in response to 'uncertain' versus 'certain' anticipation of positive stimuli.

    Science.gov (United States)

    Alkozei, Anna; Smith, Ryan; Killgore, William D S

    2016-03-11

    Blue wavelength light has been used as an effective treatment for some types of mood disorders and circadian rhythm related sleep problems. We hypothesized that acute exposure to blue wavelength light would directly affect the functioning of neurocircuity implicated in emotion regulation (i.e., ventromedial prefrontal cortex, amygdala, insula, and anterior cingulate cortex [ACC]) during 'certain' and 'uncertain' anticipation of negative and positive stimuli. Thirty-five healthy adults were randomized to receive a thirty-minute exposure to either blue (active) or amber (placebo) light, immediately followed by an emotional anticipation task during functional magnetic resonance imaging (fMRI). In contrast to placebo, participants in the blue light group showed significantly reduced activation within the rostral ACC during 'uncertain' anticipation (i.e., uncertainty regarding whether a positive or negative stimulus would be shown) in comparison to 'certain' anticipation of a positive stimulus. These findings may be explicable in terms of interactions between blue light exposure and the influence of specific neuromodulators on ACC-mediated decision-making mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Longer inter-lead electrical delay is associated with response to cardiac resynchronization therapy in patients with presumed optimal left ventricular lead position

    DEFF Research Database (Denmark)

    Sommer, Anders; Kronborg, Mads Brix; Nørgaard, Bjarne Linde

    2018-01-01

    was defined as ≥15% reduction in LV end-systolic volume at 6 months follow-up. Selecting a practical IED cut-off value of 100 ms, more patients with long IED than patients with short IED responded to CRT (87 vs. 68%; P = 0.004). In multivariate logistic regression analysis, IED ≥100 ms remained associated...... LV lead position. Conclusion: A longer IED was associated with more pronounced LV reverse remodelling response in CRT recipients with a presumed optimal LV lead position concordant or adjacent to the latest mechanically activated non-scarred segment....

  12. Decreased background parenchymal enhancement of the contralateral breast after two cycles of neoadjuvant chemotherapy is associated with tumor response in HER2-positive breast cancer.

    Science.gov (United States)

    You, Chao; Gu, Yajia; Peng, Wen; Li, Jianwei; Shen, Xuxia; Liu, Guangyu; Peng, Weijun

    2018-07-01

    Background Several recent studies have focused on the association between background parenchymal enhancement (BPE) and tumor response to neoadjuvant chemotherapy (NAC), but early prediction of tumor response based on BPE has yet not been investigated. Purpose To retrospectively investigate whether changes in the BPE of the contralateral breast following NAC could help predict tumor response in early stage HER2-positive breast cancer. Material and Methods Data from 71 patients who were diagnosed with unilateral HER2 positive breast cancer and then underwent NAC with trastuzumab before surgery were analyzed retrospectively. Two experienced radiologists independently categorized the patients' levels of BPE of the contralateral breast into four categories (1 = minimal, 2 = mild, 3 = moderate, 4 = marked) at baseline and after the second cycle of NAC. After undergoing surgery, 34 patients achieved pathologic complete response (pCR) and 37 patients had residual disease (non-pCR). The association between BPE and histopathologic tumor response was analyzed. Result The level of BPE was higher in premenopausal than post-menopausal women both at baseline and after the second cycle of NAC ( P < 0.005). A significant reduction in BPE ( P < 0.001) was observed after the second NAC cycle; however, a more obvious decrease in BPE was identified in premenopausal relative to post-menopausal women ( P = 0.041). No significant association was identified between pCR and baseline BPE ( P = 0.287). However, after the second NAC cycle, decreased BPE was significantly associated with pCR ( P = 0.003). Conclusion For HER2-positive patients, changes in BPE may serve as an additional imaging biomarker of treatment response at an early stage.

  13. Positive Psychology in Context: Effects of Expressing Gratitude in Ongoing Relationships Depend on Perceptions of Enactor Responsiveness.

    Science.gov (United States)

    Algoe, Sara B; Zhaoyang, Ruixue

    2016-01-01

    Recent correlational evidence implicates gratitude in personal and relational growth, for both members of ongoing relationships. From these observations, it would be tempting to prescribe interpersonal gratitude exercises to improve relationships. In this experiment, couples were randomly assigned to express gratitude over a month, or to a relationally-active control condition. Results showed modest effects of condition on personal and relational well-being. However, those whose partners were perceived as being particularly responsive when expressing gratitude at the initial lab session showed greater well-being across a range of outcomes, whereas this was not so for people in the control condition. Notably, evidence raises concerns about the effectiveness of artificial injections of gratitude when the partner is perceived to be low in responsiveness. Given the importance of close relationships, this work highlights the need for more theory-driven basic research tested in context before assuming what appears to work naturally will also work artificially.

  14. Coincidence in map positions between pathogen-induced defense-responsive genes and quantitative resistance loci in rice

    Institute of Scientific and Technical Information of China (English)

    熊敏; 王石平; 张启发

    2002-01-01

    Quantitative disease resistance conferred by quantitative trait loci (QTLs) is presumably of wider spectrum and durable. Forty-four cDNA clones, representing 44 defense-responsive genes, were fine mapped to 56 loci distributed on 9 of the 12 rice chromosomes. The locations of 32 loci detected by 27 cDNA clones were associated with previously identified resistance QTLs for different rice diseases, including blast, bacterial blight, sheath blight and yellow mottle virus. The loci detected by the same multiple-copy cDNA clones were frequently located on similar locations of different chromosomes. Some of the multiple loci detected by the same clones were all associated with resistance QTLs. These results suggest that some of the genes may be important components in regulation of defense responses against pathogen invasion and they may be the candidates for studying the mechanism of quantitative disease resistance in rice.

  15. Metabolic Response of Soil Microorganisms to Frost: A New Perspective from Position-specific 13C Labeling

    Science.gov (United States)

    Bore, E. K.; Apostel, C.; Halicki, S.; Dippold, M. A.; Kuzyakov, Y.

    2016-12-01

    Cold adapted organisms and their biomolecules have received considerable attention in the last few decades, particularly in light of the perceived biotechnological potential. Mostly, these studies are based on pure isolated cultures from permafrost or permafrost samples with inherently adapted microbes. However, microbial activities in agricultural soils that are predominantly exposed to freeze conditions during winter in temperate ecosystems remain unclear. To analyze microbial metabolism at low soil temperatures, isotopomeres of position-specifically 13C labeled glucose were incubated at three temperature; 5 (control), -5 -20 oC. Soils were sampled after 1, 3 and 10 days (and after 30 days for samples at -20 °C). 13C was quantifed in CO2, bulk soil, microbial biomass and dissolved organic carbon (DOC). Highest 13C recovery in CO2 was obtained from C-1 position in control soil. Consequently, metabolic activity was dominated by pentose phosphate pathway at 5 °C. In contrast, metabolic behaviors switched towards a preferential respiration of the glucose C-4 position at -5 and -20 °C. High 13C recovery from C-4 position confirms previous studies suggesting that fermentation increases at subzero temperature. A 3-fold higher 13C recovery in microbial biomass at -5 °C than under control conditions points towards synthesis of intracellular antifreeze metabolites such as glycerol and ethanol and it is consistent with fermentative metabolism. A 5-fold higher 13C in bulk soil than microbial biomass at -20 °C does not reflect non-metabolized glucose because 13C recovery in DOC was less than 0.4% at day 1. Therefore, high 13C recovery in bulk soil at -20 °C was attributed to extracellular metabolites secreted to overcome frost. The shift in antifreeze mechanisms with temperature was brought about by shift in microbial community structure as indicated by incorporation into 13C into PLFA which was 2-fold higher in gram negative bacteria under control than frozen

  16. Post-therapeutic recovery of serum interleukin-35 level might predict positive response to immunosuppressive therapy in pediatric aplastic anemia.

    Science.gov (United States)

    Huang, Zhen; Tong, Hongfei; Li, Yuan; Zhou, Haixia; Qian, Jiangchao; Wang, Juxiang; Ruan, Jichen

    2017-08-01

    The predictive value of interleukin-35 (IL-35) on efficacy of immunosuppressive therapy (IST) in aplastic anemia (AA) has not been well investigated. The aim of the study was to evaluate the association between serum IL-35 level and response to IST in pediatric AA. A total of 154 children with AA and 154 controls were included between January 2012 and December 2013. Blood and bone marrow fluid specimens were collected. Serum level of IL-35 was determined by enzyme-linked immunosorbent assay. Patients were treated with IST, and response to therapy was evaluated during 180-day follow-up period after starting therapy. Serum levels of IL-35 at admission decreased significantly in patients compared with that in controls (10.9 ± 5.5 pg ml -1 and 45.3 ± 8.8 pg ml -1 , p < 0.001). After starting IST, serum levels of IL-35 in patients recovered 30.7 ± 9.7 pg ml -1 in the first 28 days (p < 0.001). During the follow-up period, increased range of serum IL-35 level ≥30.7 pg ml -1 in the first 28 days was associated with effective response to therapy (odds ratio 7.97, 95% confidence interval 3.82-16.79). In addition, Fas/FasL protein expression in bone marrow mononuclear cells dropped significantly in the same group of patients in the first 28 days (p < 0.05). The study revealed that post-therapeutic recovery of circulating IL-35 concentration might be an independent predictor for effective response to IST in pediatric AA. Moreover, apoptosis might be involved in such a forecasting process.

  17. Maintaining positive

    OpenAIRE

    Gheorghe Gh. IONESCU; Adina Letitia NEGRUSA

    2004-01-01

    Maintaining positive work-force relationships includes in effective labor-management relations and making appropriate responses to current employee issues. Among the major current employee issues are protection from arbitrary dismissal, drug and alcohol abuse, privacy rights and family maters and they impact work. In our paper we discus two problems: first, the meanings of industrial democracy; second, the three principal operational concepts of industrial democracy (1) industrial democracy t...

  18. Seed germination of Pinus koraiensis Siebold and Zucc. in response to light regimes caused by shading and seed positions

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, M.; Zhu, J.; Yan, Q.

    2012-07-01

    Pinus koraiensis Siebold and Zucc. (Korean pine), the dominant tree species in the mixed broadleaved Korean pine forests (regional climax), is severely restricted by its regeneration failure. To determine the effects of light regimes on P. koraiensis regeneration, the seed germination process was examined in shade houses and forest stands (before and after leaf expansion) with various light levels created by shading and seed positions. Despite the large size of P. koraiensis seeds (500-600 mg), both light intensity and quality significantly affected the germination percentage in both shade houses and forests. Substantial changes in light intensity and quality led the majority of seeds (80%) to germinate in leafless forests and shade houses, while only a minority ({<=}20%) germinated after leaf expansion in the forests. Moreover, seed germination in shade houses and leafless forests exhibited similar patterns; they consistently reached a 70% shading degree, which was optimal for the seed germination of P. koraiensis on topsoil. Seed positioning significantly affected germination for each shading degree, especially when litter and soil coverings drastically inhibited germination. In conclusion, (1) when seeds were not stressed by temperature and moisture, light irradiance played a critical role in the seed germination of P. koraiensis; (2) seed positioning, in relation to alterations in light intensity and quality, affected the germination of P. koraiensis; (3) a shade house experiment using neutral cloth provided an applicable and controllable way to monitor the P. koraiensis seed germination in early spring before leaf expansion. The light requirement for the germination of P. koraiensis played a key role in the regeneration of P. koraiensis throughout the temperate secondary forests. (Author) 41 refs.

  19. The structurally novel Ca2+ channel blocker Ro 40-5967, which binds to the [3H] desmethoxyverapamil receptor, is devoid of the negative inotropic effects of verapamil in normal and failing rat hearts

    International Nuclear Information System (INIS)

    Clozel, J.P.; Veniant, M.; Osterrieder, W.

    1990-01-01

    Ro 40-5967 is a structurally novel Ca 2+ channel blocker that binds to the verapamil-type receptor of cardiac membranes but that has been shown in isolated guinea-pig hearts to be about ten times less potent a negative inotropic agent than verapamil. The goals of the present study were to confirm these findings in vitro in isolated perfused rat hearts as well as in vivo in conscious rats and to compare Ro 40-5967 to verapamil. The effects of Ro 40-5967 and verapamil were tested not only in normal rats, but also in rats with heart failure induced by chronic myocardial infarction. In isolated Langendorff hearts (without heart failure), no decrease of contractility was observed with Ro 40-5967 up to complete AV block. In contrast, verapamil decreased contractility with an IC50 of 100 nM. In isolated, electrically stimulated rat papillary muscles, the IC50 values for the decrease of contractile force were 15,000 and 440 nM for Ro 40-5967 and verapamil, respectively. In vivo, Ro 40-5967 did not decrease left ventricular contractility (as assessed by changes of dP/dt max +) in rats without and with heart failure. In contrast, verapamil was markedly negative inotropic in both conditions

  20. Do release-site biases reflect response to the Earth's magnetic field during position determination by homing pigeons?

    Science.gov (United States)

    Mora, Cordula V; Walker, Michael M

    2009-09-22

    How homing pigeons (Columba livia) return to their loft from distant, unfamiliar sites has long been a mystery. At many release sites, untreated birds consistently vanish from view in a direction different from the home direction, a phenomenon called the release-site bias. These deviations in flight direction have been implicated in the position determination (or map) step of navigation because they may reflect local distortions in information about location that the birds obtain from the geophysical environment at the release site. Here, we performed a post hoc analysis of the relationship between vanishing bearings and local variations in magnetic intensity using previously published datasets for pigeons homing to lofts in Germany. Vanishing bearings of both experienced and naïve birds were strongly associated with magnetic intensity variations at release sites, with 90 per cent of bearings lying within +/-29 degrees of the magnetic intensity slope or contour direction. Our results (i) demonstrate that pigeons respond in an orderly manner to the local structure of the magnetic field at release sites, (ii) provide a mechanism for the occurrence of release-site biases and (iii) suggest that pigeons may derive spatial information from the magnetic field at the release site that could be used to estimate their current position relative to their loft.

  1. Development of X-Y servo pneumatic-piezoelectric hybrid actuators for position control with high response, large stroke and nanometer accuracy.

    Science.gov (United States)

    Chiang, Mao-Hsiung

    2010-01-01

    This study aims to develop a X-Y dual-axial intelligent servo pneumatic-piezoelectric hybrid actuator for position control with high response, large stroke (250 mm, 200 mm) and nanometer accuracy (20 nm). In each axis, the rodless pneumatic actuator serves to position in coarse stroke and the piezoelectric actuator compensates in fine stroke. Thus, the overall control systems of the single axis become a dual-input single-output (DISO) system. Although the rodless pneumatic actuator has relatively larger friction force, it has the advantage of mechanism for multi-axial development. Thus, the X-Y dual-axial positioning system is developed based on the servo pneumatic-piezoelectric hybrid actuator. In addition, the decoupling self-organizing fuzzy sliding mode control is developed as the intelligent control strategies. Finally, the proposed novel intelligent X-Y dual-axial servo pneumatic-piezoelectric hybrid actuators are implemented and verified experimentally.

  2. Development of X-Y Servo Pneumatic-Piezoelectric Hybrid Actuators for Position Control with High Response, Large Stroke and Nanometer Accuracy

    Directory of Open Access Journals (Sweden)

    Mao-Hsiung Chiang

    2010-03-01

    Full Text Available This study aims to develop a X-Y dual-axial intelligent servo pneumatic-piezoelectric hybrid actuator for position control with high response, large stroke (250 mm, 200 mm and nanometer accuracy (20 nm. In each axis, the rodless pneumatic actuator serves to position in coarse stroke and the piezoelectric actuator compensates in fine stroke. Thus, the overall control systems of the single axis become a dual-input single-output (DISO system. Although the rodless pneumatic actuator has relatively larger friction force, it has the advantage of mechanism for multi-axial development. Thus, the X-Y dual-axial positioning system is developed based on the servo pneumatic-piezoelectric hybrid actuator. In addition, the decoupling self-organizing fuzzy sliding mode control is developed as the intelligent control strategies. Finally, the proposed novel intelligent X-Y dual-axial servo pneumatic-piezoelectric hybrid actuators are implemented and verified experimentally.

  3. Alu-miRNA interactions modulate transcript isoform diversity in stress response and reveal signatures of positive selection

    Science.gov (United States)

    Pandey, Rajesh; Bhattacharya, Aniket; Bhardwaj, Vivek; Jha, Vineet; Mandal, Amit K.; Mukerji, Mitali

    2016-09-01

    Primate-specific Alus harbor different regulatory features, including miRNA targets. In this study, we provide evidence for miRNA-mediated modulation of transcript isoform levels during heat-shock response through exaptation of Alu-miRNA sites in mature mRNA. We performed genome-wide expression profiling coupled with functional validation of miRNA target sites within exonized Alus, and analyzed conservation of these targets across primates. We observed that two miRNAs (miR-15a-3p and miR-302d-3p) elevated in stress response, target RAD1, GTSE1, NR2C1, FKBP9 and UBE2I exclusively within Alu. These genes map onto the p53 regulatory network. Ectopic overexpression of miR-15a-3p downregulates GTSE1 and RAD1 at the protein level and enhances cell survival. This Alu-mediated fine-tuning seems to be unique to humans as evident from the absence of orthologous sites in other primate lineages. We further analyzed signatures of selection on Alu-miRNA targets in the genome, using 1000 Genomes Phase-I data. We found that 198 out of 3177 Alu-exonized genes exhibit signatures of selection within Alu-miRNA sites, with 60 of them containing SNPs supported by multiple evidences (global-FST > 0.3, pair-wise-FST > 0.5, Fay-Wu’s H  2.0, high ΔDAF) and implicated in p53 network. We propose that by affecting multiple genes, Alu-miRNA interactions have the potential to facilitate population-level adaptations in response to environmental challenges.

  4. Intentional modulation of the late positive potential in response to smoking cues by cognitive strategies in smokers.

    Science.gov (United States)

    Littel, Marianne; Franken, Ingmar H A

    2011-01-01

    Attentional bias is considered an important concept in addiction since it has been found to correlate with subjective craving and is strongly associated with relapse after periods of abstinence. Hence, investigating in ways to regulate attention for drug cues would be of major clinical relevance. The present study examined deliberate, cognitive modulation of motivated attention for smoking cues in smokers. The effects of three different reappraisal strategies on an electrophysiological measure of attentive processing were investigated. Early and late LPP components in response to passively viewed neutral and smoking pictures were compared with LPPs in response to smoking pictures that were reappraised with three different reappraisal strategies. Results show that when smokers actively imagine how pleasant it would be to smoke (pleasant condition), their early LPP in response to smoking cues increases, but when smokers actively focus on an alternative stimulus (distraction condition) or think of a rational, uninvolved interpretation of the situation (rational condition), smoking-related late LPP amplitude decreases to the processing level of neutral stimuli. Present results are the first to indicate that smoking cue-elicited LPP amplitudes can be modulated by cognitive strategies, suggesting that attentive processing of smoking cues can be intentionally regulated by smokers with various levels of dependence. Although cognitive strategies can lead to enhanced processing of smoking cues, it is not completely clear whether cognitive strategies are also successful in reducing smoking-related motivated attention. Although findings do point in this direction, present study is best considered preliminary and a starting point for other research on this topic. A focus on the distraction strategy is proposed, as there are indications that this strategy is more successful than the rational strategy in decreasing LPP amplitude.

  5. Atoms confined in a penetrable potential: effect of the atom position on the electric and magnetic responses

    Energy Technology Data Exchange (ETDEWEB)

    Acosta Coden, Diego S; Gomez, Sergio S; Romero, Rodolfo H, E-mail: rhromero@exa.unne.edu.ar [Instituto de Modelado e Innovacion Tecnologica, CONICET and Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste, Avenida Libertad 5500 (3400) Corrientes (Argentina)

    2011-02-14

    We report results of the calculation of polarizability and the nuclear magnetic shielding tensors of two-electron atoms confined within an attractive Gaussian potential well. The electric and magnetic responses are obtained within the random phase approximation (RPA) of the polarization propagator. The influence of the depth and range of the potential on the electronic structure is also studied. The dependence of the parallel (along the displacement) and perpendicular components of the polarizability and shielding tensors on the distance of the atom to the centre of the well is calculated and rationalized as a dissociation-type process of the artificial diatomic molecule formed between the Coulomb and the well potentials.

  6. The development of the Florentine silk industry: a positive response to the crisis of the fourteenth century

    Directory of Open Access Journals (Sweden)

    Sergio Tognetti

    2012-10-01

    Full Text Available The development of the silk industry in Renaissance Florence was a response to the profound economic changes wrought by the demographic crisis of the fourteenth century. The decrease in the available labour supply, the rise in labour costs, changes in demand and consumption, encouraged entrepreneurs in Florence to direct their manufacturing interests towards the production of expensive high-quality goods. The Florentine silk industry was born in the last decades of the fourteenth century, and in the fifteenth century quickly developed into a dynamic industry capable of producing large quantities of luxury fabrics for export to all the principal European markets.

  7. Atoms confined in a penetrable potential: effect of the atom position on the electric and magnetic responses

    International Nuclear Information System (INIS)

    Acosta Coden, Diego S; Gomez, Sergio S; Romero, Rodolfo H

    2011-01-01

    We report results of the calculation of polarizability and the nuclear magnetic shielding tensors of two-electron atoms confined within an attractive Gaussian potential well. The electric and magnetic responses are obtained within the random phase approximation (RPA) of the polarization propagator. The influence of the depth and range of the potential on the electronic structure is also studied. The dependence of the parallel (along the displacement) and perpendicular components of the polarizability and shielding tensors on the distance of the atom to the centre of the well is calculated and rationalized as a dissociation-type process of the artificial diatomic molecule formed between the Coulomb and the well potentials.

  8. THE POSITION OF STATE RESPONSIBILITY FOR ENVIRONMENTAL POLLUTION BY CORPORATE : The Legal Studies of Implementation Paradigm Polluter Pay Principle in Environmental Law Enforcement in Indonesia

    Directory of Open Access Journals (Sweden)

    Maret Priyanta

    2016-12-01

    Full Text Available The development activities is one of the government's efforts in order to realize a fairness and prosperous for the society. The natural resources management through the business activities carried out by the corporation, became one of the important factors in the success of national development. One of the impacts of development activities on the environment is the environmental pollution because of the utilization of natural resources. The pollution has caused a decrease in the quality of human life and other living creatures. Differences paradigm or way people view the polluter pays principle and the position of the responsibility of States to discredit the corporation still there is a difference of view and understanding. It is see from the practice of application of the Social and Environmental Responsibility (TJSL, which seems to have been removing corporate responsibility and involvement allocationof State budget revenue and expenditure of the State to penangulangan pollution, which performed by the corporation. This has led to uncertainty in the law enforcement environment in Indonesia. This study aimed to describe the problem from the legal aspect and theory in relation to the position of state responsibility and corporate environmental pollution in the environmental legal system. This study uses normative juridical approach, through the method of approach to legislation, the conceptual approach, and an analytical approach. The scope of this normative juridical research includes the study of the principles and theory of law. Paradigm reform of the principles of pollution should be change or reform based on theory of law, whereby the position and extent of responsibility of states and corporations definitely be regulated in the Indonesia environmental legal system.

  9. Not saying I am happy does not mean I am not: cultural influences on responses to positive affect items in the CES-D.

    Science.gov (United States)

    Jang, Yuri; Kwag, Kyung Hwa; Chiriboga, David A

    2010-11-01

    Given the emphasis on modesty and self-effacement in Asian societies, the present study explored differential item responses for 2 positive affect items (5 = Hopeful and 8 = Happy) on a short form of the Center for Epidemiologic Studies-Depression scale. The samples consisted of elderly non-Hispanic Whites (n = 450), Korean Americans (n = 519), and Koreans (n = 2,030). Multiple Indicator Multiple Cause models were estimated to identify the impact of group membership on responses to the positive affect items while controlling for the latent trait of depressive symptoms. The data revealed that Koreans and Korean Americans were less likely than non-Hispanic Whites to endorse the positive affect items. Compared with Korean Americans who were more acculturated to mainstream American culture, those who were less acculturated were less likely to endorse the positive affect items. Our findings support the notion that the way in which people endorse depressive symptoms is substantially influenced by cultural orientation. These findings call into question the common use of simple mean comparisons and a universal cutoff point across diverse cultural groups.

  10. Intrinsic Subtype and Therapeutic Response Among HER2-Positive Breast Tumors from the NCCTG (Alliance) N9831 Trial

    Science.gov (United States)

    Perez, Edith A.; Ballman, Karla V.; Mashadi-Hossein, Afshin; Tenner, Kathleen S.; Kachergus, Jennifer M.; Norton, Nadine; Necela, Brian M.; Carr, Jennifer M.; Ferree, Sean; Perou, Charles M.; Baehner, Frederick; Cheang, Maggie Chon U.

    2017-01-01

    Background: Genomic data from human epidermal growth factor receptor 2–positive (HER2+) tumors were analyzed to assess the association between intrinsic subtype and clinical outcome in a large, well-annotated patient cohort. Methods: Samples from the NCCTG (Alliance) N9831 trial were analyzed using the Prosigna algorithm on the NanoString platform to define intrinsic subtype, risk of recurrence scores, and risk categories for 1392 HER2+ tumors. Subtypes were evaluated for recurrence-free survival (RFS) using Kaplan-Meier and Cox model analysis following adjuvant chemotherapy (n = 484) or chemotherapy plus trastuzumab (n = 908). All statistical tests were two-sided. Results: Patients with HER2+ tumors from N9831 were primarily scored as HER2-enriched (72.1%). These individuals received statistically significant benefit from trastuzumab (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.52 to 0.89, P = .005), as did the patients (291 of 1392) with luminal-type tumors (HR = 0.52, 95% CI = 0.32 to 0.85, P = .01). Patients with basal-like tumors (97 of 1392) did not have statistically significantly better RFS when treated with trastuzumab and chemotherapy compared with chemotherapy alone (HR = 1.06, 95% CI = 0.53 to 2.13, P = .87). Conclusions: The majority of clinically defined HER2-positive tumors were classified as HER2-enriched or luminal using the Prosigna algorithm. Intrinsic subtype alone cannot replace conventional histopathological evaluation of HER2 status because many tumors that are classified as luminal A or luminal B will benefit from adjuvant trastuzumab if that subtype is accompanied by HER2 overexpression. However, among tumors that overexpress HER2, we speculate that assessment of intrinsic subtype may influence treatment, particularly with respect to evaluating alternative therapeutic approaches for that subset of HER2-positive tumors of the basal-like subtype. PMID:27794124

  11. Intrinsic Subtype and Therapeutic Response Among HER2-Positive Breaty st Tumors from the NCCTG (Alliance) N9831 Trial.

    Science.gov (United States)

    Perez, Edith A; Ballman, Karla V; Mashadi-Hossein, Afshin; Tenner, Kathleen S; Kachergus, Jennifer M; Norton, Nadine; Necela, Brian M; Carr, Jennifer M; Ferree, Sean; Perou, Charles M; Baehner, Frederick; Cheang, Maggie Chon U; Thompson, E Aubrey

    2017-02-01

    Genomic data from human epidermal growth factor receptor 2-positive (HER2+) tumors were analyzed to assess the association between intrinsic subtype and clinical outcome in a large, well-annotated patient cohort. Samples from the NCCTG (Alliance) N9831 trial were analyzed using the Prosigna algorithm on the NanoString platform to define intrinsic subtype, risk of recurrence scores, and risk categories for 1392 HER2+ tumors. Subtypes were evaluated for recurrence-free survival (RFS) using Kaplan-Meier and Cox model analysis following adjuvant chemotherapy (n = 484) or chemotherapy plus trastuzumab (n = 908). All statistical tests were two-sided. Patients with HER2+ tumors from N9831 were primarily scored as HER2-enriched (72.1%). These individuals received statistically significant benefit from trastuzumab (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.52 to 0.89, P = .005), as did the patients (291 of 1392) with luminal-type tumors (HR = 0.52, 95% CI = 0.32 to 0.85, P = .01). Patients with basal-like tumors (97 of 1392) did not have statistically significantly better RFS when treated with trastuzumab and chemotherapy compared with chemotherapy alone (HR = 1.06, 95% CI = 0.53 to 2.13, P = .87). The majority of clinically defined HER2-positive tumors were classified as HER2-enriched or luminal using the Prosigna algorithm. Intrinsic subtype alone cannot replace conventional histopathological evaluation of HER2 status because many tumors that are classified as luminal A or luminal B will benefit from adjuvant trastuzumab if that subtype is accompanied by HER2 overexpression. However, among tumors that overexpress HER2, we speculate that assessment of intrinsic subtype may influence treatment, particularly with respect to evaluating alternative therapeutic approaches for that subset of HER2-positive tumors of the basal-like subtype. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions

  12. The NADPH-oxidase AtRbohI plays a positive role in drought-stress response in Arabidopsis thaliana.

    Science.gov (United States)

    He, Huan; Yan, Jingwei; Yu, Xiaoyun; Liang, Yan; Fang, Lin; Scheller, Henrik Vibe; Zhang, Aying

    2017-09-23

    As the major resource of reactive oxygen species (ROS), the NADPH oxidases (Rbohs) have been shown to play important roles in plant cells under normal growth and stress conditions. Although many family members of Rbohs were studied, little is known about the function of RbohI in Arabidopsis thaliana. Here, we report that exogenous ABA application decreases RbohI expression and mannitol significantly increases RbohI expression at transcript level. The RbohI transcripts were strongly detected in dry seeds and roots. The loss-of-function mutant rbohI exhibited sensitivity to ABA and mannitol stress during germination. Furthermore, the lateral root growth of rbohI was severely inhibited after treatment with mannitol stress. Overexpression of RbohI in Arabidopsis significantly improves the drought tolerance. Moreover, more H 2 O 2 accumulated in RbohI overexpressors than in wild type plants in response to mannitol stress. Our conclusion is that AtRbohI functions in drought-stress response in Arabidopsis thaliana. Copyright © 2017. Published by Elsevier Inc.

  13. The NADPH-oxidase AtRbohI plays a positive role in drought-stress response in Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    He, Huan [Nanjing Agricultural Univ. (China); Yan, Jingwei [Nanjing Agricultural Univ. (China); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Yu, Xiaoyun [Nanjing Agricultural Univ. (China); Liang, Yan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Fang, Lin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Scheller, Henrik Vibe [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Zhang, Aying [Nanjing Agricultural Univ. (China)

    2017-05-27

    As the major resource of reactive oxygen species (ROS), the NADPH oxidases (Rbohs) have been shown to play important roles in plant cells under normal growth and stress conditions. Although many family members of Rbohs were studied, little is known about the function of RbohI in Arabidopsis thaliana. Here, we report that exogenous ABA application decreases RbohI expression and mannitol significantly increases RbohI expression at transcript level. The RbohI transcripts were strongly detected in dry seeds and roots. The loss-of-function mutant rbohI exhibited sensitivity to ABA and mannitol stress during germination. Furthermore, the lateral root growth of rbohI was severely inhibited after treatment with mannitol stress. Overexpression of RbohI in Arabidopsis significantly improves the drought tolerance. Moreover, more H2O2 accumulated in RbohI overexpressors than in wild type plants in response to mannitol stress. Our conclusion is that AtRbohI functions in drought-stress response in Arabidopsis thaliana.

  14. The immunological response of HIV-positive patients initiating HAART at the Komfo Anokye Teaching Hospital, Kumasi, Ghana.

    Science.gov (United States)

    Annison, L; Dompreh, A; Adu-Sarkodie, Y

    2013-12-01

    The study sought to document the experience of immunological improvement among Ghanaian PLHIV on HAART comparing different categories of patients. Serology Unit, Komfo Anokye Teaching Hospital, Kumasi, Ghana. The study comprised a convenient sample of 303 treatment naïve HIV patients due to start HAART. Questionnaires were used to collect patient demographic and clinical data. Four CD4 counts were measured at six-monthly intervals to determine rates of CD4 change. These were pre-therapy, 1(st) post-therapy, 2(nd) post-therapy, and 3(rd) post-therapy counts. The rates of CD4 change among the different categories of patients were also compared. At baseline, women had higher CD4 count (mean of 77.4 cells/μl), and mean age of participants was 40 years. The CD4 count increased from a mean baseline of 70.2 cells/μl to 229.2, 270.0, and 297.6 cells/μl at 6, 12, and 18 months of treatment respectively (P response. There was no difference (P=0.18) in treatment response comparing those with CD4 immunological recovery during 12 months of treatment The study, therefore, concludes that significant immunological improvement is possible among Ghanaian PLHIV on HAART as long as a high level of treatment adherence is observed.

  15. Philadelphia chromosome-positive adult acute leukemia with monosomy of chromosome number seven: a subgroup with poor response to therapy.

    Science.gov (United States)

    Maddox, A M; Keating, M J; Trujillo, J; Cork, A; Youness, E; Ahearn, M J; McCredie, K B; Freireich, E J

    1983-01-01

    Thirty-four adult patients were seen at the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Texas between 1969 and 1980 with acute leukemia (AL) and a deleted G-group chromosome that was shown by Giemsa banding to be a Philadelphia (Ph1) chromosome t(9;22) in 21 patients. Fourteen had the Ph1 chromosome as the sole abnormality, 12 had the Ph1 chromosome and loss of one chromosome of the C-group (identified by Giemsa banding analysis as number 7 in eight patients), while eight had the Ph1 chromosome and other changes. These three groups were similar in sex, age distribution and hematologic parameters. The median age of 40 was lower than usually seen in AL. The distribution of the morphologic subtypes was similar to that seen at this institution, with 50% being acute myeloblastic, 12% acute myelomonocytic, 20% lymphoblastic and 18% acute undifferentiated. The complete remission rate with chemotherapy was low: 25% in the Ph1 +/- 7, 50% in the Ph1 +/other group and 43% in the Ph1 +/other group. Median survival time was 8 months for the Ph1 +/- 7 group, 5.5 months for the Ph1 +/other group and 9.0 months for the Ph1 +/alone group. These patients with Ph1 + AL had higher white blood cell counts, increased extramedullary disease and poorer responses to therapy than usual for patients with AL. The deletion of chromosome 7 and the acquisition of the Ph1 chromosome identifies a group of patients with characteristics similar to all the patients with Ph1 + AL but a poor response to therapy and short remission duration.

  16. Positive association of the hepatic lipase gene polymorphism c.514C > T with estrogen replacement therapy response

    Directory of Open Access Journals (Sweden)

    Pulchinelli Alvaro

    2011-11-01

    Full Text Available Abstract Background Hepatic lipase (HL, an enzyme present in the hepatic sinusoids, is responsible for the lipolysis of lipoproteins. Human HL contains four polymorphic sites: G-250A, T-710C, A-763G, and C-514T single-nucleotide polymorphism (SNPs. The last polymorphism is the focus of the current study. The genotypes associated with the C-514T polymorphism are CC (normal homozygous - W, CT (heterozygous - H, and TT (minor-allele homozygous - M. HL activity is significantly impaired in individuals of the TT and CT genotypes. A total of 58 post-menopausal women were studied. The subjects were hysterectomized women receiving hormone replacement therapy consisting of 0.625 mg of conjugated equine estrogen once a day. The inclusion criteria were menopause of up to three years and normal blood tests, radiographs, cervical-vaginal cytology, and densitometry. DNA was extracted from the buccal and blood cells of all 58 patients using a commercially available kit (GFX® - Amersham-Pharmacia, USA. Results Statistically significant reductions in triglycerides (t = 2.16; n = 58; p = 0.03 but not in total cholesterol (t = 0.14; n = 58; p = 0.89 were found after treatment. This group of good responders were carriers of the T allele; the CT and TT genotypes were present significantly more frequently than in the group of non-responders (p = 0.02 or p = 0.07, respectively. However, no significant difference in HDL-C (t = 0.94; n = 58; p = 0.35 or LDL-C (t = -0.83; n = 58; p = 0.41 was found in these patients. Conclusions The variation in lipid profile associated with the C-514T polymorphism is significant, and the T allele is associated with the best response to ERT.

  17. A positive association between the human tissue kallikerin gene A2233C polymorphism and blood pressure response to benazepril.

    Science.gov (United States)

    Hong, Zhe; Pan, Liying; Fei, Jiali; Ma, Zhangqing; Hong, Zongyuan

    2017-01-01

    It is generally believed that essential hypertension is influenced by both genetic and environmental factors, as well as their interactions. Tissue kallikrein encoded by the tissue kallikrein gene (KLK1) is a key serine proteinase of kallikrein-kinin system, which is capable of generating potent vasactive peptides, kinins, by selective cleavage of the kininogen substrate. It was reported that the A2233 → C polymorphism in KLK1 gene is associated with essential hypertension. The aim of this study was to examine whether the molecular variations of KLK1 play role in determining the therapeutic response to benazepril, an ACE inhibitor. A total of 331 hypertensive individuals were recruited and treated with benazepril for 15 days. A variant impact of KLK1 A2233C was revealed. Chi-square analysis showed that the hypertensive subjects with the mutation genotype (AC + CC) had a higher proportion in systolic blood pressure (SBP, 88.1% vs. 79.0%, χ 2 = 4.141, p = 0.042) and diastolic blood pressure (DBP, 91.1% vs. 79.2%, χ 2 = 9.336, p = 0.002), respectively, to benazepril medication in good responders than in poor responders. Logistic regression analysis indicated that the hypertensive subjects with AC + CC genotype were more sensitive to the benazepril therapy in SBP (OR=1.97, 95% CI: 1.02-3.80, p = 0.044) and DBP (OR = 1.91, 95% CI: 2.69-5.16, p = 0.003), as compared with those hypertensive subjects with AA genotype. Our findings suggest that the A2233C polymorphism of KLK1 may be a marker of evaluation of hypertensive subjects' responses to angiotensin I converting enzyme inhibitors benazepril.

  18. Unsaturated fatty acids show clear elicitation responses in a modified local lymph node assay with an elicitation phase, and test positive in the direct peptide reactivity assay.

    Science.gov (United States)

    Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Miyazaki, Hiroshi; Itagaki, Hiroshi

    2015-12-01

    The Organisation for Economic Co-operation and Development (OECD) Test Guidelines (TG) adopted the murine local lymph node assay (LLNA) and guinea pig maximization test (GPMT) as stand-alone skin sensitization test methods. However, unsaturated carbon-carbon double-bond and/or lipid acids afforded false-positive results more frequently in the LLNA compared to those in the GPMT and/or in human subjects. In the current study, oleic, linoleic, linolenic, undecylenic, fumaric, maleic, and succinic acid and squalene were tested in a modified LLNA with an elicitation phase (LLNA:DAE), and in a direct peptide reactivity assay (DPRA) to evaluate their skin-sensitizing potential. Oleic, linoleic, linolenic, undecylenic and maleic acid were positive in the LLNA:DAE, of which three, linoleic, linolenic, and maleic acid were positive in the DPRA. Furthermore, the results of the cross-sensitizing tests using four LLNA:DAE-positive chemicals were negative, indicating a chemical-specific elicitation response. In a previous report, the estimated concentration needed to produce a stimulation index of 3 (EC3) of linolenic acid, squalene, and maleic acid in the LLNA was LLNA. However, the skin-sensitizing potential of all LLNA:DAE-positive chemicals was estimated as weak. These results suggested that oleic, linoleic, linolenic, undecylenic, and maleic acid had skin-sensitizing potential, and that the LLNA overestimated the skin-sensitizing potential compared to that estimated by the LLNA:DAE.

  19. Current positions in OECD member countries on competence profiles at present and requirements for the future: review of questionnaire responses

    International Nuclear Information System (INIS)

    Griffiths, J.S.

    2000-01-01

    The picture is mixed and very dependent on the state of the industry in the particular country. A key determinant is the social, political and economic views of the place of nuclear power generation within the energy policy. Where there is support at a political level or there are clearer financial incentives then the industry can develop and has the impetuous to maintain their capabilities and competence. If the industry position is not as strong the social pressures increase so that it is not viewed as a career. Recruitment and retention and maintaining competence becomes more difficult. Furthermore there are trends to move away from the traditional engineering and science degrees towards subjects which have a 'consumer vogue' and even more proven track records of employment. This in turn puts pressure on the availability of university level education at all levels. Hence if there are not well developed alternatives within a country and programmes of cooperation the very foundation of training and development is under threat. The problems have been recognised and there are a number of initiatives in place both in regulatory bodies, training establishments and the utilities. Recognition of the problem and transfer of good practices will help. Fundamentally there has to be the underpinning infrastructure to support education and training which in itself will allow for cross fertilization with the industry. It is clear that the problem is international and there has to be scope for international cooperation. (authors)

  20. Monte Carlo simulation of the X-ray response of a germanium microstrip detector with energy and position resolution

    CERN Document Server

    Rossi, G; Fajardo, P; Morse, J

    1999-01-01

    We present Monte Carlo computer simulations of the X-ray response of a micro-strip germanium detector over the energy range 30-100 keV. The detector consists of a linear array of lithographically defined 150 mu m wide strips on a high purity monolithic germanium crystal of 6 mm thickness. The simulation code is divided into two parts. We first consider a 10 mu m wide X-ray beam striking the detector surface at normal incidence and compute the interaction processes possible for each photon. Photon scattering and absorption inside the detector crystal are simulated using the EGS4 code with the LSCAT extension for low energies. A history of events is created of the deposited energies which is read by the second part of the code which computes the energy histogram for each detector strip. Appropriate algorithms are introduced to account for lateral charge spreading occurring during charge carrier drift to the detector surface, and Fano and preamplifier electronic noise contributions. Computed spectra for differen...

  1. Positive and negative emotional responses to workrelated trauma of intensive care nurses in private health care facilities

    Directory of Open Access Journals (Sweden)

    Diane Elkonin

    2011-04-01

    Opsomming Intensiewesorgverpleging is ‘n stresvolle beroep en verpleegsters word gedurig aan beide primêre en sekondêre trauma blootgestel. Reaksie hierop kan óf positief wees, in die vorm van empatie-tevredenheid, óf negatief, in die vorm van empatie-uitputting. Verpleegsters is egter geneig om die negatiewe impak van sekondêre trauma te ontken,wat gevolglik tot stilswye en uitbranding kan lei. Hierdie artikel ondersoek en beskryf die teenwoordigheid en verwantskap tussen hierdie emosies. ‘n Kwantitatiewe benadering met ‘n nie-waarskynlikheidsteekproefmetode is gebruik. Die steekproef het bestaan uit 30 geregistreerde verpleegsters wat in privaat-intensiewesorgeenhede in Oos-Londen in die Oos-Kaap werk. Data is met behulp van die vierde hersiening van die ’Professional Quality of Life Scale: Compassion Satisfaction and Fatigue Subscales’ en die ’Silencing Response Scale’ingevorder en verwerk met verwysing na beskrywende statistieke en korrelasiekoëffisiente. Die resultate dui op ‘n hoë risiko vir empatie-uitputting, ‘n matige risiko vir uitbranding en die stilswye-reaksie, sowel as ‘n matige potensiaal vir empatie-tevredenheid. ‘n Beduidende negatiewe verwantskap blyk tussen empatie-tevredenheid en uitbranding te bestaan, terwyl ‘n aansienlik positiewe verwantskap tussen empatie-uitputting en uitbranding en empatieuitputting en die stilswye-reaksie bestaan.

  2. Variations in the response of AECL random coil seals as a function of the angular position of the probe

    International Nuclear Information System (INIS)

    Silk, M.G.

    1986-04-01

    The AECL random coil seal is to be used as a Nuclear Safeguards seal to deter and detect tampering with nuclear material in store. To be effective the ultrasonic signature from the seal must remain constant and be different from that of other seals. Angular variations in the ultrasonic response from certain seals have, however, been observed and the programme of study reported here has been carried out in order to clarify the source of this variation. It is shown that the variation observed may most probably be attributed to the ultrasonic probes used in the investigation and, in particular, to deviation of the probe beam from circularity. However it is probable that the angle of the beam with respect to the probe case (squint) is also a contributory factor. In addition, to reduce the degree of angular variation it is important to exclude air bubbles and to ensure that the coil is placed as centrally in the beam as possible. It is anticipated that the exclusion of air bubbles will be easier in the field than in the laboratory studies. The need to place the seal reasonably centrally with respect to the beam places some minor limits on the coil design and also makes it essential that the probe fits closely into its holder in the seal as any slackness may give rise to signature variations. (author)

  3. Cortisol intermediates and hydrocortisone responsiveness in critical neonatal disease.

    Science.gov (United States)

    Khashana, Abdelmoneim; Saarela, Timo; Ramet, Mika; Hallman, Mikko

    2017-07-01

    Therapy-resistant hypotension complicates diseases in neonates. Our objective was to investigate whether lack of therapeutic response to plasma expanders and inotropes associates with serum levels of cortisol and its precursors. We investigated 96 infants with hypotension and critical neonatal disease for cortisol metabolism and are divided into responders and non-responders to plasma expanders and inotropes. Serum concentrations of steroids were analysed soon after the onset of volume expansion and inotrope treatment for shock. The 48 non-responders were treated with intravenous hydrocortisone (HC) and serum cortisol concentrations were monitored a week later. The mean cortisol concentrations did not differ between the responders and non-responders: 13.6 ± 2.5 and 12.5 ± 4.5 μg/dL, respectively. Dehydroepiandrosterone (37.3 ± 19.5 versus 324.0 ± 106.3; p cortisol and cortisone between the responders and non-responders. Hydrocortisone administration acutely increased blood pressure. Six non-responders who died despite HC administration had low levels of cortisol. The responders had normal serum cortisol after HC treatment. Precursors of cortisol, proximal to the 3β-hydroxysteroid dehydrogenase activity, accumulated in neonates with hypotension, responding to HC treatment.

  4. Cerebral vasoreactivity in response to a head-of-bed position change is altered in patients with moderate and severe obstructive sleep apnea.

    Science.gov (United States)

    Gregori-Pla, Clara; Cotta, Gianluca; Blanco, Igor; Zirak, Peyman; Giovannella, Martina; Mola, Anna; Fortuna, Ana; Durduran, Turgut; Mayos, Mercedes

    2018-01-01

    Obstructive sleep apnea (OSA) can impair cerebral vasoreactivity and is associated with an increased risk of cerebrovascular disease. Unfortunately, an easy-to-use, non-invasive, portable monitor of cerebral vasoreactivity does not exist. Therefore, we have evaluated the use of near-infrared diffuse correlation spectroscopy to measure the microvascular cerebral blood flow (CBF) response to a mild head-of-bed position change as a biomarker for the evaluation of cerebral vasoreactivity alteration due to chronic OSA. Furthermore, we have monitored the effect of two years of continuous positive airway pressure (CPAP) treatment on the cerebral vasoreactivity. CBF was measured at different head-of-bed position changes (supine to 30° to supine) in sixty-eight patients with OSA grouped according to severity (forty moderate to severe, twenty-eight mild) and in fourteen control subjects without OSA. A subgroup (n = 13) with severe OSA was measured again after two years of CPAP treatment. All patients and controls showed a similar CBF response after changing position from supine to 30° (p = 0.819), with a median (confidence interval) change of -17.5 (-10.3, -22.9)%. However, when being tilted back to the supine position, while the control group (p = 0.091) and the mild patients with OSA (p = 0.227) recovered to the initial baseline, patients with moderate and severe OSA did not recover to the baseline (9.8 (0.8, 12.9)%, p < 0.001) suggesting altered cerebral vasoreactivity. This alteration was correlated with OSA severity defined by the apnea-hypopnea index, and with mean nocturnal arterial oxygen saturation. The CBF response was normalized after two years of CPAP treatment upon follow-up measurements. In conclusion, microvascular CBF response to a head-of-bed challenge measured by diffuse correlation spectroscopy suggests that moderate and severe patients with OSA have altered cerebral vasoreactivity related to OSA severity. This may normalize after two years of CPAP

  5. Evaluation of false positive responses by mass spectrometry and ion mobility spectrometry for the detection of trace explosives in complex samples

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, C.L., E-mail: clcrawf@sandia.gov; Hill, H.H.

    2013-09-17

    Graphical abstract: -- Highlights: •First study to use (−)SESI-IM-TOFMS to analyze complex mixtures of personal care products. •The study demonstrated, by identifying mobility and mass interferents with explosive signatures, which, if used separately, neither IMS nor MS alone would prevent every false positive for explosives when detected in the presence of a complex sample matrix. •Ingredients in common household cleaning products were shown to either enhance or suppress the ionization of explosives in a SESI-IM-TOFMS analysis. •Mobility separation provided real-time separation of ion species that indicated overlapping isotope peak patterns -- Abstract: Secondary electrospray ionization-ion mobility-time of flight mass spectrometry (SESI-IM-TOFMS) was used to evaluate common household products and food ingredients for any mass or mobility responses that produced false positives for explosives. These products contained ingredients which shared the same mass and mobility drift time ranges as the analyte ions for common explosives. The results of this study showed that the vast array of compounds in these products can cause either mass or mobility false positive responses. This work also found that two ingredients caused either enhanced or reduced ionization of the target analytes. Another result showed that an IMS can provide real-time separation of ion species that impede accurate mass identifications due to overlapping isotope peak patterns. The final result of this study showed that, when mass and mobility values were used to identify an ion, no false responses were found for the target explosives. The wider implication of these results is that the possibility exists for even greater occurrences of false responses from complex mixtures found in common products. Neither IMS nor MS alone can provide 100% assurance from false responses. IMS, due to its low cost, ease of operation, rugged reliability, high sensitivity and tunable selectivity, will remain

  6. Using microarrays to identify positional candidate genes for QTL: the case study of ACTH response in pigs.

    Science.gov (United States)

    Jouffe, Vincent; Rowe, Suzanne; Liaubet, Laurence; Buitenhuis, Bart; Hornshøj, Henrik; SanCristobal, Magali; Mormède, Pierre; de Koning, D J

    2009-07-16

    Microarray studies can supplement QTL studies by suggesting potential candidate genes in the QTL regions, which by themselves are too large to provide a limited selection of candidate genes. Here we provide a case study where we explore ways to integrate QTL data and microarray data for the pig, which has only a partial genome sequence. We outline various procedures to localize differentially expressed genes on the pig genome and link this with information on published QTL. The starting point is a set of 237 differentially expressed cDNA clones in adrenal tissue from two pig breeds, before and after treatment with adrenocorticotropic hormone (ACTH). Different approaches to localize the differentially expressed (DE) genes to the pig genome showed different levels of success and a clear lack of concordance for some genes between the various approaches. For a focused analysis on 12 genes, overlapping QTL from the public domain were presented. Also, differentially expressed genes underlying QTL for ACTH response were described. Using the latest version of the draft sequence, the differentially expressed genes were mapped to the pig genome. This enabled co-location of DE genes and previously studied QTL regions, but the draft genome sequence is still incomplete and will contain many errors. A further step to explore links between DE genes and QTL at the pathway level was largely unsuccessful due to the lack of annotation of the pig genome. This could be improved by further comparative mapping analyses but this would be time consuming. This paper provides a case study for the integration of QTL data and microarray data for a species with limited genome sequence information and annotation. The results illustrate the challenges that must be addressed but also provide a roadmap for future work that is applicable to other non-model species.

  7. A new Integrated Negative Symptom structure of the Positive and Negative Syndrome Scale (PANSS) in schizophrenia using item response analysis.

    Science.gov (United States)

    Khan, Anzalee; Lindenmayer, Jean-Pierre; Opler, Mark; Yavorsky, Christian; Rothman, Brian; Lucic, Luka

    2013-10-01

    Debate persists with regard to how best to categorize the syndromal dimension of negative symptoms in schizophrenia. The aim was to first review published Principle Components Analysis (PCA) of the PANSS, and extract items most frequently included in the negative domain, and secondly, to examine the quality of items using Item Response Theory (IRT) to select items that best represent a measurable dimension (or dimensions) of negative symptoms. First, 22 factor analyses and PCA met were included. Second, using a large dataset (n=7187) of participants in clinical trials with chronic schizophrenia, we extracted items loading on one or more PCA. Third, items not loading with a value of ≥ 0.5, or loading on more than one component with values of ≥ 0.5 were discarded. Fourth, resulting items were included in a non-parametric IRT and retained based on Option Characteristic Curves (OCCs) and Item Characteristic Curves (ICCs). 15 items loaded on a negative domain in at least one study, with Emotional Withdrawal loading on all studies. Non-parametric IRT retained nine items as an Integrated Negative Factor: Emotional Withdrawal, Blunted Affect, Passive/Apathetic Social Withdrawal, Poor Rapport, Lack of Spontaneity/Conversation Flow, Active Social Avoidance, Disturbance of Volition, Stereotyped Thinking and Difficulty in Abstract Thinking. This is the first study to use a psychometric IRT process to arrive at a set of negative symptom items. Future steps will include further examination of these nine items in terms of their stability, sensitivity to change, and correlations with functional and cognitive outcomes. © 2013 Elsevier B.V. All rights reserved.

  8. Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer.

    Science.gov (United States)

    Yu, Ke-Da; Jiang, Yi-Zhou; Hao, Shuang; Shao, Zhi-Ming

    2015-10-05

    The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER-) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER-/PgR+/HER2- phenotype. Four study cohorts were included. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai Cancer Center (n = 2,338), respectively, for clinicopathologic and survival analysis. The third and fourth cohorts were from two independent publicly available microarray datasets including 837 operable cases and 483 cases undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene-expression analysis. Characterized genes defining subgroups within the ER-/PgR+/HER2- phenotype were determined and further validated. Clinicopathologic features and survival outcomes of the ER-/PgR+ phenotype fell in between the ER+/PgR+ and ER-/PgR- phenotypes, but were more similar to ER-/PgR-. Among the ER-/PgR+ phenotype, 30% (95% confidence interval [CI] 17-42%, pooled by a fixed-effects method) were luminal-like and 59% (95% CI 45-72%, pooled by a fixed-effects method) were basal-like. We further refined the characterized genes for subtypes within the ER-/PgR+ phenotype and developed an immunohistochemistry-based method that could determine the molecular essence of ER-/PgR+ using three markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry-defined basal-like ER-/PgR+ cases have a lower endocrine therapy sensitivity score compared with luminal-like ER-/PgR+ cases (P defined basal-like ER-/PgR+ cases might not benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus insufficient endocrine therapy). The majority of ER-/PgR+/HER2- phenotype breast cancers are basal-like and associated with a lower endocrine therapy sensitivity score. Additional studies are needed

  9. Cardiac output response to changes of the atrioventricular delay in different body positions and during exercise in patients receiving cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Ståhlberg, Marcus; Damgaard, Morten; Norsk, Peter

    2009-01-01

    AIMS: The aim of this study was to study the haemodynamic effect of atrioventricular delay (AVD) modifications within a narrow range in different body positions and during exercise in patients receiving cardiac resynchronization therapy (CRT). METHODS: The previously optimized AVD was shortened...... and prolonged by 40 ms in 27 CRT patients and 9 controls without heart failure. Cardiac output (CO) was measured by inert gas rebreathing (Innocor) as the average over different body positions (left-lateral, supine, sitting, standing, and exercise). In eight CRT patients with an implantable haemodynamic monitor......, the estimated pulmonary artery diastolic pressure (ePAD) was analysed. RESULTS: The magnitude of CO response to AVD changes was greater in CRT patients than in controls (0.25 vs. 0.20 L/min, Psize (r=0...

  10. A distal ABA responsive element in AtNCED3 promoter is required for positive feedback regulation of ABA biosynthesis in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Yan-Zhuo Yang

    Full Text Available The plant hormone abscisic acid (ABA plays a crucial role in plant development and responses to abiotic stresses. Recent studies indicate that a positive feedback regulation by ABA exists in ABA biosynthesis in plants under dehydration stress. To understand the molecular basis of this regulation, we analyzed the cis-elements of the AtNCED3 promoter in Arabidopsis. AtNCED3 encodes the first committed and highly regulated dioxygenase in the ABA biosynthetic pathway. Through delineated and mutagenesis analyses in stable-transformed Arabidopsis, we revealed that a distal ABA responsive element (ABRE: GGCACGTG, -2372 to -2364 bp is required for ABA-induced AtNCED3 expression. By analyzing the AtNCED3 expression in ABRE binding protein ABF3 over-expression transgenic plants and knock-out mutants, we provide evidence that the ABA feedback regulation of AtNCED3 expression is not mediated by ABF3.

  11. A distal ABA responsive element in AtNCED3 promoter is required for positive feedback regulation of ABA biosynthesis in Arabidopsis.

    Science.gov (United States)

    Yang, Yan-Zhuo; Tan, Bao-Cai

    2014-01-01

    The plant hormone abscisic acid (ABA) plays a crucial role in plant development and responses to abiotic stresses. Recent studies indicate that a positive feedback regulation by ABA exists in ABA biosynthesis in plants under dehydration stress. To understand the molecular basis of this regulation, we analyzed the cis-elements of the AtNCED3 promoter in Arabidopsis. AtNCED3 encodes the first committed and highly regulated dioxygenase in the ABA biosynthetic pathway. Through delineated and mutagenesis analyses in stable-transformed Arabidopsis, we revealed that a distal ABA responsive element (ABRE: GGCACGTG, -2372 to -2364 bp) is required for ABA-induced AtNCED3 expression. By analyzing the AtNCED3 expression in ABRE binding protein ABF3 over-expression transgenic plants and knock-out mutants, we provide evidence that the ABA feedback regulation of AtNCED3 expression is not mediated by ABF3.

  12. Do Family Responsibilities and a Clinical Versus Research Faculty Position Affect Satisfaction with Career and Work–Life Balance for Medical School Faculty?

    Science.gov (United States)

    Beckett, Laurel; Nettiksimmons, Jasmine; Howell, Lydia Pleotis

    2015-01-01

    Abstract Background: Balancing career and family obligations poses challenges to medical school faculty and contributes to dissatisfaction and attrition from academics. We examined the relationship between family setting and responsibilities, rank, and career and work–life satisfaction for faculty in a large U.S. medical school. Methods: Baseline faculty surveys were analyzed from the first year of a 4-year National Institutes of Health–funded study to evaluate awareness, knowledge, attitudes, and use of family friendly policies and career satisfaction. The study focus was on the impact of family responsibilities and characteristics of the faculty position (rank, clinical vs. nonclinical, and academic series) in multivariate comparisons between primary predictors and outcomes of interest. Results: Both clinical and family responsibilities for children under 18 play a major and interacting role in satisfaction with career and work–life balance. Clinical faculty respondents without children at home reported significantly greater career satisfaction and better work–life balance than their nonclinical counterparts. Nonclinical faculty respondents with children reported greater satisfaction and better balance than counterparts without family responsibilities. However, the advantage in career satisfaction and work–life balance for clinical faculty respondents disappeared for those with responsibility for young children. No gender-based differences were noted in the results or across faculty rank for respondents; however, for women, reaching associate professor resulted in greater career satisfaction. Conclusion: This study suggests that both work-related factors and family responsibilities influence satisfaction with career and work–life balance, but the predictors appear to interact in complex and nuanced ways. Further research is needed to delineate more clearly these interactions and to explore other factors that may play important additional roles. PMID

  13. Do Family Responsibilities and a Clinical Versus Research Faculty Position Affect Satisfaction with Career and Work-Life Balance for Medical School Faculty?

    Science.gov (United States)

    Beckett, Laurel; Nettiksimmons, Jasmine; Howell, Lydia Pleotis; Villablanca, Amparo C

    2015-06-01

    Balancing career and family obligations poses challenges to medical school faculty and contributes to dissatisfaction and attrition from academics. We examined the relationship between family setting and responsibilities, rank, and career and work-life satisfaction for faculty in a large U.S. medical school. Baseline faculty surveys were analyzed from the first year of a 4-year National Institutes of Health-funded study to evaluate awareness, knowledge, attitudes, and use of family friendly policies and career satisfaction. The study focus was on the impact of family responsibilities and characteristics of the faculty position (rank, clinical vs. nonclinical, and academic series) in multivariate comparisons between primary predictors and outcomes of interest. Both clinical and family responsibilities for children under 18 play a major and interacting role in satisfaction with career and work-life balance. Clinical faculty respondents without children at home reported significantly greater career satisfaction and better work-life balance than their nonclinical counterparts. Nonclinical faculty respondents with children reported greater satisfaction and better balance than counterparts without family responsibilities. However, the advantage in career satisfaction and work-life balance for clinical faculty respondents disappeared for those with responsibility for young children. No gender-based differences were noted in the results or across faculty rank for respondents; however, for women, reaching associate professor resulted in greater career satisfaction. This study suggests that both work-related factors and family responsibilities influence satisfaction with career and work-life balance, but the predictors appear to interact in complex and nuanced ways. Further research is needed to delineate more clearly these interactions and to explore other factors that may play important additional roles.

  14. Positive response to neoadjuvant cyclophosphamide and doxorubicin in topoisomerase II nonamplified/HER2/neu negative/polysomy 17 absent breast cancer patients

    Directory of Open Access Journals (Sweden)

    Henry G Kaplan

    2010-08-01

    Full Text Available Henry G Kaplan1, Judith A Malmgren2,3, Mary Atwood1, Lynn C Goldstein41Swedish Cancer Institute at Swedish Medical Center, Seattle, Washington, USA; 2HealthStat Consulting Inc., Seattle, Washington, USA; 3School of Public Health and Community Medicine, Department of Epidemiology, University of Washington, Seattle, Washington, USA; 4PhenoPath Laboratories, Seattle, Washington, USAPurpose: Human epidermal growth factor receptor 2 (HER2/neu, topoisomerase II alpha (TOP2A, and polysomy 17 may predict tumor responsiveness to doxorubicin (DOX therapy.Methods: We identified neoadjuvant DOX/cyclophosphamide treated breast cancer patients in our registry from 1997 to 2008 with sufficient tissue for testing (n = 34. Fluorescence in situ hybridization (FISH testing was done on deparaffinized tissue sections pretreated using vendor’s standard protocol modification, and incubated with US Food and Drug Administration approved Abbott Diagnostics Vysis PathVysion™ probe set, including Spectrum-Green-conjugated probe to a-satellite DNA located at the centromere of chromosome 17 (17p11.1–q11.1 and a Spectrum-Orange-conjugated probe to the TOP2A gene. Morphometric analysis was performed using a MetaSystems image analysis system. Manual counting was performed on all samples in which autofluorescence and/or artifact prevented the counting of sufficient numbers of cells. A ratio >2.0 was considered positive for TOP2A amplification. Polysomy 17 (PS17 presence was defined as signals of ≥2.5. Outcomes were pathological complete response (pCR, partial response (PR, and nonresponse (NR.Results: Of 34 patients tested, one was TOP2A amplified (hormone receptor negative/HER2 ­negative, partial responder. The subset of TOP2A nonamplified, HER2 negative, and PS17 absent (n = 23 patients had treatment response: pCR = 2 (9%, PR = 14 (61%, and NR = 7 (30%. Including the two PS17 present and HER2-positive patients (n = 33, 76% of TOP2A nonamplified patients had pCR or PR

  15. Position-Dependent Cardiovascular Response and Time-Motion Analysis During Training Drills and Friendly Matches in Elite Male Basketball Players.

    Science.gov (United States)

    Torres-Ronda, Lorena; Ric, Angel; Llabres-Torres, Ivan; de Las Heras, Bernat; Schelling I Del Alcazar, Xavi

    2016-01-01

    The purpose of this study was to measure differences in the cardiovascular workload (heart rate [HR]) and time-motion demands between positional groups, during numerous basketball training drills, and compare the results with in-game competition demands. A convenience sample of 14 top-level professional basketball players from the same club (Spanish First Division, ACB) participated in the study. A total of 146 basketball exercises per player (performed over an 8-week period in 32 team training sessions throughout the competitive season) and 7 friendly matches (FM) played during the preparatory phase were analyzed. The results reveal that HRavg and HRpeak were the highest in FM (158 ± 10; 198 ± 9 b · min(-1), respectively). Time-motion analysis showed 1v1 to be the most demanding drill (53 ± 8 and 46 ± 12 movements per minute for full and half court, respectively). During FM, players performed 33 ± 7 movements per minute. Positional differences exist for both HR and time-motion demands, ranging from moderate to very large for all basketball drills compared with FM. Constraints such as number of players, court size, work-to-rest ratios, and coach intervention are key factors influencing cardiovascular responses and time-motion demands during basketball training sessions. These results demonstrate that systematic monitoring of the physical demands and physiological responses during training and competition can inform and potentially improve coaching strategy, basketball-specific training drills, and ultimately, match performance.

  16. Apoptosis in response to heat stress is positively associated with heat-shock protein 90 expression in chicken myocardial cells in vitro.

    Science.gov (United States)

    Zhang, Xiao-Hui; Wu, Hong; Tang, Shu; Li, Qiao-Ning; Xu, Jiao; Zhang, Miao; Su, Ya-Nan; Yin, Bin; Zhao, Qi-Ling; Kemper, Nicole; Hartung, Joerg; Bao, En-Dong

    2017-06-30

    To determine heat-shock protein (Hsp)90 expression is connected with cellular apoptotic response to heat stress and its mechanism, chicken ( Gallus gallus ) primary myocardial cells were treated with the Hsp90 promoter, aspirin, and its inhibitor, geldanamycin (GA), before heat stress. Cellular viability, heat-stressed apoptosis and reactive oxygen species level under different treatments were measured, and the expression of key proteins of the signaling pathway related to Hsp90 and their colocalization with Hsp90 were detected. The results showed that aspirin treatment increased the expression of protein kinase B (Akt), the signal transducer and activator of transcription (STAT)-3 and p-IKKα/β and the colocalization of Akt and STAT-3 with Hsp90 during heat stress, which was accompanied by improved viability and low apoptosis. GA significantly inhibited Akt expression and p-IKKα/β level, but not STAT-3 quantity, while the colocalization of Akt and STAT-3 with Hsp90 was weakened, followed by lower cell viability and higher apoptosis. Aspirin after GA treatment partially improved the stress response and apoptosis rate of tested cells caused by the recovery of Akt expression and colocalization, rather than the level of STAT-3 (including its co-localization with Hsp90) and p-IKKα/β. Therefore, Hsp90 expression has a positive effect on cellular capacity to resist heat-stressed injury and apoptosis. Moreover, inhibition of Hsp90 before stress partially attenuated its positive effects.

  17. Hemispheric Asymmetries in Striatal Reward Responses Relate to Approach-Avoidance Learning and Encoding of Positive-Negative Prediction Errors in Dopaminergic Midbrain Regions.

    Science.gov (United States)

    Aberg, Kristoffer Carl; Doell, Kimberly C; Schwartz, Sophie

    2015-10-28

    Some individuals are better at learning about rewarding situations, whereas others are inclined to avoid punishments (i.e., enhanced approach or avoidance learning, respectively). In reinforcement learning, action values are increased when outcomes are better than predicted (positive prediction errors [PEs]) and decreased for worse than predicted outcomes (negative PEs). Because actions with high and low values are approached and avoided, respectively, individual differences in the neural encoding of PEs may influence the balance between approach-avoidance learning. Recent correlational approaches also indicate that biases in approach-avoidance learning involve hemispheric asymmetries in dopamine function. However, the computational and neural mechanisms underpinning such learning biases remain unknown. Here we assessed hemispheric reward asymmetry in striatal activity in 34 human participants who performed a task involving rewards and punishments. We show that the relative difference in reward response between hemispheres relates to individual biases in approach-avoidance learning. Moreover, using a computational modeling approach, we demonstrate that better encoding of positive (vs negative) PEs in dopaminergic midbrain regions is associated with better approach (vs avoidance) learning, specifically in participants with larger reward responses in the left (vs right) ventral striatum. Thus, individual dispositions or traits may be determined by neural processes acting to constrain learning about specific aspects of the world. Copyright © 2015 the authors 0270-6474/15/3514491-10$15.00/0.

  18. The onset of the progression of acute phase response mechanisms induced by extreme impacts can be followed by the decrease in blood levels of positive acute phase proteins.

    Science.gov (United States)

    Larina, Olga; Bekker, Anna

    Studies performed at space flights and earth-based simulation models detected the plasma indices of acute phase reaction (APR), i.e. the increase of APR cytokine mediators and alterations in the production of blood acute phase proteins (APP) at the initial stages of adaptation to altered gravity conditions. Acute phase response is the principal constituent of the functional activity of innate immunity system. Changes in plasma APPs contents are considered to serve the restoration of homeostasis state. According to trends of their concentration shifts at the evolving of acute phase reaction APPs are denoted as positive, neutral, or negative. Plasma concentrations of positive acute phase proteins α1-acid glycoprotein (α1-AGP), α1-antitrypsin (α1-AT), and neutral α2-macroglobulin (α2-M) were measured in human study at 12-hour antiorthostatic position (AOP) with 15° head down tilt and hypoxia experiments at 14% oxygen in pressure chamber. Both of these impacts were shown to produce alterations in the APP levels indicative for acute phase response. Nevertheless, in AOP experiment noticeable decrease in α1-AGP concentration occurred by hour 12, and even more pronounced decline of α1-AGP and α1-AT were found on hypoxia hours 12 and 36. Acute phase proteins α1-AGP and α2-M possess the features of proteinase inhibitors. This function is implemented by the formation of complexes with the molecules of proteolytic enzymes which subsequently are removed from the blood flow. Transient decrease in plasma concentrations of protease inhibitors on early phases of APR development was reported to result from the growth of plasma protease activity due to cathepsin release from activated leukocytes, which had not yet been compensated by enhanced APP synthesis. Being a carrier protein for positively charged and neutral substances, α1-AGP shows pronounced elevation in its blood content during APR development. As assumed, it is required for the transportation of the increased

  19. HER2-positive breast cancer: {sup 18}F-FDG PET for early prediction of response to trastuzumab plus taxane-based neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Humbert, Olivier; Brunotte, Francois [Centre GF Leclerc, Department of Nuclear Medicine, Dijon (France); CHU Le Bocage, Imaging Department, Dijon (France); Universite de Bourgogne, UMR CNRS 5158, Dijon (France); Cochet, Alexandre [Centre GF Leclerc, Department of Nuclear Medicine, Dijon (France); Universite de Bourgogne, UMR CNRS 5158, Dijon (France); Riedinger, Jean-Marc [Centre GF Leclerc, Department of Nuclear Medicine, Dijon (France); Centre GF Leclerc, Department of Biology and Pathology, Dijon (France); Berriolo-Riedinger, Alina; Toubeau, Michel; Dygai-Cochet, Inna [Centre GF Leclerc, Department of Nuclear Medicine, Dijon (France); Arnould, Laurent [Centre GF Leclerc, Department of Biology and Pathology, Dijon (France); Coudert, Bruno; Desmoulins, Isabelle; Guiu, Severine; Fumoleau, Pierre [Centre GF Leclerc, Department of Medical Oncology, Dijon (France); Coutant, Charles [Centre GF Leclerc, Department of Surgery, Dijon (France)

    2014-08-15

    To investigate the value of {sup 18}F-fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG PET/CT) to predict a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Fifty-seven consecutive women with HER2-positive breast cancer, treated with trastuzumab plus taxane-based NAC, were prospectively included. Maximum Standardized Uptake Value of the primary tumor and axillary nodes were measured at baseline (PET{sub 1}.SUV{sub max}) and after the first course of NAC (PET{sub 2}.SUV{sub max}). Tumor metabolic volumes were assessed to determine Total Lesion Glycolysis (TLG). The tumor metabolic response (ΔSUV{sub max} and ΔTLG) was calculated. In univariate analysis, negative hormonal receptor status (p = 0.04), high tumor grade (p = 0.03), and low tumor PET{sub 2}.SUV{sub max} (p = 0.001) were predictive of pCR. Tumor ΔSUV{sub max} correlated with pCR (p = 0.03), provided that tumors with low metabolic activity at baseline were excluded. ΔTLG did not correlate with pCR. In multivariate analysis, tumor PET{sub 2}.SUV{sub max} < 2.1 was the best independent predictive factor (Odds ratio =14.3; p = 0.004) with both negative and positive predictive values of 76 %. Although the metabolic features of the primary tumor did not depend on hormonal receptor status, both the baseline metabolism and early response of axillary nodes were higher if estrogen receptors were not expressed (p = 0.01 and p = 0.03, respectively). In HER2-positive breast cancer, very low tumor residual metabolism after the first cycle of NAC (SUV{sub max} < 2.1) was the main predictor of pCR. These results should be further explored in multicenter studies and incorporated into the design of clinical trials. (orig.)

  20. Genetic variation in STAT4 predicts response to interferon-α therapy for hepatitis B e antigen-positive chronic hepatitis B.

    Science.gov (United States)

    Jiang, De-Ke; Wu, Xiaopan; Qian, Ji; Ma, Xiao-Pin; Yang, Jingmin; Li, Zhuo; Wang, Runhua; Sun, Li; Liu, Fang; Zhang, Pengyin; Zhu, Xilin; Wu, Jia; Chen, Kangmei; Conran, Carly; Zheng, S Lilly; Lu, Daru; Yu, Long; Liu, Ying; Xu, Jianfeng

    2016-04-01

    Interferon (IFN)-α is a first-line therapy for chronic hepatitis B (CHB) patients but only initiates a response in a minority of patients. A genetic variant, rs7574865 in STAT4, was recently reported to be associated with risk of developing CHB and hepatitis B virus-related hepatocellular carcinoma. We aimed to determine whether this variant is associated with the response to IFNα treatment for hepatitis B e antigen (HBeAg)-positive CHB patients. We studied 466 HBeAg-positive CHB patients who received either IFNα-2b (n = 224) or pegylated IFNα-2a (n = 242) therapy for 48 weeks and were followed for an additional 24 weeks. The rate of sustained virologic response (SVR), defined as HBeAg seroconversion along with hepatitis B virus DNA level rs7574865. After 48 weeks of treatment and 24 weeks off treatment, the SVR rates in the IFNα-2b and pegylated IFNα-2a therapy groups were 30.4% and 28.9%, respectively. Compared to the rs7574865 GT/TT genotype, the GG genotype (a risk factor of CHB and hepatitis B virus-related hepatocellular carcinoma) was significantly associated with a reduced SVR rate in both patients who received IFNα-2b therapy (21.1% versus 37.2%, P = 0.01) and those who received pegylated IFNα-2a therapy (18.0% versus 41.2%, P = 9.74 × 10(-5) ). In joint analysis of the 466 patients, the GG genotype was associated with an approximately half SVR rate compared to the GT/TT genotype (19.3% versus 39.1%, P = 4.15 × 10(-6) ). A multivariate logistic regression model including rs7574865 and clinical variables showed that rs7574865 was the most significant factor for the prediction of SVR. STAT4 rs7574865 is a reliable predictor of response to IFNα therapy for HBeAg-positive CHB patients and may be used for optimizing the treatment of CHB. © 2015 by the American Association for the Study of Liver Diseases.

  1. Cortisol stress response is positively correlated with central obesity in obese women with binge eating disorder (BED) before and after cognitive-behavioral treatment.

    Science.gov (United States)

    Gluck, Marci E; Geliebter, Allan; Lorence, Margarita

    2004-12-01

    Stress is the most commonly reported trigger of binge eating, and high cortisol levels are positively related to both central body fat and food intake after laboratory stress. We therefore examined waist circumference (WHR) and cortisol stress responsivity after a cold pressor stress test (CPT) in 22 obese (BMI > 27) women (11 BED, 11 non-BED). BMI and WHR did not differ between groups. The BED group had higher morning basal cortisol than the non-BED group (P = .03) and greater AUC cortisol after CPT, after controlling for AUC insulin (P = .04). In the BED group, WHR was related to AUC cortisol (P = .002) and peak cortisol stress responsivity (P = .003). Twenty (10 non-BED, 10 BED) were randomized to a 6-week treatment program (CBT + Diet) or Wait-List (WL) control group. There were no BED group or treatment-group differences in WHR, morning basal cortisol, or AUC cortisol after CPT. The relationship between WHR and both AUC cortisol (P = .002) and peak cortisol stress responsivity after CPT (P = .008) remained significant in the BED group. In BED, there is a hyperactive HPA axis related to abdominal obesity that persists even after treatment, suggesting that cortisol might be a primary factor in the disorder.

  2. The Positive Correlation of the Enhanced Immune Response to PCV2 Subunit Vaccine by Conjugation of Chitosan Oligosaccharide with the Deacetylation Degree.

    Science.gov (United States)

    Zhang, Guiqiang; Cheng, Gong; Jia, Peiyuan; Jiao, Siming; Feng, Cui; Hu, Tao; Liu, Hongtao; Du, Yuguang

    2017-07-26

    Chitosan oligosaccharides (COS), the degraded products of chitosan, have been demonstrated to have versatile biological functions. In primary studies, it has displayed significant adjuvant effects when mixed with other vaccines. In this study, chitosan oligosaccharides with different deacetylation degrees were prepared and conjugated to porcine circovirus type 2 (PCV2) subunit vaccine to enhance its immunogenicity. The vaccine conjugates were designed by the covalent linkage of COSs to PCV2 molecules and administered to BALB/c mice three times at two-week intervals. The results indicate that, as compared to the PCV2 group, COS-PCV2 conjugates remarkably enhanced both humoral and cellular immunity against PCV2 by promoting lymphocyte proliferation and initiating a mixed T-helper 1 (Th1)/T-helper 2 (Th2) response, including raised levels of PCV2-specific antibodies and an increased production of inflammatory cytokines. Noticeably, with the increasing deacetylation degree, the stronger immune responses to PCV2 were observed in the groups with COS-PCV2 vaccination. In comparison with NACOS (chitin oligosaccharides)-PCV2 and LCOS (chitosan oligosaccharides with low deacetylation degree)-PCV2, HCOS (chitosan oligosaccharides with high deacetylation degree)-PCV2 showed the highest adjuvant effect, even comparable to that of PCV2/ISA206 (a commercialized adjuvant) group. In summary, COS conjugation might be a viable strategy to enhance the immune response to PCV2 subunit vaccine, and the adjuvant effect was positively correlated with the deacetylation degree of COS.

  3. Transdiagnostic assessment of repetitive negative thinking and responses to positive affect: Structure and predictive utility for depression, anxiety, and mania symptoms.

    Science.gov (United States)

    McEvoy, Peter M; Hyett, Matthew P; Ehring, Thomas; Johnson, Sheri L; Samtani, Suraj; Anderson, Rebecca; Moulds, Michelle L

    2018-05-01

    Repetitive negative thinking (RNT) is a cognitive process that is repetitive, passive, relatively uncontrollable, and focused on negative content, and is elevated in emotional disorders including depression and anxiety disorders. Repetitive positive thinking is associated with bipolar disorder symptoms. The unique contributions of positive versus negative repetitive thinking to emotional symptoms are unknown. The first aim of this study was to use confirmatory factor analyses to evaluate the psychometrics of two transdiagnostic measures of RNT, the Repetitive Thinking Questionnaire (RTQ-10) and Perseverative Thinking Questionnaire (PTQ), and a measure of repetitive positive thinking, the Responses to Positive Affect (RPA) Questionnaire. The second aim was to determine incremental predictive utility of these measures. All measures were administered to a sample of 2088 undergraduate students from the Netherlands (n = 992), Australia (n = 698), and America (n = 398). Unidimensional, bifactor, and three-factor models were supported for the RTQ-10, PTQ, and RPA, respectively. A common factor measured by all PTQ items explained most variance in PTQ scores suggesting that this measure is essentially unidimensional. The RNT factor of the RTQ-10 demonstrated the strongest predictive utility, although the PTQ was also uniquely although weakly associated with anxiety, depression, and mania symptoms. The RPA dampening factor uniquely predicted anxiety and depression symptoms, suggesting that this scale is a separable process to RNT as measured by the RTQ-10 and PTQ. Findings were cross-sectional and need to be replicated in clinical samples. Transdiagnostic measures of RNT are essentially unidimensional, whereas RPA is multidimensional. RNT and RPA have unique predictive utility. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Prevalence of Vitamin B12 and folic acid deficiency in HIV-positive patients and its association with neuropsychiatric symptoms and immunological response.

    Science.gov (United States)

    Adhikari, Prabha M R; Chowta, Mukta N; Ramapuram, John T; Rao, Satish; Udupa, Karthik; Acharya, Sahana Devdas

    2016-01-01

    Deficiency of micronutrients is prevalent even before the development of symptoms of HIV disease and is associated with accelerated HIV disease progression. This study evaluates the prevalence of folate and Vitamin B 12 deficiency in HIV-positive patients with or without tuberculosis (TB) and its association with neuropsychiatric symptoms and immunological response. Cross-sectional, observational study in an outpatient setting. Four groups of HIV-positive patients with TB (Group I), HIV-positive patients with neuropsychiatric symptoms (Group II), HIV-positive patients without neuropsychiatric symptoms or TB (Group III), and HIV-negative controls with neuropsychiatric symptoms (Group IV). Vitamin B 12 and folate estimation was done using carbonyl metallo-immunoassay method. ANOVA, Kruskal-Wallis and Mann-Whitney, Pearson's correlation. The prevalence of folic acid deficiency was 27.1% in the Group I, 31.9% in the Group II, 23.4% in the Group III, and 32% in the Group IV being higher in patients with neuropsychiatric symptoms in both HIV and non-HIV patients. The prevalence of Vitamin B 12 deficiency was 18.8% in Group I, 9.1% in Group II, 4.8% in Group III, and 16.7% in Group IV. The patients with folate deficiency had more severe depression and anxiety. Nearly, 30% of the HIV patients had a folic acid deficiency, and about 10% of the HIV patients had Vitamin B 12 deficiency. The folate deficiency was highest among neuropsychiatric patients with or without HIV infection and Vitamin B 12 deficiency was higher among HIV patients with TB.

  5. Reliability, Validity, and Responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) Scores in Influenza-Positive Patients.

    Science.gov (United States)

    Powers, John H; Bacci, Elizabeth D; Guerrero, M Lourdes; Leidy, Nancy Kline; Stringer, Sonja; Kim, Katherine; Memoli, Matthew J; Han, Alison; Fairchok, Mary P; Chen, Wei-Ju; Arnold, John C; Danaher, Patrick J; Lalani, Tahaniyat; Ridoré, Michelande; Burgess, Timothy H; Millar, Eugene V; Hernández, Andrés; Rodríguez-Zulueta, Patricia; Smolskis, Mary C; Ortega-Gallegos, Hilda; Pett, Sarah; Fischer, William; Gillor, Daniel; Macias, Laura Moreno; DuVal, Anna; Rothman, Richard; Dugas, Andrea; Ruiz-Palacios, Guillermo M

    2018-02-01

    To assess the reliability, validity, and responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) scores for quantifying the presence and severity of influenza symptoms. An observational prospective cohort study of adults (≥18 years) with influenza-like illness in the United States, the United Kingdom, Mexico, and South America was conducted. Participants completed the 37-item draft FLU-PRO daily for up to 14 days. Item-level and factor analyses were used to remove items and determine factor structure. Reliability of the final tool was estimated using Cronbach α and intraclass correlation coefficients (2-day reliability). Convergent and known-groups validity and responsiveness were assessed using global assessments of influenza severity and return to usual health. Of the 536 patients enrolled, 221 influenza-positive subjects comprised the analytical sample. The mean age of the patients was 40.7 years, 60.2% were women, and 59.7% were white. The final 32-item measure has six factors/domains (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic), with a higher order factor representing symptom severity overall (comparative fit index = 0.92; root mean square error of approximation = 0.06). Cronbach α was high (total = 0.92; domain range = 0.71-0.87); test-retest reliability (intraclass correlation coefficient, day 1-day 2) was 0.83 for total scores and 0.57 to 0.79 for domains. Day 1 FLU-PRO domain and total scores were moderately to highly correlated (≥0.30) with Patient Global Rating of Flu Severity (except nose and throat). Consistent with known-groups validity, scores differentiated severity groups on the basis of global rating (total: F = 57.2, P FLU-PRO score improvement by day 7 than did those who did not, suggesting score responsiveness. Results suggest that FLU-PRO scores are reliable, valid, and responsive to change in influenza-positive adults. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes

  6. Getting off on the wrong foot? How community groups in Zimbabwe position themselves for partnerships with external agencies in the HIV response.

    Science.gov (United States)

    Skovdal, Morten; Magutshwa-Zitha, Sitholubuhle; Campbell, Catherine; Nyamukapa, Constance; Gregson, Simon

    2017-06-01

    Partnerships are core to global public health responses. The HIV field embraces partnership working, with growing attention given to the benefits of involving community groups in the HIV response. However, little has been done to unpack the social psychological foundation of partnership working between well-resourced organisations and community groups, and how community representations of partnerships and power asymmetries shape the formation of partnerships for global health. We draw on a psychosocial theory of partnerships to examine community group members' understanding of self and other as they position themselves for partnerships with non-governmental organisations. This mixed qualitative methods study was conducted in the Matobo district of Matabeleland South province in Zimbabwe. The study draws on the perspectives of 90 community group members (29 men and 61 women) who participated in a total of 19 individual in-depth interviews and 9 focus group discussions (n = 71). The participants represented an array of different community groups and different levels of experience of working with NGOs. Verbatim transcripts were imported into Atlas.Ti for thematic indexing and analysis. Group members felt they played a central role in the HIV response. Accepting there is a limit to what they can do in isolation, they actively sought to position themselves as potential partners for NGOs. Partnerships with NGOs were said to enable community groups to respond more effectively as well as boost their motivation and morale. However, group members were also acutely aware of how they should act and perform if they were to qualify for a partnership. They spoke about how they had to adopt various strategies to become attractive partners and 'supportable' - including being active and obedient. Many community groups in Zimbabwe recognise their role in the HIV response and actively navigate representational systems of self and other to showcase themselves as capable actors

  7. Measurements and simulations on position dependencies in the response of single PWO crystals and a prototype for the $\\overline{P}ANDA$ EMC

    CERN Document Server

    Bremer, Daniel Andreas

    The PANDA experiment, which will be located at the future Facility for Antiproton and Ion Research, aims at the study of strong interaction within the charm sector via antiproton- proton collisions. An essential component of the PANDA detector to achieve the ambitious physics goals is the Electromagnetic Calorimeter (EMC). Reason for this is particularly its high detection efficiency for photons and electrons over a large dynamic range, since most of the expected physics channels are accompanied by secondary photons. The EMC is based on second generation lead tungstate scintillator crystals and thus features a very compact design and improved performance. To guarantee a homogeneous and precise energy and momentum response, an exact knowledge on the incident particle position is mandatory. In the scope of this work, non-uniformities in the light yield of single lead tungstate crystals with tapered geometry are investigated. This effect was studied with the SLitrani simulation package in comparison to a series ...

  8. Use of NON-PARAMETRIC Item Response Theory to develop a shortened version of the Positive and Negative Syndrome Scale (PANSS)

    Science.gov (United States)

    2011-01-01

    Background Nonparametric item response theory (IRT) was used to examine (a) the performance of the 30 Positive and Negative Syndrome Scale (PANSS) items and their options ((levels of severity), (b) the effectiveness of various subscales to discriminate among differences in symptom severity, and (c) the development of an abbreviated PANSS (Mini-PANSS) based on IRT and a method to link scores to the original PANSS. Methods Baseline PANSS scores from 7,187 patients with Schizophrenia or Schizoaffective disorder who were enrolled between 1995 and 2005 in psychopharmacology trials were obtained. Option characteristic curves (OCCs) and Item Characteristic Curves (ICCs) were constructed to examine the probability of rating each of seven options within each of 30 PANSS items as a function of subscale severity, and summed-score linking was applied to items selected for the Mini-PANSS. Results The majority of items forming the Positive and Negative subscales (i.e. 19 items) performed very well and discriminate better along symptom severity compared to the General Psychopathology subscale. Six of the seven Positive Symptom items, six of the seven Negative Symptom items, and seven out of the 16 General Psychopathology items were retained for inclusion in the Mini-PANSS. Summed score linking and linear interpolation was able to produce a translation table for comparing total subscale scores of the Mini-PANSS to total subscale scores on the original PANSS. Results show scores on the subscales of the Mini-PANSS can be linked to scores on the original PANSS subscales, with very little bias. Conclusions The study demonstrated the utility of non-parametric IRT in examining the item properties of the PANSS and to allow selection of items for an abbreviated PANSS scale. The comparisons between the 30-item PANSS and the Mini-PANSS revealed that the shorter version is comparable to the 30-item PANSS, but when applying IRT, the Mini-PANSS is also a good indicator of illness severity

  9. Use of non-parametric item response theory to develop a shortened version of the Positive and Negative Syndrome Scale (PANSS).

    Science.gov (United States)

    Khan, Anzalee; Lewis, Charles; Lindenmayer, Jean-Pierre

    2011-11-16

    Nonparametric item response theory (IRT) was used to examine (a) the performance of the 30 Positive and Negative Syndrome Scale (PANSS) items and their options ((levels of severity), (b) the effectiveness of various subscales to discriminate among differences in symptom severity, and (c) the development of an abbreviated PANSS (Mini-PANSS) based on IRT and a method to link scores to the original PANSS. Baseline PANSS scores from 7,187 patients with Schizophrenia or Schizoaffective disorder who were enrolled between 1995 and 2005 in psychopharmacology trials were obtained. Option characteristic curves (OCCs) and Item Characteristic Curves (ICCs) were constructed to examine the probability of rating each of seven options within each of 30 PANSS items as a function of subscale severity, and summed-score linking was applied to items selected for the Mini-PANSS. The majority of items forming the Positive and Negative subscales (i.e. 19 items) performed very well and discriminate better along symptom severity compared to the General Psychopathology subscale. Six of the seven Positive Symptom items, six of the seven Negative Symptom items, and seven out of the 16 General Psychopathology items were retained for inclusion in the Mini-PANSS. Summed score linking and linear interpolation was able to produce a translation table for comparing total subscale scores of the Mini-PANSS to total subscale scores on the original PANSS. Results show scores on the subscales of the Mini-PANSS can be linked to scores on the original PANSS subscales, with very little bias. The study demonstrated the utility of non-parametric IRT in examining the item properties of the PANSS and to allow selection of items for an abbreviated PANSS scale. The comparisons between the 30-item PANSS and the Mini-PANSS revealed that the shorter version is comparable to the 30-item PANSS, but when applying IRT, the Mini-PANSS is also a good indicator of illness severity.

  10. Phantom position dependence

    International Nuclear Information System (INIS)

    Thorson, M.R.; Endres, G.W.R.

    1981-01-01

    Sensitivity of the Hanford dosimeter response to its position relative to the phantom and the neutron source has always been recognized. A thorough investigation was performed to quantify dosimeter response according to: (a) dosimeter position on phantom, (b) dosimeter distance from phantom, and (c) angular relationship of dosimeter relative to neutron source and phantom. Results were obtained for neutron irradiation at several different energies

  11. Lenalidomide combined with R-GDP in a patient with refractory CD5-positive diffuse large B-cell lymphoma: A promising response and review.

    Science.gov (United States)

    Zhang, Yaping; Wang, Xinfeng; Liu, Yifei; Sun, Chunfeng; Shi, Wenyu; Huang, Hongming

    2018-07-03

    CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) is associated with poor survival compared with CD5-negative DLBCL. The clinical characteristics of CD5+ DLBCL are different from both CD5-negative DLBCL and other CD5+ B cell lymphomas. There is currently no promising chemotherapy for CD5+ DLBCL. Herein, we report a 49-year-old Asian male with refractory CD5+ DLBCL. He complained of aggravated abdominal pain and weight loss. Computed tomography scan revealed abdominal masses, widespread lymphadenopathy, splenomegaly, and intussusception of the ileocecal junction with bowel wall thickening. Core needle aspiration biopsy of an abdominal mass was performed and immunohistochemistry revealed DLBCL of nongerminal center type. In this report, the dose-intensified R-Hyper CVAD (A) regimen as salvage therapy was introduced but failed to result in substantial improvement over the initially standard R-CHOP regimen. Next, the R-GDP regimen was administered as second-line treatment, but only resulted in a partial response. However, the addition of lenalidomide to R-GDP (R2-GDP) resulted in complete remission. The clinical features, pathogenesis, and possible mechanism of action of lenalidomide in CD5+ DLBCL have been described in the literature. The results of the present case report and literature searches indicate that CD5+ DLBCL may share a common pathway with activated B-cell like (ABC) DLBCL as determined by gene expression profiling. Lenalidomide is expected to induce favorable responses in patients with CD5+ DLBCL.

  12. A Wheat R2R3-type MYB Transcription Factor TaODORANT1 Positively Regulates Drought and Salt Stress Responses in Transgenic Tobacco Plants

    Directory of Open Access Journals (Sweden)

    Qiuhui Wei

    2017-08-01

    Full Text Available MYB transcription factors play important roles in plant responses to biotic and abiotic stress. In this study, TaODORANT1, a R2R3-MYB gene, was cloned from wheat (Triticum aestivum L.. TaODORANT1 was localized in the nucleus and functioned as a transcriptional activator. TaODORANT1 was up-regulated in wheat under PEG6000, NaCl, ABA, and H2O2 treatments. TaODORANT1-overexpressing transgenic tobacco plants exhibited higher relative water content and lower water loss rate under drought stress, as well as lower Na+ accumulation in leaves under salt stress. The transgenic plants showed higher CAT activity but lower ion leakage, H2O2 and malondialdehyde contents under drought and salt stresses. Besides, the transgenic plants also exhibited higher SOD activity under drought stress. Our results also revealed that TaODORANT1 overexpression up-regulated the expression of several ROS- and stress-related genes in response to both drought and salt stresses, thus enhancing transgenic tobacco plants tolerance. Our studies demonstrate that TaODORANT1 positively regulates plant tolerance to drought and salt stresses.

  13. Efficacy of Bilevel-auto Treatment in Patients with Obstructive Sleep Apnea Not Responsive to or Intolerant of Continuous Positive Airway Pressure Ventilation.

    Science.gov (United States)

    Carlucci, Annalisa; Ceriana, Piero; Mancini, Marco; Cirio, Serena; Pierucci, Paola; D'Artavilla Lupo, Nadia; Gadaleta, Felice; Morrone, Elisa; Fanfulla, Francesco

    2015-09-15

    Ventilation with continuous positive airway pressure (CPAP) is the gold standard therapy for obstructive sleep apnea (OSA). However, it was recently suggested that a novel mode of ventilation, Bilevel-auto, could be equally effective in treating patients unable to tolerate CPAP. The aim of this study was to investigate the ability of Bilevel-auto to treat OSA patients whose nocturnal ventilatory disturbances are not completely corrected by CPAP. We enrolled 66 consecutive OSA patients, not responsive to (group A) or intolerant of (group B) CPAP treatment, after a full night of manual CPAP titration in a laboratory. Full polysomnography data and daytime sleepiness score were compared for each group in the three different conditions: basal, during CPAP, and during Bilevel-auto. The apnea-hypopnea index decreased significantly during CPAP in both groups; however, in the group A, there was a further significant improvement during Bilevel-auto. The same trend was observed for oxygenation indices, while the distribution and the efficiency of sleep did not differ following the switch from CPAP to Bilevel-auto. This study confirmed the role of Bilevel-auto as an effective therapeutic alternative to CPAP in patients intolerant of this latter mode of ventilation. Moreover, extending the use of Bilevel-auto to those OSA patients not responsive to CPAP, we showed a significantly better correction of nocturnal respiratory disturbances. © 2015 American Academy of Sleep Medicine.

  14. Capsicum annuum transcription factor WRKYa positively regulates defense response upon TMV infection and is a substrate of CaMK1 and CaMK2.

    Science.gov (United States)

    Huh, Sung Un; Lee, Gil-Je; Jung, Ji Hoon; Kim, Yunsik; Kim, Young Jin; Paek, Kyung-Hee

    2015-01-23

    Plants are constantly exposed to pathogens and environmental stresses. To minimize damage caused by these potentially harmful factors, plants respond by massive transcriptional reprogramming of various stress-related genes via major transcription factor families. One of the transcription factor families, WRKY, plays an important role in diverse stress response of plants and is often useful to generate genetically engineered crop plants. In this study, we carried out functional characterization of CaWRKYa encoding group I WRKY member, which is induced during hypersensitive response (HR) in hot pepper (Capsicum annuum) upon Tobacco mosaic virus (TMV) infection. CaWRKYa was involved in L-mediated resistance via transcriptional reprogramming of pathogenesis-related (PR) gene expression and affected HR upon TMV-P0 infection. CaWRKYa acts as a positive regulator of this defense system and could bind to the W-box of diverse PR genes promoters. Furthermore, we found Capsicum annuum mitogen-activated protein kinase 1 (CaMK1) and 2 (CaMK2) interacted with CaWRKYa and phosphorylated the SP clusters but not the MAPK docking (D)-domain of CaWRKYa. Thus, these results demonstrated that CaWRKYa was regulated by CaMK1 and CaMK2 at the posttranslational level in hot pepper.

  15. Rapid Assessment of Resistance to Antibiotic Inhibitors of Protein Synthesis in the Gram-Positive Pathogens, Enterococcus faecalis and Streptococcus pneumoniae, Based on Evaluation of the Lytic Response.

    Science.gov (United States)

    Otero, Fátima; Tamayo, María; Santiso, Rebeca; Gosálvez, Jaime; Bou, Germán; Fernández, José Luis

    2017-04-01

    A novel assay for rapid determination of resistance to antibiotic inhibitors of protein synthesis was developed for the gram-positive pathogens, Enterococcus faecalis and Streptococcus pneumoniae. To this purpose, a lytic response was obtained by a brief incubation with lysozyme or a mixture of lysozyme, Triton X-100, and EDTA for E. faecalis (n = 82) and S. pneumoniae (n = 51), respectively. Lysis was quantified by visualizing the released nucleoids. Antibiotic-susceptible bacteria treated with Clinical and Laboratory Standards Institute (CLSI) breakpoint doses of erythromycin, azithromycin, or doxycycline that inhibited protein synthesis demonstrated a large reduction of lysed cells with respect to the control, that is, without antibiotics. However, cell lysis prevention was much lower in nonsusceptible strains, with unsuccessful inhibition of protein synthesis. ROC analysis showed that a reduction value of ≥35.6% and ≥40.4% discriminates susceptible and nonsusceptible strains for erythromycin and for doxycycline, respectively, in E. faecalis, whereas ≥20.0% is adequate for both macrolides and doxycycline in S. pneumoniae. Resistant stains were identified in 90-120 min with sensitivity and specificity between 91.7% and 100%. This is a proof of concept that evaluation of the lytic response may be a rapid and efficient test for determination of resistance to antibiotic inhibitors of protein synthesis.

  16. Keratinocyte-derived IL-24 plays a role in the positive feedback regulation of epidermal inflammation in response to environmental and endogenous toxic stressors.

    Science.gov (United States)

    Jin, Sun Hee; Choi, Dalwoong; Chun, Young-Jin; Noh, Minsoo

    2014-10-15

    Keratinocytes are the major cellular components of human epidermis and play a key role in the modulating cutaneous inflammation and toxic responses. In human chronic skin diseases, the common skin inflammatory phenotypes like skin barrier disruption and epidermal hyperplasia are manifested in epidermal keratinocytes by interactions with T helper (Th) cells. To find a common gene expression signature of human keratinocytes in chronic skin diseases, we performed a whole genome microarray analysis on normal human epidermal keratinocytes (NHKs) treated with IFNγ, IL-4, IL-17A or IL-22, major cytokines from Th1, Th2, Th17 or Th22 cells, respectively. The microarray results showed that the four genes, IL-24, PDZK1IP1, H19 and filaggrin, had common expression profiles in NHKs exposed to Th cell cytokines. In addition, the acute phase pro-inflammatory cytokines, IL-1β, IL-6 and TNFα, also change the gene transcriptional profile of IL-24, PDZK1IP1, H19, and filaggrin in NHKs as those of Th cytokines. Therefore, the signature gene set, consisting of IL-24, PDZK1IP1, H19, and filaggrin, provides essential insights for understanding the process of cutaneous inflammation and toxic responses. We demonstrate that environmental toxic stressors, such as chemical irritants and ultraviolet irradiation stimulate the production of IL-24 in NHKs. IL-24 stimulates the JAK1-STAT3 and MAPK pathways in NHKs, and promotes the secretion of pro-inflammatory mediators IL-8, PGE2, and MMP-1. These results suggest that keratinocyte-derived IL-24 participates in the positive feedback regulation of epidermal inflammation in response to both endogenous and environmental toxic stressors. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Differential Patterns of Large Tumor Antigen-Specific Immune Responsiveness in Patients with BK Polyomavirus-Positive Prostate Cancer or Benign Prostatic Hyperplasia

    Science.gov (United States)

    Sais, Giovanni; Wyler, Stephen; Hudolin, Tvrtko; Banzola, Irina; Mengus, Chantal; Bubendorf, Lukas; Wild, Peter J.; Hirsch, Hans H.; Sulser, Tullio; Spagnoli, Giulio C.

    2012-01-01

    The role of the polyomavirus BK (BKV) large tumor antigen (L-Tag) as a target of immune response in patients with prostate cancer (PCa) has not been investigated thus far. In this study, we comparatively analyzed humoral and cellular L-Tag-specific responsiveness in age-matched patients bearing PCa or benign prostatic hyperplasia, expressing or not expressing BKV L-Tag-specific sequences in their tissue specimens, and in non-age-matched healthy individuals. Furthermore, results from patients with PCa were correlated to 5-year follow-up clinical data focusing on evidence of biochemical recurrence (BR) after surgery (prostate specific antigen level of ≥0.2 ng/ml). In peripheral blood mononuclear cells (PBMC) from patients with PCa with evidence of BR and BKV L-Tag-positive tumors, stimulation with peptides derived from the BKV L-Tag but not those derived from Epstein-Barr virus, influenza virus, or cytomegalovirus induced a peculiar cytokine gene expression profile, characterized by high expression of interleukin-10 (IL-10) and transforming growth factor β1 and low expression of gamma interferon genes. This pattern was confirmed by protein secretion data and correlated with high levels of anti-BKV L-Tag IgG. Furthermore, in PBMC from these PCa-bearing patients, L-Tag-derived peptides significantly expanded an IL-10-secreting CD4+ CD25+(high) CD127− FoxP3+ T cell population with an effector memory phenotype (CD103+) capable of inhibiting proliferation of autologous anti-CD3/CD28-triggered CD4+ CD25− T cells. Collectively, our findings indicate that potentially tolerogenic features of L-Tag-specific immune response are significantly associated with tumor progression in patients with BKV+ PCa. PMID:22647697

  18. Response

    Science.gov (United States)

    Higgins, Chris

    2012-01-01

    This article presents the author's response to the reviews of his book, "The Good Life of Teaching: An Ethics of Professional Practice." He begins by highlighting some of the main concerns of his book. He then offers a brief response, doing his best to address the main criticisms of his argument and noting where the four reviewers (Charlene…

  19. Characterization of a Toxin A-Negative, Toxin B-Positive Strain of Clostridium difficile Responsible for a Nosocomial Outbreak of Clostridium difficile-Associated Diarrhea

    Science.gov (United States)

    Alfa, Michelle J.; Kabani, Amin; Lyerly, David; Moncrief, Scott; Neville, Laurie M.; Al-Barrak, Ali; Harding, Godfrey K. H.; Dyck, Brenda; Olekson, Karen; Embil, John M.

    2000-01-01

    Clostridium difficile-associated diarrhea (CAD) is a very common nosocomial infection that contributes significantly to patient morbidity and mortality as well as to the cost of hospitalization. Previously, strains of toxin A-negative, toxin B-positive C. difficile were not thought to be associated with clinically significant disease. This study reports the characterization of a toxin A-negative, toxin B-positive strain of C. difficile that was responsible for a recently described nosocomial outbreak of CAD. Analysis of the seven patient isolates from the outbreak by pulsed-field gel electrophoresis indicated that this outbreak was due to transmission of a single strain of C. difficile. Our characterization of this strain (HSC98) has demonstrated that the toxin A gene lacks 1.8 kb from the carboxy repetitive oligopeptide (CROP) region but apparently has no other major deletions from other regions of the toxin A or toxin B gene. The remaining 1.3-kb fragment of the toxin A CROP region from strain HSC98 showed 98% sequence homology with strain 1470, previously reported by M. Weidmann in 1997 (GenBank accession number Y12616), suggesting that HSC98 is toxinotype VIII. The HSC98 strain infecting patients involved in this outbreak produced the full spectrum of clinical illness usually associated with C. difficile-associated disease. This pathogenic spectrum was manifest despite the inability of this strain to alter tight junctions as determined by using in vitro tissue culture testing, which suggested that no functional toxin A was produced by this strain. PMID:10878068

  20. Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1.

    Science.gov (United States)

    Eggler, Aimee L; Small, Evan; Hannink, Mark; Mesecar, Andrew D

    2009-07-29

    Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that activates transcription of a battery of cytoprotective genes by binding to the ARE (antioxidant response element). Nrf2 is repressed by the cysteine-rich Keap1 (kelch-like ECH-associated protein 1) protein, which targets Nrf2 for ubiquitination and subsequent degradation by a Cul3 (cullin 3)-mediated ubiquitination complex. We find that modification of Cys(151) of human Keap1, by mutation to a tryptophan, relieves the repression by Keap1 and allows activation of the ARE by Nrf2. The Keap1 C151W substitution has a decreased affinity for Cul3, and can no longer serve to target Nrf2 for ubiquitination, though it retains its affinity for Nrf2. A series of 12 mutant Keap1 proteins, each containing a different residue at position 151, was constructed to explore the chemistry required for this effect. The series reveals that the extent to which Keap1 loses the ability to target Nrf2 for degradation, and hence the ability to repress ARE activation, correlates well with the partial molar volume of the residue. Other physico-chemical properties do not appear to contribute significantly to the effect. Based on this finding, a structural model is proposed whereby large residues at position 151 cause steric clashes that lead to alteration of the Keap1-Cul3 interaction. This model has significant implications for how electrophiles which modify Cys(151), disrupt the repressive function of Keap1.

  1. ON THE PRO-METASTATIC STRESS RESPONSE TO CANCER THERAPIES: EVIDENCE FOR A POSITIVE CO-OPERATION BETWEEN TIMP-1, HIF-1α, AND miR-210

    Directory of Open Access Journals (Sweden)

    Haissi eCui

    2012-07-01

    Full Text Available In contrast to expectations in the past that tumor starvation or unselective inhibition of proteolytic activity would cure cancer, there is accumulating evidence that microenvironmental stress, such as hypoxia or broad spectrum inhibition of metalloproteinases can promote metastasis. In fact, malignant tumor cells, due to their genetic and epigenetic instability, are predisposed to react to stress by adaptation and, if the stress persists, by escape and formation of metastasis. Recent recognition of the concepts of dynamic evolution as well as population and systems biology is extremely helpful to understand the disappointments of clinical trials with new drugs and may lead to paradigm-shifts in therapy strategies. This must be complemented by an increased understanding of molecular mechanism involved in stress response. Here, we review new roles of Hypoxia-inducible factor-1 (HIF-1, one transcription factor regulating stress response-related gene expression: HIF-1 is crucial for invasion and metastasis, independent from its pro-survival function. In addition, HIF-1 mediates pro-metastatic microenvironmental changes of the proteolytic balance as triggered by high systemic levels of tissue inhibitor of metalloproteinases-1 (TIMP-1, typical for many aggressive cancers, and regulates the metabolic switch to glycolysis, notably via activation of the microRNA miR-210. There is preliminary evidence that TIMP-1 also induces miR-210. Such positive-regulatory co-operation of HIF-1α, miR-210, and TIMP-1, all described to correlate with bad prognosis of cancer patients, opens new perspectives of gaining insight into molecular mechanisms of metastasis-inducing evasion of tumor cells from stress.

  2. FDG-PET Response Prediction in Pediatric Hodgkin’s Lymphoma: Impact of Metabolically Defined Tumor Volumes and Individualized SUV Measurements on the Positive Predictive Value

    Energy Technology Data Exchange (ETDEWEB)

    Hussien, Amr Elsayed M. [Department of Nuclear Medicine (KME), Forschungszentrum Jülich, Medical Faculty, Heinrich-Heine-University Düsseldorf, Jülich, 52426 (Germany); Department of Nuclear Medicine, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, 40225 (Germany); Furth, Christian [Department of Radiology and Nuclear Medicine, Medical School, Otto-von-Guericke University Magdeburg, Magdeburg, 39120 (Germany); Schönberger, Stefan [Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children’s Hospital, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, 40225 (Germany); Hundsdoerfer, Patrick [Department of Pediatric Oncology and Hematology, Charité Campus Virchow, Humboldt-University Berlin, Berlin, 13353 (Germany); Steffen, Ingo G.; Amthauer, Holger [Department of Radiology and Nuclear Medicine, Medical School, Otto-von-Guericke University Magdeburg, Magdeburg, 39120 (Germany); Müller, Hans-Wilhelm; Hautzel, Hubertus, E-mail: h.hautzel@fz-juelich.de [Department of Nuclear Medicine (KME), Forschungszentrum Jülich, Medical Faculty, Heinrich-Heine-University Düsseldorf, Jülich, 52426 (Germany); Department of Nuclear Medicine, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, 40225 (Germany)

    2015-01-28

    Background: In pediatric Hodgkin’s lymphoma (pHL) early response-to-therapy prediction is metabolically assessed by (18)F-FDG PET carrying an excellent negative predictive value (NPV) but an impaired positive predictive value (PPV). Aim of this study was to improve the PPV while keeping the optimal NPV. A comparison of different PET data analyses was performed applying individualized standardized uptake values (SUV), PET-derived metabolic tumor volume (MTV) and the product of both parameters, termed total lesion glycolysis (TLG); Methods: One-hundred-eight PET datasets (PET1, n = 54; PET2, n = 54) of 54 children were analysed by visual and semi-quantitative means. SUVmax, SUVmean, MTV and TLG were obtained the results of both PETs and the relative change from PET1 to PET2 (Δ in %) were compared for their capability of identifying responders and non-responders using receiver operating characteristics (ROC)-curves. In consideration of individual variations in noise and contrasts levels all parameters were additionally obtained after threshold correction to lean body mass and background; Results: All semi-quantitative SUV estimates obtained at PET2 were significantly superior to the visual PET2 analysis. However, ΔSUVmax revealed the best results (area under the curve, 0.92; p < 0.001; sensitivity 100%; specificity 85.4%; PPV 46.2%; NPV 100%; accuracy, 87.0%) but was not significantly superior to SUVmax-estimation at PET2 and ΔTLGmax. Likewise, the lean body mass and background individualization of the datasets did not impove the results of the ROC analyses; Conclusions: Sophisticated semi-quantitative PET measures in early response assessment of pHL patients do not perform significantly better than the previously proposed ΔSUVmax. All analytical strategies failed to improve the impaired PPV to a clinically acceptable level while preserving the excellent NPV.

  3. FDG-PET Response Prediction in Pediatric Hodgkin’s Lymphoma: Impact of Metabolically Defined Tumor Volumes and Individualized SUV Measurements on the Positive Predictive Value

    International Nuclear Information System (INIS)

    Hussien, Amr Elsayed M.; Furth, Christian; Schönberger, Stefan; Hundsdoerfer, Patrick; Steffen, Ingo G.; Amthauer, Holger; Müller, Hans-Wilhelm; Hautzel, Hubertus

    2015-01-01

    Background: In pediatric Hodgkin’s lymphoma (pHL) early response-to-therapy prediction is metabolically assessed by (18)F-FDG PET carrying an excellent negative predictive value (NPV) but an impaired positive predictive value (PPV). Aim of this study was to improve the PPV while keeping the optimal NPV. A comparison of different PET data analyses was performed applying individualized standardized uptake values (SUV), PET-derived metabolic tumor volume (MTV) and the product of both parameters, termed total lesion glycolysis (TLG); Methods: One-hundred-eight PET datasets (PET1, n = 54; PET2, n = 54) of 54 children were analysed by visual and semi-quantitative means. SUVmax, SUVmean, MTV and TLG were obtained the results of both PETs and the relative change from PET1 to PET2 (Δ in %) were compared for their capability of identifying responders and non-responders using receiver operating characteristics (ROC)-curves. In consideration of individual variations in noise and contrasts levels all parameters were additionally obtained after threshold correction to lean body mass and background; Results: All semi-quantitative SUV estimates obtained at PET2 were significantly superior to the visual PET2 analysis. However, ΔSUVmax revealed the best results (area under the curve, 0.92; p < 0.001; sensitivity 100%; specificity 85.4%; PPV 46.2%; NPV 100%; accuracy, 87.0%) but was not significantly superior to SUVmax-estimation at PET2 and ΔTLGmax. Likewise, the lean body mass and background individualization of the datasets did not impove the results of the ROC analyses; Conclusions: Sophisticated semi-quantitative PET measures in early response assessment of pHL patients do not perform significantly better than the previously proposed ΔSUVmax. All analytical strategies failed to improve the impaired PPV to a clinically acceptable level while preserving the excellent NPV

  4. Adjuvant Radiation Therapy for Margin-Positive Vulvar Squamous Cell Carcinoma: Defining the Ideal Dose-Response Using the National Cancer Data Base

    International Nuclear Information System (INIS)

    Chapman, Bhavana V.; Gill, Beant S.; Viswanathan, Akila N.; Balasubramani, Goundappa K.; Sukumvanich, Paniti; Beriwal, Sushil

    2017-01-01

    Purpose: Positive surgical margins after radical vulvectomy for vulvar cancer portend a high risk for local relapse, which may be challenging to salvage. We assessed the impact of adjuvant radiation therapy (aRT) on overall survival (OS) and the dose-response relationship using the National Cancer Data Base. Methods and Materials: Patients with vulvar squamous cell carcinoma who underwent initial extirpative surgery with positive margins from 1998 to 2012 were included. Factors associated with aRT and specific dose levels were analyzed using logistic regression. Log-rank and multivariable Cox proportional hazards modeling were used for OS analysis. Results: We identified 3075 patients with a median age of 66 years (range, 22-90 years); the median follow-up time was 36.4 months (interquartile range [IQR] 15.4-71.0 months). Stage IA/B disease represented 41.2% of the cohort. Sixty-three percent underwent lymph node assessment, with a 45% positivity rate. In total, 1035 patients (35.3%) received aRT, with a median dose of 54.0 Gy (IQR 48.6-60.0 Gy). The 3-year OS improved from 58.5% to 67.4% with aRT (P<.001). On multivariable analysis, age, Charlson-Deyo score ≥1, stage ≥II, tumors ≥4 cm, no aRT, and adverse nodal characteristics led to inferior survival. Dose of aRT was positively associated with OS as a continuous variable on univariate analysis (P<.001). The unadjusted 3-year OS for dose subsets 30.0 to 45.0 Gy, 45.1 to 53.9 Gy, 54.0 to 59.9 Gy, and ≥60 Gy was 54.3%, 55.7%, 70.1%, and 65.3%, respectively (P<.001). Multivariable analysis using a 4-month conditional landmark revealed that the greatest mortality reduction occurred in cumulative doses ≥54 Gy: 45.1 to 53.9 Gy (hazard ratio [HR] 0.94, P=.373), 54.0 to 59.9 Gy (HR 0.75, P=.024), ≥60 Gy (HR 0.71, P=.015). No survival benefit was seen with ≥60 Gy compared with 54.0 to 59.9 Gy (HR 0.95, P=.779). Conclusions: Patients with vulvar squamous cell carcinoma and positive surgical

  5. Keratinocyte-derived IL-24 plays a role in the positive feedback regulation of epidermal inflammation in response to environmental and endogenous toxic stressors

    International Nuclear Information System (INIS)

    Jin, Sun Hee; Choi, Dalwoong; Chun, Young-Jin; Noh, Minsoo

    2014-01-01

    Keratinocytes are the major cellular components of human epidermis and play a key role in the modulating cutaneous inflammation and toxic responses. In human chronic skin diseases, the common skin inflammatory phenotypes like skin barrier disruption and epidermal hyperplasia are manifested in epidermal keratinocytes by interactions with T helper (Th) cells. To find a common gene expression signature of human keratinocytes in chronic skin diseases, we performed a whole genome microarray analysis on normal human epidermal keratinocytes (NHKs) treated with IFNγ, IL-4, IL-17A or IL-22, major cytokines from Th1, Th2, Th17 or Th22 cells, respectively. The microarray results showed that the four genes, IL-24, PDZK1IP1, H19 and filaggrin, had common expression profiles in NHKs exposed to Th cell cytokines. In addition, the acute phase pro-inflammatory cytokines, IL-1β, IL-6 and TNFα, also change the gene transcriptional profile of IL-24, PDZK1IP1, H19, and filaggrin in NHKs as those of Th cytokines. Therefore, the signature gene set, consisting of IL-24, PDZK1IP1, H19, and filaggrin, provides essential insights for understanding the process of cutaneous inflammation and toxic responses. We demonstrate that environmental toxic stressors, such as chemical irritants and ultraviolet irradiation stimulate the production of IL-24 in NHKs. IL-24 stimulates the JAK1-STAT3 and MAPK pathways in NHKs, and promotes the secretion of pro-inflammatory mediators IL-8, PGE2, and MMP-1. These results suggest that keratinocyte-derived IL-24 participates in the positive feedback regulation of epidermal inflammation in response to both endogenous and environmental toxic stressors. - Highlights: • Cutaneous inflammatory gene signature consists of PDZK1IP1, IL-24, H19 and filaggrin. • Pro-inflammatory cytokines increase IL-24 production in human keratinocytes. • Environmental toxic stressors increase IL-24 production in human keratinocytes. • IL-24 stimulates human keratinocytes to

  6. Associations of social environment, socioeconomic position and social mobility with immune response in young adults: the Jerusalem Perinatal Family Follow-Up Study.

    Science.gov (United States)

    Lawrence, Gabriella M; Friedlander, Yehiel; Calderon-Margalit, Ronit; Enquobahrie, Daniel A; Huang, Jonathan Yinhao; Tracy, Russell P; Manor, Orly; Siscovick, David S; Hochner, Hagit

    2017-12-21

    Immune response to cytomegalovirus (CMV) impacts adult chronic disease. This study investigates associations of childhood and adulthood social environment, socioeconomic position (SEP) and social mobility with CMV response in young adults. Historical prospective study design. Subcohort of all 17 003 births to residents of Jerusalem between 1974 and 1976. Participants included 1319 young adults born in Jerusalem with extensive archival and follow-up data, including childhood and adulthood SEP-related factors and anti-CMV IgG titre levels and seroprevalence measured at age 32. Principal component analysis was used to transform correlated social environment and SEP-related variables at two time points (childhood and adulthood) into two major scores reflecting household (eg, number of siblings/children, religiosity) and socioeconomic (eg, occupation, education) components. Based on these components, social mobility variables were created. Linear and Poisson regression models were used to investigate associations of components and mobility with anti-CMV IgG titre level and seroprevalence, adjusted for confounders. Lower levels of household and socioeconomic components in either childhood or adulthood were associated with higher anti-CMV IgG titre level and seropositivity at age 32. Compared with individuals with stable favourable components, anti-CMV IgG titre level and risk for seropositivity were higher in stable unfavourable household and socioeconomic components (household: β=3.23, P<0.001; relative risk (RR)=1.21, P<0.001; socioeconomic: β=2.20, P=0.001; RR=1.14, P=0.01), downward household mobility (β=4.32, P<0.001; RR=1.26, P<0.001) and upward socioeconomic mobility (β=1.37, P=0.04; RR=1.19, P<0.001). Among seropositive individuals, associations between household components and mobility with anti-CMV IgG titre level were maintained and associations between socioeconomic components and mobility with anti-CMV IgG titre level were attenuated. Our study

  7. Keratinocyte-derived IL-24 plays a role in the positive feedback regulation of epidermal inflammation in response to environmental and endogenous toxic stressors

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Sun Hee [Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of); Choi, Dalwoong [Department of Public Health Science, Korea University, Seoul 136-701 (Korea, Republic of); Chun, Young-Jin [College of Pharmacy, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Noh, Minsoo, E-mail: minsoo@alum.mit.edu [Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2014-10-15

    Keratinocytes are the major cellular components of human epidermis and play a key role in the modulating cutaneous inflammation and toxic responses. In human chronic skin diseases, the common skin inflammatory phenotypes like skin barrier disruption and epidermal hyperplasia are manifested in epidermal keratinocytes by interactions with T helper (Th) cells. To find a common gene expression signature of human keratinocytes in chronic skin diseases, we performed a whole genome microarray analysis on normal human epidermal keratinocytes (NHKs) treated with IFNγ, IL-4, IL-17A or IL-22, major cytokines from Th1, Th2, Th17 or Th22 cells, respectively. The microarray results showed that the four genes, IL-24, PDZK1IP1, H19 and filaggrin, had common expression profiles in NHKs exposed to Th cell cytokines. In addition, the acute phase pro-inflammatory cytokines, IL-1β, IL-6 and TNFα, also change the gene transcriptional profile of IL-24, PDZK1IP1, H19, and filaggrin in NHKs as those of Th cytokines. Therefore, the signature gene set, consisting of IL-24, PDZK1IP1, H19, and filaggrin, provides essential insights for understanding the process of cutaneous inflammation and toxic responses. We demonstrate that environmental toxic stressors, such as chemical irritants and ultraviolet irradiation stimulate the production of IL-24 in NHKs. IL-24 stimulates the JAK1-STAT3 and MAPK pathways in NHKs, and promotes the secretion of pro-inflammatory mediators IL-8, PGE2, and MMP-1. These results suggest that keratinocyte-derived IL-24 participates in the positive feedback regulation of epidermal inflammation in response to both endogenous and environmental toxic stressors. - Highlights: • Cutaneous inflammatory gene signature consists of PDZK1IP1, IL-24, H19 and filaggrin. • Pro-inflammatory cytokines increase IL-24 production in human keratinocytes. • Environmental toxic stressors increase IL-24 production in human keratinocytes. • IL-24 stimulates human keratinocytes to

  8. Position Information

    Data.gov (United States)

    Social Security Administration — The Position Information Data Asset provides the ability to search for active SSA position descriptions using various search criteria. An individual may search by PD...

  9. Positive Psychology

    Science.gov (United States)

    Peterson, Christopher

    2009-01-01

    Positive psychology is a deliberate correction to the focus of psychology on problems. Positive psychology does not deny the difficulties that people may experience but does suggest that sole attention to disorder leads to an incomplete view of the human condition. Positive psychologists concern themselves with four major topics: (1) positive…

  10. Ubiquitous positioning

    CERN Document Server

    Mannings, Robin

    2008-01-01

    This groundbreaking resource offers a practical, in-depth understanding of Ubiquitous Positioning - positioning systems that identify the location and position of people, vehicles and objects in time and space in the digitized networked economy. The future and growth of ubiquitous positioning will be fueled by the convergence of many other areas of technology, from mobile telematics, Internet technology, and location systems, to sensing systems, geographic information systems, and the semantic web. This first-of-its-kind volume explores ubiquitous positioning from a convergence perspective, of

  11. Hemodynamic responses to external counterbalancing of auto-positive end-expiratory pressure in mechanically ventilated patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Baigorri, F; de Monte, A; Blanch, L; Fernández, R; Vallés, J; Mestre, J; Saura, P; Artigas, A

    1994-11-01

    To study the effect of positive end-expiratory pressure (PEEP) on right ventricular hemodynamics and ejection fraction in patients with chronic obstructive pulmonary disease and positive alveolar pressure throughout expiration by dynamic hyperinflation (auto-PEEP). Open, prospective, controlled trial. General intensive care unit of a community hospital. Ten patients sedated and paralyzed with an acute exacerbation of chronic obstructive pulmonary disease undergoing mechanical ventilation. Insertion of a pulmonary artery catheter modified with a rapid response thermistor and a radial arterial catheter. PEEP was then increased from 0 (PEEP 0) to auto-PEEP level (PEEP = auto-PEEP) and 5 cm H2O above that (PEEP = auto-PEEP +5). At each level of PEEP, airway pressures, flow and volume, hemodynamic variables (including right ventricular ejection fraction by thermodilution technique), and blood gas analyses were recorded. The mean auto-PEEP was 6.6 +/- 2.8 cm H2O and the total PEEP reached was 12.2 +/- 2.4 cm H2O. The degree of lung inflation induced by PEEP averaged 145 +/- 87 mL with PEEP = auto-PEEP and 495 +/- 133 mL with PEEP = auto-PEEP + 5. The PEEP = auto-PEEP caused a right ventricular end-diastolic pressure increase, but there was no other significant hemodynamic change. With PEEP = auto-PEEP + 5, there was a significant increase in intravascular pressures; this amount of PEEP reduced cardiac output (from 4.40 +/- 1.38 L/min at PEEP 0 to 4.13 +/- 1.48 L/min; p 10% in only five cases and this group of patients had significantly lower right ventricular volumes than the group with less cardiac output variation (right ventricular end-diastolic volume: 64 +/- 9 vs. 96 +/- 26 mL/m2; right ventricular end-systolic volume: 38 +/- 6 vs. 65 +/- 21 mL/m2; p < .05) without significant difference in the other variables that were measured. Neither right ventricular ejection fraction nor right ventricle volumes changed as PEEP increased, but there were marked interpatient

  12. Positioning consumption

    DEFF Research Database (Denmark)

    Halkier, Bente; Keller, Margit

    2014-01-01

    positionings emerges based on empirical examples of research in parent–children consumption. Positionings are flexible discursive fixations of the relationship between the performances of the practitioner, other practitioners, media discourse and consumption activities. The basic positioning types...... are the practice maintenance and the practice change position, with different sorts of adapting in between. Media discourse can become a resource for a resistant position against social control or for an appropriating position in favour of space for action. Regardless of the current relation to a particular media......This article analyses the ways in which media discourses become a part of contested consumption activities. We apply a positioning perspective with practice theory to focus on how practitioners relate to media discourse as a symbolic resource in their everyday practices. A typology of performance...

  13. Expression of the alaE gene is positively regulated by the global regulator Lrp in response to intracellular accumulation of l-alanine in Escherichia coli.

    Science.gov (United States)

    Ihara, Kohei; Sato, Kazuki; Hori, Hatsuhiro; Makino, Yumiko; Shigenobu, Shuji; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2017-04-01

    The alaE gene in Escherichia coli encodes an l-alanine exporter that catalyzes the active export of l-alanine using proton electrochemical potential. In our previous study, alaE expression was shown to increase in the presence of l-alanyl-l-alanine (Ala-Ala). In this study, the global regulator leucine-responsive regulatory protein (Lrp) was identified as an activator of the alaE gene. A promoter less β-galactosidase gene was fused to an alaE upstream region (240 nucleotides). Cells that were lacZ-deficient and harbored this reporter plasmid showed significant induction of β-galactosidase activity (approximately 17-fold) in the presence of 6 mM l-alanine, l-leucine, and Ala-Ala. However, a reporter plasmid possessing a smaller alaE upstream region (180 nucleotides) yielded transformants with strikingly low enzyme activity under the same conditions. In contrast, lrp-deficient cells showed almost no β-galactosidase induction, indicating that Lrp positively regulates alaE expression. We next performed an electrophoretic mobility shift assay (EMSA) and a DNase I footprinting assay using purified hexahistidine-tagged Lrp (Lrp-His). Consequently, we found that Lrp-His binds to the alaE upstream region spanning nucleotide -161 to -83 with a physiologically relevant affinity (apparent K D , 288.7 ± 83.8 nM). Furthermore, the binding affinity of Lrp-His toward its cis-element was increased by l-alanine and l-leucine, but not by Ala-Ala and d-alanine. Based on these results, we concluded that the gene expression of the alaE is regulated by Lrp in response to intracellular levels of l-alanine, which eventually leads to intracellular homeostasis of l-alanine concentrations. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. Gender Related Differences in Response to “In Favor of Myself” Wellness Program to Enhance Positive Self & Body Image among Adolescents

    Science.gov (United States)

    Golan, Moria; Hagay, Noa; Tamir, Snait

    2014-01-01

    Background Physical, neurological and psychological changes are often experienced differently by male and female adolescents. Positive self-esteem, emotional well-being, school achievements, and family connectedness are considered as protective factors against health-compromising behaviors. This study examines the gender differences in respect to the effect of a school-based interactive wellness program – “In Favor of Myself” – on self-image, body image, eating attitudes and behaviors of young adolescents. Methods Two hundred and ten adolescents (mean age 13.5) participated in the intervention group, 55% were girls and 45% boys. Program consisted of eight 90-minutes structured sessions integrated into a regular school coping skills curriculum. The program focused on self-esteem, self-image, body image, media literacy and cognitive dissonance. The overall impact of the program and the study protocol were previously published. Results Overall, there are gender related differences in respect to body image and self-image in young adolescents in response to “In Favor of Myself”. Compared to boys, girls reported at baseline higher self-esteem, being more contingent by appearance, and their self-image was more influenced by popularity, appearance, interpersonal communication and admired people. Furthermore girls presented greater gap between current body figure and perceived ideal figure. Not only were girls more dissatisfied with their body, but they were more active in attempts to become and/or remain “thin”. At program termination, gender × time effect was detected in reduction of self-worth contingent by others, change in importance given to achievements at schools, parents' perceptions, as well as the impact of comparisons to friends and family members on self-image. Conclusions Girls exhibited more gains than boys from ‘In Favor of Myself’ which raise the questions about how effective would be the program when delivered in mixed gender groups vs

  15. Association of myocardial inotropic reserve and adrenergic nerve alterations in idiopathic dilated cardiomyopathy. A dobutamine stress echocardiographic and 123-I-MIBG scintigraphic study

    International Nuclear Information System (INIS)

    Prassopoulos, V.P.; Koukouraki, S.; Velidaki, A.; Karkavitsas, N.; Parthenakis, F.; Patrianakos, A.; Kochiadakis, G.; Papadimitriou, E.; Vardas, P.

    2002-01-01

    Aim: Evaluation of contractile reserve is important in congestive hear failure. The aim of this study was to examine the relationship between the myocardial response to dobutamine by stress echocardiography and the sympathetic nerve alterations by 123-I-Metaiodobenzylguanidine (MIBG)scintigraphy and how both contribute to predict exercise capacity in patients with idiopathic dilated cardiomyopathy. Materials-Methods: We studied 20 patients with idiopathic dilated cardiomyopathy (IDC) and ejection fraction < 45% (M/F 13/7, age 56±11 years) while 15 healthy individuals served as controls. Echocardiography and myocardial scintigraphic study with 123-I- MIBG, provided quantitative assessment of left ventricular (LV) wall motion and heart to mediastinum uptake(H/M) ratio and washout. All patients underwent a cardiopulmonary exercise test with a modified Naughton protocol and gas exchange data were analyzed. According to LV response to dobutamine, patients were divided into two groups: those in whom contractility improved in ≥ five segments (Group I: 11 patients) and those in whom contractility improved in < 5 segments (Group II : 9 patients). Results: MIBG uptake was significantly lower in patients than in controls (p < 0.001). MIBG uptake and washout was higher in Group I compared to Group II (P<0,01 and p<0,05). Late MIBG H/M was correlated with resting ejection fraction (r=0,70), wall motion score index (WMSI) (r=-0,50), end systolic wall stress (r=-0,61), washout (r=-0,57), and oxygen consumption at peak exercise (r=0,64) and at anaerobic threshold (r=0,67). LV ejection fraction increased in both groups at Dobutamine, with a higher increase in Group I (p=0,008). WMSI changes at dobutamine correlated significantly with resting ejection fraction (r=0,46) early (r=0,53) and late (r=0,54) MIBG. Multivariate analysis revealed that only the late MIBG uptake was independently associated with the improvement in WMSI. Conclusions: The present data indicate that in

  16. Two anomalous cardiovascular responses to active standing in essential hypertension.

    Science.gov (United States)

    Bettencourt, M Joaquina; Pinto, Basílio Gomes; de Oliveira, E Infante; Silva-Carvalho, L

    2008-05-01

    In a previous work we studied, non-invasively, autonomic nervous system control of circulation in healthy subjects, observing the hemodynamic reaction to active standing. We now propose to extend this analysis to essential hypertension (EH), investigating possible autonomic dysfunction. The cardiovascular response to postural change from the supine position to active standing of 48 EH patients, of both sexes, with and without medication, was compared with that obtained for healthy subjects. We evaluated arterial systolic (SBP) and diastolic (DBP) blood pressure, stroke volume (SV), inotropic index (INOI), total vascular resistance (TVR), cardiac work (W), stroke work (SW), arterial compliance (AC) and heart rate (HR), using the entirely non-invasive BoMed NCCOM3 thoracic electrical bioimpedance monitor and sphygmomanometry. We found two patient groups characterized by different linear relationships between values of cardiovascular variables in active standing and in supine positions. Except for HR, in both groups these regression lines differed from normal. Compared to the supine position, in active standing, one group (EH-I) presented increased TVR, diminished SV, INOI, W, SW, and AC, and normal HR; the other group (EH-II) presented diminished TVR and HR and increased SV, INOI, W, SW and AC. The two patient groups could be separated on the basis of their age, but not on the basis of their systolic, diastolic and mean arterial blood pressures, gender or medication. The younger patient group (EH-I) included 28 subjects aged 24 to 69 years (50+/-10), of whom 11 were unmedicated, and the older patient group (EH-II) included 20 subjects aged 35 to 75 years (62+/-11), of whom 7 were unmedicated. Our results show a depressed response in postural change for older patients, which in the autonomic control of circulation expresses carotid baroreflex impairment, and conversely an enhanced response for younger patients, which can be caused by a maladjustment of the influence

  17. Functional characterization of a Nudix hydrolase AtNUDX8 upon pathogen attack indicates a positive role in plant immune responses.

    Directory of Open Access Journals (Sweden)

    Jose Pedro Fonseca

    Full Text Available Nudix hydrolases comprise a large gene family of twenty nine members in Arabidopsis, each containing a conserved motif capable of hydrolyzing specific substrates like ADP-glucose and NADH. Until now only two members of this family, AtNUDX6 and AtNUDX7, have been shown to be involved in plant immunity. RPP4 is a resistance gene from a multigene family that confers resistance to downy mildew. A time course expression profiling after Hyaloperonospora arabidopsidis inoculation in both wild-type (WT and the rpp4 mutant was carried out to identify differentially expressed genes in RPP4-mediated resistance. AtNUDX8 was one of several differentially expressed, downregulated genes identified. A T-DNA knockout mutant (KO-nudx8 was obtained from a Salk T-DNA insertion collection, which exhibited abolished AtNUDX8 expression. The KO-nudx8 mutant was infected separately from the oomycete pathogen Hpa and the bacterial pathogen Pseudomonas syringae pv. maculicola ES4326. The mutant displayed a significantly enhanced disease susceptibility to both pathogens when compared with the WT control. We observed a small, stunted phenotype for KO-nudx8 mutant plants when grown over a 12/12 hour photoperiod but not over a 16/8 hour photoperiod. AtNUDX8 expression peaked at 8 hours after the lights were turned on and this expression was significantly repressed four-fold by salicylic acid (SA. The expression of three pathogen-responsive thioredoxins (TRX-h2, TRX-h3 and TRX-h5 were downregulated at specific time points in the KO-nudx8 mutant when compared with the WT. Furthermore, KO-nudx8 plants like the npr1 mutant, displayed SA hypersensitivity. Expression of a key SA biosynthetic gene ICS1 was repressed at specific time points in the KO-nudx8 mutant suggesting that AtNUDX8 is involved in SA signaling in plants. Similarly, NPR1 and PR1 transcript levels were also downregulated at specific time points in the KO-nudx8 mutant. This study shows that AtNUDX8 is involved in

  18. Evolution of Recognition of Ligands from Gram-Positive Bacteria: Similarities and Differences in the TLR2-Mediated Response between Mammalian Vertebrates and Teleost Fish

    NARCIS (Netherlands)

    Ribeiro, Carla M. S.; Hermsen, Trudi; Taverne-Thiele, Anja J.; Savelkoul, Huub F. J.; Wiegertjes, Geert F.

    2010-01-01

    We investigated the role of the TLR2 receptor in the recognition of ligands from Gram-positive bacteria in fish. Comparative sequence analysis showed a highly conserved Toll/IL-1 receptor domain. Although the leucine-rich repeat domain was less conserved, the position of the critical peptidoglycan

  19. FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures

    DEFF Research Database (Denmark)

    Wong, Kah Keng; Gascoyne, Duncan M; Soilleux, Elizabeth J

    2016-01-01

    frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which...

  20. Researcher positioning

    DEFF Research Database (Denmark)

    Mørck, Line Lerche; Khawaja, Iram

    2009-01-01

    abstract  This article focuses on the complex and multi-layered process of researcher positioning, specifically in relation to the politically sensitive study of marginalised and ‘othered' groups such as Muslims living in Denmark. We discuss the impact of different ethnic, religious and racial...... political and personal involvement by the researcher, which challenges traditional perspectives on research and researcher positioning. A key point in this regard is the importance of constant awareness of and reflection on the multiple ways in which one's positioning as a researcher influences the research...

  1. Radiographic positioning

    International Nuclear Information System (INIS)

    Eisenberg, R.L.; Dennis, C.A.; May, C.

    1989-01-01

    This book concentrates on the routine radiographic examinations commonly performed. It details the wide variety of examinations possible and their place in initial learning and in the radiology department as references for those occasions when an unusual examination is requested. This book provides information ranging from basic terminology to skeletal positioning to special procedures. Positions are discussed and supplemented with a picture of a patient, the resulting radiograph, and a labeled diagram. Immobilization and proper shielding of the patient are also shown

  2. Position encoder

    International Nuclear Information System (INIS)

    Goursky, Vsevolod

    1975-01-01

    A circuitry for deriving the quotient of signal delivered by position-sensitive detectors is described. Digital output is obtained in the form of 10- to 12-bit words. Impact position may be determined with 0.25% accuracy when the dynamic range of the energy signal is less 1:10, and 0.5% accuracy when the dynamic range is 1:20. The division requires an average time of 5μs for 10-bit words

  3. Position encoder

    International Nuclear Information System (INIS)

    Goursky, V.

    1975-05-01

    This paper describes circuitry for deriving the quotient of signals delivered by position-sensitive detectors. Digital output is obtained in the form of 10 to 12 bit words. Impact position may be determined with 0.25% accuracy when the dynamic range of the energy signal is less than 1:10, and 0.5% accuracy when the dynamic range is 1:20. The division requires an average time of 5μs for 10-bit words [fr

  4. Changes in seed oil and protein contents of maize cultivars at different positions on the ear in response to water limitation

    Directory of Open Access Journals (Sweden)

    Kazem Ghassemi-Golezani

    2016-10-01

    Full Text Available A field experiment was carried out as split-split plot in 2014 to assess the effects of four irrigation treatments (irrigations after 60, 80, 100 and 120 mm evaporation, respectively on oil and protein changes of maize cultivars (SC704, NS640 and DC303: Late, mid and early maturing cultivars, respectively at different seed positions on the ear (upper, middle and lower positions on the ear. Overall, the highest seed yield was obtained from SC704, followed by NS640 and DC303 cultivars. Seed yield of all cultivars was higher at lower seed position on ear than at middle and upper parts of the ear under different irrigation treatments. The highest oil and protein yields were also recorded for seeds at lower position on the ear. Seed yield of all maize cultivars at various seed positions decreased with increasing irrigation intervals. Oil percentage decreased, but protein percentage increased with decreasing water availability. Water limitation decreased oil and protein yields of maize cultivars. Changes in protein and oil yields of maize cultivars at different seed positions and irrigation treatments were attributed to changes in seed yield.

  5. Positional games

    CERN Document Server

    Hefetz, Dan; Stojaković, Miloš; Szabó, Tibor

    2014-01-01

    This text serves as a thorough introduction to the rapidly developing field of positional games. This area constitutes an important branch of combinatorics, whose aim it is to systematically develop an extensive mathematical basis for a variety of two-player perfect information games. These range from such popular games as Tic-Tac-Toe and Hex to purely abstract games played on graphs and hypergraphs. The subject of positional games is strongly related to several other branches of combinatorics such as Ramsey theory, extremal graph and set theory, and the probabilistic method. These notes cover a variety of topics in positional games, including both classical results and recent important developments. They are presented in an accessible way and are accompanied by exercises of varying difficulty, helping the reader to better understand the theory. The text will benefit both researchers and graduate students in combinatorics and adjacent fields.

  6. The effect of health, socio-economic position, and mode of data collection on non-response in health interview surveys

    DEFF Research Database (Denmark)

    Ekholm, Ola; Gundgaard, Jens; Rasmussen, Niels K R

    2010-01-01

    AIMS: To investigate the relationship between potential explanatory factors (socio-economic factors and health) and non-response in two general population health interview surveys (face-to-face and telephone), and to compare the effects of the two interview modes on non-response patterns. METHODS...... in health interview surveys, but the non-response rate is higher in lower socio-economic groups. Analyses of non-response should be performed to understand the implications of survey findings.......: Data derives from The Danish Health Interview Survey 2000 (face-to-face interview) and The Funen County Health Survey 2000/2001 (telephone interview). Data on all invited individuals were obtained from administrative registers and linked to survey data at individual level. Multiple logistic regression...

  7. Beat-by-beat analysis of cardiac output and blood pressure responses to short-term barostimulation in different body positions

    Science.gov (United States)

    Hildebrandt, Wulf; Schütze, Harald; Stegemann, J.

    Rapid quantification of the human baro-reflex control of heart rate has been achieved on a beat-by-beat basis using a neck-chamber with quick ECG-triggered pressure changes. Referring to recent findings on heart rate and stroke volume, the present study uses this technique to compare cardiac output as well as blood pressure changes in supine and upright position to investigate feedback effects and to confirm postural reflex modifications not revealed by RR-interval changes. A suction profile starting at +40 mmHg and running 7 steps of pressure decrease down to -65 mmHg was examined in 0° and 90° tilting position while beat-by-beat recordings were done of heart rate, stroke volume (impedance-cardiography) and blood pressure (Finapres tm) (n=16). The percentual heart rate decrease failed to be significantly different between positions. A suction-induced stroke volume increase led to a cardiac output almost maintained when supine and significantly increased when upright. A decrease in all blood pressure values was found during suction, except for systolic values in upright position which increased. Conclusively, (a) it is confirmed that different inotropy accounts for the seen gravitational effect on the cardiac output not represented by heart rate; (b) identical suction levels in different positions lead to different stimuli at the carotid receptor. This interference has to be considered in microgravity studies by beat-by-beat measurement of cardiac output and blood pressure.

  8. Response to an unsolicited intervention offer to persons aged ≥ 75 years after screening positive for depressive symptoms: a qualitative study.

    Science.gov (United States)

    van der Weele, Gerda M; de Jong, Roos; de Waal, Margot W M; Spinhoven, Philip; Rooze, Herman A H; Reis, Ria; Assendelft, Willem J J; Gussekloo, Jacobijn; van der Mast, Roos C

    2012-02-01

    Screening can increase detection of clinically relevant depressive symptoms, but screen-positive persons are not necessarily willing to accept a subsequent unsolicited treatment offer. Our objective was to explore limiting and motivating factors in accepting an offer to join a "coping with depression" course, and perceived needs among persons aged ≥75 years who screened positive for depressive symptoms in general practice. In a randomized controlled trial, in which 101 persons who had screened positive for depressive symptoms were offered a "coping with depression" course, a sample of 23 persons were interviewed, of whom five (22%) accepted the treatment offer. Interview transcripts were coded independently by two researchers. All five individuals who accepted a place on the course felt depressed and/or lonely and had positive expectations about the course. The main reasons for declining to join the course were: not feeling depressed, or having negative thoughts about the course effect, concerns about group participation, or about being too old to change and learn new things. Although perceived needs to relieve depressive symptoms largely matched the elements of the course, most of those who had been screened were not (yet) prepared to accept an intervention offer. Many expressed the need to discuss this treatment decision with their general practitioner. Although the unsolicited treatment offer closely matched the perceived needs of people screening positive for depressive symptoms, only those who combined feelings of being depressed or lonely with positive expectations about the offered course accepted it. Treatment should perhaps be more individually tailored to the patient's motivational stage towards change, a process in which general practitioners can play an important role.

  9. Researcher Positioning

    DEFF Research Database (Denmark)

    Khawaja, Iram; Mørck, Line Lerche

    2009-01-01

    involvement by the researcher, which challenges traditional perspectives onresearch and researcher positioning. A key point in this regard is the importance ofconstant awareness of and reflection on the multiple ways in which one's positioningas a researcher influences the research process. Studying the other...

  10. Position detector

    International Nuclear Information System (INIS)

    Hayakawa, Toshifumi.

    1985-01-01

    Purpose: To enable to detect the position of an moving object in a control rod position detector, stably in a digital manner at a high accuracy and free from the undesired effects of circumstantial conditions such as the reactor temperature. Constitution: Coils connected in parallel with each other are disposed along the passage of a moving object and variable resistors and relays are connected in series with each of the coils respectively. Light emitting diodes is connected in series with the contacts of the respective relays. The resistance value of the variable resistors are adjusted depending on the changes in the circumstantial conditions and temperature distribution upon carrying out the positional detection. When the object is inserted into a coils, the relevant relay is deenergized, by which the relay contacts are closed to light up the diode. In the same manner, as the object is successively inserted into the coils, the diodes are lighted-up successively thereby enabling highly accurate and stable positional detection in a digital manner, free from the undesired effects of the circumstantial conditions. (Horiuchi, T.)

  11. Stimulus-Food Pairings Produce Stimulus-Directed Touch Screen Responding in Cynomolgus Monkeys ("Macaca Fascicularis") with or without a Positive Response Contingency

    Science.gov (United States)

    Bullock, Christopher E.; Myers, Todd M.

    2009-01-01

    Acquisition and maintenance of touch-screen responding was examined in naive cynomolgus monkeys ("Macaca fascicularis") under automaintenance and classical conditioning arrangements. In the first condition of Experiment 1, we compared acquisition of screen touching to a randomly positioned stimulus (a gray square) that was either stationary or…

  12. ¿Usted Va Al Capitolio También?: Adult Immigrants' Positioning in Response to News and Digital Media about Immigration Policy

    Science.gov (United States)

    Noguerón-Liu, Silvia

    2016-01-01

    This article explores the ways in which adult immigrants engaged in discussion about immigration news at a web design course during the passing of Senate Bill 1070 in Arizona. Drawing on the method and theory of mediated discourse analysis, two focal interactions reveal the diverse positions that students took up in relation to anti-immigrant…

  13. Spatial pattern formation of coastal vegetation in response to external gradients and positive feedbacks affecting soil porewater salinity: A model study

    Science.gov (United States)

    Jiang, J.; DeAngelis, D.L.; Smith, T. J.; Teh, S.Y.; Koh, H. L.

    2012-01-01

    Coastal vegetation of South Florida typically comprises salinity-tolerant mangroves bordering salinity-intolerant hardwood hammocks and fresh water marshes. Two primary ecological factors appear to influence the maintenance of mangrove/hammock ecotones against changes that might occur due to disturbances. One of these is a gradient in one or more environmental factors. The other is the action of positive feedback mechanisms, in which each vegetation community influences its local environment to favor itself, reinforcing the boundary between communities. The relative contributions of these two factors, however, can be hard to discern. A spatially explicit individual-based model of vegetation, coupled with a model of soil hydrology and salinity dynamics is presented here to simulate mangrove/hammock ecotones in the coastal margin habitats of South Florida. The model simulation results indicate that an environmental gradient of salinity, caused by tidal flux, is the key factor separating vegetation communities, while positive feedback involving the different interaction of each vegetation type with the vadose zone salinity increases the sharpness of boundaries, and maintains the ecological resilience of mangrove/hammock ecotones against small disturbances. Investigation of effects of precipitation on positive feedback indicates that the dry season, with its low precipitation, is the period of strongest positive feedback. ?? 2011 Springer Science+Business Media B.V. (outside the USA).

  14. Positive Criminology and Rethinking the Response to Adolescent Addiction: Evidence on the Role of Social Support, Religiosity, and Service to Others.

    Science.gov (United States)

    Johnson, Byron R; Lee, Matthew T; Pagano, Maria E; Post, Stephen G

    2016-01-01

    Adolescent addiction has emerged as a major public health problem. The greatest increase in alcohol and other drug use disorders can be found among youth. Concurrently, technological advances in policing coupled with aggressive prosecuting and sentencing practices have contributed to the growth of America's correctional system. The assertive response of policing, courts, and corrections, however, have not prevented the dramatic rise of adolescent addiction. Unfortunately, there is no national data tracking addicted youth in the criminal justice system to evaluate what works when it comes to youth with addiction. This article reviews justice system responses to adolescent offenders with addiction, and promising approaches engaging juveniles in programmatic components of Alcoholics Anonymous (AA). This study highlights the role of spirituality, service to others, and social support in maintaining sobriety, reducing arrests, and lowering recidivism for adolescents court-referred to treatment. Recommendations for improving the response to adolescent offenders with addiction are offered.

  15. Do Family Responsibilities and a Clinical Versus Research Faculty Position Affect Satisfaction with Career and Work–Life Balance for Medical School Faculty?

    OpenAIRE

    Beckett, Laurel; Nettiksimmons, Jasmine; Howell, Lydia Pleotis; Villablanca, Amparo C.

    2015-01-01

    Background: Balancing career and family obligations poses challenges to medical school faculty and contributes to dissatisfaction and attrition from academics. We examined the relationship between family setting and responsibilities, rank, and career and work–life satisfaction for faculty in a large U.S. medical school.

  16. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up

    NARCIS (Netherlands)

    Baay, M. F.; Duk, J. M.; Burger, M. P.; de Bruijn, H. W.; Stolz, E.; Herbrink, P.

    1999-01-01

    To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the

  17. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up

    NARCIS (Netherlands)

    Baay, MFD; Duk, JM; Burger, MPM; de Bruijn, HWA; Stolz, E; Herbrink, P

    To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the

  18. Impact of a new vaccine clinic on hepatitis B vaccine completion and immunological response rates in an HIV-positive cohort.

    Science.gov (United States)

    Rock, Clare; de Barra, Eoghan; Sadlier, Corinna; Kelly, Sinead; Dowling, Catherine; McNally, Cora; Bergin, Colm

    2013-06-01

    Hepatitis B virus vaccination (HBVV) in the HIV-infected population has poor reported completion rates and immunological response rates. At our HIV clinic, we established a vaccine clinic to improve HBVV outcomes using interventions such as SMS text reminders and double-dose (DD) HBVV for standard-dose non-responders (SD NRs). A five-year (2003-2008) retrospective review of the completion rates and immunological response rates for HBVV after the establishment of the dedicated vaccine clinic was conducted. Statistical significance was assumed at presponse rate to DD HBVV among SD NRs. On-treatment analysis showed an 88% (155/176) overall immunological response to SD HBVV and DD HBVV, if required. High HBVV completion and response rates in this HIV cohort were enabled through the use of multiple interventions, including the use of SMS text message reminders and routine referral for DD vaccination. Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  19. A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism

    NARCIS (Netherlands)

    Louis, E.; Vermeire, S.; Rutgeerts, P.; de Vos, M.; van Gossum, A.; Pescatore, P.; Fiasse, R.; Pelckmans, P.; Reynaert, H.; D'Haens, G.; Malaise, M.; Belaiche, J.

    2002-01-01

    Two-thirds to three-fourths of patients with either refractory luminal or fistulizing Crohn disease respond to infliximab treatment. The ability or inability to respond seems to persist over time. Biological characteristics and/or genetic background can influence the response to treatment. The aim

  20. Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity

    DEFF Research Database (Denmark)

    Abate, E; Belayneh, M; Idh, J

    2015-01-01

    BACKGROUND: The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as wel...

  1. Gender Related Differences in Response to “In Favor of Myself” Wellness Program to Enhance Positive Self & Body Image among Adolescents

    OpenAIRE

    Golan, Moria; Hagay, Noa; Tamir, Snait

    2014-01-01

    BACKGROUND: Physical, neurological and psychological changes are often experienced differently by male and female adolescents. Positive self-esteem, emotional well-being, school achievements, and family connectedness are considered as protective factors against health-compromising behaviors. This study examines the gender differences in respect to the effect of a school-based interactive wellness program--"In Favor of Myself"--on self-image, body image, eating attitudes and behaviors of young...

  2. Non-response to a life course socioeconomic position indicator in surveillance: comparison of telephone and face-to-face modes

    OpenAIRE

    Chittleborough, Catherine R; Taylor, Anne W; Baum, Fran E; Hiller, Janet E

    2008-01-01

    Abstract Background Measurement of socioeconomic position (SEP) over the life course in population health surveillance systems is important for examining differences in health and illness between different population groups and for monitoring the impact of policies and interventions aimed at reducing health inequities and intergenerational disadvantage over time. While face-to-face surveys are considered the gold standard of interviewing techniques, computer-assisted telephone interviewing is...

  3. Nasal carriage of mecA-positive methicillin-resistant Staphylococcus aureus in pigs exhibits dose-response to zinc supplementation.

    Science.gov (United States)

    Amachawadi, Raghavendra G; Scott, Harvey M; Nitikanchana, Sureemas; Vinasco, Javier; Tokach, Mike D; Dritz, Steve S; Nelssen, Jim L; Goodband, Robert D; Nagaraja, Tiruvoor G

    2015-02-01

    Zinc (Zn) is often supplemented at elevated concentrations in swine diets, particularly in piglets, to prevent enteric infections and promote growth. Previous studies from Denmark have suggested a genetic linkage and a phenotypic association between Zn resistance, encoded by czrC, and methicillin-resistance conferred by mecA in Staphylococcus aureus. Such an association has not been reported in the U.S. swine population. We conducted an analysis of the effects of Zn, supplemented as zinc oxide (ZnO), on the nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) in nursery (n=40) and finisher pigs (n=40) enrolled in a nutritional study. Nasal swabs, collected from nursery and finisher pigs, were inoculated onto MRSA CHROMagar and presumptive MRSA colonies were tested for the presence of mecA and czrC genes by polymerase chain reaction. Zinc susceptibility was determined by the agar dilution method. The prevalence of mecA-positive MRSA was 10% (4/40) and 20% (8/40) among nursery and finisher pigs, respectively. Of the 12 mecA-positive S. aureus isolates, 7 had the czrC gene (58.3%) compared to none among the 68 mecA-negative isolates. The presence of both mecA (p=0.002) and czrC (p=0.006) genes were positively associated with higher levels of Zn supplementation. The median minimum inhibitory concentrations of Zn for czrC-positive and czrC-negative isolates were 12 and 2 mM, respectively (presistance among S. aureus in pigs.

  4. Effects of Lignocaine Administered Intravenously or Intratracheally on Airway and Hemodynamic Responses during Emergence and Extubation in Patients Undergoing Elective Craniotomies in Supine Position.

    Science.gov (United States)

    Shabnum, Tabasum; Ali, Zulfiqar; Naqash, Imtiaz Ahmad; Mir, Aabid Hussain; Azhar, Khan; Zahoor, Syed Amer; Mir, Abdul Waheed

    2017-01-01

    Sympathoadrenergic responses during emergence and extubation can lead to an increase in heart rate (HR) and blood pressure whereas increased airway responses may lead to coughing and laryngospasm. The aim of our study was to compare the effects of lignocaine administered intravenously (IV) or intratracheally on airway and hemodynamic responses during emergence and extubation in patients undergoing elective craniotomies. Sixty patients with physical status American Society of Anaesthesiologists Classes I and II aged 18-70 years, scheduled to undergo elective craniotomies were included. The patients were randomly divided into three groups of twenty patients; Group 1 receiving IV lignocaine and intratracheal placebo (IV group), Group 2 receiving intratracheal lignocaine and IV placebo (I/T group), and Group 3 receiving IV and intratracheal placebo (placebo group). The tolerance to the endotracheal tube was monitored, and number of episodes of cough was recorded during emergence and at the time of extubation. Hemodynamic parameters such as HR and blood pressure (systolic, diastolic, mean arterial pressure) were also recorded. There was a decrease of HR in both IV and intratracheal groups in comparison with placebo group ( P < 0.005). Rise in blood pressure (systolic blood pressure, diastolic blood pressure and mean arterial pressure) was comparable in both Groups 1 and 2 but was lower in comparison with placebo group ( P < 0.005). Cough suppression was comparable in all the three groups. Grade III cough (15%) was documented only in placebo group. Both IV and intratracheal lignocaine are effective in attenuation of hemodynamic response if given within 20 min from skull pin removal to extubation. There was comparable cough suppression through intratracheal route and IV routes than the placebo group.

  5. Favorable Response of Metastatic Merkel Cell Carcinoma to Targeted 177Lu-DOTATATE Therapy: Will PRRT Evolve to Become an Important Approach in Receptor-Positive Cases?

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit

    2016-06-01

    This report illustrates an excellent partial response of Merkel cell carcinoma with multiple bilobar hepatic metastases to a single cycle of peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE. This response, coupled with minimal side effects, warrants consideration of this therapy early in the disease course (rather than at an advanced stage after failure of other therapies) if the metastatic lesions exhibit adequate tracer avidity on somatostatin receptor-based imaging. Our patient showed progression of systemic disease after having undergone a second surgery and adjuvant radiotherapy to the head and neck, as well as chemotherapy, and hence was considered a candidate for PRRT. In a pretreatment study, the metastatic lesions demonstrated avidity to both somatostatin receptors and (18)F-FDG. Three months after the first cycle of treatment, when the patient was being evaluated for a second cycle, both imaging parameters showed evidence of a partial response that included nearly complete resolution of the two previously seen lesions. In view of the relatively good tolerability, minimal side effects, and targeted nature of the treatment, PRRT may evolve to become the first-line therapy for metastatic Merkel cell carcinoma and should be examined further in a larger number of patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  6. Differences in response to antiretroviral therapy in HIV-positive patients being treated for tuberculosis in Eastern Europe, Western Europe and Latin America

    DEFF Research Database (Denmark)

    Caro-Vega, Yanink; Schultze, Anna; W Efsen, Anne Marie

    2018-01-01

    -positive patients aged ≥16 years with a diagnosis of tuberculosis recruited to the TB:HIV study between Jan 1, 2011, and Dec 31, 2013 in 19 countries in Eastern Europe (EE), Western Europe (WE), and Latin America (LA) who received ART concomitantly with TB treatment were included. Patients either received efavirenz......-containing ART, and 318 a non-efavirenz regimen) 50% were from EE, 28% from WE, and 22% from LA. Among those not receiving efavirenz-containing ART, regimens mainly contained a ritonavir-boosted protease inhibitor (57%), or raltegravir (22%). At 12 months 1.4% of patients in WE had died, compared to 20% in EE...

  7. Positive Response to Thermobalancing Therapy Enabled by Therapeutic Device in Men with Non-Malignant Prostate Diseases: BPH and Chronic Prostatitis

    Directory of Open Access Journals (Sweden)

    Ivan Gerasimovich Aghajanyan

    2016-04-01

    Full Text Available Background: The most common types of non-malignant prostate diseases are benign prostatic hyperplasia (BPH and chronic prostatitis (CP. The aim of this study was to find out whether thermobalancing therapy with a physiotherapeutic device is effective for BPH and CP. Methods: During a 2.5-year period, 124 men with BPH over the age of 55 were investigated. Clinical parameters were tested twice: via the International Prostate Symptom Score (IPSS and via ultrasound measurement of prostate volume (PV and uroflowmetry maximum flow rate (Qmax, before and after six months of therapy. In 45 men with CP under the age of 55, the dynamics of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI were studied. Results: The results of the investigated index tests in men with BPH confirmed a decrease in IPSS (p < 0.001, a reduction in PV (p < 0.001, an increase in Qmax (p < 0.001, and an improvement of quality of life (QoL (p < 0.001. NIH-CPSI scores in men with CP indicated positive dynamics. Conclusions: The observed positive changes in IPSS, PV, and Qmax in men with BPH and the improvement in NIH-CPSI-QoL in patients with CP after using a physiotherapeutic device for six months as mono-therapy, support the view that thermobalancing therapy with the device can be recommended for these patients. Furthermore, the therapeutic device is free of side effects.

  8. MLH1 V384D polymorphism associates with poor response to EGFR tyrosine kinase inhibitors in patients with EGFR L858R-positive lung adenocarcinoma.

    Science.gov (United States)

    Chiu, Chao-Hua; Ho, Hsiang-Ling; Doong, Howard; Yeh, Yi-Chen; Chen, Mei-Yu; Chou, Teh-Ying; Tsai, Chun-Ming

    2015-04-10

    A significant fraction of patients with lung adenocarcinomas harboring activating epidermal growth factor receptor (EGFR) mutations do not experience clinical benefits from EGFR tyrosine kinase inhibitor (TKI) therapy. Using next-generation sequencing, we screened 739 mutation hotspots in 46 cancer-related genes in EGFR L858R-mutant lung adenocarcinomas from 29 patients who received EGFR-TKI therapy; 13 had short ( 1 year) progression-free survival (PFS). We discovered MLH1 V384D as a genetic variant enriched in the group of patients with short PFS. Next, we investigated this genetic variation in 158 lung adenocarcinomas with the EGFR L858R mutation and found 14 (8.9%) patients had MLH1 V384D; available blood or non-tumor tissues from patients were also tested positive for MLH1 V384D. Patients with MLH1 V384D had a significantly shorter median PFS than those without (5.1 vs. 10.6 months; P= 0.001). Multivariate analysis showed that MLH1 V384D polymorphism was an independent predictor for a reduced PFS time (hazard ratio, 3.5; 95% confidence interval, 1.7 to 7.2; P= 0.001). In conclusion, MLH1 V384D polymorphism is associated with primary resistance to EGFR-TKIs in patients with EGFR L858R-positive lung adenocarcinoma and may potentially be a novel biomarker to guide treatment decisions.

  9. [A case of an anti-Ma2 antibody-positive patient presenting with variable CNS symptoms mimicking multiple system atrophy with a partial response to immunotherapy].

    Science.gov (United States)

    Shiraishi, Wataru; Iwanaga, Yasutaka; Yamamoto, Akifumi

    2015-01-01

    A 70-year-old man with a 5-month history of progressive bradykinesia of the bilateral lower extremities was admitted to our hospital. At the age of 64, he underwent proximal gastrectomy for gastric cancer. He also had a history of subacute combined degeneration of the spinal cord since the age of 67, which was successfully treated with vitamin B12 therapy. Four weeks before admission to our hospital, he admitted himself to his former hospital complaining of walking difficulty. Two weeks later, however, his symptoms progressed rapidly; he was immobilized for two weeks and did not respond to the vitamin therapy. On admission to our hospital, he showed moderate paralysis of the lower extremities, cog-wheel rigidity of the four extremities, and dystonic posture of his left hand. He also showed orthostatic hypotension and vesicorectal disorders. Blood examination and cerebrospinal fluid analysis revealed no remarkable abnormalities. Electroencephalography showed frontal dominant, high voltage, sharp waves. His brain and spinal MRI revealed no notable abnormalities. We suspected autoimmune disease and commenced one course of intravenous methylprednisolone therapy, resulting in improvement of the parkinsonism and orthostatic hypotension. Based on these results, we investigated possible neural antigens and detected anti-Ma2 antibody. In addition to limbic encephalitis, anti-Ma2 antibody-positive neural disorders are characterized by rapid eye movement sleep behavior disorders or parkinsonism. Here, we report an anti-Ma2 antibody positive patient presenting variable CNS symptoms mimicking multiple system atrophy, who responded to immunotherapy.

  10. Kit for the preparation of 111In-labeled pertuzumab injection for imaging response of HER2-positive breast cancer to trastuzumab (Herceptin)

    International Nuclear Information System (INIS)

    Lam, Karen; Scollard, Deborah A.; Chan, Conrad; Levine, Mark N.; Reilly, Raymond M.

    2015-01-01

    We previously reported that 111 In-labeled pertuzumab imaged trastuzumab (Herceptin)-mediated changes in HER2 expression preclinically in breast cancer tumors. To advance 111 In-labeled pertuzumab to a Phase I/II clinical trial, a kit was designed for preparing this agent in a form suitable for human administration. Unit-dose kits containing pertuzumab modified with 2-(4-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (BzDTPA) were prepared that labeled to high efficiency (>90%) with 111 In and met specifications for pharmaceutical quality. The kits were stable for 4 months and the final radiopharmaceutical was stable for 24 h. Imaging studies demonstrated high and specific uptake in HER2-positive tumors in mice using this clinical kit formulation. - Highlights: • Kits for preparing 111 In-BzDTPA-pertuzumab were prepared which met specifications for pharmaceutical quality. • The kits were stable for at least 4 months and the final radiopharmaceutical was stable for 24 h when stored at 2–8 °C. • High labeling efficiency (>90%) of the kits was achieved with 111 In. • 111 In-BzDTPA-pertuzumab exhibited stability in human plasma. • Biodistribution and microSPECT imaging showed specific targeting of HER2-positive tumors in mice using the kit formulation

  11. Anti-HER2 CD4(+) T-helper type 1 response is a novel immune correlate to pathologic response following neoadjuvant therapy in HER2-positive breast cancer.

    Science.gov (United States)

    Datta, Jashodeep; Berk, Erik; Xu, Shuwen; Fitzpatrick, Elizabeth; Rosemblit, Cinthia; Lowenfeld, Lea; Goodman, Noah; Lewis, David A; Zhang, Paul J; Fisher, Carla; Roses, Robert E; DeMichele, Angela; Czerniecki, Brian J

    2015-05-23

    A progressive loss of circulating anti-human epidermal growth factor receptor-2/neu (HER2) CD4(+) T-helper type 1 (Th1) immune responses is observed in HER2(pos)-invasive breast cancer (IBC) patients relative to healthy controls. Pathologic complete response (pCR) following neoadjuvant trastuzumab and chemotherapy (T + C) is associated with decreased recurrence and improved prognosis. We examined differences in anti-HER2 Th1 responses between pCR and non-pCR patients to identify modifiable immune correlates to pathologic response following neoadjuvant T + C. Anti-HER2 Th1 responses in 87 HER2(pos)-IBC patients were examined using peripheral blood mononuclear cells pulsed with 6 HER2-derived class II peptides via IFN-γ ELISPOT. Th1 response metrics were anti-HER2 responsivity, repertoire (number of reactive peptides), and cumulative response across 6 peptides (spot-forming cells [SFC]/10(6) cells). Anti-HER2 Th1 responses of non-pCR patients (n = 4) receiving adjuvant HER2-pulsed type 1-polarized dendritic cell (DC1) vaccination were analyzed pre- and post-immunization. Depressed anti-HER2 Th1 responses observed in treatment-naïve HER2(pos)-IBC patients (n = 22) did not improve globally in T + C-treated HER2(pos)-IBC patients (n = 65). Compared with adjuvant T + C receipt, neoadjuvant T + C - utilized in 61.5 % - was associated with higher anti-HER2 Th1 repertoire (p = 0.048). While pCR (n = 16) and non-pCR (n = 24) patients did not differ substantially in demographic/clinical characteristics, pCR patients demonstrated dramatically higher anti-HER2 Th1 responsivity (94 % vs. 33 %, p = 0.0002), repertoire (3.3 vs. 0.3 peptides, p vs. 22.4 SFC/10(6), p non-pCR patients. After controlling for potential confounders, anti-HER2 Th1 responsivity remained independently associated with pathologic response (odds ratio 8.82, p = 0.016). This IFN-γ(+) immune disparity was mediated by anti-HER2 CD4(+)T-bet(+)IFN-γ(+) (i.e., Th1) - not CD4(+)GATA-3(+)IFN-γ(+) (i.e., Th2

  12. False-negative type-specific glycoprotein G antibody responses in STI clinic patients with recurrent HSV-1 or HSV-2 DNA positive genital herpes, The Netherlands.

    Science.gov (United States)

    van Rooijen, Martijn S; Roest, Wim; Hansen, Gino; Kwa, David; de Vries, Henry J C

    2016-06-01

    Herpes simplex virus (HSV) type-discriminating antibody tests (glycoprotein G (gG) directed) are used to identify naïve persons and differentiate acute infections from recurrences. We studied test characteristics of three commercially available antibody tests in patients with recurrent (established by viral PCR tests) herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) genital herpes episodes. Serum samples (at minimum 3 months after t=0) were examined for the presence of gG-1-specific or gG-2-specific antibodies using the HerpeSelect 1 and 2 Immunoblot IgG, the HerpeSelect 1 and 2 enzyme linked immunoassays IgG and the LIAISON HSV-1 and HSV-2 IgG indirect chemiluminescence immunoassays. The immunoblot was HSV-1 positive in 70.6% (95% CI 44.0% to 89.7%), the LIAISON in 88.2% (95% CI 63.5% to 98.5%) and the ELISA in 82.4% (95% CI 56.6% to 96.2%) of the 17 patients with a recurrent HSV-1 episode. From 33 patients with a recurrent HSV-2 episode, the immunoblot was HSV-2 positive in 84.8% (95% CI 68.1% to 94.9%), the LIAISON in 69.7% (95% CI 51.3% to 84.4%) and the ELISA in 84.8% (95% CI 68.1% to 94.9%). Among 15/17 (88.2%; 95% CI 63.5% to 98.5%) patients with HSV-1 and 30/33 (90.1%; 95% CI 75.7% to 98.1%) patients with HSV-2, HSV-1 or HSV-2 antibodies, respectively, were detected in at least one of the three antibody tests. Commercial type-specific gG HSV-1 or HSV-2 antibody assays were false negative in 12-30% of patients with recurrent HSV-1 or HSV-2 DNA positive genital lesions. The clinical and epidemiological use of type-specific HSV serology can be hampered by false-negative results, especially if based on a single test. 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/

  13. FIP1L1-PDGFRA-Positive Chronic Eosinophilic Leukemia: A Low-Burden Disease with Dramatic Response to Imatinib - A Report of 5 Cases from South India

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    Anıl Kumar N.

    2014-12-01

    Full Text Available OBJECTIVE: Eosinophilia associated with FIP1L1-PDGFRA rearrangement represents a subset of chronic eosinophilic leukemia and affected patients are sensitive to imatinib treatment. This study was undertaken to learn the prevalence and associated clinicopathologic and genetic features of FIP1L1-PDGFRA rearrangement in a cohort of 26 adult patients presenting with profound eosinophilia (>1.5x109/L. METHODS: Reverse-transcriptase polymerase chain reaction and gel electrophoresis were used for the detection of FIP1L1-PDGFRA rearrangement. RESULTS: Five male patients with splenomegaly carried the FIP1L1-PDGFRA gene rearrangement. All patients achieved complete hematological response within 4 weeks of starting imatinib. One patient had previous deep vein thrombosis and 1 patient had cardiomyopathy, which improved with steroids and imatinib. Conventional cytogenetics was normal in all these patients. No primary resistance to imatinib was noted. CONCLUSION: This study indicates the need to do the FIP1L1-PDGFRA assay in patients with hypereosinophilic syndrome. Prompt treatment of this condition with imatinib can lead to complete hematological response and resolution of the organ damage that can be seen in this setting.

  14. Skeletal Muscle PGC1α -1 Nucleosome Position and -260 nt DNA Methylation Determine Exercise Response and Prevent Ectopic Lipid Accumulation in Men.

    Science.gov (United States)

    Bajpeyi, Sudip; Covington, Jeffrey D; Taylor, Erin M; Stewart, Laura K; Galgani, Jose E; Henagan, Tara M

    2017-07-01

    Endurance exercise has been shown to improve lipid oxidation and increase mitochondrial content in skeletal muscle, two features that have shown dependence on increased expression of the peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α). It is also hypothesized that exercise-related alterations in PGC1α expression occur through epigenetic regulation of nucleosome positioning in association with differential DNA methylation status within the PGC1α promoter. In this study, we show that when primary human myotubes from obese patients with type 2 diabetes are exposed to lipolytic stimulus (palmitate, forskolin, inomycin) in vitro, nucleosome occupancy surrounding the -260 nucleotide (nt) region, a known regulatory DNA methylation site, is reduced. This finding is reproduced in vivo in the vastus lateralis from 11 healthy males after a single, long endurance exercise bout in which participants expended 650 kcal. Additionally, we show a significant positive correlation between fold change of PGC1α messenger RNA expression and -1 nucleosome repositioning away from the -260 nt methylation site in skeletal muscle tissue following exercise. Finally, we found that when exercise participants are divided into high and low responders based on the -260 nt methylation status, the -1 nucleosome is repositioned away from the regulatory -260 nt methylation site in high responders, those exhibiting a significant decrease in -260 nt methylation, but not in low responders. Additionally, high but not low responders showed a significant decrease in intramyocellular lipid content after exercise. These findings suggest a potential target for epigenetic modification of the PGC1α promoter to stimulate the therapeutic effects of endurance exercise in skeletal muscle. Copyright © 2017 Endocrine Society.

  15. Symptom structure and severity: a comparison of responses to the positive and negative syndrome scale (PANSS) between patients with PTSD or schizophrenia.

    Science.gov (United States)

    Stefanovics, Elina A; Krystal, John H; Rosenheck, Robert A

    2014-05-01

    To describe and compare the structure and relative severity of symptoms in clinical trial patients diagnosed with Post Traumatic Stress Disorder (PTSD) or schizophrenia using the Positive and Negative Syndrome Scale (PANSS), developed originally to evaluate symptoms of schizophrenia. This secondary data analysis used baseline PANSS symptom ratings (n=267) from a six-month multicenter randomized placebo-controlled trial of adjunctive risperidone in patients with chronic military-related PTSD. First, using a split-half design, Exploratory Factor Analysis (EFA) was employed to identify independent factors which were then compared to published factor structures for schizophrenia. Next, Confirmatory Factor Analysis (CFA) was applied to the second half of the sample to compare the results of the EFA and published factor structures. Finally, T-tests were used to compare the severity of factor scores between the PTSD sample and the baseline PANSS ratings from the Clinical Antipsychotic Trial for Intervention Effectiveness (CATIE) schizophrenia sample (n=1460). EFA suggested five factors similar to those identified in a summary of 29 schizophrenia studies by Wallwork (Schizophrenia Research, 137:246-250). CFA showed that the five factor Wallwork model fit the data better than the EFA, although both had relatively high goodness of fit. T-tests showed that the PTSD sample had more severe symptoms on the Depressive factor, and the schizophrenia sample on the Positive, Negative, and Disorganized factors, with no significant difference on the Excited factor. Veterans with PTSD had similar symptom structure to patients with schizophrenia on the PANSS, but were less symptomatic on psychosis-related factors and more symptomatic on depression. Dimensional symptom factors can be virtually the same across diagnoses. Published by Elsevier Inc.

  16. CYP2W1 is highly expressed in adrenal glands and is positively associated with the response to mitotane in adrenocortical carcinoma.

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    Cristina L Ronchi

    Full Text Available Adrenocortical tumors comprise frequent adenomas (ACA and rare carcinomas (ACC. Human cytochrome P450 2W1 (CYP2W1 is highly expressed in some cancers holding the potential to activate certain drugs into tumor cytotoxins.To investigate the CYP2W1 expression in adrenal samples and its relationship with clinical outcome in ACC.CYP2W1 expression was investigated by qRT-PCR in 13 normal adrenal glands, 32 ACA, 25 ACC, and 9 different non-adrenal normal tissue samples and by immunohistochemistry in 352 specimens (23 normal adrenal glands, 33 ACA, 239 ACC, 67 non-adrenal normal or neoplastic samples.CYP2W1 mRNA expression was absent/low in normal non-adrenal tissues, but high in normal and neoplastic adrenal glands (all P<0.01 vs non-adrenal normal tissues. Accordingly, CYP2W1 immunoreactivity was absent/low (H-score 0-1 in 72% of non-adrenal normal tissues, but high (H-score 2-3 in 44% of non-adrenal cancers, in 65% of normal adrenal glands, in 62% of ACAs and in 50% of ACCs (all P<0.001 vs non-adrenal normal tissues, being significantly increased in steroid-secreting compared to non-secreting tumors. In ACC patients treated with mitotane only, high CYP2W1 immunoreactivity adjusted for ENSAT stage was associated with longer overall survival and time to progression (P<0.05 and P<0.01, respectively, and with a better response to therapy both as palliative (response/stable disease in 42% vs 6%, P<0.01 or adjuvant option (absence of disease recurrence in 69% vs 45%, P<0.01.CYP2W1 is highly expressed in both normal and neoplastic adrenal glands making it a promising tool for targeted therapy in ACC. Furthermore, CYP2W1 may represent a new predictive marker for the response to mitotane treatment.

  17. Impact of T300A Variant of ATG16L1 on Antibacterial Response, Risk of Culture Positive Infections, and Clinical Course of Crohn's Disease

    DEFF Research Database (Denmark)

    Salem, Mohammad; Nielsen, Ole Haagen; Nys, Kris

    2015-01-01

    OBJECTIVES: Autophagy-related 16-like 1 (ATG16L1) deficiency leads to impaired cellular autophagy and bacterial degradation as well as an altered cytokine production. The single-nucleotide polymorphism rs2241880 (T300A) is associated with an increased risk for Crohn's disease (CD). ATG16L1...... polymorphisms could therefore have an impact on the risk of infectious complications and disease course in CD. We examined the impact of the T300A genotype on the antibacterial response toward a panel of pathogenic bacteria in vitro, as well as clinical infectious complications in vivo and the disease course...... risk variant, AG heterozygous variant, respectively). The median duration of disease was 128 months (range, 30-175). The cumulative follow-up of this cohort was 2,366 patient-years. ATG16L1 gene variations interfered with the production of IL-1β, which was significantly increased in PBMCs from GG...

  18. BRCA Mutation Frequency and Patterns of Treatment Response in BRCA Mutation–Positive Women With Ovarian Cancer: A Report From the Australian Ovarian Cancer Study Group

    Science.gov (United States)

    Alsop, Kathryn; Fereday, Sian; Meldrum, Cliff; deFazio, Anna; Emmanuel, Catherine; George, Joshy; Dobrovic, Alexander; Birrer, Michael J.; Webb, Penelope M.; Stewart, Colin; Friedlander, Michael; Fox, Stephen; Bowtell, David; Mitchell, Gillian

    2012-01-01

    Purpose The frequency of BRCA1 and BRCA2 germ-line mutations in women with ovarian cancer is unclear; reports vary from 3% to 27%. The impact of germ-line mutation on response requires further investigation to understand its impact on treatment planning and clinical trial design. Patients and Methods Women with nonmucinous ovarian carcinoma (n = 1,001) enrolled onto a population-based, case-control study were screened for point mutations and large deletions in both genes. Survival outcomes and responses to multiple lines of chemotherapy were assessed. Results Germ-line mutations were found in 14.1% of patients overall, including 16.6% of serous cancer patients (high-grade serous, 22.6%); 44% had no reported family history of breast or ovarian cancer. Patients carrying germ-line mutations had improved rates of progression-free and overall survival. In the relapse setting, patients carrying mutations more frequently responded to both platin- and nonplatin-based regimens than mutation-negative patients, even in patients with early relapse after primary treatment. Mutation-negative patients who responded to multiple cycles of platin-based treatment were more likely to carry somatic BRCA1/2 mutations. Conclusion BRCA mutation status has a major influence on survival in ovarian cancer patients and should be an additional stratification factor in clinical trials. Treatment outcomes in BRCA1/2 carriers challenge conventional definitions of platin resistance, and mutation status may be able to contribute to decision making and systemic therapy selection in the relapse setting. Our data, together with the advent of poly(ADP-ribose) polymerase inhibitor trials, supports the recommendation that germ-line BRCA1/2 testing should be offered to all women diagnosed with nonmucinous, ovarian carcinoma, regardless of family history. PMID:22711857

  19. Nicotinic acetylcholine receptors containing the α7-like subunit mediate contractions of muscles responsible for space positioning of the snail, Helix pomatia L. tentacle.

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    Tibor Kiss

    Full Text Available Three recently discovered tentacle muscles are crucial to perform patterned movements of upper tentacles of the terrestrial snail, Helix pomatia. The muscles receive central and peripheral excitatory cholinergic innervation lacking inhibitory innervation. Here, we investigate the pharmacology of acetylcholine (ACh responses in muscles to determine the properties of the ACh receptor (AChR, the functional availability of which was assessed using isotonic contraction measurement. Using broad spectrum of nicotinic and muscarinic ligands, we provide the evidence that contractions in the muscles are attributable to the activation of nAChRs that contain the α7-like subunit. Contractions could be evoked by nicotine, carbachol, succinylchloride, TMA, the selective α7-nAChR agonist choline chloride, 3-Bromocytisine and PNU-282987, and blocked by nAChR selective antagonists such as mytolon, hexamethonium, succinylchloride, d-tubocurarine, hemicholinium, DMDA (decamethonium, methyllycaconitine, α-Bungarotoxin (αBgTx and α-Conotoxin IMI. The specific muscarinic agonist oxotremorine and arecoline failed to elicit contractions. Based on these pharmacological properties we conclude that the Na+ and Ca2+ permeable AChRs of the flexor muscle are nicotinic receptors that contain the α7-like subunit. Immunodetection experiments confirmed the presence of α7- or α7-like AChRs in muscle cells, and α4-AChRs in nerves innervating the muscle. These results support the conclusion that the slowly desensitizing αBgTx-sensitive responses obtained from flexor muscles are produced by activation of α7- like AChRs. This is the first demonstration of postsynaptic expression and an obligatory role for a functional α7-like nAChR in the molluscan periphery.

  20. Fluorescent optical position sensor

    Science.gov (United States)

    Weiss, Jonathan D.

    2005-11-15

    A fluorescent optical position sensor and method of operation. A small excitation source side-pumps a localized region of fluorescence at an unknown position along a fluorescent waveguide. As the fluorescent light travels down the waveguide, the intensity of fluorescent light decreases due to absorption. By measuring with one (or two) photodetectors the attenuated intensity of fluorescent light emitted from one (or both) ends of the waveguide, the position of the excitation source relative to the waveguide can be determined by comparing the measured light intensity to a calibrated response curve or mathematical model. Alternatively, excitation light can be pumped into an end of the waveguide, which generates an exponentially-decaying continuous source of fluorescent light along the length of the waveguide. The position of a photodetector oriented to view the side of the waveguide can be uniquely determined by measuring the intensity of the fluorescent light emitted radially at that location.

  1. Automatic affective-motivational regulation processes underlying supportive dyadic coping: the role of increased implicit positive attitudes toward communal goals in response to a stressed relationship partner.

    Science.gov (United States)

    Koranyi, Nicolas; Hilpert, Peter; Job, Veronika; Bodenmann, Guy

    2017-09-01

    We examined the implicit affective mechanisms underlying provision of support in intimate dyads. Specifically, we hypothesized that in individuals with high relationship satisfaction, the perception that one's partner is stressed leads to increased implicit positive attitudes toward communal goals. In turn, this change in implicit attitudes facilitates supportive behavior. In two studies, we induced partner stress by instructing participants to either recall a situation where their partner was highly stressed (Study 1; N = 47 university students) or imagine a specific stressful event (excessive workload; Study 2; N = 85 university students). Subsequently, implicit attitudes toward communal goals were assessed with an Implicit Association Test. In both studies, we found that among participants with high relationship satisfaction partner stress increases preferences for communal goals. In addition, implicit preferences for communal goals predicted stronger inclinations to engage in supportive dyadic coping (Study 2). The current findings provide important insights into the implicit cognitive-affective mechanics of dyadic coping. Moreover, they can explain how people manage to avoid experiencing motivational conflicts between partner-oriented and self-oriented goals in situations characterized by high partner stress.

  2. Arabidopsis C3HC4-RING finger E3 ubiquitin ligase AtAIRP4 positively regulates stress-responsive abscisic acid signaling.

    Science.gov (United States)

    Yang, Liang; Liu, Qiaohong; Liu, Zhibin; Yang, Hao; Wang, Jianmei; Li, Xufeng; Yang, Yi

    2016-01-01

    Degradation of proteins via the ubiquitin system is an important step in many stress signaling pathways in plants. E3 ligases recognize ligand proteins and dictate the high specificity of protein degradation, and thus, play a pivotal role in ubiquitination. Here, we identified a gene, named Arabidopsis thaliana abscisic acid (ABA)-insensitive RING protein 4 (AtAIRP4), which is induced by ABA and other stress treatments. AtAIRP4 encodes a cellular protein with a C3HC4-RING finger domain in its C-terminal side, which has in vitro E3 ligase activity. Loss of AtAIRP4 leads to a decrease in sensitivity of root elongation and stomatal closure to ABA, whereas overexpression of this gene in the T-DNA insertion mutant atairp4 effectively recovered the ABA-associated phenotypes. AtAIRP4 overexpression plants were hypersensitive to salt and osmotic stresses during seed germination, and showed drought avoidance compared with the wild-type and atairp4 mutant plants. In addition, the expression levels of ABA- and drought-induced marker genes in AtAIRP4 overexpression plants were markedly higher than those in the wild-type and atairp4 mutant plants. Hence, these results indicate that AtAIRP4 may act as a positive regulator of ABA-mediated drought avoidance and a negative regulator of salt tolerance in Arabidopsis. © 2015 The Authors. Journal of Integrative Plant Biology published by Wiley Publishing Asia Pty Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.

  3. Global Positioning System Derived Performance Measures Are Responsive Indicators of Physical Activity, Disease and the Success of Clinical Treatments in Domestic Dogs

    Science.gov (United States)

    Bruno, Elizabeth A.; Guthrie, James W.; Ellwood, Stephen A.; Mellanby, Richard J.; Clements, Dylan N.

    2015-01-01

    Objective To assess the use of Global Positioning System receiver (GPS) derived performance measures for differentiating between: 1) different outdoor activities in healthy dogs; 2) healthy dogs and those with osteoarthritis; 3) osteoarthritic dogs before and after treatment with non-steroidal anti-inflammatory analgesia. Design Prospective study. Animals Ten healthy dogs and seven dogs with osteoarthritis of the elbow joint (OA dogs). Procedure Healthy dogs were walked on a standard route on-lead, off-lead and subjected to playing activity (chasing a ball) whilst wearing a GPS collar. Each dog was walked for five consecutive days. Dogs with OA were subjected to a single off-lead walk whilst wearing a GPS collar, and then administered oral Carprofen analgesia daily for two weeks. OA dogs were then subjected to the same walk, again wearing a GPS collar. Results GPS derived measures of physical performance could differentiate between on-lead activity, off-lead activity and playing activity in healthy dogs, and between healthy dogs and OA dogs. Variation in the performance measures analysed was greater between individual dogs than for individual dogs on different days. Performance measures could differentiate healthy dogs from OA dogs. OA Dogs treated with Carprofen analgesia showed improvements in their physical performance, which returned to values indistinguishable from those of healthy dogs on nearly all the measures assessed. Conclusions and Clinical Relevance GPS derived measures of physical performance in dogs are objective, easy to quantify, and can be used to gauge the effects of disease and success of clinical treatments. Specific stimuli can be used to modulate physical performance beyond the self-governed boundaries that dogs will naturally express when allowed to exercise freely without stimulation. PMID:25692761

  4. Global positioning system derived performance measures are responsive indicators of physical activity, disease and the success of clinical treatments in domestic dogs.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Bruno

    Full Text Available To assess the use of Global Positioning System receiver (GPS derived performance measures for differentiating between: 1 different outdoor activities in healthy dogs; 2 healthy dogs and those with osteoarthritis; 3 osteoarthritic dogs before and after treatment with non-steroidal anti-inflammatory analgesia.Prospective study.Ten healthy dogs and seven dogs with osteoarthritis of the elbow joint (OA dogs.Healthy dogs were walked on a standard route on-lead, off-lead and subjected to playing activity (chasing a ball whilst wearing a GPS collar. Each dog was walked for five consecutive days. Dogs with OA were subjected to a single off-lead walk whilst wearing a GPS collar, and then administered oral Carprofen analgesia daily for two weeks. OA dogs were then subjected to the same walk, again wearing a GPS collar.GPS derived measures of physical performance could differentiate between on-lead activity, off-lead activity and playing activity in healthy dogs, and between healthy dogs and OA dogs. Variation in the performance measures analysed was greater between individual dogs than for individual dogs on different days. Performance measures could differentiate healthy dogs from OA dogs. OA Dogs treated with Carprofen analgesia showed improvements in their physical performance, which returned to values indistinguishable from those of healthy dogs on nearly all the measures assessed.GPS derived measures of physical performance in dogs are objective, easy to quantify, and can be used to gauge the effects of disease and success of clinical treatments. Specific stimuli can be used to modulate physical performance beyond the self-governed boundaries that dogs will naturally express when allowed to exercise freely without stimulation.

  5. Long-term fertilization determines different metabolomic profiles and responses in saplings of three rainforest tree species with different adult canopy position.

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    Albert Gargallo-Garriga

    Full Text Available Tropical rainforests are frequently limited by soil nutrient availability. However, the response of the metabolic phenotypic plasticity of trees to an increase of soil nutrient availabilities is poorly understood. We expected that increases in the ability of a nutrient that limits some plant processes should be detected by corresponding changes in plant metabolome profile related to such processes.We studied the foliar metabolome of saplings of three abundant tree species in a 15 year field NPK fertilization experiment in a Panamanian rainforest. The largest differences were among species and explained 75% of overall metabolome variation. The saplings of the large canopy species, Tetragastris panamensis, had the lowest concentrations of all identified amino acids and the highest concentrations of most identified secondary compounds. The saplings of the "mid canopy" species, Alseis blackiana, had the highest concentrations of amino acids coming from the biosynthesis pathways of glycerate-3P, oxaloacetate and α-ketoglutarate, and the saplings of the low canopy species, Heisteria concinna, had the highest concentrations of amino acids coming from the pyruvate synthesis pathways.The changes in metabolome provided strong evidence that different nutrients limit different species in different ways. With increasing P availability, the two canopy species shifted their metabolome towards larger investment in protection mechanisms, whereas with increasing N availability, the sub-canopy species increased its primary metabolism. The results highlighted the proportional distinct use of different nutrients by different species and the resulting different metabolome profiles in this high diversity community are consistent with the ecological niche theory.

  6. Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients

    Science.gov (United States)

    Napolitano, Maria; D'Alterio, Crescenzo; Cardone, Eleonora; Trotta, Anna Maria; Pecori, Biagio; Rega, Daniela; Pace, Ugo; Scala, Dario; Scognamiglio, Giosuè; Tatangelo, Fabiana; Cacciapuoti, Carmela; Pacelli, Roberto; Delrio, Paolo; Scala, Stefania

    2015-01-01

    Short-course preoperative radiotherapy (SC-RT) followed by total mesorectal excision (TME) is one therapeutic option for locally advanced rectal cancer (LARC) patients. Since radio-induced DNA damage may affect tumor immunogenicity, Myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) were evaluated in 13 patients undergoing SC-RT and TME for LARC. Peripheral Granulocytic-MDSCs (G-MDSC) [LIN−/HLA-DR−/CD11b+/CD14−/CD15+/CD33+], Monocytic (M-MDSC) [CD14+/HLA-DR−/lowCD11b+/CD33+] and Tregs [CD4+/CD25hi+/FOXP3+- CTLA-4/PD1] basal value was significantly higher in LARC patients compared to healthy donors (HD). Peripheral MDSC and Tregs were evaluated at time 0 (T0), after 2 and 5 weeks (T2-T5) from radiotherapy; before surgery (T8) and 6–12 months after surgery (T9, T10). G-MDSC decreased at T5 and further at T8 while M-MDSC cells decreased at T5; Tregs reached the lowest value at T5. LARC poor responder patients displayed a major decrease in M-MDSC after SC-RT and an increase of Treg-PD-1. In this pilot study MDSCs and Tregs decrease during the SC-RT treatment could represent a biomarker of response in LARC patients. Further studies are needed to confirm that the deepest M-MDSC reduction and increase in Treg-PD1 cells within 5–8 weeks from the beginning of treatment could discriminate LARC patients poor responding to SC-RT. PMID:25823653

  7. Nucleosome Positioning and Epigenetics

    Science.gov (United States)

    Schwab, David; Bruinsma, Robijn

    2008-03-01

    The role of chromatin structure in gene regulation has recently taken center stage in the field of epigenetics, phenomena that change the phenotype without changing the DNA sequence. Recent work has also shown that nucleosomes, a complex of DNA wrapped around a histone octamer, experience a sequence dependent energy landscape due to the variation in DNA bend stiffness with sequence composition. In this talk, we consider the role nucleosome positioning might play in the formation of heterochromatin, a compact form of DNA generically responsible for gene silencing. In particular, we discuss how different patterns of nucleosome positions, periodic or random, could either facilitate or suppress heterochromatin stability and formation.

  8. Tree mortality in response to typhoon-induced floods and mudslides is determined by tree species, size, and position in a riparian Formosan gum forest in subtropical Taiwan.

    Science.gov (United States)

    Tzeng, Hsy-Yu; Wang, Wei; Tseng, Yen-Hsueh; Chiu, Ching-An; Kuo, Chu-Chia; Tsai, Shang-Te

    2018-01-01

    Global warming-induced extreme climatic changes have increased the frequency of severe typhoons bringing heavy rains; this has considerably affected the stability of the forest ecosystems. Since the Taiwan 921 earthquake occurred in 21 September 1999, the mountain geology of the Island of Taiwan has become unstable and typhoon-induced floods and mudslides have changed the topography and geomorphology of the area; this has further affected the stability and functions of the riparian ecosystem. In this study, the vegetation of the unique Aowanda Formosan gum forest in Central Taiwan was monitored for 3 years after the occurrence of floods and mudslides during 2009-2011. Tree growth and survival, effects of floods and mudslides, and factors influencing tree survival were investigated. We hypothesized that (1) the effects of floods on the survival are significantly different for each tree species; (2) tree diameter at breast height (DBH) affects tree survival-i.e., the larger the DBH, the higher the survival rate; and (3) the relative position of trees affects tree survival after disturbances by floods and mudslides-the farther trees are from the river, the higher is their survival rate. Our results showed that after floods and mudslides, the lifespans of the major tree species varied significantly. Liquidambar formosana displayed the highest flood tolerance, and the trunks of Lagerstoemia subcostata began rooting after disturbances. Multiple regression analysis indicated that factors such as species, DBH, distance from sampled tree to the above boundary of sample plot (far from the riverbank), and distance from the upstream of the river affected the lifespans of trees; the three factors affected each tree species to different degrees. Furthermore, we showed that insect infestation had a critical role in determining tree survival rate. Our 3-year monitoring investigation revealed that severe typhoon-induced floods and mudslides disturbed the riparian vegetation in the

  9. Tree mortality in response to typhoon-induced floods and mudslides is determined by tree species, size, and position in a riparian Formosan gum forest in subtropical Taiwan

    Science.gov (United States)

    Tzeng, Hsy-Yu; Wang, Wei; Tseng, Yen-Hsueh; Chiu, Ching-An; Kuo, Chu-Chia

    2018-01-01

    Global warming-induced extreme climatic changes have increased the frequency of severe typhoons bringing heavy rains; this has considerably affected the stability of the forest ecosystems. Since the Taiwan 921 earthquake occurred in 21 September 1999, the mountain geology of the Island of Taiwan has become unstable and typhoon-induced floods and mudslides have changed the topography and geomorphology of the area; this has further affected the stability and functions of the riparian ecosystem. In this study, the vegetation of the unique Aowanda Formosan gum forest in Central Taiwan was monitored for 3 years after the occurrence of floods and mudslides during 2009–2011. Tree growth and survival, effects of floods and mudslides, and factors influencing tree survival were investigated. We hypothesized that (1) the effects of floods on the survival are significantly different for each tree species; (2) tree diameter at breast height (DBH) affects tree survival–i.e., the larger the DBH, the higher the survival rate; and (3) the relative position of trees affects tree survival after disturbances by floods and mudslides–the farther trees are from the river, the higher is their survival rate. Our results showed that after floods and mudslides, the lifespans of the major tree species varied significantly. Liquidambar formosana displayed the highest flood tolerance, and the trunks of Lagerstoemia subcostata began rooting after disturbances. Multiple regression analysis indicated that factors such as species, DBH, distance from sampled tree to the above boundary of sample plot (far from the riverbank), and distance from the upstream of the river affected the lifespans of trees; the three factors affected each tree species to different degrees. Furthermore, we showed that insect infestation had a critical role in determining tree survival rate. Our 3-year monitoring investigation revealed that severe typhoon-induced floods and mudslides disturbed the riparian vegetation

  10. Trends in CD4 cell count response to first-line antiretroviral treatment in HIV-positive patients from Asia, 2003-2013: TREAT Asia HIV Observational Database Low Intensity Transfer.

    Science.gov (United States)

    De La Mata, Nicole L; Ly, Penh S; Ng, Oon T; Nguyen, Kinh V; Merati, Tuti P; Pham, Thuy T; Lee, Man P; Choi, Jun Y; Sohn, Annette H; Law, Matthew G; Kumarasamy, Nagalingeswaran

    2017-11-01

    Antiretroviral treatment (ART) guidelines have changed over the past decade, recommending earlier initiation and more tolerable regimens. The study objective was to examine the CD4 response to ART, depending on the year of ART initiation, in HIV-positive patients in the Asia-Pacific. We included HIV-positive adult patients who initiated ART between 2003 and 2013 in our regional cohort from eight urban referral centres in seven countries within Asia. We used mixed-effects linear regression models to evaluate differences in CD4 response by year of ART initiation during 36 months of follow-up, adjusted a priori for other covariates. Overall, 16,962 patients were included. Patients initiating in 2006-9 and 2010-13 had an estimated mean CD4 cell count increase of 8 and 15 cells/µl, respectively, at any given time during the 36-month follow-up, compared to those in 2003-5. The median CD4 cell count at ART initiation also increased from 96 cells/µl in 2003-5 to 173 cells/µl in 2010-13. Our results suggest that the CD4 response to ART is modestly higher for those initiating ART in more recent years. Moreover, fewer patients are presenting with lower absolute CD4 cell counts over time. This is likely to reduce their risk of opportunistic infections and future non-AIDS defining cancers.

  11. Disparity between General Symptom Relief and Remission Criteria in the Positive and Negative Syndrome Scale (PANSS): A Post-treatment Bifactor Item Response Theory Model.

    Science.gov (United States)

    Anderson, Ariana E; Reise, Steven P; Marder, Stephen R; Mansolf, Maxwell; Han, Carol; Bilder, Robert M

    2017-12-01

    Objective: Total scale scores derived by summing ratings from the 30-item PANSS are commonly used in clinical trial research to measure overall symptom severity, and percentage reductions in the total scores are sometimes used to document the efficacy of treatment. Acknowledging that some patients may have substantial changes in PANSS total scores but still be sufficiently symptomatic to warrant diagnosis, ratings on a subset of 8 items, referred to here as the "Remission set," are sometimes used to determine if patients' symptoms no longer satisfy diagnostic criteria. An unanswered question remains: is the goal of treatment better conceptualized as reduction in overall symptom severity, or reduction in symptoms below the threshold for diagnosis? We evaluated the psychometric properties of PANSS total scores, to assess whether having low symptom severity post-treatment is equivalent to attaining Remission. Design: We applied a bifactor item response theory (IRT) model to post-treatment PANSS ratings of 3,647 subjects diagnosed with schizophrenia assessed at the termination of 11 clinical trials. The bifactor model specified one general dimension to reflect overall symptom severity, and five domain-specific dimensions. We assessed how PANSS item discrimination and information parameters varied across the range of overall symptom severity (θ), with a special focus on low levels of symptoms (i.e., θexpected PANSS item score of 1.83, a rating between "Absent" and "Minimal" for a PANSS symptom. Results: The application of the bifactor IRT model revealed: (1) 88% of total score variation was attributable to variation in general symptom severity, and only 8% reflected secondary domain factors. This implies that a general factor may provide a good indicator of symptom severity, and that interpretation is not overly complicated by multidimensionality; (2) Post-treatment, 534 individuals (about 15% of the whole sample) scored in the "Relief" range of general symptom

  12. KIR3DS1/HLA-B Bw4-80Ile Genotype Is Correlated with the IFN-α Therapy Response in hepatitis B e antigen-Positive Chronic Hepatitis B

    Directory of Open Access Journals (Sweden)

    Wenting Li

    2017-10-01

    Full Text Available To date, several on-treatment-level virological and serological indices that may predict the response to interferon alpha (IFN-α have been reported. However, no effective predictors, such as drug–response genes, that can be detected before administration of anti-hepatitis B virus (HBV therapy with IFN-α, have been found. In the diverse range of chronic viral infection, genes that affect human immunity play important roles in understanding host and viral co-evolution. Killer-cell immunoglobulin-like receptors (KIRs, which are highly polymorphic at the allele and haplotype levels, participate in the antiviral function of natural killer (NK cells via fine-tuning inhibition and activation of NK-cell responses that occur when the NK cells interact with human leukocyte antigen (HLA class I molecules on target cells. For each individual, the pairing of KIR and HLA ligand is genetically determined. To investigate whether a particular KIR and HLA repertoire influences the risk of HBV infection and response to IFN-α treatment for chronic hepatitis B (CHB, we genotyped the KIRs and HLA ligands of 119 hepatitis B e antigen (HBeAg-positive CHB patients. These patients included 43 patients who achieved sustained response (SR induced by IFN-α treatment for 48 weeks, 76 patients who achieved no response (NR, and 96 healthy subjects as controls. SR was defined as HBeAg loss with HBV DNA < 2,000 IU/ml and alanine aminotransferase normalization at 24 weeks posttreatment (week 72. In this study, we showed that activating KIR genes were less prevalent in Han Chinese, especially in Han Chinese with CHB, than in Caucasians. Furthermore, the KIR3DS1 gene, in combination with HLA-B Bw4-80Ile, strongly influenced the therapeutic outcomes for CHB patients who were treated with IFN-α. The frequency of the combination of genes encoding KIR3DS1 and HLA-B Bw4-80Ile was higher in patients who had a sustained treatment response than in patients who had NR [35

  13. Position reconstruction in LUX

    Science.gov (United States)

    Akerib, D. S.; Alsum, S.; Araújo, H. M.; Bai, X.; Bailey, A. J.; Balajthy, J.; Beltrame, P.; Bernard, E. P.; Bernstein, A.; Biesiadzinski, T. P.; Boulton, E. M.; Brás, P.; Byram, D.; Cahn, S. B.; Carmona-Benitez, M. C.; Chan, C.; Currie, A.; Cutter, J. E.; Davison, T. J. R.; Dobi, A.; Druszkiewicz, E.; Edwards, B. N.; Fallon, S. R.; Fan, A.; Fiorucci, S.; Gaitskell, R. J.; Genovesi, J.; Ghag, C.; Gilchriese, M. G. D.; Hall, C. R.; Hanhardt, M.; Haselschwardt, S. J.; Hertel, S. A.; Hogan, D. P.; Horn, M.; Huang, D. Q.; Ignarra, C. M.; Jacobsen, R. G.; Ji, W.; Kamdin, K.; Kazkaz, K.; Khaitan, D.; Knoche, R.; Larsen, N. A.; Lenardo, B. G.; Lesko, K. T.; Lindote, A.; Lopes, M. I.; Manalaysay, A.; Mannino, R. L.; Marzioni, M. F.; McKinsey, D. N.; Mei, D.-M.; Mock, J.; Moongweluwan, M.; Morad, J. A.; Murphy, A. St. J.; Nehrkorn, C.; Nelson, H. N.; Neves, F.; O'Sullivan, K.; Oliver-Mallory, K. C.; Palladino, K. J.; Pease, E. K.; Rhyne, C.; Shaw, S.; Shutt, T. A.; Silva, C.; Solmaz, M.; Solovov, V. N.; Sorensen, P.; Sumner, T. J.; Szydagis, M.; Taylor, D. J.; Taylor, W. C.; Tennyson, B. P.; Terman, P. A.; Tiedt, D. R.; To, W. H.; Tripathi, M.; Tvrznikova, L.; Uvarov, S.; Velan, V.; Verbus, J. R.; Webb, R. C.; White, J. T.; Whitis, T. J.; Witherell, M. S.; Wolfs, F. L. H.; Xu, J.; Yazdani, K.; Young, S. K.; Zhang, C.

    2018-02-01

    The (x, y) position reconstruction method used in the analysis of the complete exposure of the Large Underground Xenon (LUX) experiment is presented. The algorithm is based on a statistical test that makes use of an iterative method to recover the photomultiplier tube (PMT) light response directly from the calibration data. The light response functions make use of a two dimensional functional form to account for the photons reflected on the inner walls of the detector. To increase the resolution for small pulses, a photon counting technique was employed to describe the response of the PMTs. The reconstruction was assessed with calibration data including 83mKr (releasing a total energy of 41.5 keV) and 3H (β- with Q = 18.6 keV) decays, and a deuterium-deuterium (D-D) neutron beam (2.45 MeV) . Within the detector's fiducial volume, the reconstruction has achieved an (x, y) position uncertainty of σ = 0.82 cm and σ = 0.17 cm for events of only 200 and 4,000 detected electroluminescence photons respectively. Such signals are associated with electron recoils of energies ~0.25 keV and ~10 keV, respectively. The reconstructed position of the smallest events with a single electron emitted from the liquid surface (22 detected photons) has a horizontal (x, y) uncertainty of 2.13 cm.

  14. Dissociation between spontaneously hypertensive (SHR) andWistar–Kyoto (WKY) rats in baseline performance and methylphenidate response on measures of attention, impulsivity and hyperactivity in a Visual Stimulus Position Discrimination Task

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.

    2009-10-08

    The spontaneously hypertensive rat (SHR) is a widely accepted rodent model of Attention Deficit/Hyperactivity Disorder (ADHD), and methylphenidate (MP) is a central nervous systemstimulant that has been shown to have a dose-related positive effect on attention task performance in humans with ADHD. The current study was undertaken to compare SHR to its typical control strain, Wistar-Kyoto(WKY) rats, on the performance of a Visual Stimulus Position Discrimination Task (VSPDT) as well as of the responsiveness of the two rat strains to MP treatment. The rats were initially trained on the VSPDT, in which a light cue was presented randomly at three different cue-light intervals (1 s, 300 ms and 100 ms) over one of two levers, and presses on the lever corresponding to the light cue were reinforced with a food pellet. Once rats reached stable performance, the treatment phase of the study began, during which they received daily intraperitoneal (IP) injections of saline, 2 mg/kg, 5 mg/kg, and 10 mg/kg of MP in a randomized order immediately prior to being tested on the VSPDT. Baseline performance accuracy on the VSPDT did not differ between the groups. Furthermore, a striking strain dissociation was evident in the response of the two strains to treatment; VSPDT performance was substantially disrupted by the 5 and 10 mg/kg dose in the WKY rats but only mildly in the SHR rats. Response omissions were also increased only in WKY rats. Finally, both strains had increased locomotor activity in the operant chamber following MP treatment. These findings point to an important difference in response tendency toMP in the two strains that supports a view that a critical difference between these strains may suggest neurochemical and neuroadaptive differences associated with the behavioral impairments of ADHD.

  15. Selective lesion of septal cholinergic neurons in rats impairs acquisition of a delayed matching to position T-maze task by delaying the shift from a response to a place strategy.

    Science.gov (United States)

    Fitz, Nicholas F; Gibbs, Robert B; Johnson, David A

    2008-12-16

    This study tested the hypothesis that septal cholinergic lesions impair acquisition of a delayed matching to position (DMP) T-maze task in male rats by affecting learning strategy. Rats received either the selective cholinergic immunotoxin, 192 IgG-saporin (SAP) or artificial cerebrospinal fluid directly into the medial septum. Two weeks later, animals were trained to acquire the DMP task. SAP-treated rats took significantly longer to acquire the task than corresponding controls. Both SAP-treated and control rats adopted a persistent turn and utilized a response strategy during early periods of training. By the time rats reached criterion the persistent turn was no longer evident, and all rats had shifted to an allocentric strategy, i.e., were relying on extramaze cues to a significant degree. During the acquisition period, SAP-treated rats spent significantly more days showing a persistent turn and using a response strategy than corresponding controls. The added time spent using a response strategy accounted entirely for the added days required to reach criterion among the SAP-treated rats. This suggests that the principal mechanism by which septal cholinergic lesions impair DMP acquisition in male rats is by increasing the predisposition to use a response vs. a place strategy, thereby affecting the ability to switch from one strategy to another.

  16. Inhibitory effects of tiamulin on contractile and electrical responses in isolated thoracic aorta and cardiac muscle of guinea-pigs.

    Science.gov (United States)

    Nakajyo, S; Hara, Y; Hirano, S; Agata, N; Shimizu, K; Urakawa, N

    1992-09-01

    The inhibitory effect of tiamulin, an antibiotic produced by Pleurotus mutilis, on contractile and electrical responses in isolated thoracic aorta and cardiac muscle of guinea-pigs was studied. In the thoracic aorta, tiamulin with an IC50 of 9.7 x 10(-6) M inhibited sustained contractions induced by isosmotically added 60 mM KCl. The inhibitory effect of tiamulin on a Ca(2+)-induced contraction in a depolarized muscle was competitively antagonized by raising external Ca2+ concentration. Bay K 8644 (10(-7) M) antagonized tiamulin's inhibition of the Ca(2+)-induced contraction. Tiamulin (2 x 10(-5) M) decreased the elevated cytoplasmic Ca2+ level measured by the fura 2 AM method in the depolarized muscle. In high K(+)-isoprenaline-treated left atria, tiamulin (2 x 10(-5)-2 x 10(-4) M) produced negative inotropic effects. On the other hand in the membrane action potential of papillary muscles, tiamulin (2 x 10(-6)-2 x 10(-4) M) produced decreases in action potential and durations and 2 x 10(-4) M tiamulin depressed the slow response action potential in depolarized muscles. Tiamulin produced prolongations of the PR interval in ECG, negative chrono- and inotropic effects, and an increase in perfusion flow in guinea-pig isolated and perfused hearts. These effects of tiamulin on the aorta or cardiac muscle were similar to those of verapamil and nifedipine. These results suggest that both the inhibitory action of tiamulin on the high K(+)-induced contraction in the aorta and the negative inotropic effect of tiamulin on the cardiac muscle are due to an inhibition of Ca2+ entry through the voltage-dependent Ca2+ channels of cells of both these muscles.

  17. Plasma position control device

    International Nuclear Information System (INIS)

    Takase, Haruhiko.

    1987-01-01

    Purpose: To conduct position control stably to various plasmas and reduce the burden on the control coil power source. Constitution: Among the proportional, integration and differentiation controls, a proportional-differentiation control section and an integration control section are connected in parallel. Then, a signal switching circuit is disposed to the control signal input section for the proportional-differentiation control section such that either a present position of plasmas or deviation between the present plasma position and an aimed value can be selected as a control signal depending on the control procedures or the state of the plasmas. For instance, if a rapid response is required for the control, the deviation between the present plasma position and the aimed value is selected as the input signal to conduct proportional, integration and differentiation controls. While on the other hand, if it is intended to reduce the burden on the control coil power source, it is adapted such that the control signal inputted to the proportional-differentiation control section itself can select the present plasma position. (Yoshihara, H.)

  18. Position indicating device

    International Nuclear Information System (INIS)

    Fellchenfeld, M.M.; Connors, G.R.

    1987-01-01

    This patent describes a position indicating device for producing an indication of the position of a displaceable structure comprising: a position representing member mounted for movement in response to displacement of the structure; sensing elements spaced apart along the defined path such that each element is associated with a respective location along the defined path; means operatively coupling the elements into respective pairs of elements, having, for each pair of elements, an output producing a signal only when a single element of its respective pair is responding to the presence of the member; signal producing members each operative for producing a signal representing a predetermined logic state in response to a predetermined input signal, the number of the signal producing members being smaller than the number of the sensing elements; and circuit means operatively connecting the outputs to the signal producing members for causing a signal at each output to produce a predetermined input signal at a corresponding signal producing member and for causing a predetermined input signal to be produced at least one the signal producing member whenever a signal is present at either one of at least two of the outputs

  19. DC cancellation as a method of generating a t2-response and of solving the radial position error in a concentric free-falling two-sphere equivalence-principle experiment in a drag-free satellite

    International Nuclear Information System (INIS)

    Lange, Benjamin

    2010-01-01

    This paper presents a new method for doing a free-fall equivalence-principle (EP) experiment in a satellite at ambient temperature which solves two problems that have previously blocked this approach. By using large masses to change the gravity gradient at the proof masses, the orbit dynamics of a drag-free satellite may be changed in such a way that the experiment can mimic a free-fall experiment in a constant gravitational field on the earth. An experiment using a sphere surrounded by a spherical shell both completely unsupported and free falling has previously been impractical because (1) it is not possible to distinguish between a small EP violation and a slight difference in the semi-major axes of the orbits of the two proof masses and (2) the position difference in the orbit due to an EP violation only grows as t whereas the largest disturbance grows as t 3/2 . Furthermore, it has not been known how to independently measure the positions of a shell and a solid sphere with sufficient accuracy. The measurement problem can be solved by using a two-color transcollimator (see the main text), and since the radial-position-error and t-response problems arise from the earth's gravity gradient and not from its gravity field, one solution is to modify the earth's gravity gradient with local masses fixed in the satellite. Since the gravity gradient at the surface of a sphere, for example, depends only on its density, the gravity gradients of laboratory masses and of the earth unlike their fields are of the same order of magnitude. In a drag-free satellite spinning perpendicular to the orbit plane, two fixed spherical masses whose connecting line parallels the satellite spin axis can generate a dc gravity gradient at test masses located between them which cancels the combined gravity gradient of the earth and differential centrifugal force. With perfect cancellation, the position-error problem vanishes and the response grows as t 2 along a line which always points toward

  20. Prevalence of positive antibody test results for canine parvovirus (CPV) and canine distemper virus (CDV) and response to modified live vaccination against CPV and CDV in dogs entering animal shelters.

    Science.gov (United States)

    Litster, Annette; Nichols, Jamieson; Volpe, Allison

    2012-05-25

    Canine parvovirus (CPV) and canine distemper virus (CDV) infections are relatively common in animal shelters and are important population management issues since the immune status of incoming dogs is usually unknown. This study aimed to determine the prevalence of positive antibody test results for CPV and CDV in incoming dogs aged ≥ 4 months and to measure antibody response over 2 weeks following vaccination with a modified live vaccine (MLV). Dogs aged 4-24 months entering an adoption-guarantee shelter (Shelter 1, n=51) and aged ≥ 4 months entering a limited admission shelter (Shelter 2; n=51) were enrolled. Dogs from Shelter 1 had been vaccinated with MLV at a municipal shelter 5 days before enrollment, whereas dogs from Shelter 2 had no known history of vaccination at enrollment. Sera were obtained on day 1, immediately prior to CPV/CDV MLV, and tested using an in-clinic ELISA kit to detect CPV/CDV antibodies. Dogs negative for CPV and/or CDV were retested at day 6-8 and those dogs still negative at day 6-8 were retested at day 13-15. Prior to CPV/CDV MLV on day 1, more dogs tested positive for CPV (Shelter 1 - 68.6%; Shelter 2 - 84.3%) than for CDV (Shelter 1 - 37.3%; Shelter 2 - 41.2%). On day 1, prior to MLV, all spayed/neutered animals tested CPV antibody-positive (n=17/102) and CPV antibody-positive dogs were older than serologically negative dogs (Shelter 1, P=0.0029; Shelter 2, P=0.0042). By day 13-15, almost all dogs were CPV antibody-positive (Shelter 1 - 97.9%; Shelter 2 - 100.0%) and CDV antibody-positive (Shelter 1 - 93.8%; Shelter 2 - 97.8%). MLV induces protective antibody titers against CPV/CDV in almost all dogs after 13-15 days. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Net positive energy buildings

    International Nuclear Information System (INIS)

    Romero, A.; Barreiro, E.; Sanchez Zabala, V.

    2010-01-01

    Buildings are great consumers of energy, being responsible for almost 36% of CO2 emissions in Europe. Though there are many initiatives towards the reduction of energy consumption and CO2 emissions in buildings, many of the alternatives are diminished due to a lack of a unique and holistic approach to the problem. This paper reports a new innovative concept of Positive Energy Buildings (EB+), as well as an integral methodology that covers the overall design process for achieving them. The methodology evaluates energy efficiency solutions at different scales, from building site to generation systems. An educational building design in Navarra serves as a case study to check the feasibility of the proposed methodology. The study concludes that the key to achieve a Positive Energy Building is a minimized energy demand, complemented by efficient facilities and enhanced by distributed power generation from renewable sources. (Author).

  2. Conflict, Memory, and Positioning

    DEFF Research Database (Denmark)

    Brescó, Ignacio

    2016-01-01

    The aim of this paper was to bring the dialogical and multivoiced dimension of conflict to the fore in the study of how people remember a particular event in the past. Drawing from different case studies, it contains analyses of how subjects identifying with different political actors in the Basque...... conflict adopted their respective positions, and interpretation of the conflict, and how, in light of same, they reconstruct the failed peace process that took place in 2006 between the terrorist group ETA (Euzkadi ta Azcatasuna, or Basque Country and Freedom in English) and the Spanish government. Results...... show that the positioning adopted by participants gives rise to a certain form of interpreting the conflict, which, in turn, affects how the peace process is remembered. This occurs within a particular argumentative context in which each version constitutes an implicit response to a competing...

  3. Impact of somatic PI3K pathway and ERBB family mutations on pathological complete response (pCR) in HER2-positive breast cancer patients who received neoadjuvant HER2-targeted therapies.

    LENUS (Irish Health Repository)

    Toomey, Sinead

    2017-07-27

    The Cancer Genome Atlas analysis revealed that somatic EGFR, receptor tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 receptor tyrosine kinase 3 (ERBB3) and Erb-B2 receptor tyrosine kinase 4 (ERBB4) gene mutations (ERBB family mutations) occur alone or co-occur with somatic mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) in 19% of human epidermal growth factor receptor 2 (HER2)-positive breast cancers. Because ERBB family mutations can activate the PI3K\\/AKT pathway and likely have similar canonical signalling effects to PI3K pathway mutations, we investigated their combined impact on response to neoadjuvant HER2-targeted therapies.

  4. Activation of phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin pathway and response to everolimus in endocrine receptor-positive metastatic breast cancer – A retrospective pilot analysis and viewpoint

    Directory of Open Access Journals (Sweden)

    Jyoti Bajpai

    2017-01-01

    Full Text Available Introduction: Biomarkers predictive of response to mechanistic target of rapamycin (mTOR inhibitor, everolimus, in endocrine receptor (ER-positive metastatic breast cancer (MBC are a work in progress. We evaluated the feasibility of directly measuring mTOR activity and phosphatase and tensin homolog (PTEN expression and correlating their expression with response and survival. Materials and Methods: MBC patients who received everolimus with endocrine therapy (ET after progression on an aromatase inhibitor and had adequate tissue preservation for estimation of mTOR activity and PTEN expression were selected for analysis from a prospectively maintained database. Progression-free survival (PFS and overall survival (OS were estimated by Kaplan–Meier method, and correlation between mTOR activity and PTEN expression with survival was done by log-rank test. Results: Thirteen ER-positive MBC patients were available for analysis. PTEN expression was lost in 11/13 (84.6% patients and retained in 2/13 patients (15.4%. mTOR activity was absent in four patients (30.7%, weak in six patients (46.1%, and moderate in 3 patients (23.2%. Median PFS for the entire population was 2.5 months while median OS was not reached. Patients with an absent mTOR activity showed a longer PFS (5 vs. 1.5 vs. 2 months than those with weak and moderate activity, respectively (P = 0.043. There was no correlation between loss of PTEN expression and PFS. Conclusions: Measurement of direct mTOR activity in patients with MBC receiving everolimus/ET combination appears feasible. Absent mTOR activity may predict for longer PFS with everolimus-ET combination and requires further study.

  5. Benign positional vertigo

    Science.gov (United States)

    Vertigo - positional; Benign paroxysmal positional vertigo; BPPV: dizziness- positional ... Benign positional vertigo is also called benign paroxysmal positional vertigo (BPPV). It is caused by a problem in the inner ear. ...

  6. De-Escalation Strategies in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer (BC): Final Analysis of the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early BC HER2- and Hormone Receptor-Positive Phase II Randomized Trial-Efficacy, Safety, and Predictive Markers for 12 Weeks of Neoadjuvant Trastuzumab Emtansine With or Without Endocrine Therapy (ET) Versus Trastuzumab Plus ET.

    Science.gov (United States)

    Harbeck, Nadia; Gluz, Oleg; Christgen, Matthias; Kates, Ronald Ernest; Braun, Michael; Küemmel, Sherko; Schumacher, Claudia; Potenberg, Jochem; Kraemer, Stefan; Kleine-Tebbe, Anke; Augustin, Doris; Aktas, Bahriye; Forstbauer, Helmut; Tio, Joke; von Schumann, Raquel; Liedtke, Cornelia; Grischke, Eva-Maria; Schumacher, Johannes; Wuerstlein, Rachel; Kreipe, Hans Heinrich; Nitz, Ulrike Anneliese

    2017-09-10

    Purpose Human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-positive breast cancer is a distinct subgroup associated with lower chemotherapy sensitivity and slightly better outcome than HER2-positive/HR-negative disease. Little is known about the efficacy of the combination of endocrine therapy (ET) with trastuzumab or with the potent antibody-cytotoxic, anti-HER2 compound trastuzumab emtansine (T-DM1) with or without ET for this subgroup. The West German Study Group trial, ADAPT (Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer) compares pathologic complete response (pCR) rates of T-DM1 versus trastuzumab with ET in early HER2-positive/HR-positive breast cancer. Patients and Methods In this prospective, neoadjuvant, phase II trial, 375 patients with early breast cancer with HER2-positive and HR-positive status (n = 463 screened) were randomly assigned to 12 weeks of T-DM1 with or without ET or to trastuzumab with ET. The primary end point was pCR (ypT0/is/ypN0). Early response was assessed in 3-week post-therapeutic core biopsies (proliferation decrease ≥ 30% Ki-67 or cellularity response). Secondary end points included safety and predictive impact of early response on pCR. Adjuvant therapy followed national standards. Results Baseline characteristics were well balanced among the arms. More than 90% of patients completed the therapy per protocol. pCR was observed in 41.0% of patients treated with T-DM1, 41.5% of patients treated with T-DM1 and ET, and 15.1% with trastuzumab and ET ( P < .001). Early responders (67% of patients with assessable response) achieved pCR in 35.7% compared with 19.8% in nonresponders (odds ratio, 2.2; 95% CI, 1.24 to 4.19). T-DM1 was associated with a significantly higher prevalence of grade 1 to 2 toxicities, especially thrombocytopenia, nausea, and elevation of liver enzymes. Overall toxicity was low; seventeen

  7. Responsibility and Responsiveness

    DEFF Research Database (Denmark)

    Nissen, Ulrik Becker

    2011-01-01

    The debate on the role and identity of Christian social ethics in liberal democracy touches upon the question about the relationship between universality and speci-ficity. Rather than argue for the difference between these approaches, it can be argued that they are to be understood in a different......The debate on the role and identity of Christian social ethics in liberal democracy touches upon the question about the relationship between universality and speci-ficity. Rather than argue for the difference between these approaches, it can be argued that they are to be understood...... contemporary positions of communicative ethics, H. Richard Niebuhr’s understanding of responsibility as responsiveness, and Dietrich Bonhoeffer’s Christological concept of responsibility in a constructive dialogue with each other, the article has attempted to outline main tenets of a responsive concept...

  8. Position automatic determination technology

    International Nuclear Information System (INIS)

    1985-10-01

    This book tells of method of position determination and characteristic, control method of position determination and point of design, point of sensor choice for position detector, position determination of digital control system, application of clutch break in high frequency position determination, automation technique of position determination, position determination by electromagnetic clutch and break, air cylinder, cam and solenoid, stop position control of automatic guide vehicle, stacker crane and automatic transfer control.

  9. A Reply to ''Reinterpretation of Students' Ideas When Reasoning about Particle Model Illustrations. A Response to ''Using Animations in Identifying General Chemistry Students' Misconceptions and Evaluating Their Knowledge Transfer Relating to Particle Position in Physical Changes'' by Smith and Villarreal (2015)''

    Science.gov (United States)

    Smith, K. Christopher; Villarreal, Savannah

    2015-01-01

    In this reply to Elon Langbeheim's response to an article recently published in this journal, authors Smith and Villarreal identify several types of general chemistry students' misconceptions concerning the concept of particle position during physical change. They focus their response on one of the misconceptions identified as such: Given a solid…

  10. Positive Psychology: Positive Emotions and Emotional Intelegence

    OpenAIRE

    Miloseva, Lence

    2008-01-01

    The paper focuses on the and emotional intelligence. We try to answer on some questions regarding the role which positive emotions have in our life’s. The broaden-and-build theory (Fredrickson, 1998; 2001) predicts that positive emotions are useful in several ways. They guide present behavior, by broadening one’s attention and cognition, setting the stage for creative, explorative, and innovative pursuits. As well, positive emotions build personal and social resources to help individuals achi...

  11. Positive Psychology: Transforming Young Lives

    Science.gov (United States)

    Brendtro, Larry K.; Mitchell, Martin L.

    2011-01-01

    To reach responsible independence, young people must become invested in setting their life course. A rich history of research and practice shows that democratic group climates foster autonomy and prosocial behavior. This article explores principles and practices for creating positive peer cultures to develop strengths and help youth meet their…

  12. A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.

    Science.gov (United States)

    Armenia, Daniele; Soulie, Cathia; Di Carlo, Domenico; Fabeni, Lavinia; Gori, Caterina; Forbici, Federica; Svicher, Valentina; Bertoli, Ada; Sarmati, Loredana; Giuliani, Massimo; Latini, Alessandra; Boumis, Evangelo; Zaccarelli, Mauro; Bellagamba, Rita; Andreoni, Massimo; Marcelin, Anne-Geneviève; Calvez, Vincent; Antinori, Andrea; Ceccherini-Silberstein, Francesca; Perno, Carlo-Federico; Santoro, Maria Mercedes

    2014-01-01

    We previously found that a very low geno2pheno false positive rate (FPR ≤ 2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤ 2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART. The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤ 2; 2-5; 5-10; 10-20; 20-60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥ 150 cells/mm(3)) and on the time to achieve virological success (the first HIV-RNA measurement immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤ 2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2-5; 77.5%, FPR 5-10; 71.7%, FPR 10-20; 81.8%, FPR 20-60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤ 2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20-0.71], p = 0.003) and to achieve virological success (0.50 [0.26-0.94], p = 0.031) than those with pre-HAART FPR >60%. Beyond the genotypically-inferred tropism determination, FPR ≤ 2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability.

  13. Want Positive Behavior? Use Positive Language

    Science.gov (United States)

    Wood, Chip; Freeman-Loftis, Babs

    2012-01-01

    Positive adult language is the professional use of words and tone of voice to enable students to learn in an engaged, active way. This includes learning social skills. To guide children toward choosing and maintaining positive behaviors, adults need to carefully choose the words and tone of voice used when speaking to them. Learning to use…

  14. Benign positional vertigo - aftercare

    Science.gov (United States)

    Vertigo - positional - aftercare; Benign paroxysmal positional vertigo - aftercare; BPPV - aftercare; Dizziness - positional vertigo ... Your health care provider may have treated your vertigo with the Epley maneuver . These are head movements ...

  15. CSR Position in the Top Management Team

    DEFF Research Database (Denmark)

    Strand, Robert

    Recently, a number of positions with corporate social responsibility (CSR) in the position title have been introduced to the top management teams (TMTs) of some of the world’s largest corporations. I explore this phenomenon. I revisit 10 such positions identified in a previous study to add...

  16. Cardiac actions of phencyclidine in isolated guinea pig and rat heart: possible involvement of slow channels

    International Nuclear Information System (INIS)

    Temma, K.; Akera, T.; Ng, Y.C.

    1985-01-01

    The mechanisms responsible for the positive inotropic effect of phencyclidine were studied in isolated preparations of guinea pig and rat heart. In electrically paced left atrial muscle preparations, phencyclidine increased the force of contraction; rat heart muscle preparations were more sensitive than guinea pig heart muscle preparations. The positive inotropic effect of phencyclidine was not significantly reduced by a combination of phentolamine and nadolol; however, the effect was competitively blocked by verapamil in the presence of phentolamine and nadolol. Inhibition of the outward K+ current by tetraethylammonium chloride also produced a positive inotropic effect; however, the effect of tetraethylammonium was reduced by phentolamine and nadolol, and was almost insensitive to verapamil. The inotropic effect of phencyclidine was associated with a marked prolongation of the action potential duration and a decrease in maximal upstroke velocity of the action potential, with no change in the resting membrane potential. The specific [ 3 H]phencyclidine binding observed with membrane preparations from guinea pig ventricular muscle was saturable with a single class of high-affinity binding site. This binding was inhibited by verapamil, diltiazem, or nitrendipine, but not by ryanodine or tetrodotoxin. These results suggest that the positive inotropic effect of phencyclidine results from enhanced Ca 2+ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K + currents

  17. Multi-technology positioning

    CERN Document Server

    Lohan, Elena-Simona; Wymeersch, Henk; Seco-Granados, Gonzalo; Nykänen, Ossi

    2017-01-01

    This book provides an overview of positioning technologies, applications and services in a format accessible to a wide variety of readers. Readers who have always wanted to understand how satellite-based positioning, wireless network positioning, inertial navigation, and their combinations work will find great value in this book. Readers will also learn about the advantages and disadvantages of different positioning methods, their limitations and challenges. Cognitive positioning, adding the brain to determine which technologies to use at device runtime, is introduced as well. Coverage also includes the use of position information for Location Based Services (LBS), as well as context-aware positioning services, designed for better user experience. • Brings understanding of positioning technology to readers from a variety of disciplines • Reviews multiple techniques, providing insight on the pros, cons and challenges related to each • Designed to be a tutorial on basic principles, avoiding unnecessary de...

  18. Navicular bone position determined by positional MRI

    DEFF Research Database (Denmark)

    Hansen, Philip; Johannsen, Finn E; Hangaard, Stine

    2016-01-01

    -scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). RESULTS...

  19. Climate change policy position

    International Nuclear Information System (INIS)

    2002-11-01

    The Canadian Association of Petroleum Producers (CAPP) is a firm believer in the need to take action to mitigate the risks associated with climate change, and that clear government policy is called for. The principles of sustainable development must guide this policy development effort. The initiatives required to address greenhouse gas emissions over both the short and long term must be carefully considered, and it is up to industries to ensure their production efficiency and emission intensity. Promoting improved performance of industries in Canada and developing technology that can be deployed internationally for larger global effects represents Canada's best contribution to progress on greenhouse gas emissions. The increase in energy demand along with increases in population and economic growth have contributed to an increase in greenhouse gas emissions despite improved energy efficiency in industry. Significant damage to the economy will result if Canada is to meet its commitment under the Kyoto Protocol, forcing the country to buy large quantities of foreign credits instead of using those funds for increased research and development. CAPP indicated that an effective plan must be: balanced, equitable, responsible, competitive, focused on technology and innovation, and based on agreements on sectoral plans. Each of these principles were discussed, followed by the fundamentals of approach for upstream oil and gas. The framework for climate change policy was described as well as the elements of a sector plan. CAPP wants to work with all levels of government on an appropriate plan for Canada, that considers our unique circumstances. Canada can play a significant role on the international stage by properly implementing the policy position proposed by the CAPP without unnecessary risks to the economy. refs

  20. Pretty Easy Pervasive Positioning

    DEFF Research Database (Denmark)

    Hansen, Rene; Wind, Rico; Jensen, Christian Søndergaard

    2009-01-01

    With the increasing availability of positioning based on GPS, Wi-Fi, and cellular technologies and the proliferation of mobile devices with GPS, Wi-Fi and cellular connectivity, ubiquitous positioning is becoming a reality. While offerings by companies such as Google, Skyhook, and Spotigo render...... positioning possible in outdoor settings, including urban environments with limited GPS coverage, they remain unable to offer accurate indoor positioning. We will demonstrate a software infrastructure that makes it easy for anybody to build support for accurate Wi-Fi based positioning in buildings. All...... that is needed is a building with Wi-Fi coverage, access to the building, a floor plan of the building, and a Wi-Fi enabled device. Specifically, we will explain the software infrastructure and the steps that must be completed to obtain support for positioning. And we will demonstrate the positioning obtained...

  1. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD With the European Crohn's and Colitis Organization: When to Start, When to Stop, Which Drug to Choose, and How to Predict Response

    NARCIS (Netherlands)

    D'Haens, Geert R.; Panaccione, Remo; Higgins, Peter D. R.; Vermeire, Severine; Gassull, Miquel; Chowers, Yehuda; Hanauer, Stephen B.; Herfarth, Hans; Hommes, Daan W.; Kamm, Michael; Löfberg, Robert; Quary, A.; Sands, Bruce; Sood, A.; Watermayer, G.; Lashner, Bret; Lémann, Marc; Plevy, Scott; Reinisch, Walter; Schreiber, Stefan; Siegel, Corey; Targan, Stephen; Watanabe, M.; Feagan, Brian; Sandborn, William J.; Colombel, Jean Frédéric; Travis, Simon

    2011-01-01

    The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability,

  2. Positive criminology in practice.

    Science.gov (United States)

    Ronel, Natti; Segev, Dana

    2014-11-01

    The discourse regarding offender rehabilitation has been criticized by various scholars who have claimed that reducing negative causes and managing risk will not automatically prompt positive human development and elements that are associated with desistance. Positive criminology is an innovative concept that challenges the common preoccupation with negative elements, by placing emphasis on human encounters and forces of inclusion that are experienced positively by target individuals and that can promote crime desistance. However, as the concept is relatively new, there are still no guiding principles for the practice of positive criminology that could direct research and the criminal justice system. This article attempts to fill that gap by providing principles that could be practiced by criminal justice personnel and examples of different interventions that reflect positive criminology. The article also provides ideological explanations for adopting the concept of positive criminology in practice. © The Author(s) 2013.

  3. Scalability Optimization of Seamless Positioning Service

    Directory of Open Access Journals (Sweden)

    Juraj Machaj

    2016-01-01

    Full Text Available Recently positioning services are getting more attention not only within research community but also from service providers. From the service providers point of view positioning service that will be able to work seamlessly in all environments, for example, indoor, dense urban, and rural, has a huge potential to open new markets. However, such system does not only need to provide accurate position estimates but have to be scalable and resistant to fake positioning requests. In the previous works we have proposed a modular system, which is able to provide seamless positioning in various environments. The system automatically selects optimal positioning module based on available radio signals. The system currently consists of three positioning modules—GPS, GSM based positioning, and Wi-Fi based positioning. In this paper we will propose algorithm which will reduce time needed for position estimation and thus allow higher scalability of the modular system and thus allow providing positioning services to higher amount of users. Such improvement is extremely important, for real world application where large number of users will require position estimates, since positioning error is affected by response time of the positioning server.

  4. Position Statement on Active Outdoor Play

    OpenAIRE

    Tremblay, Mark S.; Gray, Casey; Babcock, Shawna; Barnes, Joel; Costas Bradstreet, Christa; Carr, Dawn; Chabot, Guylaine; Choquette, Louise; Chorney, David; Collyer, Cam; Herrington, Susan; Janson, Katherine; Janssen, Ian; Larouche, Richard; Pickett, William

    2015-01-01

    A diverse, cross-sectorial group of partners, stakeholders and researchers, collaborated to develop an evidence-informed Position Statement on active outdoor play for children aged 3–12 years. The Position Statement was created in response to practitioner, academic, legal, insurance and public debate, dialogue and disagreement on the relative benefits and harms of active (including risky) outdoor play. The Position Statement development process was informed by two systematic reviews, a critic...

  5. Técnica de oscilações forçadas na análise da resposta broncodilatadora em voluntários sadios e indivíduos portadores de asma brônquica com resposta positiva Using the forced oscillation technique to evaluate bronchodilator response in healthy volunteers and in asthma patients presenting a verified positive response

    Directory of Open Access Journals (Sweden)

    Juliana Veiga Cavalcanti

    2006-04-01

    Full Text Available OBJETIVO: Analisar, através da técnica de oscilações forçadas, pacientes asmáticos com resposta broncodilatadora positiva pelo laudo espirométrico e comparar esses resultados com os obtidos em indivíduos sadios. MÉTODOS: Foram analisados 53 indivíduos não tabagistas, sendo 24 sadios sem história de doença pulmonar e 29 asmáticos com resposta broncodilatadora positiva segundo o laudo espirométrico. Todos foram submetidos à técnica de oscilações forçadas e a espirometria antes e após vinte minutos da administração de salbutamol spray (300 g. Os parâmetros derivados da técnica de oscilações forçadas foram: resistência total, reatância total, resistência extrapolada para o eixo y, coeficiente angular da reta de resistência e complacência dinâmica. Na espirometria, os parâmetros utilizados foram o volume expiratório forçado no primeiro segundo e a capacidade vital forçada. RESULTADOS: No grupo controle, a utilização do broncodilatador produziu alteração significativa na resistência extrapolada para o eixo y (p OBJECTIVE: To use the forced oscillation technique to evaluate asthma patients presenting positive bronchodilator responses (confirmed through spirometry and compare the results with those obtained in healthy individuals. METHODS: The study sample consisted of 53 non-smoking volunteers: 24 healthy subjects with no history of pulmonary disease and 29 asthmatics presenting positive bronchodilator response, as determined through analysis of spirometry findings. All of the subjects were submitted to forced oscillation technique and spirometry immediately before and 20 minutes after the administration of salbutamol spray (300 g. The parameters derived from the forced oscillation technique were total respiratory resistance, total respiratory reactance, resistance extrapolated to the y axis, the slope of resistance, and dynamic compliance. The parameters measured in the spirometry evaluation tests were forced

  6. Den positive psykologis metoder

    DEFF Research Database (Denmark)

    Andersen, Frans Ørsted; Mørck, Line Lerche; Nissen, Poul Erik

    En antologi der giver en introduktion til en række af de metoder der anvendes til forskning, assessment, test, udviklingsarbejde og intervention indenfor den positive psykologi.......En antologi der giver en introduktion til en række af de metoder der anvendes til forskning, assessment, test, udviklingsarbejde og intervention indenfor den positive psykologi....

  7. Modern management positions

    Directory of Open Access Journals (Sweden)

    Jovanović Petar M.

    2015-01-01

    Full Text Available In this paper we analyze contemporary managerial positions such as program manager, project portfolio manager, crisis manager and others. The idea is to promote managerial positions in Serbia, which is quite unjustifiably undervalued, primarily because of the lack of knowledge in the field of management and other issues related to management education.

  8. Positioning and locking apparatus

    Science.gov (United States)

    Hayward, M.L.; Harper, W.H.

    1985-06-19

    A positioning and locking apparatus including a fixture having a rotatable torque ring provided with a plurality of cam segments for automatically guiding a container into a desired location within the fixture. Rotation of the ring turns the container into a final position in pressure sealing relation against a hatch member.

  9. Positioning health professional identity

    DEFF Research Database (Denmark)

    Lund, Ole; Krogh Christensen, Mette; Mørcke, Anne Mette

    2017-01-01

    Drawing on positioning theory, the purpose of this paper is to characterize the activities and positions of students and supervisors at workplaces and on-campus skills training sites across the higher health professional educations of medicine, sports science, and nursing. Furthermore, the study ...... explored the impact of work-based learning (WBL) and skills training on students’ personal professional identity development....

  10. Position display device

    International Nuclear Information System (INIS)

    Nishizawa, Yukio.

    1974-01-01

    Object: To provide a device capable of easily and quickly reading mutual mounting relations of control bodies such as control rods mounted on a nuclear reactor and positions to which the control bodies are driven. Structure: A scanning circuit is provided to scan positions of controllably mounted control bodies such as control rods. Values detected by scanning the positions are converted into character signals according to the values and converted into preranked color signals. The character signals and color signals are stored in a memory circuit by synchronous signals in synchronism with the scanning in the scanning circuit. Outputs of the memory circuit are displayed by a display unit such as a color Braun tube in accordance with the synchronous signals to provide color representations according to positions to which control bodies are driven in the same positional relation as the mounting of the control bodies. (Kamimura, M.)

  11. Review of Positional Nystagmus

    Directory of Open Access Journals (Sweden)

    José Ignacio BENITO-OREJAS

    2018-01-01

    Full Text Available Introduction and objective: Any change of position of the head (dynamic or static can trigger a nystagmus or increase the spontaneous. This nystagmus we call it positional. We intend to review in this chapter its definition, clinical features, etiology and the way of exploring it. Method: narrative review. Results: Positional vertigo is the most frequent vestibular disorder, and most of the times of peripheral cause. Characteristics of nystagmus or its association with other neurological symptoms are sufficient grounds to request a magnetic resonance, which will provide additional information on very few occasions. Discussion: The study of the positional nystagmus as a procedure to rule out central pathology has lost much of its relevance. Signs that Nylén defined mixed findings peripheral and central, making complex classification. Conclusion: Regardless of how to bring the patient change position (very slow or fast, if it appears an atypical nystagmus should rule out a central origin.

  12. POSITIONING STRATEGIES DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Shakhshir Ghassan

    2014-07-01

    Full Text Available The positioning strategy has suffered serious changes in the last few decades, being influenced by the rapid development of competition and the growing focus on specific traits belonging to the market, to the consumer or to the product. The purpose of this paper is to present the developments of theoretical positioning strategies and the orientation from more simple, product oriented strategies, to ones more oriented towards the client and with a briefer period of time. The world is moving in a much faster pace than in the past, thanks to communication development so companies are obliged to adopt more specific strategies in order for them to be effective. This essay represents a literary review presenting a documentary research within the scientific articles and strategy and positioning books. The paper begins with the analysis of company strategies and the marketing strategies in general. The first author to group the product positioning strategies is Porter with his three generic strategies. Following the development of brands and because of the lack of competitiveness in the simple generic positioning strategies, this paper has also presented the newer positioning strategies proposed by Kotler, Treacy & Wiersema, and also more complex ones such as Bowman's Strategy Clock and Blankson and Kalafatis positioning strategy based on the type of the consumer. The fast expansion of local brands in all categories has led to mistakes in positioning strategies, categories also presented in the current essay. The results of this study show that new positioning strategies are more and more based on the consumer and market segments and on the product specification - which have also evolved in the last decades. Adaptability to fast changes in the competitive market will represent the future positioning strategies.

  13. Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society.

    Science.gov (United States)

    Mallone, R; Mannering, S I; Brooks-Worrell, B M; Durinovic-Belló, I; Cilio, C M; Wong, F S; Schloot, N C

    2011-01-01

    Autoimmune T cell responses directed against insulin-producing β cells are central to the pathogenesis of type 1 diabetes (T1D). Detection of such responses is therefore critical to provide novel biomarkers for T1D 'immune staging' and to understand the mechanisms underlying the disease. While different T cell assays are being developed for these purposes, it is important to optimize and standardize methods for processing human blood samples for these assays. To this end, we review data relevant to critical parameters in peripheral blood mononuclear cell (PBMC) isolation, (cryo)preservation, distribution and usage for detecting antigen-specific T cell responses. Based on these data, we propose recommendations on processing blood samples for T cell assays and identify gaps in knowledge that need to be addressed. These recommendations may be relevant not only for the analysis of T cell responses in autoimmune disease, but also in cancer and infectious disease, particularly in the context of clinical trials. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

  14. Positional Concerns and Institutions

    DEFF Research Database (Denmark)

    Landes, Xavier

    2013-01-01

    that invoking envy or subjective well-being is not fully satisfying for regulating positional concerns. More compelling reasons seem, in complement with efficiency, to be related to considerations for equality. In other words, if institutions could have strong reasons to pay attention to and regulate positional...... their implications for economics, positional concerns imply important normative dimensions. There have been presumed to be a symptom of envy, reduce people’s happiness, and create problems of social interaction or economic inefficiencies. Individuals are, for instance, prone to pick states of the world that improve...... concerns, it would be in virtue of their impact on the social product and individuals’ conditions of living....

  15. Control rod position detector for nuclear reactor

    International Nuclear Information System (INIS)

    Kudo, Mitsuru; Fujiwara, Hiroshi.

    1981-01-01

    Purpose: To improve the reliability of a control rod position detector by detecting a reactive code with a combination of control rod position change signals produced from vertical and horizontal axis decoders, generation an error signal and thus simultaneously detecting the operation of more than two lead switches. Constitution: Horizontal and vertical axis position signals responsive to changes in the control rod position are applied from lead switches connected in a predetermined matrix connection corresponding to the notches of the positions of respective position detecting probes, the reactive output from the decoder is detected by a reactive code detecting circuit, which in turn generates a fault signal, and the control rod position code converted in a notch number generating circuit is converted to a predetermined value indicating invalidity. Accordingly, a fault caused by the simultaneous operation of a plurality of failed lead switches can be effectively detected. (Yoshino, Y.)

  16. a Continuous-Time Positive Linear System

    Directory of Open Access Journals (Sweden)

    Kyungsup Kim

    2013-01-01

    Full Text Available This paper discusses a computational method to construct positive realizations with sparse matrices for continuous-time positive linear systems with multiple complex poles. To construct a positive realization of a continuous-time system, we use a Markov sequence similar to the impulse response sequence that is used in the discrete-time case. The existence of the proposed positive realization can be analyzed with the concept of a polyhedral convex cone. We provide a constructive algorithm to compute positive realizations with sparse matrices of some positive systems under certain conditions. A sufficient condition for the existence of a positive realization, under which the proposed constructive algorithm works well, is analyzed.

  17. 5th International Symposium on Positive Systems

    CERN Document Server

    Farina, Lorenzo; Setola, Roberto; Germani, Alfredo

    2017-01-01

    This book presents high-quality original contributions on positive systems, including topics such as: monotone dynamical systems in mathematical biology and game theory; mathematical developments for networked systems in biology, chemistry and the social sciences; linear and nonlinear positive operators; dynamical analysis, observation and control of positive distributed parameter systems; stochastic realization theory; biological systems with positive variables and positive controls; iterated function systems; nonnegative dynamic processes; and dimensioning problems for collaborative systems. The book comprises a selection of the best papers presented at the POSTA 2016, the 5th International Symposium on Positive Systems, which was held in Rome, Italy, in September 2016. This conference series represents a targeted response to the growing need for research that reports on and critically discusses a wide range of topics concerning the theory and applications of positive systems.

  18. CD4 T cells mediate both positive and negative regulation of the immune response to HIV infection: complex role of T follicular helper cells and Regulatory T cells in pathogenesis

    Directory of Open Access Journals (Sweden)

    Chansavath ePhetsouphanh

    2015-01-01

    Full Text Available HIV-1 infection results in chronic activation of cells in lymphoid tissue, including T cells, B cells and myeloid lineage cells. The resulting characteristic hyperplasia is an amalgam of proliferating host immune cells in the adaptive response, increased concentrations of innate response mediators due to viral and bacterial products, and homeostatic responses to inflammation. While it is generally thought that CD4 T cells are greatly depleted, in fact, two types of CD4 T cells appear to be increased, namely regulatory T cells (Tregs and T follicular helper cells (Tfh. These cells have opposing roles, but may both be important in the pathogenic process. Whether Tregs are failing in their role to limit lymphocyte activation is unclear, but there is no doubt now that Tfh are associated with B cell hyperplasia and increased germinal centre activity. Antiretroviral therapy (ART may reduce the lymphocyte activation, but not completely, and therefore there is a need for interventions that selectively enhance normal CD4 function without exacerbating Tfh, B cell or Treg dysfunction.

  19. Stress Management: Positive Thinking

    Science.gov (United States)

    Healthy Lifestyle Stress management Positive thinking helps with stress management and can even improve your health. Practice overcoming negative self-talk ... with optimism is a key part of effective stress management. And effective stress management is associated with ...

  20. Den positive psykologis metoder

    DEFF Research Database (Denmark)

    Bogen introducerer til de mange metoder, som anvendes i positiv psykologi. dette sker ud fra en reflekteret tilgang, der ligeledes rummer bidrag fra kritisk psykologi med det formål at nuancere den positive psykologis forståelser...

  1. Clinical Positioning Space

    DEFF Research Database (Denmark)

    Williams, Lars Peter Hedegaard; Christensen, Mette Krogh; Rytter, Carsten

    2014-01-01

    In this article, we present a case study of residents’ clinical experiences and communication in outpatient oncology consultations. We apply positioning theory, a dynamic alternative to role theory, to investigate how oncology residents and patients situate themselves as persons with rights...... and duties. Drawing from seven qualitative interviews and six days of observation, we investigate the residents’ social positioning and their conversations with patients or supervisors. Our focus is on how (a) relational shifts in authority depend on each situation and its participants; (b) storylines...... establish acts and positions and narratively frame what participants can expect from a medical consultation viewed as a social episode; and (c) the positioning of rights and duties can lead to misunderstandings and frustrations. We conclude that residents and patients locate themselves in outpatient...

  2. Head and neck position sense.

    Science.gov (United States)

    Armstrong, Bridget; McNair, Peter; Taylor, Denise

    2008-01-01

    Traumatic minor cervical strains are common place in high-impact sports (e.g. tackling) and premature degenerative changes have been documented in sports people exposed to recurrent impact trauma (e.g. scrummaging in rugby) or repetitive forces (e.g. Formula 1 racing drivers, jockeys). While proprioceptive exercises have been an integral part of rehabilitation of injuries in the lower limb, they have not featured as prominently in the treatment of cervical injuries. However, head and neck position sense (HNPS) testing and re-training may have relevance in the management of minor sports-related neck injuries, and play a role in reducing the incidence of ongoing pain and problems with function. For efficacious programmes to be developed and tested, fundamental principles associated with proprioception in the cervical spine should be considered. Hence, this article highlights the importance of anatomical structures in the cervical spine responsible for position sense, and how their interaction with the CNS affects our ability to plan and execute effective purposeful movements. This article includes a review of studies examining position sense in subjects with and without pathology and describes the effects of rehabilitation programmes that have sought to improve position sense. In respect to the receptors providing proprioceptive information for the CNS, the high densities and complex arrays of spindles found in cervical muscles suggest that these receptors play a key role. There is some evidence suggesting that ensemble encoding of discharge patterns from muscle spindles is relayed to the CNS and that a pattern recognition system is used to establish joint position and movement. Sensory information from neck proprioceptive receptors is processed in tandem with information from the vestibular system. There are extensive anatomical connections between neck proprioceptive inputs and vestibular inputs. If positional information from the vestibular system is inaccurate or

  3. POSITIONING STRATEGIES DEVELOPMENT

    OpenAIRE

    Shakhshir Ghassan

    2014-01-01

    The positioning strategy has suffered serious changes in the last few decades, being influenced by the rapid development of competition and the growing focus on specific traits belonging to the market, to the consumer or to the product. The purpose of this paper is to present the developments of theoretical positioning strategies and the orientation from more simple, product oriented strategies, to ones more oriented towards the client and with a briefer period of time. The world is moving in...

  4. Position measuring device

    International Nuclear Information System (INIS)

    Maeda, Kazuyuki; Takahashi, Shuichi; Maruyama, Mayumi

    1998-01-01

    The present invention provides a device capable of measuring accurate position and distance easily even at places where operator can not easily access, such as cell facilities for vitrifying radioactive wastes. Referring to a case of the vitrifying cell, an objective equipment settled in the cell is photographed by a photographing device. The image is stored in a position measuring device by way of an image input device. After several years, when the objective equipment is exchanged, a new objective equipment is photographed by a photographing device. The image is also stored in the position measuring device. The position measuring device compares the data of both of the images on the basis of pixel unit. Based on the image of the equipment before the exchange as a reference, extent of the displacement of the installation position of the equipment on the image after the exchange caused by installation error and manufacturing error is determined to decide the position of the equipment after exchange relative to the equipment before exchange. (I.S.)

  5. Efecto de la posición inicial sobre la respuesta de reacción en las acciones de ataque en esgrima. [Effect of the initial position on the reaction response in the actions of attack in fencing].

    Directory of Open Access Journals (Sweden)

    Marcos Gutiérrez-Dávila

    2013-10-01

    Full Text Available El propósito de este estudio ha sido comprobar el efecto que produce el desplazamiento del peso del cuerpo hacia el apoyo más retrasado, en la posición de “en guardia”, con respecto a una distribución equidistante de los dos apoyos y la posición habitual, sobre la velocidad de desplazamiento horizontal del centro de masas, CM, durante las acciones posteriores de ataque con fondo. Han participado 19 esgrimistas (14 hombres y 5 mujeres, con una experiencia en competición regional de más de cinco años. Para el registro de los datos, se han utilizado dos plataformas de fuerza, operando a 500 Hz, una cámara de vídeo, a 210 Hz y un cronómetro electrónico adaptado al sistema de cableado de las armas. Una señal electrónica se utilizó para sincronizar temporalmente todos los registros. Para la situación experimental donde el CM se desplazaba hacia el apoyo posterior (retrasada, el esgrimista partía de la posición de “en guardia” manteniendo una fuerza vertical sobre la el pie más retrasado, entre el 65% y 75% del peso corporal, siendo entre el 45% y 55% para la situación experimental de distribución equidistante de los dos apoyos (equidistante. En una tercera situación, se pidió al esgrimista que partiera de su posición habitual de “en guardia”. Los resultados han puesto de manifiesto que, cuando se parte de una posición retrasada del CM para realizar una acción de ataque con fondo, el tiempo de movimiento se incrementa y la velocidad del CM es menor durante los primeros instantes del movimiento.AbstractThe main aim of this study was to determine the effect that produced the displacement of the weight of the body towards the back foot, in the position of "en garde", with regard to an equidistant distribution of both supports and the habitual position, on the speed of horizontal displacement of the center of mass, CM, during a lunge attack in fencing. 19 fencers (14 men and 5 women, with an experience in regional

  6. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?

    Science.gov (United States)

    D'Haens, Geert R; Panaccione, Remo; Higgins, Peter D R; Vermeire, Severine; Gassull, Miquel; Chowers, Yehuda; Hanauer, Stephen B; Herfarth, Hans; Hommes, Daan W; Kamm, Michael; Löfberg, Robert; Quary, A; Sands, Bruce; Sood, A; Watermeyer, G; Watermayer, G; Lashner, Bret; Lémann, Marc; Plevy, Scott; Reinisch, Walter; Schreiber, Stefan; Siegel, Corey; Targan, Stephen; Watanabe, M; Feagan, Brian; Sandborn, William J; Colombel, Jean Frédéric; Travis, Simon

    2011-02-01

    The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

  7. Uncharged positive electrode composition

    Science.gov (United States)

    Kaun, Thomas D.; Vissers, Donald R.; Shimotake, Hiroshi

    1977-03-08

    An uncharged positive-electrode composition contains particulate lithium sulfide, another alkali metal or alkaline earth metal compound other than sulfide, e.g., lithium carbide, and a transition metal powder. The composition along with a binder, such as electrolytic salt or a thermosetting resin is applied onto an electrically conductive substrate to form a plaque. The plaque is assembled as a positive electrode within an electrochemical cell opposite to a negative electrode containing a material such as aluminum or silicon for alloying with lithium. During charging, lithium alloy is formed within the negative electrode and transition metal sulfide such as iron sulfide is produced within the positive electrode. Excess negative electrode capacity over that from the transition metal sulfide is provided due to the electrochemical reaction of the other than sulfide alkali metal or alkaline earth metal compound.

  8. Position indication apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Masuda, T

    1964-02-24

    A plurality of magnetically operated switches are spaced equally in the hollow tube of a control rod actuating mechanism. One side of each switch is connected, via a low resistance, to a corresponding tap of a low resistance voltage divider network consisting of an equivalent number of low resistance sections with the opposite side of each switch connected to a common conducting wire A. To both ends of the voltage dividing network are connected, respectively, conducting wires B and C. Wires A, B, and C are further coupled to a fuel rod position indicator comprising a voltmeter and power source external to the control rod actuating member. The control rod actuating member is adapted to slide in the hollow tube so that switches passing a position facing a magnet secured to the lower end of the actuating member are rendered closed. Hence, the position of the control rod may be read by reading the voltage off the meter.

  9. Positioning devices for patients

    International Nuclear Information System (INIS)

    Heavens, M.

    1981-01-01

    It has been suggested that it is very important to position patients reproducibly at different stages of radiotherapy treatment planning and treatment, or similar procedures. Devices have been described for positioning a patient's upper and lower thorax. This invention provides reproducible positioning for a female patient's breasts, for example in planning treatment of and treating breast tumours. The patient is placed prone, using for example an upper thorax device. A support device is placed central to and beneath her breasts to partially displace them outwards. The device may be triangular in section with one apex contacting the chest wall at the sternum. Restraining straps may be provided to hold the breasts against the support device. Means may be provided to take a healthy breast from the path of radiation through the tumour. (author)

  10. Positioning and applications

    Directory of Open Access Journals (Sweden)

    Rogowski Jerzy B.

    2015-12-01

    Full Text Available The paper presents national report of Poland for IAG on positioning and applications. The selected research presented was carried out at leading Polish research institutions and concern precise multi-GNSS satellite positioning - relative and absolute - and also GNSS-based ionosphere and troposphere modelling and studies. The research resulted in noticeable advancements in these subjects confirmed by the development of new algorithms and methods. New and improved methods of precise GNSS positioning were developed, and also GNSS metrology was studied. New advanced troposphere models were presented and tested. In particular, these models allowed testing IPW variability on regional and global scales. Also, new regional ionosphere monitoring web-based services were developed and launched.

  11. Massive Galileon positivity bounds

    Science.gov (United States)

    de Rham, Claudia; Melville, Scott; Tolley, Andrew J.; Zhou, Shuang-Yong

    2017-09-01

    The EFT coefficients in any gapped, scalar, Lorentz invariant field theory must satisfy positivity requirements if there is to exist a local, analytic Wilsonian UV completion. We apply these bounds to the tree level scattering amplitudes for a massive Galileon. The addition of a mass term, which does not spoil the non-renormalization theorem of the Galileon and preserves the Galileon symmetry at loop level, is necessary to satisfy the lowest order positivity bound. We further show that a careful choice of successively higher derivative corrections are necessary to satisfy the higher order positivity bounds. There is then no obstruction to a local UV completion from considerations of tree level 2-to-2 scattering alone. To demonstrate this we give an explicit example of such a UV completion.

  12. Bradykinin induced a positive chronotropic effect via stimulation of T- and L-type calcium currents in heart cells.

    Science.gov (United States)

    El-Bizri, Nesrine; Bkaily, Ghassan; Wang, Shimin; Jacques, Danielle; Regoli, Domenico; D'Orléans-Juste, Pedro; Sukarieh, Rami

    2003-03-01

    Using Fluo-3 calcium dye confocal microscopy and spontaneously contracting embryonic chick heart cells, bradykinin (10(-10) M) was found to induce positive chronotropic effects by increasing the frequency of the transient increase of cytosolic and nuclear free Ca2+. Pretreatment of the cells with either B1 or B2 receptor antagonists (R126 and R817, respectively) completely prevented bradykinin (BK) induced positive chronotropic effects on spontaneously contracting single heart cells. Using the whole-cell voltage clamp technique and ionic substitution to separate the different ionic current species, our results showed that BK (10(-6) M) had no effect on fast Na+ inward current and delayed outward potassium current. However, both L- and T-type Ca2+ currents were found to be increased by BK in a dose-dependent manner (10(-10)-10(-7) M). The effects of BK on T- and L-type Ca2+ currents were partially blocked by the B1 receptor antagonist [Leu8]des-Arg9-BK (R592) (10(-7) M) and completely reversed by the B2 receptor antagonist D-Arg[Hyp3,D-Phe7,Leu8]BK (R-588) (10(-7) M) or pretreatment with pertussis toxin (PTX). These results demonstrate that BK induced a positive chronotropic effect via stimulation of T- and L-type Ca2+ currents in heart cells mainly via stimulation of B2 receptor coupled to PTX-sensitive G-proteins. The increase of both types of Ca2+ current by BK in heart cells may explain the positive inotropic and chronotropic effects of this hormone.

  13. E2A-positive gastric MALT lymphoma has weaker plasmacytoid infiltrates and stronger expression of the memory B-cell-associated miR-223: possible correlation with stage and treatment response.

    Science.gov (United States)

    Liu, Ting-Yun; Chen, Shee-Uan; Kuo, Sung-Hsin; Cheng, Ann-Lii; Lin, Chung-Wu

    2010-11-01

    Extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach (gastric MALT lymphoma) is derived from memory B cells of the marginal zone. Normal memory B cells do not express markers of germinal-center B cells, such as E2A (immunoglobulin enhancer-binding factor E12/E47), B-cell chronic lymphocytic leukemia/lymphoma 6 (BCL6), or activation-induced cytidine deaminase (AID). E2A is a transcription factor that induces somatic hypermutations and blocks plasma cell differentiation. In 50 stage-I(E)/II(E1) gastric MALT lymphomas, we confirmed that all cases were BCL6(-)/AID(-), but a subset (50%, 25/50) was E2A(+). As E2A(-) and E2A(+) gastric MALT lymphomas had similar numbers of somatic hypermutations without intraclonal variations, which implied an origin from memory B cells, the expression of E2A was best regarded as a marker of aberrant follicular differentiation. Although the status of somatic hypermutation was not affected by E2A, E2A(+) gastric MALT lymphoma showed less plasmacytoid infiltrates and higher expressions of miRNA-223, a microRNA associated with memory B cells. Clinically, E2A(+) gastric MALT lymphomas were more likely to spread to perigastric lymph nodes and were less responsive to Helicobacter eradication therapy than were E2A(-) gastric MALT lymphomas. Taken together, aberrant E2A expression is a diagnostic feature of a subtype of gastric MALT lymphoma with weaker plasmacytoid infiltrates and stronger miR-223 expression. A prospective study would be necessary to verify the association between E2A expression and a poor response to Helicobacter eradication therapy.

  14. Attitude and position tracking

    CSIR Research Space (South Africa)

    Candy, LP

    2011-01-01

    Full Text Available Several applications require the tracking of attitude and position of a body based on velocity data. It is tempting to use direction cosine matrices (DCM), for example, to track attitude based on angular velocity data, and to integrate the linear...

  15. Logotherapy and positive psychology

    Directory of Open Access Journals (Sweden)

    Oscar R. Oro

    2015-09-01

    Full Text Available Psychology omitted to approach, during almost a century, the positive aspects from persons, like creativity, humor, optimism, hope, forgiveness, life meaning, and happiness. These themes are approached by Positive Psychology, with Seligman like the principal exponent. Psychology was dedicated to explore the negative aspects from human b