Science.gov

Sample records for clopidogrel response evaluated

  1. Clopidogrel Responsiveness in Patients Undergoing Peripheral Angioplasty

    SciTech Connect

    Pastromas, Georgios Spiliopoulos, Stavros Katsanos, Konstantinos Diamantopoulos, Athanasios Kitrou, Panagiotis Karnabatidis, Dimitrios Siablis, Dimitrios

    2013-12-15

    Purpose: To investigate the incidence and clinical significance of platelet responsiveness in patients receiving clopidogrel after peripheral angioplasty procedures. Materials and Methods: This prospective study included patients receiving antiplatelet therapy with clopidogrel 75 mg after infrainguinal angioplasty or stenting and who presented to our department during routine follow-up. Clopidogrel responsiveness was tested using the VerifyNow P2Y12 Assay. Patients with residual platelet reactivity units (PRU) {>=} 235 were considered as nonresponders (NR group NR), whereas patients with PRU < 235 were considered as normal (responders [group R]). Primary end points were incidence of resistance to clopidogrel and target limb reintervention (TLR)-free survival, whereas secondary end points included limb salvage rates and the identification of any independent predictors influencing clinical outcomes. Results: In total, 113 consecutive patients (mean age 69 {+-} 8 years) with 139 limbs were enrolled. After clopidogrel responsiveness analysis, 61 patients (53.9 %) with 73 limbs (52.5 %) were assigned to group R and 52 patients (46.1 %) with 66 limbs (47.5 %) to group NR. Mean follow-up interval was 27.7 {+-} 22.9 months (range 3-95). Diabetes mellitus, critical limb ischemia, and renal disease were associated with clopidogrel resistance (Fisher's exact test; p < 0.05). According to Kaplan-Meier analysis, TLR-free survival was significantly superior in group R compared with group NR (20.7 vs. 1.9 %, respectively, at 7-year follow-up; p = 0.001), whereas resistance to clopidogrel was identified as the only independent predictor of decreased TLR-free survival (hazard rate 0.536, 95 % confidence interval 0.31-0.90; p = 0.01). Cumulative TLR rate was significantly increased in group NR compared with group R (71.2 % [52 of 73] vs. 31.8 % [21 of 66], respectively; p < 0.001). Limb salvage was similar in both groups. Conclusion: Clopidogrel resistance was related with

  2. Evaluation of CYP2C19, P2Y12, and ABCB1 polymorphisms and phenotypic response to clopidogrel in healthy Indian adults

    PubMed Central

    Sridharan, Kannan; Kataria, Rachna; Tolani, Drishti; Bendkhale, Shital; Gogtay, Nithya J.; Thatte, Urmila M.

    2016-01-01

    Introduction: CYP2C19 and P2Y12 polymorphisms have been claimed to alter the pharmacodynamic response to clopidogrel. ABCB1 polymorphism has been associated with the efflux of clopidogrel resulting in decreased bioavailability. Due to paucity of data from Indian population, the present study was undertaken to evaluate the association of genetic polymorphisms of CYP2C19, P2Y12, and ABCB1 with inhibition of platelet aggregation (IPA) by clopidogrel. Methods: Healthy adults (n = 90) of either gender were administered single dose of 300 mg clopidogrel. Baseline, 4 h postdose, and day 7 assessment of platelet aggregation and genotype of CYP2C19, P2Y12, and ABCB1 were carried out using standardized laboratory methods. The difference in the maximum platelet aggregation (MPA) between baseline and 4 h postdose was considered as delta-MPA (DMPA), and percentage change of MPA at 4 h from baseline was considered as IPA. Those with an IPA of <30% were considered as poor responders. Inferential statistics was applied to find out significant difference of these parameters between various groups of genetic polymorphisms. Results: Mean (standard deviation [SD]) of MPA (%) at baseline, 4 h postdose, and day 7 were 78 (5), 56 (16), and 71 (8), respectively. Similarly, mean (SD) of DMPA (%) and IPA (%) were 23 (17) and 29 (21), respectively. A total of 54/90 (60%) cases were found to be poor responders to clopidogrel. A wild genotype (*1/*1) of CYP2C19 was observed in 35 (40.2%), 42 (48.3%) had *1/*2, 2 (2.3%) individuals had *1/*3, and 8 (9.2%) had *2/*2 mutant genotypes. Although statistically not significant (P = 0.09), a trend was observed in having decreased inhibition values (both MPA and IPA) as we proceed from wild genotype (*1/*1) to mutant genotypes in the order of *1/*2, *1/*3, and *2/*2. Similarly, in P2Y12, a wild haplotype (H1/H1) was present in 77 (89.5%) and 9 (10.5%) individuals had H1/H2 type. A statistically significant difference in DMPA and IPA was observed with

  3. Impact of genetic polymorphisms and drug-drug interactions on clopidogrel and prasugrel response variability.

    PubMed

    Ancrenaz, V; Daali, Y; Fontana, P; Besson, M; Samer, C; Dayer, P; Desmeules, J

    2010-10-01

    Thienopyridine antiaggregating platelet agents (clopidogrel and prasugrel) act as irreversible P2Y12 receptor inhibitors. They are used with aspirin to prevent thrombotic complications after an acute coronary syndrome or percutaneous coronary intervention. A large interindividual variability in response to clopidogrel and to a lesser extent to prasugrel is observed and may be related to their metabolism. Clopidogrel and prasugrel are indeed prodrugs converted into their respective active metabolites by several cytochromes P450 (CYPs). Besides clopidogrel inactivation (85%) by esterases to the carboxylic acid, clopidogrel is metabolized by CYPs to 2-oxo-clopidogrel (15%) and further metabolized to an unstable but potent platelet-aggregating inhibitor. Prasugrel is more potent than clopidogrel with a better bioavailability and lower pharmacodynamic variability. Prasugrel is completely converted by esterases to an intermediate oxo-metabolite (R-95913) further bioactivated by CYPs. Numerous clinical studies have shown the influence of CYP2C19 polymorphism on clopidogrel antiplatelet activity. Moreover, unwanted drug-drug pharmacokinetic interactions influencing CYP2C19 activity and clopidogrel bioactivation such as with proton pump inhibitors remain a matter of intense controversy. Several studies have also demonstrated that CYP3A4/5 and CYP1A2 are important in clopidogrel bioactivation and should also be considered as potential targets for unwanted drug-drug interactions. Prasugrel bioactivation is mainly related to CYP3A4 and 2B6 activity and therefore the question of the effect of drug-drug interaction on its activity is open. The purpose of this review is to critically examine the current literature evaluating the influence of genetic and environmental factors such as unwanted drug-drug interaction affecting clopidogrel and prasugrel antiplatelet activity. PMID:20942779

  4. Determinants to optimize response to clopidogrel in acute coronary syndrome

    PubMed Central

    Giusti, Betti; Gori, Anna Maria; Marcucci, Rossella; Saracini, Claudia; Vestrini, Anna; Abbate, Rosanna

    2010-01-01

    The inhibition of platelet function by antiplatelet therapy determines the improvement of the survival of patients with clinically evident cardiovascular disease. Clopidogrel in combination with aspirin is the recommended standard of care for reducing the occurrence of cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary intervention. However, major adverse cardiovascular events including stent thrombosis occur in patients taking clopidogrel and aspirin. A growing body of evidence demonstrates that high post-treatment platelet reactivity on antiplatelet treatment is associated with increased risk of adverse clinical events. Clopidogrel requires conversion to active metabolite by cytochrome P450 isoenzymes. The active metabolite inhibits ADP-stimulated platelet activation by irreversibly binding to P2Y12 receptors. Recently, the loss-of-function CYP2C19*2 allele has been associated with decreased metabolization of clopidogrel, poor antiaggregant effect, and increased cardiovascular events. In high risk vascular patients, the CYP2C19*2 polymorphism is a strong predictor of adverse cardiovascular events and particularly of stent thrombosis. Prospective studies evaluating if an antiplatelet treatment tailored on individual characteristics of patients, CYP2C19*2 genotypes, platelet phenotype, drug–drug interaction, as well as traditional and procedural risk factors, are now urgently needed for the identification of therapeutic strategies providing the best benefit for the single subject. PMID:23226041

  5. The use of amlodipine, but not of P-glycoprotein inhibiting calcium channel blockers is associated with clopidogrel poor-response.

    PubMed

    Harmsze, Ankie M; Robijns, Karen; van Werkum, Jochem W; Breet, Nicoline J; Hackeng, Christian M; Ten Berg, Jurrien M; Ruven, Hendrik J T; Klungel, Olaf H; de Boer, Anthonius; Deneer, Vera H M

    2010-05-01

    Clopidogrel is a prodrug that has to be converted in vivo to its active metabolite by cytochrome (CYP)P450 iso-enzymes. As calcium channel blockers (CCBs) are inhibitors of CYP3A4, concomitant use of these drugs might play a role in the wide inter-individual variability in the response to clopidogrel. However, some CCBs also have strong inhibitory effects on the drug transporter P-glycoprotein (Pgp), which mediates clopidogrel's intestinal absorption. It was the aim of this study to evaluate the effect of co-administration of Pgp-inhibiting and non-Pgp-inhibiting CCBs on on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective percutaneous coronary intervention (PCI). In a total of 623 consecutive patients undergoing elective PCI treated with clopidogrel and aspirin, platelet reactivity to 5 and 20 muM adenosine diphospate (ADP) and clopidogrel poor-response (defined as > 70% platelet aggregation to 20 muM ADP) were evaluated by light transmittance aggregometry. A total of 222 patients (35.6%) were on CCB treatment, of which 98 used Pgp-inhibiting CCBs (verapamil, nifedipine, diltiazem, barnidipine) and 124 patients used the non-Pgp-inhibiting CCB amlodipine. Adjusted mean ADP-induced on-clopidogrel platelet reactivity was significantly higher in both users of Pgp-inhibiting CCBs and amlodipine as compared to CCB non-users (all p<0.05). However, only the use of amlodipine was significantly associated with a 2.3-fold increased risk of clopidogrel poor-response. This study demonstrates that concomitant use of Pgp-inhibiting CCBs and amlodipine increases on-clopidogrel platelet reactivity. Only amlodipine was associated with clopidogrel poor-response. The drug-drug interaction between clopidogrel and amlodipine might be more clinically relevant as compared to P-glycoprotein-inhibiting CCBs. PMID:20352154

  6. Evaluation of Clopidogrel Conjugation Metabolism: PK Studies in Man and Mice of Clopidogrel Acyl Glucuronide.

    PubMed

    Savu, Simona Nicoleta; Silvestro, Luigi; Surmeian, Mariana; Remis, Lina; Rasit, Yuksel; Savu, Simona Rizea; Mircioiu, Constantin

    2016-09-01

    The existence of a glucuronide conjugate of the major circulating clopidogrel metabolites, called clopidogrel acyl glucuronide (CAG), is already known. However, information regarding its pharmacokinetics (PK), metabolism, and clearance are modest. We investigated in vivo the potential CAG trans-esterification to clopidogrel (reaction occurring in vitro in particular conditions) by administering the metabolite to mice. Experiments were then carried out on men, clopidogrel administered alone or followed by activated charcoal intake (intestinal reabsorption blockade). Study objectives included: PK comparison of CAG, clopidogrel carboxylic acid (CCA), and clopidogrel in plasma, determination of their elimination patterns in urine and feces, and tracking of charcoal-induced changes in PK and/or urinary excretion that would indicate relevant enterohepatic recycling of CAG. In mice, CAG was rapidly hydrolyzed to CCA after oral administration, whereas by intravenous route metabolic conversion to CCA was delayed. No levels of clopidogrel were detected in mice plasma, excluding any potential trans-esterification or other form of back-conversion in vivo. PK experiments in man showed that CAG is hydrolyzed in the gastrointestinal tract (very low concentrations in feces), but there is no evidence of enterohepatic recirculation. Quantitation of the three moieties in stool samples accounted for only 1.2% of an administered dose, suggesting that other yet unknown metabolites/degradation products formed through metabolic processes and/or the activity of local microflora are mainly excreted by this route. In man CAG was confirmed as one of the major terminal metabolites of clopidogrel, with a PK behavior similar to CCA. PMID:27402727

  7. Effect of genetic and coexisting polymorphisms on platelet response to clopidogrel in Chinese Han patients with acute coronary syndrome.

    PubMed

    Liu, Xu; Luo, Yu; Lai, Yan; Yao, Yian; Li, Jimin; Wang, Yunkai; Zheng, S Lilly; Xu, Jianfeng; Liu, Xuebo

    2016-06-01

    Polymorphisms of CYP2C19 are associated with platelet response to clopidogrel. This study was conducted to evaluate the contribution of the previously identified polymorphisms to the response of clopidogrel in a cohort of Chinese Han patients. A total of 222 acute coronary syndrome patients undergoing percutaneous coronary intervention treated with clopidogrel were enrolled from September 2012 to June 2013. Residual platelet aggregations for all patients were measured by the Verify Now P2Y12 system. Sixteen single-nucleotide polymorphisms among nine genes were genotyped including CYP2C19, ABCB1 and PON1. In this study, CYP2C19*2 and CYP2C19*17 were strongly associated with higher platelet aggregation and lower platelet aggregation to clopidogrel treatment, respectively (P <0.001). Patients with CYP2C19*2 allele had a higher risk of high on-treatment platelet reactivity than non carriers (adjusted OR, 5.434; 95% CI, 1.918-15.399, P =0.01). The coexistence of CYP2B6*9 (rs8192719) and P2Y12 (rs2046934) and the coexistence of CYP2B6*1B (rs7254579) and P2Y12 (rs2046934) were also associated with poor response to clopidogrel. No significant relation of CYP2C19*3 and other polymorphisms to the platelet aggregation was found. In conclusion, CYP2C19*2, CYP2C19*17 coexistence of CYP2B6*9 (rs8192719) and P2Y12 (rs2046934) and coexistence of CYP2B6*1B (rs7254579) and P2Y12 (rs2046934) were identified to be associated with response to clopidogrel treatment in Chinese Han patients. PMID:27350664

  8. Genetic and Nongenetic Factors Affecting Clopidogrel Response in the Egyptian Population.

    PubMed

    Khalil, B M; Shahin, M H; Solayman, M H M; Langaee, T; Schaalan, M F; Gong, Y; Hammad, L N; Al-Mesallamy, H O; Hamdy, N M; El-Hammady, W A; Johnson, J A

    2016-02-01

    Aspirin and clopidogrel are the mainstay oral antiplatelet regimens, yet a substantial number of major adverse cardiac events (MACE) still occur. Herein, we investigated genetic and nongenetic factors associated with clopidogrel response in Egyptians. In all, 190 Egyptians with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), treated with clopidogrel (75 mg/day) for at least a month, were genotyped for CYP2C19 *2, *3, *6, *8, *10, and *17, CES1 G143E and ABCB1*6 and *8. These variants along with nongenetic factors were tested for association with the risk of having MACE in clopidogrel-treated patients. CYP2C19 loss-of-function (LOF) alleles carriers had increased risk of MACE vs. noncarriers (odds ratio 2.52; 95% confidence interval 1.23-5.15, P = 0.011). In a logistic regression, CYP2C19 LOF variants (P = 0.011), age (P = 0.032), and body mass index (BMI, P = 0.039) were significantly associated with the incidence of MACE in patients taking clopidogrel. CYP2C19 genetic variants, age, and BMI are potential predictors associated with variability to clopidogrel response in Egyptians.

  9. Genetic and Nongenetic Factors Affecting Clopidogrel Response in the Egyptian Population

    PubMed Central

    Khalil, BM; Shahin, MH; Solayman, MHM; Langaee, T; Schaalan, MF; Gong, Y; Hammad, LN; Al‐Mesallamy, HO; Hamdy, NM; El‐Hammady, WA

    2016-01-01

    Aspirin and clopidogrel are the mainstay oral antiplatelet regimens, yet a substantial number of major adverse cardiac events (MACE) still occur. Herein, we investigated genetic and nongenetic factors associated with clopidogrel response in Egyptians. In all, 190 Egyptians with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), treated with clopidogrel (75 mg/day) for at least a month, were genotyped for CYP2C19 *2, *3, *6, *8, *10, and *17, CES1 G143E and ABCB1*6 and *8. These variants along with nongenetic factors were tested for association with the risk of having MACE in clopidogrel‐treated patients. CYP2C19 loss‐of‐function (LOF) alleles carriers had increased risk of MACE vs. noncarriers (odds ratio 2.52; 95% confidence interval 1.23–5.15, P = 0.011). In a logistic regression, CYP2C19 LOF variants (P = 0.011), age (P = 0.032), and body mass index (BMI, P = 0.039) were significantly associated with the incidence of MACE in patients taking clopidogrel. CYP2C19 genetic variants, age, and BMI are potential predictors associated with variability to clopidogrel response in Egyptians. PMID:26757134

  10. Snapshot of the prescribing practice for the clopidogrel and esomeprazole coprescription and cost evaluation of the application guidelines.

    PubMed

    Vernaz, Nathalie; Rollason, Victoria; Adlere, Liene; Combescure, Christophe; Poncet, Antoine; Bonnabry, Pascal; Desmeules, Jules

    2016-06-01

    The antiplatelet clopidogrel and the proton pump inhibitor esomeprazole demonstrate a pharmacokinetic interaction through CYP2C19 that could translate into clinical inefficacy of clopidogrel. No medical consensus as to their coprescription has been reached, and different guidelines are available. We evaluated the prescribing practices at the Geneva University Hospitals (HUG) by measuring whether the coprescription was staggered as suggested by experts. We estimated the financial impact of different implementation guidelines. We used the HUG electronic patient records to follow the physicians' prescriptions and the administration by nurses from January 2013 to April 2014. We performed a time series analysis to assess 15 years of proton pump inhibitors (PPIs) and antiplatelet drug use. "Extra costs" were calculated assuming that clopidogrel or esomeprazole would replace prasugrel or ticagrelor and pantoprazole or ranitidine, respectively. Only 10.8% of the patient medical orders for the clopidogrel and esomeprazole coprescription specified to stagger the administration, 12.6% specified a concomitant coprescription, and 76.6% had no clear information. A high rate of 49.6% of the nurses staggered the clopidogrel and esomeprazole coprescription when no clear information was given. We found a statistically significant decrease in clopidogrel use after the publication of the OCLA (Omeprazole-CLopidogrel-Aspirin) study and a significant increase in the trend of esomeprazole. Alternative treatments to avoid this interaction are cost ineffective or offer therapeutic options of lesser quality. We observed a high rate of 56.2% of the clopidogrel and esomeprazole coprescription in our hospital and can therefore not ignore the PK/PD interaction. The most common prescription practice was to not specify the time frame of administration, which was translated by nurses in 49.6% of the cases to a scheduled staggered coprescription of clopidogrel and esomeprazole. As long as no

  11. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin.

    PubMed

    Bozzi, Laura M; Mitchell, Braxton D; Lewis, Joshua P; Ryan, Kathy A; Herzog, William R; O'Connell, Jeffrey R; Horenstein, Richard B; Shuldiner, Alan R; Yerges-Armstrong, Laura M

    2016-01-01

    Clopidogrel and aspirin are commonly prescribed anti-platelet medications indicated for patients who have experienced, or are at risk for, ischemic cardiovascular events. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study was designed to characterize determinants of clopidogrel and dual anti-platelet therapy (DAPT) response in a healthy cohort of Old Order Amish from Lancaster, PA. Following a loading dose, clopidogrel was taken once a day for 7 days. One hour after the last dose of clopidogrel, 325 mg of aspirin was given. Ex vivo platelet aggregometry was performed at baseline, post-clopidogrel, and post-DAPT. Platelet aggregation measurements were significantly lower after both interventions for all agonists tested (p <0.05), although there was large inter-individual variation in the magnitude of anti-platelet response. Female sex and older age were associated with higher platelet aggregation at all three time-points. Change in aggregation was correlated among the various agonists at each time point. Heritability (h2) of change in platelet aggregation was significant for most traits at all time-points (range h2=0.14-0.57). Utilization of a standardized, short-term intervention provided a powerful approach to investigate sources of variation in platelet aggregation response due to drug therapy. Further, this short-term intervention approach may provide a useful paradigm for pharmacogenomics studies.

  12. [Polymorphs of clopidogrel bisulfate].

    PubMed

    Liu, Yi; Huang, Hai-Wei; Wu, Jian-Min; Shi, Ya-Qin; Yang, La-Hu

    2013-08-01

    This paper is to report the polymorphism of raw materials of clopidogrel bisulfate at home and abroad. By the analysis of Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (p-XRD), samples are roughly classified into two groups, except one patent material. And the differential scanning calorimeter (DSC) examination showed more detailed information for these materials. The results of the study could provide comprehensive basis for the quality evaluation of clopidogrel bisulfate. PMID:24187849

  13. Does "smoker's paradox" exist in clopidogrel-treated Turkish patients with acute coronary syndrome.

    PubMed

    Edem, Efe; Kirdök, Ali Hikmet; Kınay, Ahmet Ozan; Tekin, Ümit İlker; Taş, Sedat; Alpaslan, Erkan; Pabuccu, Mustafa Türker; Akdeniz, Bahri

    2016-01-01

    Previously conducted studies revealed that smoking enhanced the efficacy of clopidogrel by increasing formation of the active metabolite (AM) from the prodrug through induction of the cytochrome CYP1A2. The expression of cytochrome enzymes depends on genotype and no data exists in literature conducted in Turkish patients comparing the clopidogrel responsiveness between active smokers and non-active smokers treated with clopidogrel. In this study, our aim was to investigate the clopidogrel responsiveness in clopidogrel-treated Turkish acute coronary syndrome (ACS) patients according to their smoking status. We retrospectively enrolled 258 patients who were hospitalized due to ACS. Clinical variables of the patients, especially smoking status were recorded. Clopidogrel resistance was evaluated by using adenosine diphosphate (ADP) induced platelet aggregometry. Clopidogrel resistance was detected as a change in maximal aggregation ≤20% from baseline. A total of 139 patients were active smokers while 12 were former smokers. 107 patients did not have a history of smoking. Ten of the smokers were hyporesponsive to clopidogrel, whereas 36 of non-smokers were hyporesponsive to clopidogrel (p < 0.001). Receiver-operating characteristic curve analysis demonstrated that Au-min value >612.5 predicted the clopidogrel resistance with a sensitivity of 60% (OR: 100.65, %95 CI = 19.996-506.615 p < 0.001). Results of this study demonstrated that ADP responses were lower in smokers receiving clopidogrel and aspirin than in non-smokers receiving the same drug regimen. This finding indicates that smoking was related to an enhanced clopidogrel responsiveness in Turkish patients hospitalized due to ACS, suggesting that "smoker's paradox" probably exists in Turkish ACS patients. PMID:26367336

  14. Development of a physiology-directed population pharmacokinetic and pharmacodynamic model for characterizing the impact of genetic and demographic factors on clopidogrel response in healthy adults.

    PubMed

    Jiang, Xi-Ling; Samant, Snehal; Lewis, Joshua P; Horenstein, Richard B; Shuldiner, Alan R; Yerges-Armstrong, Laura M; Peletier, Lambertus A; Lesko, Lawrence J; Schmidt, Stephan

    2016-01-20

    Clopidogrel (Plavix®), is a widely used antiplatelet agent, which shows high inter-individual variability in treatment response in patients following the standard dosing regimen. In this study, a physiology-directed population pharmacokinetic/pharmacodynamic (PK/PD) model was developed based on clopidogrel and clopidogrel active metabolite (clop-AM) data from the PAPI and the PGXB2B studies using a step-wise approach in NONMEM (version 7.2). The developed model characterized the in vivo disposition of clopidogrel, its bioactivation into clop-AM in the liver and subsequent platelet aggregation inhibition in the systemic circulation reasonably well. It further allowed the identification of covariates that significantly impact clopidogrel's dose-concentration-response relationship. In particular, CYP2C19 intermediate and poor metabolizers converted 26.2% and 39.5% less clopidogrel to clop-AM, respectively, compared to extensive metabolizers. In addition, CES1 G143E mutation carriers have a reduced CES1 activity (82.9%) compared to wild-type subjects, which results in a significant increase in clop-AM formation. An increase in BMI was found to significantly decrease clopidogrel's bioactivation, whereas increased age was associated with increased platelet reactivity. Our PK/PD model analysis suggests that, in order to optimize clopidogrel dosing on a patient-by-patient basis, all of these factors have to be considered simultaneously, e.g. by using quantitative clinical pharmacology tools.

  15. Development of a physiology-directed population pharmacokinetic and pharmacodynamic model for characterizing the impact of genetic and demographic factors on clopidogrel response in healthy adults.

    PubMed

    Jiang, Xi-Ling; Samant, Snehal; Lewis, Joshua P; Horenstein, Richard B; Shuldiner, Alan R; Yerges-Armstrong, Laura M; Peletier, Lambertus A; Lesko, Lawrence J; Schmidt, Stephan

    2016-01-20

    Clopidogrel (Plavix®), is a widely used antiplatelet agent, which shows high inter-individual variability in treatment response in patients following the standard dosing regimen. In this study, a physiology-directed population pharmacokinetic/pharmacodynamic (PK/PD) model was developed based on clopidogrel and clopidogrel active metabolite (clop-AM) data from the PAPI and the PGXB2B studies using a step-wise approach in NONMEM (version 7.2). The developed model characterized the in vivo disposition of clopidogrel, its bioactivation into clop-AM in the liver and subsequent platelet aggregation inhibition in the systemic circulation reasonably well. It further allowed the identification of covariates that significantly impact clopidogrel's dose-concentration-response relationship. In particular, CYP2C19 intermediate and poor metabolizers converted 26.2% and 39.5% less clopidogrel to clop-AM, respectively, compared to extensive metabolizers. In addition, CES1 G143E mutation carriers have a reduced CES1 activity (82.9%) compared to wild-type subjects, which results in a significant increase in clop-AM formation. An increase in BMI was found to significantly decrease clopidogrel's bioactivation, whereas increased age was associated with increased platelet reactivity. Our PK/PD model analysis suggests that, in order to optimize clopidogrel dosing on a patient-by-patient basis, all of these factors have to be considered simultaneously, e.g. by using quantitative clinical pharmacology tools. PMID:26524713

  16. Effects of cytochrome P450 2C19 and paraoxonase 1 polymorphisms on antiplatelet response to clopidogrel therapy in patients with coronary artery disease.

    PubMed

    Tresukosol, Damrus; Suktitipat, Bhoom; Hunnangkul, Saowalak; Kamkaew, Ruttakarn; Poldee, Saiphon; Tassaneetrithep, Boonrat; Likidlilid, Atip

    2014-01-01

    Clopidogrel is an antiplatelet prodrug that is recommended to reduce the risk of recurrent thrombosis in coronary artery disease (CAD) patients. Paraoxonase 1 (PON1) is suggested to be a rate-limiting enzyme in the conversion of 2-oxo-clopidogrel to active thiol metabolite with inconsistent results. Here, we sought to determine the associations of CYP2C19 and PON1 gene polymorphisms with clopidogrel response and their role in ADP-induced platelet aggregation. Clopidogrel response and platelet aggregation were determined using Multiplate aggregometer in 211 patients with established CAD who received 75 mg clopidogrel and 75-325 mg aspirin daily for at least 14 days. Polymorphisms in CYP2C19 and PON1 were genotyped and tested for association with clopidogrel resistance. Linkage disequilibrium (LD) and their epistatic interaction effects on ADP-induced platelet aggregation were analysed. The prevalence of clopidogrel resistance in this population was approximately 33.2% (n = 70). The frequencies of CYP2C19*2 and *3 were significantly higher in non-responder than those in responders. After adjusting for established risk factors, CYP2C19*2 and *3 alleles independently increased the risk of clopidogrel resistance with adjusted ORs 2.94 (95%CI, 1.65-5.26; p<0.001) and 11.26 (95%CI, 2.47-51.41; p = 0.002, respectively). Patients with *2 or *3 allele and combined with smoking, diabetes and increased platelet count had markedly increased risk of clopidogrel resistance. No association was observed between PON1 Q192R and clopidogrel resistance (adjusted OR = 1.13, 95%CI, 0.70-1.82; p = 0.622). Significantly higher platelet aggregation values were found in CYP2C19*2 and *3 patients when compared with *1/*1 allele carriers (p = 1.98 × 10(-6)). For PON1 Q192R genotypes, aggregation values were similar across all genotype groups (p = 0.359). There was no evidence of gene-gene interaction or LD between CYP2C19 and PON1 polymorphisms on ADP-induced platelet aggregation. Our

  17. Positive clinical response to clopidogrel is independent of paraoxonase 1 Q192R and CYP2C19 genetic variants.

    PubMed

    Martínez-Quintana, Efrén; Medina-Gil, José M; Rodríguez-González, Fayna; Garay-Sánchez, Paloma; Limiñana, José M; Saavedra, Pedro; Tugores, Antonio

    2014-08-01

    There is increasing controversy about the influence of serum paraoxonase type 1 and cytochrome CYP2C19 in the conversion of clopidogrel to its pharmaceutically active metabolite. The effect of concomitant medication with the proton pump inhibitor omeprazole has been also subject of intense scrutiny. We present a cohort of 263 patients receiving anti-platelet aggregation treatment with clopidogrel and aspirin for 1 year. The paraoxonase 1 gene Q192R variant along with the presence of CYP2C19*2 and *3 loss of function alleles, concomitant medication with proton pump inhibitors and known cardiovascular risk factors were examined to determine their influence in disease relapse due to an ischaemic event during the 12 month treatment period. The low number of patients suffering a relapse (20 out of 263), indicates that double anti-aggregation therapy with aspirin and clopidogrel was very effective in our patients. Among the relapsers, evidence of coronary heart disease was the most influencial factor affecting response to therapy, while the presence of the paraoxonase 1 Q192R variant, loss of function of CYP2C19, and concomitant medication with omeprazole were non-significant. PMID:24504666

  18. Is TRAP-6 suitable as a positive control for platelet reactivity when assessing response to clopidogrel?

    PubMed

    Gremmel, Thomas; Calatzis, Andreas; Steiner, Sabine; Kaider, Alexandra; Seidinger, Daniela; Koppensteiner, Renate; Kopp, Christoph W; Panzer, Simon

    2010-01-01

    Adenosine 5′-diphosphate (ADP) inducible aggregation is used to assess platelet response to thienopyridines. Thrombin receptor-activating peptide-6 (TRAP-6) inducible aggregation may serve as a positive control because it acts via the thrombin receptor protease-activating receptor-1, which is not blocked by thienopyridines. We therefore investigated if TRAP-6 is suitable as a positive control when assessing residual platelet reactivity to ADP. Platelet response to clopidogrel was assessed in 200 patients on dual antiplatelet therapy using ADP inducible platelet aggregation by light transmission aggregometry (LTA), multiple electrode aggregometry (MEA), and the shear-dependent Impact-R. Test specificities were monitored by TRAP-6 inducible platelet aggregation. The aggregation-independent vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay served for comparisons. ADP inducible aggregation was correlated to that by TRAP-6 (r = 0.33 to 0.72; p < 0.001 for all assays). A linear correlation was seen within MEA (r = 0.72). LTA TRAP-6 correlated weakly with the VASP assay (r = 0.19; p = 0.01), while there were no correlations of TRAP-6 responses by MEA or the Impact-R with the VASP assay (r = 0.03 and −0.09; p > 0.05). In all three assays, differences between ADP and TRAP-6 inducible aggregation varied considerably. Within MEA, TRAP-6 inducible aggregation was almost always stronger than ADP inducible aggregation, while within LTA and the Impact-R, weak responses to ADP were associated with both, weak and strong responses to TRAP-6. In conclusion, the application of TRAP-6 as a positive control for platelet reactivity has major limitations and results need to be cautiously interpreted on an individual basis. PMID:20624009

  19. Clopidogrel: A multifaceted affair.

    PubMed

    Martínez-Quintana, Efrén; Tugores, Antonio

    2015-01-01

    Clopidogrel has been the therapy of choice, combined with aspirin, against platelet aggregation in patients at risk of suffering a vascular thrombotic event. Not all patients respond equally to clopidogrel, an observation that has led to searching for a test that, in the clinical setting, could predict patients' "resistance" to therapy. The evidence reveals a complex pharmacokinetic profile for clopidogrel, with multiple players involved, including cytochromes, characteristics of the target tissue, and accompanying clinical conditions. Despite FDA black box warnings recommending CYP2C19 genotyping before clopidogrel use, no robust evidence indicates that CYP2C19 function determines clinical response to the drug, either based on the presence of loss of function alleles or drug interactions with CYP2C19 inhibitors, like omeprazole. A tailored anti-aggregation treatment based on ex vivo platelet reactivity also seems unlikely due to the lack of robustness of most assays. The identification of clinical conditions that are at higher risk of new cardiovascular events, such as diabetes, obesity, coronary artery disease, or specific stenting procedures, seems to be a prudent approach to tailor anti-platelet therapy with more powerful drugs, accompanied by careful counseling to promote patient compliance. PMID:25328019

  20. Prasugrel compared with high-dose clopidogrel in acute coronary syndrome. The randomised, double-blind ACAPULCO study.

    PubMed

    Montalescot, Gilles; Sideris, Georgios; Cohen, Remy; Meuleman, Catherine; Bal dit Sollier, Claire; Barthélémy, Olivier; Henry, Patrick; Lim, Pascal; Beygui, Farzin; Collet, Jean-Philippe; Marshall, Debra; Luo, Junxiang; Petitjean, Helene; Drouet, Ludovic

    2010-01-01

    Compared with the approved dose regimen of clopidogrel (300-mg loading dose [LD], 75-mg maintenance dose [MD]), prasugrel has been demonstrated to reduce ischaemic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). In ACS, antiplatelet effects of a prasugrel MD regimen have not been previously compared with either a higher clopidogrel MD or after switching from a higher clopidogrel LD. The objective of this study was to evaluate the antiplatelet effect of a prasugrel 10-mg MD versus a clopidogrel 150-mg MD in patients with ACS who had received a clopidogrel 900-mg LD. Patients with non-ST elevation ACS, treated with aspirin and a clopidogrel 900-mg LD, were randomised within 24 hours post-LD to receive a prasugrel 10-mg or clopidogrel 150-mg MD. After 14 days of the initial MD, subjects switched to the alternative treatment for 14 days. The primary endpoint compared maximum platelet aggregation (MPA, 20 microM adenosine diphosphate [ADP]) between prasugrel and clopidogrel MDs for both periods. Responder analyses between treatments were performed using several platelet-function methods. Of 56 randomised subjects, 37 underwent PCI. MPA was 26.2% for prasugrel 10 mg and 39.1% for clopidogrel 150 mg (p<0.001). The prasugrel MD regimen reduced MPA from the post-900-mg LD level (41.2% to 29.1%, p=0.003). Poor response ranged from 0% to 6% for prasugrel 10 mg and 4% to 34% for clopidogrel 150 mg. Thus, in ACS patients a prasugrel 10-mg MD regimen resulted in significantly greater platelet inhibition than clopidogrel at twice its approved MD or a 900-mg LD.

  1. Exome sequencing of extreme clopidogrel response phenotypes identifies B4GALT2 as a determinant of on-treatment platelet reactivity.

    PubMed

    Scott, S A; Collet, J-P; Baber, U; Yang, Y; Peter, I; Linderman, M; Sload, J; Qiao, W; Kini, A S; Sharma, S K; Desnick, R J; Fuster, V; Hajjar, R J; Montalescot, G; Hulot, J-S

    2016-09-01

    Interindividual variability in platelet aggregation is common among patients treated with clopidogrel and both high on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) increase risks for adverse clinical outcomes. CYP2C19 influences clopidogrel response but only accounts for ∼12% of the variability in platelet reactivity. To identify novel variants implicated in on-treatment platelet reactivity, patients with coronary artery disease (CAD) with extreme pharmacodynamic responses to clopidogrel and wild-type CYP2C19 were subjected to exome sequencing. Candidate variants that clustered in the LTPR subgroup subsequently were genotyped across the discovery cohort (n = 636). Importantly, carriers of B4GALT2 c.909C>T had lower on-treatment P2Y12 reaction units (PRUs; P = 0.0077) and residual platelet aggregation (P = 0.0008) compared with noncarriers, which remained significant after adjusting for CYP2C19 and other clinical variables in both the discovery (P = 0.0298) and replication (n = 160; PRU: P = 0.0001) cohorts. B4GALT2 is a platelet-expressed galactosyltransferase, indicating that B4GALT2 c.909C>T may influence clopidogrel sensitivity through atypical cell-surface glycoprotein processing and platelet adhesion.

  2. Integrated analysis of miRNA and mRNA gene expression microarrays: Influence on platelet reactivity, clopidogrel response and drug-induced toxicity.

    PubMed

    Freitas, Renata Caroline Costa de; Bortolin, Raul Hernandes; Lopes, Mariana Borges; Hirata, Mario Hiroyuki; Hirata, Rosario Dominguez Crespo; Silbiger, Vivian Nogueira; Luchessi, André Ducati

    2016-11-15

    Genetic and epigenetic variability may influence the efficacy and safety of antiplatelet therapies, including clopidogrel. Therefore, the miRNA-mRNA interactions and drug toxicity were investigated in silico using available microarray data. Expressions profiles of platelet miRNA (GSE59488) from acute coronary syndrome and mRNA in peripheral blood cells (GSE32226) from coronary artery disease patients were used to miRNA-target mRNA integrated analysis by Ingenuity Pathways Analysis 6 software (IPA). Results showed that ST13 mRNA is regulated by hsa-miR-107 (miR-103-3p); BTNL3 and CFD mRNAs are regulated by hsa-miR-4701-3p (miR-1262); SLC7A8 is regulated by hsa-miR-145-5p (miR-145-5p); and SENP5 mRNA is regulated by hsa-miR-15b-5p (miR-16-5p) and hsa-miR-26a-5p (miR-26a-5p). Drug toxicity IPA tool showed that these miRNAs/mRNAs are associated with clopidogrel-related liver and renal injury. In conclusion, these results demonstrate that differential expression of miRNAs in platelets and interactions with their target mRNAs are associated with variability in platelet reactivity, clopidogrel response and drug-induced toxicity. PMID:27543010

  3. Prevalence and Clinical Characteristics of Intracerebral Hemorrhages Associated with Clopidogrel

    PubMed Central

    Cordina, Steve M; Hassan, Ameer E; Ezzeddine, Mustapha A.

    2009-01-01

    Background: As clopidogrel is being increasingly used, intracerebral hemorrhage (ICH) associated with clopidogrel are expected to increase. We assessed the prevalence and clinical characteristics of of ICH with clopidogrel in a consecutive series of patients in two hospitals. Methods: We retrospectively reviewed the medication history of 204 patients (112 in one hospital and 92 in another – both individually consecutive) admitted with ICH. We identified the patients who were using clopidogrel prior to ICH occurrence. The etiology of the ICH was categorized on the basis of clinical history and diagnostic imaging, and outcome was subsequently evaluated. Results: A total of 8 (4%) of the 204 patients were using clopidogrel prior to onset of ICH. Clopidogrel was the only medication in 3 patients and was used with aspirin or warfarin in 3 and 2 patients, respectively. Aspirin or warfarin was the only medication in 23 (%) and 14 (%) patients associated with ICH, respectively. The hematoma was located in the basal ganglia (n=2), lobes (n=2), thalamus (n=1), intraventricular (n=2), and cerebellar (n=2). One patient had secondary intraventricular extension. All patients using a combination of clopidogrel and warfarin prior to ICH died. Conclusion: The prevalence of ICH associated with clopidogrel is approximating the prevalence of aspirin- or warfarin-associated ICH. The mortality with clopidogrel related ICH appears to be high particularly when in combination with another antithrombotic agent. PMID:22518241

  4. Von Willebrand Factor Antigen Predicts Response to Double Dose of Aspirin and Clopidogrel by PFA-100 in Patients Undergoing Primary Angioplasty for St Elevation Myocardial Infarction

    PubMed Central

    Gianetti, Jacopo; Parri, Maria Serena; Della Pina, Francesca; Marchi, Federica; Koni, Endrin; De Caterina, Alberto; Maffei, Stefano

    2013-01-01

    Von Willebrand factor (VWF) is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100) with Collagen/Epinephrine (CEPI) is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR). The objective of this study was to verify the effect of double dose (DD) of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n = 58) or DD of aspirin and clopidogrel (DD, n = 58), maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2). At Times 1 and 2 we observed a significantly higher CEPI closure times (CT) in DD as compared to SD (P < 0.001). Delta of CEPI-CT (T1 − T0) was significantly related to VWF (P < 0.001) and inversely related to ADAMTS-13 (0.01). Responders had a significantly higher level of VWF at T0. Finally, in a multivariate model analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT response (P = 0.02). HRP detected by PFA-100 in acute myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF. PMID:24453831

  5. Relation between clopidogrel active metabolite levels and different platelet aggregation methods in patients receiving clopidogrel and aspirin.

    PubMed

    Liang, Yan; Johnston, Marilyn; Hirsh, Jack; Pare, Guillaume; Li, Chunjian; Mehta, Shamir; Teo, Koon K; Sloane, Debi; Yi, Qilong; Zhu, Jun; Eikelboom, John W

    2012-11-01

    Clopidogrel is a prodrug that undergoes bioconversion via cytochrome P450 system to form an active metabolite (AM) that binds to the platelet ADP receptor. The antiplatelet effect of clopidogrel is commonly assessed by measuring the aggregatory response to 5 μM ADP by light transmission aggregation (LTA) or multiple electrode aggregometry (MEA) or by the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI). To determine which of these three tests of platelet ADP receptor pathway inhibition most closely correlates with clopidogrel AM levels. We analyzed blood samples from 82 patients with coronary artery disease who were randomized to receive double-dose or standard dose clopidogrel for 2 weeks. We measured peak clopidogrel AM levels, platelet aggregation in response to ADP and VASP-PRI on days 1, and repeated all the measures on days 7 and 14. Linear regression analysis was used to examine the correlation between clopidogrel AM and LTA, MEA and VASP-PRI. Bland-Altman plots were used to explore the agreement between tests of the antiplatelet effects of clopidogrel. Clopidogrel AM on day 1 correlated most closely with VASP-PRI (r = -0.5767) and demonstrated weaker correlations with LTA (r = -0.4656) and MEA (r = -0.3384) (all p < 0.01). Intra-class correlation (ICC) between VASP-PRI and LTA was 0.6446; VASP-PRI and MEA was 0.4720; and LTA and MEA was 0.4693. Similar results were obtained on days 7 and 14. Commonly used pharmacodynamic measures of clopidogrel response are only moderately correlated with clopidogrel AM levels and may not be suitable to measure the adequacy of clopidogrel therapy. PMID:22797934

  6. Relation of genetic polymorphisms in the cytochrome P450 gene with clopidogrel resistance after drug-eluting stent implantation in Koreans.

    PubMed

    Lee, Jung Myung; Park, Sungha; Shin, Dong-Jik; Choi, Donghoon; Shim, Chi Young; Ko, Young-Guk; Kim, Jung-Sun; Shin, Eun-Soon; Chang, Chong Won; Lee, Jong-Eun; Jang, Yangsoo

    2009-07-01

    Clopidogrel is a prodrug that has to be converted to an active metabolite by hepatic cytochrome P450 (CYP) isoenzymes to inhibit platelet aggregation. Individual variability of platelet inhibition by clopidogrel suggests a possibility for genetic factors having a significant influence on clopidogrel responsiveness. In this study, we sought to determine the relation of genetic polymorphisms of CYP genes to clopidogrel resistance in Koreans. Four hundred fifty patients who underwent successful percutaneous coronary intervention with drug-eluting stents were randomly assigned to treatment with dual antiplatelet regimen (aspirin plus clopidogrel) or triple antiplatelet regimen (aspirin plus clopidogrel plus cilostazol). Clopidogrel resistance using VerifyNow P2Y12 assay and genetic analysis were performed in 387 patients. Clopidogrel resistance was found in 112 patients (28.9%). In the clopidogrel-responsive group, there was a significantly higher proportion of cilostazol use. Because cilostazol showed a significant influence on clopidogrel resistance, we examined the association of single-nucleotide polymorphisms and clopidogrel resistance in the dual and triple antiplatelet therapy groups, respectively. In all subjects, the CYP2C19*3A allele was significantly more prevalent in the clopidogrel-resistant group compared with the clopidogrel-responsive group. Multiple logistic regression analysis demonstrated that CYP2C19*3 is an independent predictor of clopidogrel resistance. In conclusion, CYP2C19*3 single-nucleotide polymorphisms is an independent risk factor of clopidogrel resistance in Korean subjects with coronary artery disease. PMID:19576320

  7. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine. PMID:26341013

  8. Determination of clopidogrel main metabolite in plasma: a useful tool for monitoring therapy?

    PubMed

    Mani, Helen; Toennes, Stefan W; Linnemann, Birgit; Urbanek, Dorota A; Schwonberg, Jan; Kauert, Gerold F; Lindhoff-Last, Edelgard

    2008-02-01

    This study was performed to determine whether analysis of clopidogrel and its main carboxylic acid metabolite in plasma provides additional information about the wide variability of platelet aggregation inhibition in clopidogrel-treated patients with peripheral arterial occlusive disease. Consecutive outpatients (n = 56) with stable peripheral arterial occlusive disease treated with 75 mg clopidogrel daily, without co-administration of aspirin, were investigated. With use of a standardized questionnaire, the time of drug intake was documented. Blood sampling was performed within 24 hours after the most recent drug intake. Platelet function was measured by optical aggregometry using adenosine diphosphate (ADP) (2 mumol/L) as the agonist. Plasma concentrations of clopidogrel and its main metabolite, clopidogrel carboxylic acid, were quantitated using high-performance liquid chromatography analysis coupled to mass spectrometry. In 95% (53/56) of patients, clopidogrel carboxylic acid was detected. In 40% (22/56) of patients, the ADP-induced aggregation response was within the normal range despite clopidogrel treatment. In 14% (3/22) of these patients, neither clopidogrel nor its main metabolite could be detected. Two of these patients agreed to ingest 75 mg/d clopidogrel under observation and to undergo blood sampling after 2, 12, and 24 hours. Clopidogrel carboxylic acid and a significant inhibition of platelet aggregation were detected even after 24 hours in both patients, confirming noncompliance as the reason for the lack of inhibition of ADP-induced platelet aggregation observed in the initial measurements. In the subgroup of patients who had taken clopidogrel within 4 hours before blood sampling, a large range of carboxylic acid concentrations was detected, indicating a high variability of drug metabolism among patients. In conclusion, determining clopidogrel metabolite plasma concentrations could be a useful tool for identifying poor compliance and variable

  9. Clopidogrel-Induced Recurrent Polyarthritis

    PubMed Central

    Harburger, Joseph; Stallings, Gary; Agrawal, Nikhil; Garg, Jalaj

    2013-01-01

    Clopidogrel is an oral thienopyridine and together with aspirin is a component of dual antiplatelet therapy for the prevention of stent thrombosis after intracoronary stent placement. The common adverse effects from its use are an increased risk of bleeding, neutropenia, and rash. Arthralgia and backache are also known to occur with its use. There have been case reports linking arthritis with the use of clopidogrel. We describe the case of a 64-year-old man who reported symptoms of fever and joint pains following initiation of therapy with clopidogrel. Acute-phase reactants were elevated. Laboratory and radiologic testing were unremarkable. Incidentally, he reported experiencing a similar arthritis after he received a loading dose of clopidogrel prior to a diagnostic coronary angiography in the past. The symptoms improved dramatically on discontinuation of clopidogrel. There was no recurrence of symptoms with prasugrel. This describes possibly the second incidence of recurrent arthritis with clopidogrel therapy. PMID:26425581

  10. Clopidogrel use After Myocardial Revascularization: Prevalence, Predictors, and One-Year Survival Rate

    PubMed Central

    Prates, Paulo Roberto L.; Williams, Judson B.; Mehta, Rajendra H.; Stevens, Susanna R.; Thomas, Laine; Smith, Peter K.; Newby, L. Kristin; Kalil, Renato A. K.; Alexander, John H.; Lopes, Renato D.

    2016-01-01

    Introduction Antiplatelet therapy after coronary artery bypass graft (CABG) has been used. Little is known about the predictors and efficacy of clopidogrel in this scenario. Objective Identify predictors of clopidogrel following CABG. Methods We evaluated 5404 patients who underwent CABG between 2000 and 2009 at Duke University Medical Center. We excluded patients undergoing concomitant valve surgery, those who had postoperative bleeding or death before discharge. Postoperative clopidogrel was left to the discretion of the attending physician. Adjusted risk for 1-year mortality was compared between patients receiving and not receiving clopidogrel during hospitalization after undergoing CABG. Results At hospital discharge, 931 (17.2%) patients were receiving clopidogrel. Comparing patients not receiving clopidogrel at discharge, users had more comorbidities, including hyperlipidemia, hypertension, heart failure, peripheral arterial disease and cerebrovascular disease. Patients who received aspirin during hospitalization were less likely to receive clopidogrel at discharge (P≤0.0001). Clopidogrel was associated with similar 1-year mortality compared with those who did not use clopidogrel (4.4% vs. 4.5%, P=0.72). There was, however, an interaction between the use of cardiopulmonary bypass and clopidogrel, with lower 1-year mortality in patients undergoing off-pump CABG who received clopidogrel, but not those undergoing conventional CABG (2.6% vs 5.6%, P Interaction = 0.032). Conclusion Clopidogrel was used in nearly one-fifth of patients after CABG. Its use was not associated with lower mortality after 1 year in general, but lower mortality rate in those undergoing off-pump CABG. Randomized clinical trials are needed to determine the benefit of routine use of clopidogrel in CABG. PMID:27556308

  11. Chiral Stability of an Extemporaneously Prepared Clopidogrel Bisulfate Oral Suspension

    PubMed Central

    Tynes, Clay R.; Livingston, Brad; Patel, Hetesh; Arnold, John J.

    2014-01-01

    OBJECTIVES The purpose of this study was to evaluate the chiral stability of clopidogrel bisulfate in an extemporaneously compounded oral suspension for a period of 60 days. METHODS A 5 mg/mL oral suspension of clopidogrel bisulfate was prepared from commercially available Plavix tablets. The clopidogrel suspension was then evenly divided between two light-resistant prescription bottles and stored either under refrigeration (4°C) or at room temperature (25°C). Samples were drawn from the stored suspensions immediately after preparation and on days 7, 14, 28, and 60. Samples were subsequently analyzed at each time point by high-performance liquid chromatography using a reversed-phase column, with chemical stability defined as the retention of at least 90% of the initial intact clopidogrel concentration measured. To determine the chiral stability of the suspension, samples were also analyzed by high-performance liquid chromatography using a chiral column to investigate possible enantiomeric inversion. Chiral stability was defined as the retention of at least 90% of the initial concentration of the suspension as the S-enantiomer, the active moiety of Plavix. RESULTS Regardless of storage conditions, the oral suspension of clopidogrel retained at least 98% of the active S-enantiomer for 60 days after preparation. Compared with the clopidogrel suspension stored in the refrigerator, more chiral inversion was noted in the clopidogrel suspension stored at room temperature. CONCLUSIONS Our investigation of chiral stability indicates that a 5 mg/mL clopidogrel oral suspension stored under refrigeration and at room temperature maintains chiral stability as the active S-enantiomer. PMID:24782688

  12. Intensified Antiplatelet Treatment Reduces Major Cardiac Events in Patients with Clopidogrel Low Response: A Meta-analysis of Randomized Controlled Trials

    PubMed Central

    Xu, Lei; Hu, Xiao-Wei; Zhang, Shu-Hua; Li, Ji-Min; Zhu, Hui; Xu, Ke; Chen, Jun; Li, Chun-Jian

    2016-01-01

    Background: Clopidogrel low response (CLR) is an independent risk factor of adverse outcomes in patients undergoing percutaneous coronary intervention (PCI), and intensified antiplatelet treatments (IAT) guided by platelet function assays might overcome laboratory CLR. However, whether IAT improves clinical outcomes is controversial. Methods: Relevant trials were identified in PubMed, the Cochrane Library, and the Chinese Medical Journal Network databases from their establishment to September 9, 2014. Trials were screened using predefined inclusion criteria. Conventional meta-analysis and cumulative meta-analysis were performed using the Review Manager 5.0 and STATA 12.0 software programs. Results: Thirteen randomized controlled trials involving 5111 patients with CLR were recruited. During a follow-up period of 1–12 months, the incidences of cardiovascular (CV) death, nonfatal myocardial infarction (MI), and stent thrombosis were significantly lower in the IAT arm than in the conventional antiplatelet treatment arm (relative risk [RR] = 0.45, 95% confidence interval [CI]: 0.36–0.57, P < 0.000,01), whereas bleeding was similar between the two arms (RR = 1.05, 95% CI: 0.86–1.27, P = 0.65). Conclusions: IAT guided by platelet function assays reduces the risk of CV death, nonfatal MI, and stent thrombosis (ST) without an increased risk of bleeding in patients undergoing PCI and with CLR. PMID:27064045

  13. Differences in Whole Blood Platelet Aggregation at Baseline and in Response to Aspirin and Aspirin Plus Clopidogrel in Patients With Versus Without Chronic Kidney Disease.

    PubMed

    Jain, Nishank; Li, Xilong; Adams-Huet, Beverley; Sarode, Ravi; Toto, Robert D; Banerjee, Subhash; Hedayati, S Susan

    2016-02-15

    Thrombotic events while receiving antiplatelet agents (APAs) are more common in subjects with versus without chronic kidney disease (CKD). Data on antiplatelet effects of APA in CKD are scarce and limited by lack of baseline platelet function before APA treatment. We hypothesized subjects with stages 4 to 5 CKD versus no CKD have greater baseline platelet aggregability and respond poorly to aspirin and clopidogrel. In a prospective controlled study, we measured whole blood platelet aggregation (WBPA) in 28 CKD and 16 non-CKD asymptomatic stable outpatients not on APA, frequency-matched for age, gender, obesity, and diabetes mellitus. WBPA was remeasured after 2 weeks of each aspirin and aspirin plus clopidogrel. The primary outcome was percent inhibition of platelet aggregation (IPA) from baseline. The secondary outcome was residual platelet aggregability (RPA; proportion with <50% IPA). Baseline platelet aggregability was similar between groups except adenosine diphosphate-induced WBPA, which was higher in CKD versus non-CKD; median (interquartile range) = 13.5 (9.5 to 16.0) versus 9.0 (6.0 to 12.0) Ω, p = 0.007. CKD versus non-CKD participants had lower clopidogrel-induced IPA, 38% versus 72%, p = 0.04. A greater proportion of CKD versus non-CKD participants had RPA after clopidogrel treatment (56% vs 8.3%, p = 0.01). There were no significant interactions between CKD and the presence of cytochrome P450 2C19 polymorphisms for platelet aggregability in clopidogrel-treated participants. In conclusion, CKD versus non-CKD subjects exhibited similar platelet aggregation at baseline, similar aspirin effects and greater RPA on clopidogrel, which was independent of cytochrome P450 2C19 polymorphisms. PMID:26725101

  14. Differences in Whole Blood Platelet Aggregation at Baseline and in Response to Aspirin and Aspirin Plus Clopidogrel in Patients With Versus Without Chronic Kidney Disease.

    PubMed

    Jain, Nishank; Li, Xilong; Adams-Huet, Beverley; Sarode, Ravi; Toto, Robert D; Banerjee, Subhash; Hedayati, S Susan

    2016-02-15

    Thrombotic events while receiving antiplatelet agents (APAs) are more common in subjects with versus without chronic kidney disease (CKD). Data on antiplatelet effects of APA in CKD are scarce and limited by lack of baseline platelet function before APA treatment. We hypothesized subjects with stages 4 to 5 CKD versus no CKD have greater baseline platelet aggregability and respond poorly to aspirin and clopidogrel. In a prospective controlled study, we measured whole blood platelet aggregation (WBPA) in 28 CKD and 16 non-CKD asymptomatic stable outpatients not on APA, frequency-matched for age, gender, obesity, and diabetes mellitus. WBPA was remeasured after 2 weeks of each aspirin and aspirin plus clopidogrel. The primary outcome was percent inhibition of platelet aggregation (IPA) from baseline. The secondary outcome was residual platelet aggregability (RPA; proportion with <50% IPA). Baseline platelet aggregability was similar between groups except adenosine diphosphate-induced WBPA, which was higher in CKD versus non-CKD; median (interquartile range) = 13.5 (9.5 to 16.0) versus 9.0 (6.0 to 12.0) Ω, p = 0.007. CKD versus non-CKD participants had lower clopidogrel-induced IPA, 38% versus 72%, p = 0.04. A greater proportion of CKD versus non-CKD participants had RPA after clopidogrel treatment (56% vs 8.3%, p = 0.01). There were no significant interactions between CKD and the presence of cytochrome P450 2C19 polymorphisms for platelet aggregability in clopidogrel-treated participants. In conclusion, CKD versus non-CKD subjects exhibited similar platelet aggregation at baseline, similar aspirin effects and greater RPA on clopidogrel, which was independent of cytochrome P450 2C19 polymorphisms.

  15. Changes in CYP2C19 enzyme activity evaluated by the [(13)C]-pantoprazole breath test after co-administration of clopidogrel and proton pump inhibitors following percutaneous coronary intervention and correlation to platelet reactivity.

    PubMed

    Harvey, Adrien; Modak, Anil; Déry, Ugo; Roy, Mélanie; Rinfret, Stéphane; Bertrand, Olivier F; Larose, Éric; Rodés-Cabau, Josep; Barbeau, Gérald; Gleeton, Onil; Nguyen, Can Manh; Proulx, Guy; Noël, Bernard; Roy, Louis; Paradis, Jean-Michel; De Larochellière, Robert; Déry, Jean-Pierre

    2016-03-01

    Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is used for the prevention of cardiovascular events following percutaneous coronary intervention (PCI). These agents increase the risk of gastrointestinal bleeding. To prevent these events, proton pump inhibitors (PPI) are routinely prescribed. It has been reported that with the exception of pantoprazole and dexlanzoprazole, PPIs can impede conversion of clopidogrel by cytochrome P450 2C19 (CYP2C19) to its active metabolite, a critical step required for clopidogrel efficacy. Changes in CYP2C19 enzyme activity (phenotype) and its correlation with platelet reactivity following PPI therapy has not yet been fully described. In this study we attempted to determine if the [ (13)C]-pantoprazole breath test (Ptz-BT) can evaluate changes in CYP2C19 enzyme activity (phenoconversion) following the administration of PPI in coronary artery disease (CAD) patients treated with DAPT after PCI. Thirty (30) days after successful PCI with stent placement, 59 patients enrolled in the Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects (SPICE) trial (ClinicalTrials.gov Identifier: NCT00930670) were recruited to participate in this sub study. Patients were randomized to one of 4 antacid therapies (omeprazole, esomeprazole. pantoprazole or ranitidine). Subjects were administered the Ptz-BT and platelet function was evaluated by vasodilator-stimulated phosphoprotein (VASP) phosphorylation and light transmittance aggregometry before and 30 d after treatment with antacid therapy. Patients randomized to esomeprazole and omeprazole had greater high on-treatment platelet reactivity and lowering of CYP2C19 enzyme activity at Day 60 after 30 d of PPI therapy. Patients randomized to ranitidine and pantoprazole did not show any changes in platelet activity or CYP 2C19 enzyme activity. In patients treated with esomeprazole and omeprazole, changes in CYP2C19 enzyme activity

  16. Genetics Home Reference: clopidogrel resistance

    MedlinePlus

    ... be divided into two categories: intermediate metabolizers and poor metabolizers. Intermediate metabolizers are able to process some ... not protected from developing a harmful blood clot. Poor metabolizers process little or no clopidogrel, so they ...

  17. Clopidogrel and genetic testing: is it necessary for everyone?

    PubMed

    Goswami, Sweta; Cheng-Lai, Angela; Nawarskas, James

    2012-01-01

    Clopidogrel is a widely used antiplatelet agent to treat and prevent a variety of atherothrombotic diseases. More than a decade after its initial Food and Drug Administration approval, studies have emerged raising concerns regarding its possible reduced efficacy in patients who have impaired conversion of clopidogrel to its active metabolite (ie, poor metabolizers). Research has implicated genetic variations in the CYP2C19 isozyme as at least partly responsible for the variable antiplatelet response seen with clopidogrel. Studies have shown that patients possessing genetic variants of the CYP2C19 isozyme may be at increased risk of adverse cardiovascular events due to impaired clopidogrel efficacy, although this has not been definitively demonstrated. The Food and Drug Administration has issued a boxed warning regarding this concern. However, specific recommendations on genetic testing and alternative therapeutic strategies are not currently available. Genetic testing is commercially available to test patients for variability in the CYP2C19 isozyme, but altering antiplatelet therapy based on the results of this testing has not been adequately studied, and it is therefore not clear how to adjust therapy based on the results of this genetic testing. In addition, there are many other factors that may contribute to the variability in antiplatelet effect seen with clopidogrel besides CYP2C19 genetic polymorphisms. Ongoing trials dealing with adjusting antiplatelet therapy based on genetic testing will hopefully provide more useful information on how to appropriately integrate pharmacogenomics with the care of patients with atherothrombotic disease.

  18. Variability of residual platelet function despite clopidogrel treatment in patients with peripheral arterial occlusive disease.

    PubMed

    Linnemann, Birgit; Schwonberg, Jan; Toennes, Stefan W; Mani, Helen; Lindhoff-Last, Edelgard

    2010-04-01

    Residual platelet function despite treatment with clopidogrel may predict an unfavourable cardiovascular outcome. The majority of studies have investigated the effects of clopidogrel administration in conjunction with aspirin in patients undergoing percutaneous coronary intervention. The primary objective of the present study was to assess the platelet response to clopidogrel in the absence of aspirin in patients with peripheral arterial occlusive disease (PAOD) and to investigate whether non-responsiveness to clopidogrel is reproducible during long-term follow-up. Fifty-four clinically stable PAOD patients on a maintenance dose of 75 mg/d clopidogrel were enrolled in this study. Platelet function was assessed at baseline and after a median follow-up of 18 months using light transmittance aggregometry (LTA) with 2 microM ADP as an agonist. HPLC-coupled mass spectrometry was used to detect clopidogrel and clopidogrel carboxylic acid, the main metabolite of clopidogrel. Residual platelet function, as defined by late aggregation values within the reference range (i.e., >43%), was observed in 35.2% of patients at baseline and 17.6% during follow-up. During the observation period, 26.5% had switched from responder to non-responder status or vice versa. Among non-responders, either clopidogrel or its metabolite was detected in 89.5% and 83.3% of patients at baseline and at follow-up, respectively. We conclude that non-responsiveness to clopidogrel as determined by ADP-induced LTA is not stable over time. This phenomenon cannot be attributed to non-compliance alone. PMID:20153859

  19. Plateletworks: A screening assay for clopidogrel therapy monitoring in healthy cats

    PubMed Central

    Hamel-Jolette, Avril; Dunn, Marilyn; Bédard, Christian

    2009-01-01

    Plateletworks is a screening assay used in human medicine to monitor platelet-inhibiting drugs. As arterial thromboembolism is a common complication in cats suffering from cardiomyopathy, they are often treated with anti-platelet medication. Clopidogrel (Plavix), an anti-platelet aggregation drug, has recently been evaluated in healthy cats. The purpose of this study was to determine if the Plateletworks method can detect a decrease in platelet aggregation in cats receiving clopidogrel. Nine healthy adult cats were used for this study. Platelet aggregation was measured before and after a 3-day clopidogrel treatment (18.75 mg SID). Platelet aggregation after the clopidogrel treatment was significantly lower (P < 0.01). The Plateletworks method appears to be a promising test to monitor clopidogrel therapy in cats. PMID:19337399

  20. Relational responsibilities in responsive evaluation.

    PubMed

    Visse, Merel; Abma, Tineke A; Widdershoven, Guy A M

    2012-02-01

    This article explores how we can enhance our understanding of the moral responsibilities in daily, plural practices of responsive evaluation. It introduces an interpretive framework for understanding the moral aspects of evaluation practice. The framework supports responsive evaluators to better understand and handle their moral responsibilities. A case is introduced to illustrate our argument. Responsive evaluation contributes to the design and implementation of policy by working with stakeholders and coordinating the evaluation process as a relationally responsible practice. Responsive evaluation entails a democratic process in which the evaluator fosters and enters a partnership with stakeholders. The responsibilities of an evaluator generally involve issues such as 'confidentiality', 'accountability' and 'privacy'. The responsive evaluator has specific responsibilities, for example to include stakeholders and vulnerable groups and to foster an ongoing dialogue. In addition, responsive evaluation involves a relational responsibility, which becomes present in daily situations in which stakeholders express expectations and voice demands. In our everyday work as evaluators, it is difficult to respond to all these demands at the same time. In addition, this article demonstrates that novice evaluators experience challenges concerning over- and underidenfitication with stakeholders. Guidelines and quality criteria on how to act are helpful, but need interpretation and application to the unique situation at hand.

  1. CYP2C19 polymorphisms in the Thai population and the clinical response to clopidogrel in patients with atherothrombotic-risk factors

    PubMed Central

    Sukasem, Chonlaphat; Tunthong, Ramaimon; Chamnanphon, Montri; Santon, Siwalee; Jantararoungtong, Thawinee; Koomdee, Napatrupron; Prommas, Santirhat; Puangpetch, Apichaya; Vathesatogkit, Prin

    2013-01-01

    Genetic variation in the cytochrome P450 2C19 (CYP2C19) gene has been documented gradually as the determinant conversion and variability in the antiplatelet effect of clopidogrel. The aims of this study were to determine the prevalence of clinically relevant allele variants (CYP2C19*2, CYP2C19*3, and CYP2C19*17) in a Thai study population, and finally determine whether the allele distributes and predicts metabolic phenotypes in clopidogrel treated patients. A total of 1,051 Thai patients participated in this study. Genotypes for CYP2C19 polymorphisms were detected by the microarray-based technique. Furthermore, results of genotyping and platelet aggregation in 96 cardiovascular disease patients on 75 mg clopidogrel maintenance daily dose therapy also were analyzed. Among 1,051 samples, the allele frequencies of CYP2C19 *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and *1/*17 were found in 428 (40.72%), 369 (35.10%), 72 (6.85%), 77 (7.32%), 59 (5.61%), and 45 (4.30%) of the patients, respectively. Homozygous CYP2C19 *3/*3 was found in one patient (0.10%). Therefore, 40.72% of the patients were predicted as extensive metabolizers, 41.95% as intermediate metabolizers, 13.03% as poor metabolizers, and 4.30% as ultra-rapid metabolizers. Among 96 patients, the frequency of poor metabolizers was significantly higher in the clopidogrel non-responder group than in the responder group (36.0% and 15.5%, respectively, P = 0.03). CYP2C19*1/*17 was observed in responders (n = 2; 2.8%). As a result, CYP2C19 variants were associated with clopidogrel non-responders. However, there is a need for further elucidation of the clinical importance and use of this finding to make firm and cost-effective recommendations for drug treatment in the future. PMID:24019752

  2. Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel: Determination of Structure and Analyte Development.

    PubMed

    Shaw, Scott A; Balasubramanian, Balu; Bonacorsi, Samuel; Cortes, Janet Caceres; Cao, Kevin; Chen, Bang-Chi; Dai, Jun; Decicco, Carl; Goswami, Animesh; Guo, Zhiwei; Hanson, Ronald; Humphreys, W Griffith; Lam, Patrick Y S; Li, Wenying; Mathur, Arvind; Maxwell, Brad D; Michaudel, Quentin; Peng, Li; Pudzianowski, Andrew; Qiu, Feng; Su, Shun; Sun, Dawn; Tymiak, Adrienne A; Vokits, Benjamin P; Wang, Bei; Wexler, Ruth; Wu, Dauh-Rurng; Zhang, Yingru; Zhao, Rulin; Baran, Phil S

    2015-07-17

    Clopidogrel is a prodrug anticoagulant with active metabolites that irreversibly inhibit the platelet surface GPCR P2Y12 and thus inhibit platelet activation. However, gaining an understanding of patient response has been limited due to imprecise understanding of metabolite activity and stereochemistry, and a lack of acceptable analytes for quantifying in vivo metabolite formation. Methods for the production of all bioactive metabolites of clopidogrel, their stereochemical assignment, and the development of stable analytes via three conceptually orthogonal routes are disclosed.

  3. Program Evaluation Particularly Responsive Evaluation

    ERIC Educational Resources Information Center

    Stake, Robert E.

    2011-01-01

    In this paper, the author talks about some recent developments in the methodology of program evaluation and about what he calls "responsive evaluation." He discusses two models for program evaluation, namely (1) informal study or self-study; and (2) the pretest/posttest model. Then, he describes an approach that he has been working on, which will…

  4. An allele-specific PCR system for rapid detection and discrimination of the CYP2C19∗4A, ∗4B, and ∗17 alleles: implications for clopidogrel response testing.

    PubMed

    Scott, Stuart A; Tan, Qian; Baber, Usman; Yang, Yao; Martis, Suparna; Bander, Jeffrey; Kornreich, Ruth; Hulot, Jean-Sébastien; Desnick, Robert J

    2013-11-01

    CYP2C19 is involved in the metabolism of clinically relevant drugs, including the antiplatelet prodrug clopidogrel, which has prompted interest in clinical CYP2C19 genotyping. The CYP2C19∗4B allele is defined by both gain-of-function [c.-806C>T (∗17)] and loss-of-function [c.1A>G (∗4)] variants on the same haplotype; however, current genotyping and sequencing assays are unable to determine the phase of these variants. Thus, the aim of this study was to develop an assay that could rapidly detect and discriminate the related ∗4A, ∗4B, and ∗17 alleles. An allele-specific PCR assay, composed of four unique primer mixes that specifically interrogate the defining ∗17 and ∗4 variants, was developed by using samples (n = 20) with known genotypes, including the ∗4A, ∗4B, and/or ∗17 alleles. The assay was validated by testing 135 blinded samples, and the results were correlated with CYP2C19 genotyping and allele-specific cloning/sequencing. Importantly, among the six ∗4 carriers in the validation cohort, after allele-specific PCR testing both samples with a ∗1/∗4 genotype were reclassified to ∗1/∗4A, all three samples with a ∗4/∗17 genotype were reclassified to ∗1/∗4B, and a sample with a ∗4/∗17/∗17 genotype was reclassified to ∗4B/∗17. In conclusion, this rapid and robust allele-specific PCR assay can refine CYP2C19 genotyping and metabolizer phenotype classification by determining the phase of the defining ∗17 and ∗4 variants, which may have utility when testing CYP2C19 for clopidogrel response.

  5. Evaluator Responsiveness to Stakeholders

    ERIC Educational Resources Information Center

    Azzam, Tarek

    2010-01-01

    A simulation study was conducted in an attempt to examine how evaluators modify their evaluation design in response to differing stakeholder groups. In this study, evaluators were provided with a fictitious description of a school-based program. They were then asked to design an evaluation of the program. After the evaluation design decisions were…

  6. The Effect of Enoxaparin and Clopidogrel on Survival of Random Skin Flap in Rat Animal Model

    PubMed Central

    Fatemi, Mohammad Javad; S Forootan, Kamal; S Jalali, Seyed Ziaaddin; Mousavi, Seyed Jaber; Pedram, Mir Sepehr

    2012-01-01

    BACKGROUND Necrosis of skin flaps is considered as an important complication in reconstructive surgery. We conducted an experimental study to investigate the efficacy of low-molecular weight heparin, clopidogrel and their combination to improve the flap survival. METHODS Forty male, adult Sprague-Dawlay rats were divided randomly into 4 groups. Standard rectangular, distally based dorsal random pattern skin flap was elevated. To prevent the graft effect, a sterile sheet was put under the flap. No pharmacological agent was administered for the control group. In group 2, single subcutaneous dose of enoxaparin (3.2 mg/kg) was immediately administrated after surgery. In group 3, clopidogrel (25 mg/kg) was given orally for 7 days. In group 4, both enoxaparin and clopidogrel were administrated. The rats were evaluated on post-operative day 7 for viable and necrotic portions of flaps. RESULTS The mean and SD of necrosis was 17.79+2.5 cm in the control group, 16.20±3.1 cm in low-molecular weight heparin, 15.25+3.8 cm in combined therapy group and 13.69+2.7 cm in clopidogrel group. Clopidogrel was the only pharmaceutical agent that produced a significant increase in the flap survival area. CONCLUSION Clopidogrel may be an effective pharmaceutical agent that significantly increases viability of random skin flaps in rats, but low-molecular weight heparin and their combination did not have any significant beneficial effects. PMID:25734046

  7. Clopidogrel delays gastric ulcer healing in rats.

    PubMed

    Luo, Jiing-Chyuan; Huo, Teh-Ia; Hou, Ming-Chih; Lin, Hsiao-Yi; Li, Chung-Pin; Lin, Han-Chieh; Chang, Full-Young; Lee, Fa-Yauh

    2012-11-15

    Clopidogrel is not safe enough for the gastric mucosa in patients with high risk of peptic ulcer. This study aimed to explore if clopidogrel delays gastric ulcer healing and elucidate the involved mechanisms. Gastric ulcer was induced in rats and the ulcer size, mucosal epithelial cell proliferation of the ulcer margin, expression of growth factors [epidermal growth factor (EGF), basic fibroblast growth factor] and their receptors, and signal transduction pathways for cell proliferation were measured and compared between the clopidogrel-treated group and untreated controls. For the in vitro part, rat gastric mucosal epithelial cell line (RGM-1 cells) was used to establish EGF receptor over-expressed cells. Cell proliferation and molecular change under EGF treatment (10ng/ml) with and without clopidogrel (10(-6)M) were demonstrated. Ulcer size was significantly larger in the clopidogrel-treated group compared to the control and mucosal epithelial cell proliferation of the ulcer margin was significantly decreased in the clopidogrel-treated group (P<0.05). Clopidogrel (2mg and 10mg/kg/day) significantly decreased ulcer-induced gastric epithelial cell proliferation and ulcer-stimulated expressions of EGF receptor and phosphorylated extracellular signal-regulated kinase (PERK) at the ulcer margin (P<0.05). Clopidogrel (10(-6)M) also inhibited EGF-stimulated EGF receptor, PERK expression, and cell proliferation in RGM-1 cells (P<0.05), and caused much less inhibition of EGF-stimulated cell proliferation in EGF receptor over-expressed RGM-1 cells than in RGM-1 cells (22% vs. 32% reduction). In conclusion, clopidogrel delays gastric ulcer healing in rats via inhibiting gastric epithelial cell proliferation, at least by inhibition of the EGF receptor-ERK signal transduction pathway.

  8. Consumer interpretation of ramipril and clopidogrel medication risk information – implications for risk communication strategies

    PubMed Central

    Tong, Vivien; Raynor, David K; Blalock, Susan J; Aslani, Parisa

    2015-01-01

    Purpose Side effects and side-effect risk information can be provided using written medicine information. However, challenges exist in effectively communicating this information to consumers. This study aimed to explore broad consumer profiles relevant to ramipril and clopidogrel side-effect risk information interpretation. Methods Three focus groups were conducted (n=18 consumers) exploring consumer perspectives, understanding and treatment decision making in response to ramipril and clopidogrel written medicine information leaflets containing side effects and side-effect risk information. All discussions were audio recorded, transcribed verbatim, and analyzed to explore consumer profiles pertaining to side-effect risk appraisal. Results Three consumer profiles emerged: glass half-empty, glass half-full, and middle-of-the-road consumers, highlighting the influence of perceived individual susceptibility, interpretation of side-effect risk information, and interindividual differences, on consumers’ understanding of side-effect risk information. All profiles emphasized the importance of gaining an understanding of individual side-effect risk when taking medicines. Conclusion Written side-effect risk information is not interpreted uniformly by consumers. Consumers formulated their own construct of individual susceptibility to side effects. Health care professionals should consider how consumers interpret side-effect risk information and its impact on medication use. Existing risk communication strategies should be evaluated in light of these profiles to determine their effectiveness in conveying information. PMID:26185427

  9. The clopidogrel after surgery for coronary artery disease (CASCADE) randomized controlled trial: clopidogrel and aspirin versus aspirin alone after coronary bypass surgery [NCT00228423

    PubMed Central

    Kulik, Alexander; Le May, Michel; Wells, George A; Mesana, Thierry G; Ruel, Marc

    2005-01-01

    Background Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery. The process of saphenous vein intimal hyperplasia begins just days after surgical revascularization, setting the stage for graft atherosclerotic disease and its sequalae. Clopidogrel improves outcomes in patients with atherosclerotic disease, and is effective at reducing intimal hyperplasia in animal models of thrombosis. Therefore, the goal of this study will be to evaluate the efficacy of clopidogrel and aspirin therapy versus aspirin alone in the prevention of saphenous vein graft intimal hyperplasia following coronary artery bypass surgery. Methods Patients undergoing multi-vessel coronary artery bypass grafting and in whom at least two saphenous vein grafts will be used are eligible for the study. Patients will be randomized to receive daily clopidogrel 75 mg or placebo, in addition to daily aspirin 162 mg, for a one year duration starting on the day of surgery (as soon as postoperative bleeding has been excluded). At the end of one year, all patients will undergo coronary angiography and intravascular ultrasound assessment of one saphenous vein graft as selected by randomization. The trial will be powered to test the hypothesis that clopidogrel and aspirin will reduce vein graft intimal hyperplasia by 20% compared to aspirin alone at one year following bypass surgery. Discussion This trial is the first prospective human study that will address the question of whether clopidogrel therapy improves outcomes and reduces saphenous vein graft intimal hyperplasia following cardiac surgery. Should the combination of clopidogrel and aspirin reduce the process of vein graft intimal hyperplasia, the results of this study will help redefine modern antiplatelet management of coronary artery bypass patients. PMID:16219100

  10. Clopidogrel

    MedlinePlus

    ... Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for ...

  11. Efficacy of Clopidogrel and Clinical Outcome When Clopidogrel Is Coadministered With Atorvastatin and Lansoprazole

    PubMed Central

    Zhang, Jian-rong; Wang, Di-qing; Du, Jun; Qu, Guang-su; Du, Jian-lin; Deng, Song-bai; Liu, Ya-jie; Cai, Jin-xi; She, Qiang

    2015-01-01

    Abstract This prospective, randomized, nonblind, controlled trial evaluated the effects of clopidogrel on platelet function upon coadministration with atorvastatin and lansoprazole. One hundred four adult patients with non-ST-segment elevated acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI) with drug-eluting stent implantation were included. All patients were treated with standard dual antiplatelet therapy (DAPT) plus rosuvastatin 10 mg daily after the operation. On the sixth day after PCI, patients were randomly divided into 4 groups, Group A: DAPT + atorvastatin 20 mg daily (a change from rosuvastatin to atorvastatin) + lansoprazole 30 mg daily, Group B: DAPT + atorvastatin 20 mg daily (a change from rosuvastatin to atorvastatin), Group C: DAPT + lansoprazole 30 mg daily (continuing to take rosuvastatin), Group D is the control group. Additional drugs were used according to the situation of patients. Platelet function and concentrations of platelet activation markers (granular membrane protein 140 (P-selectin), thromboxane B2 (TXB2), and human soluble cluster of differentiation 40 ligand (sCD40L)) were assessed before randomization and at 15- and 30-day follow-up visits. All patients were maintained on treatment for 6 months and observed for bleeding and ischemic events. A total of 104 patients were enrolled, 27 patients in group A, 26 patients in Group B/C, 25 patients in Group D separately, and all the patients were analyzed. There were no differences in platelet function and the levels of platelet activation markers (P-selectin, TXB2, and sCD40L) among or within the 4 groups at the 3 time points of interest (P > 0.05). In the subsequent 6 months, no significant bleeding events occurred, and 12 patients experienced ischemic events, these results were also not significantly different among the groups (P > 0.05). In patients diagnosed with NSTE-ACS who have had drug-eluting stent

  12. Predictors of biochemical aspirin and clopidogrel resistance in patients with ischemic stroke.

    PubMed

    Fong, Joanna; Cheng-Ching, Esteban; Hussain, Muhammad Shazam; Katzan, Irene; Gupta, Rishi

    2011-01-01

    Variable platelet response to aspirin and clopidogrel is a well-established phenomenon in patients with coronary artery disease. We sought to determine the predictors of an impaired biochemical response to aspirin and clopidogrel in patients with ischemic stroke. Patients with established cerebrovascular disease who underwent an aspirin/clopidogrel response panel (ie, light transmittance aggregometry) between June 2003 and March 2007 were identified through an electronic database. The medical records of these patients were retrospectively reviewed, and demographic characteristics, medical history, and laboratory results were recorded. Univariate and multivariate logistic regression analyses were performed to assess for factors associated with antiplatelet resistance. Of the 465 patients included in this study, 120 (28%) were biochemical aspirin nonresponders and 83 (28%) were biochemical clopidogrel nonresponders. Of the 270 patients on dual antiplatelet therapy, 25 (9.3%) were dual biochemical nonresponders. In binary logistic regression modeling, patients with congestive heart failure (odds ratio [OR] = 4.54; 95% confidence interval [CI] = 1.33-15.5; P = .02) and those with higher hemoglobin A1c values (OR = 1.41; 95% CI = 1.12-1.79; P = .004) had a significantly greater likelihood of having a biochemical nonresponse to aspirin therapy. African-American patients (OR = 2.19; 95% CI = 1.23-3.91; P < .007) were significantly more likely to be nonresponders to clopidogrel. This preliminary study shows that aspirin and clopidogrel biochemical nonresponse frequently occurs in ischemic stroke patients. In addition, some associated variables may affect the biochemical response to antiplatelet therapy. Further study is needed to explore whether this nonresponse has an impact on clinical outcomes. PMID:20621513

  13. Stent Thrombosis Patients with Hyporesponsiveness to Clopidogrel, Prasugrel, and Ticagrelor: A Case Series Using Short Thromboelastography

    PubMed Central

    Sambu, Nalyaka; Mahmoudi, Michael; Curzen, Nick

    2016-01-01

    Patients after percutaneous coronary intervention (PCI) with stent implantation and functional hyporesponsiveness to P2Y12 inhibitors are at higher risk of ischaemic events, particularly stent thrombosis (ST). It is currently not routine practice to assess the functional response to these agents. However, concern over functional hyporesponsiveness to clopidogrel has led to widespread uptake of prasugrel and ticagrelor as the default P2Y12 inhibitor after stent implantation in patients with acute coronary syndrome. Here we report, for the first time, 3 cases in which patients who have had ST exhibit hyporesponsiveness to clopidogrel, prasugrel, and ticagrelor. PMID:27799942

  14. Aspirin decreases systemic exposure to clopidogrel through modulation of P-glycoprotein but does not alter its antithrombotic activity.

    PubMed

    Oh, J; Shin, D; Lim, K S; Lee, S; Jung, K-H; Chu, K; Hong, K S; Shin, K-H; Cho, J-Y; Yoon, S H; Ji, S C; Yu, K-S; Lee, H; Jang, I-J

    2014-06-01

    Decreased oral clopidogrel absorption caused by induction of intestinal permeability glycoprotein (P-gp) expression after aspirin administration was observed in rats. This study evaluated the effect of aspirin coadministration on the pharmacokinetics/pharmacodynamics of clopidogrel in humans. A single 75-mg dose of clopidogrel was orally administered before and after 2 and 4 weeks of once-daily 100-mg aspirin administration in 18 healthy volunteers who were recruited based on CYP2C19 and PON1 genotypes. Plasma concentrations of clopidogrel and its active metabolite, H4, and relative platelet inhibition (RPI) were determined. The P-gp microRNA miR-27a increased by up to 7.67-fold (P = 0.004) and the clopidogrel area under the concentration-time curve (AUC) decreased by 14% (P > 0.05), but the AUC of H4 remained unchanged and RPI increased by up to 15% (P = 0.002) after aspirin administration. These findings indicate low-dose aspirin coadministration may decrease clopidogrel bioavailability but does not decrease its efficacy. PMID:24566733

  15. Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989–2008)

    PubMed Central

    Zakarija, Anaadriana; Kwaan, Hau C.; Moake, Joel L.; Bandarenko, Nicholas; Pandey, Dilip K.; McKoy, June M.; Yarnold, Paul R.; Raisch, Dennis W.; Winters, Jeffrey L.; Raife, Thomas J.; Cursio, John F.; Luu, Thanh Ha; Richey, Elizabeth A.; Fisher, Matthew J.; Ortel, Thomas L.; Tallman, Martin S.; Zheng, X. Long; Matsumoto, Masanori; Fujimura, Yoshihiro; Bennett, Charles L.

    2012-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a fulminant disease characterized by platelet aggregates, thrombocytopenia, renal insufficiency, neurologic changes, and mechanical injury to erythrocytes. Most idiopathic cases of TTP are characterized by a deficiency of ADAMTS13 (a disintegrin and metalloprotease, with thrombospondin-1-like domains) metalloprotease activity. Ironically, use of anti-platelet agents, the thienopyridine derivates clopidogrel and ticlopidine, is associated with drug induced TTP. Data were abstracted from a systematic review of English-language literature for thienopyridine-associated TTP identified in MEDLINE, EMBASE, the public website of the Food and Drug Administration, and abstracts from national scientific conferences from 1991 to April 2008. Ticlopidine and clopidogrel are the two most common drugs associated with TTP in FDA safety databases. Epidemiological studies identify recent initiation of anti-platelet agents as the most common risk factor associated with risks of developing TTP. Laboratory studies indicate that most cases of thienopyridine-associated TTP involve an antibody to ADAMTS13 metalloprotease, present with severe thrombocytopenia, and respond to therapeutic plasma exchange (TPE); a minority of thienopyridine-associated TTP presents with severe renal insufficiency, involves direct endothelial cell damage, and is less responsive to TPE. The evaluation of this potentially fatal drug toxicity can serve as a template for future efforts to comprehensively characterize other severe adverse drug reactions. PMID:19180126

  16. Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways.

    PubMed

    Braun, Oscar Ö; Angiolillo, Dominick J; Ferreiro, Jose L; Jakubowski, Joseph A; Winters, Kenneth J; Effron, Mark B; Duvvuru, Suman; Costigan, Timothy M; Sundseth, Scott; Walker, Joseph R; Saucedo, Jorge F; Kleiman, Neal S; Varenhorst, Christoph

    2013-12-01

    Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow® P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PRI) after 14 days of maintenance dosing. Clopidogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but not ABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention. PMID:24009042

  17. Comparison of P2Y12 receptor inhibition by clopidogrel and prasugrel in patients undergoing percutaneous coronary intervention.

    PubMed

    Haq, M M; Ahsan, C H; Amin, M N; Karim, M R; Ali, M L; Khan, S R; Chowdhury, M Z; Mansur, M; Millat, M H; Rashid, M A

    2013-12-01

    Dual antiplatelet treatment (DAPT) with aspirin and clopidogrel is vital after percutaneous coronary intervention (PCI). Clopidogrel and prasugrel act on P2Y12 platelet surface receptors. Both these P2Y12 inhibitors are pro-drugs and depend on cytochrome system of the liver for their conversion to active metabolite. There is growing concern regarding suboptimal response in platelet inhibition by clopidogrel. Verify Now system got approval by Federal Drug Administration, USA, for assessing platelet function as its result is almost comparable to gold standard Light Transmission Aggregometry (LTA). There are no data on the prevalence of clopidogrel resistance in Bangladeshi population. Prasugrel, as an antiplatelet drug, is a newer introduction in this country. This study will show light on the efficacy of these drugs on our population especially in patients who undergo PCI where DAPT is mandatory. A total 120 (60 diabetics) patients with Acute Coronary Syndrome (ACS), were alternatively given 600 mg clopidogrel loading dose (LD) followed by 75 mg maintenance dose (MD) daily or 60 mg LD of prasugrel followed by 10 mg MD daily. Five samples of blood were taken at different time intervals over a period of 2 weeks. Measurement of percent inhibition of P2Y12 was done by VerifyNow. Patients who showed less than 20% inhibition (clopidogrel resistant) at any stage were switched to prasugrel. The outcomes of clopidogrel, prasugrel and clopidogrel switched to prasugrel groups were then compared. Nearly half (46.7%) of the patients in the clopidogrel group was found resistant to the drug as opposed to none in the prasugrel group. No difference was found between diabetic and non-diabetic subjects with respect to drug resistance. Intracoronary blood samples showed high degree of platelet inhibition with prasugrel. There was a gradual decline of platelet inhibition over two weeks with prasugrel. Almost fifty percent of the population is clopidogrel resistant in our study

  18. [Proton pump inhibitors and clopidogrel: a hazardous association?].

    PubMed

    Szymezak, J; Gaussem, P

    2013-02-01

    Proton pump inhibitors (PPI) and antiplatelet agents, especially aspirin and clopidogrel, are among the most prescribed medications worldwide. Their co-administration is justified by the increased risk of gastrointestinal bleeding related to the antiplatelet therapy. The issue of the interaction between PPI and clopidogrel has been raised with the emergence of the concept of "high on-clopidogrel platelet reactivity" (or "clopidogrel resistance") together with the discovery of the role of CYP2C19 isoform in the pharmacokinetics of those two medications. Indeed, CYP2C19 is involved in the conversion of the clopidogrel pro-drug into its active metabolite and is involved in the metabolisation of PPI into inactive metabolites, acting as substrates/inhibitors of CYP2C19. Despite their heterogeneity, most pharmacodynamic studies have shown a decreased clopidogrel antiplatelet effect when associated to PPI, especially those with the highest CYP2C19 inhibiting activity (omeprazole, lansoprazole, rabeprazole). On the other hand, clinical studies are inconclusive. Retrospective studies have shown an increased risk of major cardiovascular events or mortality when clopidogrel and PPI are associated in comparison with clopidogrel alone, particularly in the patients with the higher cardiovascular risk. However, the two prospective randomized studies published so far did not find any interaction and confirmed the benefit of PPI on the gastrointestinal bleeding. As a conclusion, as the clinical studies are not conclusive, the French health authorities have recently removed the alert about this interaction. PPI and clopidogrel can thus be co-prescribed. PMID:23200799

  19. Bleeding risk with clopidogrel and percutaneous endoscopic gastrostomy

    PubMed Central

    Sohail, Umair; Harleen, Chela; Mahdi, Amin O; Arif, Murtaza; Nguyen, Douglas L; Bechtold, Matthew L

    2016-01-01

    AIM To compare bleeding within 48 h in patients undergoing percutaneous endoscopic gastrostomy (PEG) with or without clopidogrel. METHODS After institutional review board approval, a retrospective study involving a single center was conducted on adult patients having PEG (1/08-1/14). Patients were divided into two groups: Clopidogrel group consisting of those patients taking clopidogrel within 5 d of PEG and the non-clopidogrel group including those patients not taking clopidogrel within 5 d of the PEG. RESULTS Three hundred and nineteen PEG patients were found. One hundred and sixty-eight males and 151 females with mean body mass index 28.47 ± 9.75 kg/m2 and mean age 65.03 ± 16.11 years were identified. Thirty-three patients were on clopidogrel prior to PEG with 286 patients not on clopidogrel. No patients in either group developed hematochezia, melena, or hematemesis within 48 h of percutaneous endoscopic gastrostomy (PEG). No statistical differences were observed between the two groups with 48 h for hemoglobin decrease of > 2 g/dL (2 vs 5 patients; P = 0.16), blood transfusions (2 vs 7 patients; P = 0.24), and repeat endoscopy for possible gastrointestinal bleeding (no patients in either group). CONCLUSION Based on the results, no significant post-procedure bleeding was observed in patients undergoing PEG with recent use of clopidogrel. PMID:27621767

  20. Variability of on-treatment platelet reactivity in patients on clopidogrel.

    PubMed

    Freynhofer, Matthias K; Bruno, Veronika; Brozovic, Ivan; Jarai, Rudolf; Vogel, Birgit; Farhan, Serdar; Hübl, Wolfgang; Willheim, Martin; Wojta, Johann; Huber, Kurt

    2014-01-01

    Response to clopidogrel therapy is subject to inter-individual variability. However, data with regard to on-treatment platelet reactivity over time in patients undergoing coronary stenting are scarce. For this prospective observational study, 102 consecutive patients on dual antiplatelet therapy undergoing coronary stenting due to stable coronary artery disease (CAD; n = 29), non ST-elevation acute coronary syndrome (NSTE-ACS; n = 45) and ST-elevation myocardial infarction (STEMI; n = 28) were enrolled. Vasodilator-stimulated phosphoprotein-phosphorylation assay was performed at baseline, as well as 1, 3 and 6 months thereafter. Platelet reactivity index (PRI) measured after 1, 3 and 6 months was lower compared to baseline values (p < 0.001). Variables responsible for reduced response to clopidogrel at baseline (reticulated platelet fraction, simvastatin therapy) and during steady-state phase (body mass index, blood glucose concentrations, cholesterol/HDL-ratio and quality of life score) were different. High on-treatment platelet reactivity (HTPR)-phenotype (cut-off = 50% PRI) within the first month changed in 31% of stable CAD, 33% of NSTE-ACS and 39% of STEMI patients, respectively. HTPR-phenotype in the steady-state phase (month 1 to 6) changed in 45% of stable CAD, 33% of NSTE-ACS and 25% of STEMI patients. Response to clopidogrel and accordingly platelet function might vary over time, especially when a cut-off based approach, is used. There was a significant reduction of on-treatment platelet reactivity within the first month after percutaneous coronary intervention with stenting which was maintained for up to 6 months. Variables associated with reduced response to clopidogrel at baseline and during steady-state phase were different, as the latter mainly reflected an unfavorable metabolic profile, comprising elevated BMI, blood glucose levels as well as cholesterol/HDL-ratio.

  1. Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy: A Randomized Controlled Trial

    PubMed Central

    Wu, Jie; Duan, Shu-Wei; Sun, Xue-Feng; Li, Wen-Ge; Wang, Ya-Ping; Liu, Wen-Hu; Zhang, Jian-Rong; Lun, Li-De; Li, Xue-Mei; Zhou, Chun-Hua; Li, Ji-Jun; Liu, Shu-Wen; Xie, Yuan-Sheng; Cai, Guang-Yan; Ma, Lu; Huang, Wen; Wu, Hua; Jia, Qiang; Chen, Xiang-Mei

    2016-01-01

    Background: The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. Methods: It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry. Results: The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18–0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44–96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54–12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (−6.72 [95% CI −9.46 to −3.98] ml∙min−1∙1.73 m−2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed. Conclusions: Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain

  2. Pharmacodynamic effects of standard dose prasugrel versus high dose clopidogrel in non-diabetic obese patients with coronary artery disease.

    PubMed

    Darlington, Andrew; Tello-Montoliu, Antonio; Rollini, Fabiana; Ueno, Masafumi; Ferreiro, José Luis; Patel, Ronakkumar; Desai, Bhaloo; Guzman, Luis A; Bass, Theodore A; Angiolillo, Dominick J

    2014-02-01

    Increased body weight is independently associated with impaired clopidogrel pharmacodynamic (PD) response. Prasugrel has more potent PD effects compared with clopidogrel, although its PD effects in obese patients are unknown. The aim of this prospective, randomised, study was to compare the PD effects of standard-dose prasugrel [60 mg loading dose (LD)/10 mg daily maintenance dose (MD)] with high-dose clopidogrel (900 mg LD/150 mg daily MD) in non-diabetic obese [body mass index (BMI) ≥30 kg/m²] patients, with coronary artery disease (CAD) on aspirin therapy. PD assessments (baseline, 2 hours post-LD and 6 ± 2 days after MD) were conducted using four platelet function assays, and the platelet reactivity index (PRI) assessed by VASP was used for sample size estimation. A total of 42 patients with a BMI of 36.42 ± 5.6 kg/m² completed the study. There were no differences in baseline PD measures between groups. At 2 hours post-LD, prasugrel was associated with lower PRI compared with clopidogrel (24.3 ± 5.5 vs 58.7 ± 5.7, p≤0.001), with consistent findings for all assays. At one-week, PRI values on prasugrel MD were lower than clopidogrel MD without reaching statistical significance (34.7 ± 5.8 vs 42.9 ± 5.8, p=0.32), with consistent findings for all assays. Accordingly, rates of high on-treatment platelet reactivity were markedly reduced after prasugrel LD, but not after MD. In conclusion, in non-diabetic obese patients with CAD, standard prasugrel dosing achieved more potent PD effects than high-dose clopidogrel in the acute phase of treatment, but this was not sustained during maintenance phase treatment. Whether an intensified prasugrel regimen is required in obese patients warrants investigation.

  3. Development and validation of an HPLC-MS/MS method to quantify clopidogrel acyl glucuronide, clopidogrel acid metabolite, and clopidogrel in plasma samples avoiding analyte back-conversion.

    PubMed

    Silvestro, Luigi; Gheorghe, Mihaela; Iordachescu, Adriana; Ciuca, Valentin; Tudoroniu, Ariana; Rizea Savu, Simona; Tarcomnicu, Isabela

    2011-08-01

    A new sensitive and fast quantitative analytical method for the simultaneous determination of clopidogrel, its main metabolite clopidogrel carboxylic acid, and the newly described acyl glucuronide metabolite, in human plasma samples, is presented. The analytical procedures (plasma storage, handling, and extract storage in the autosampler) were optimized in order to avoid back-conversion; a known drawback in measurements of clopidogrel. Clopidogrel acyl glucuronide was confirmed as a major source of back-conversion to the parent drug in the presence of methanol, and thorough stability experiments were carried out to find the most appropriate conditions for an accurate analysis of clopidogrel and the two metabolites. The method was validated by assessing selectivity, sensitivity, linearity, accuracy, and precision for all three analytes, in accordance to Food and Drug Administration guidelines. Spiked quality controls in plasma as well as incurred samples were used to verify back-conversion in the selected conditions, with results meeting European Medicines Agency acceptance criteria (concentrations within 80-120% of the first reading). The method was then applied to a pharmacokinetic study, and for the first time, a pharmacokinetic curve of clopidogrel acyl glucuronide in human plasma is presented. The concentrations ranged up to 1,048.684 ng/mL, with a mean of 470.268 ng/mL, while clopidogrel had a mean C(max) of 1.348 ng/mL; these orders of magnitude show how much the back-conversion of this metabolite may influence clopidogrel quantification if it is not properly controlled.

  4. Online Course Evaluations Response Rates

    ERIC Educational Resources Information Center

    Guder, Faruk; Malliaris, Mary

    2013-01-01

    This paper studies the reasons for low response rates in online evaluations. Survey data are collected from the students to understand factors that might affect student participation in the course evaluation process. When course evaluations were opened to the student body, an email announcement was sent to all students, and a reminder email was…

  5. Use of a Thrombelastograph Platelet Mapping Assay for Diagnosis of Clopidogrel Resistance: A Case Report

    PubMed Central

    Morton, John; Nelluri, Satyanarayana

    2009-01-01

    Abstract: A 62-year-old woman presented to the emergency department with sudden collapse, intractable ventricular fibrillation, and an inferior wall myocardial infarction (MI). An emergent cardiac catheterization showed a totally occluded right coronary artery (RCA). A bare-metal stent was placed in the stenosis, resulting in thrombolysis in myocardial infarction (TIMI)-III flow with 0% residual stenosis. Four days after stenting, the patient developed chest pain. A repeat cardiac catheterization showed a totally occluded stent. The patient was subsequently tested using a thrombelastograph (TEG) Platelet Mapping assay to exclude clopidogrel resistance. The assay confirmed the patient to be non-responsive to clopidogrel for the inhibition of platelet ADP receptors. In an attempt to increase ADP inhibition, the ADP antagonist was changed to ticlopidine. Further testing was confounded by the presence of abciximab; however, the patient has remained free of cardiac events. PMID:19361030

  6. Cytochrome allelic variants and clopidogrel metabolism in cardiovascular diseases therapy.

    PubMed

    Jarrar, Mohammed; Behl, Shalini; Manyam, Ganiraju; Ganah, Hany; Nazir, Mohammed; Nasab, Reem; Moustafa, Khaled

    2016-06-01

    Clopidogrel and aspirin are among the most prescribed dual antiplatelet therapies to treat the acute coronary syndrome and heart attacks. However, their potential clinical impacts are a subject of intense debates. The therapeutic efficiency of clopidogrel is controlled by the actions of hepatic cytochrome P450 (CYPs) enzymes and impacted by individual genetic variations. Inter-individual polymorphisms in CYPs enzymes affect the metabolism of clopidogrel into its active metabolites and, therefore, modify its turnover and clinical outcome. So far, clinical trials fail to confirm higher or lower adverse cardiovascular effects in patients treated with combinations of clopidogrel and proton pump inhibitors, compared with clopidogrel alone. Such inconclusive findings may be due to genetic variations in the cytochromes CYP2C19 and CYP3A4/5. To investigate potential interactions/effects of these cytochromes and their allele variants on the treatment of acute coronary syndrome with clopidogrel alone or in combination with proton pump inhibitors, we analyze recent literature and discuss the potential impact of the cytochrome allelic variants on cardiovascular events and stent thrombosis treated with clopidogrel. The diversity of CYP2C19 polymorphisms and prevalence span within various ethnic groups, subpopulations and demographic areas are also debated. PMID:27072373

  7. Sustained increase in platelet aggregation after the cessation of clopidogrel.

    PubMed

    Djukanovic, Nina; Todorovic, Zoran; Zamaklar-Trifunovic, Danijela; Protic, Dragana; Dzudovic, Boris; Ostojic, Miodrag; Obradovic, Slobodan

    2016-02-01

    This study shows that the abrupt cessation of one-year clopidogrel treatment was not associated with thrombotic events in a prospective, multicentre study that enrolled 200 patients subjected to coronary stent implantation and treated with aspirin + clopidogrel 1 year after the stent placement. The aim of the study was to investigate the causes of a sustained increase of platelet aggregability, considering that the values of platelet aggregation stimulated with ADP + PGE1 (ADPHS values) significantly increased 10-90 days after the cessation of clopidogrel. Values of platelet aggregation induced by thrombin receptor activating peptide (TRAP values) and arachidonic acid (ASPI values) were divided into quartiles on the basis of ADPHS values 10 days after stopping clopidogrel (ADPHS10 ). There was a significant difference between TRAP values divided into quartiles according to ADPHS10 , 10, 45 and 90 days after stopping clopidogrel (P < 0.001, all), and ASPI values across the same quartiles 10 and 45 days after the cessation of clopidogrel (P = 0.028 and 0.003). The results of the study indicate that patients with early pronounced rebound phenomena to clopidogrel termination have a long-term (at least 90 days) increased platelet aggregation to other agonists such as thrombin-related activated protein and arachidonic acid, suggesting the complex mutual relationship of various factors/agonists influencing the function of platelets. PMID:26515635

  8. Information Science and Responsive Evaluation

    ERIC Educational Resources Information Center

    Stake, Robert E.

    2014-01-01

    Responsive evaluation builds upon the methods of informal evaluation in disciplined ways: getting personally acquainted with the evaluand, observation of activities, interviewing people who are in different ways familiar with the evaluand, searching documents that reveal what happened in the past or somewhere else. It calls for sustained effort to…

  9. Population pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in aspirin-treated patients with stable coronary artery disease.

    PubMed

    Ernest, C Steven; Small, David S; Rohatagi, Shashank; Salazar, Daniel E; Wallentin, Lars; Winters, Kenneth J; Wrishko, Rebecca E

    2008-12-01

    The aim of the current analysis was to characterize the population PK of prasugrel and clopidogrel metabolites, the resulting PD response, and identification of covariates for key PK/PD parameters. Aspirin-treated subjects with coronary artery disease were randomized to double-blind treatment with clopidogrel 600 mg loading dose (LD) followed by daily 75 mg maintenance dose (MD) or prasugrel 60 mg LD and daily 10 mg MD for 28 days. Plasma concentrations of prasugrel active metabolite (Pras-AM) and prasugrel's inactive thiolactone metabolite (Pras-thiolactone) were simultaneously fit to a multicompartmental model; a similar model adequately described clopidogrel's active metabolite (Clop-AM) PK. By linking to the PK model through the active metabolite concentrations, the PK/PD model characterized the irreversible inhibition of platelet aggregation through a sigmoidal Emax model. Although dose, sex, and weight were identified as significant covariates in the prasugrel PK model, only the effect of body weight produced significant changes in Pras-AM exposure. Generally, these factors resulted in only minor changes in Pras-AM exposures such that, overall, the change in the resulting maximal platelet aggregation (MPA) was predicted to be < or =10% points on average. The clopidogrel PK model included dose as a covariate indicating that a significantly less-than-proportional increase in Clop-AM exposure is expected over the dose range of 75-600 mg, thus, the model-predicted PD response is lower than might be anticipated given an 8-fold difference in dose and lower than that typically achieved following prasugrel 60 mg LD. The greater PD response with prasugrel compared with clopidogrel was accounted for by greater conversion of dose to active metabolite. PMID:19023649

  10. The active metabolite of Clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts

    PubMed Central

    Savi, Pierre; Zachayus, Jean-Luc; Delesque-Touchard, Nathalie; Labouret, Catherine; Hervé, Caroline; Uzabiaga, Marie-Françoise; Pereillo, Jean-Marie; Culouscou, Jean-Michel; Bono, Françoise; Ferrara, Pascual; Herbert, Jean-Marc

    2006-01-01

    P2Y12, a G protein-coupled receptor that plays a central role in platelet activation has been recently identified as the receptor targeted by the antithrombotic drug, clopidogrel. In this study, we further deciphered the mechanism of action of clopidogrel and of its active metabolite (Act-Met) on P2Y12 receptors. Using biochemical approaches, we demonstrated the existence of homooligomeric complexes of P2Y12 receptors at the surface of mammalian cells and in freshly isolated platelets. In vitro treatment with Act-Met or in vivo oral administration to rats with clopidogrel induced the breakdown of these oligomers into dimeric and monomeric entities in P2Y12 expressing HEK293 and platelets respectively. In addition, we showed the predominant association of P2Y12 oligomers to cell membrane lipid rafts and the partitioning of P2Y12 out of rafts in response to clopidogrel and Act-Met. The raft-associated P2Y12 oligomers represented the functional form of the receptor, as demonstrated by binding and signal transduction studies. Finally, using a series of receptors individually mutated at each cysteine residue and a chimeric P2Y12/P2Y13 receptor, we pointed out the involvement of cysteine 97 within the first extracellular loop of P2Y12 in the mechanism of action of Act-Met. PMID:16835302

  11. Different effects of proton pump inhibitors and famotidine on the clopidogrel metabolic activation by recombinant CYP2B6, CYP2C19 and CYP3A4.

    PubMed

    Ohbuchi, Masato; Noguchi, Kiyoshi; Kawamura, Akio; Usui, Takashi

    2012-07-01

    Inhibitory potential of proton pump inhibitors (PPIs) and famotidine, an H(2) receptor antagonist, on the metabolic activation of clopidogrel was evaluated using recombinant CYP2B6, CYP2C19 and CYP3A4. Formation of the active metabolite from an intermediate metabolite, 2-oxo-clopidogrel, was investigated by liquid chromatography-tandem mass spectrometry and three peaks corresponding to the pharmacologically active metabolite and its stereoisomers were detected. Omeprazole potently inhibited clopidogrel activation by CYP2C19 with an IC(50) of 12.8 μmol/L and more weakly inhibited that by CYP2B6 and CYP3A4. IC(50) of omeprazole for CYP2C19 and CYP3A4 was decreased about two- and three-fold, respectively, by 30-min preincubation with NADPH. Lansoprazole, esomeprazole, pantoprazole, rabeprazole and rabeprazole thioether, a major metabolite, also inhibited metabolic activation by CYP2C19, with an IC(50) of 4.3, 8.9, 48.3, 36.2 and 30.5 μmol/L, respectively. In contrast, famotidine showed no more than 20% inhibition of clopidogrel activation by CYP2B6, CYP2C19 and CYP3A4 at up to 100 μmol/L and had no time-dependent CYP2C19 and CYP3A4 inhibition. These results provide direct evidence that PPIs inhibit clopidogrel metabolic activation and suggest that CYP2C19 inhibition is the main cause of drug-drug interaction between clopidogrel and omeprazole. Famotidine is considered as a safe anti-acid agent for patients taking clopidogrel. PMID:22313038

  12. Comparative fasting bioavailability of two clopidogrel formulations in healthy Mediterranean volunteers: an in vitro–in vivo correlation

    PubMed Central

    Zaid, Abdel Naser; Al Ramahi, Rowa’; Bustami, Rana; Mousa, Ayman; Khasawneh, Sewar

    2015-01-01

    Objective The aim of this study was to evaluate the bioequivalence of two drug products, generic clopidogrel bisulfate 75 mg film-coated tablets versus the reference Plavix® clopidogrel bisulfate 75 mg film-coated tablets. Methods Bioequivalence of tablets was tested by comparisons against the reference brand product in accordance with the requirements of the Declaration of Helsinki, the current Good Clinical Practice Guidelines, and the International Conference on Harmonization. Results The relationship between concentration and peak area ratio was found to be linear within the range 24.500–1,836.600 pg/mL for clopidogrel. The correlation coefficient (r) was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between test and reference. The point estimates (ratios of geometric mean) were 104.122%, 104.184%, and 109.091% for areas under the plasma concentration–time curve (AUC) AUC0-last, AUC0-∞, and peak plasma concentration Cmax, respectively. These pharmacokinetic parameter values of clopidogrel and its main metabolite lie within the bioequivalence limit (80%–125%) specified by the US Food and Drug Administration and the European Medicines Agency. Conclusion The tested drug product was bioequivalent to the reference drug under fasting conditions and had the same safety profile, which is important to achieve equivalent therapeutic effect with the reference. PMID:25987833

  13. Role of phenotypic and genetic testing in managing clopidogrel therapy.

    PubMed

    Chan, Noel C; Eikelboom, John W; Ginsberg, Jeffrey S; Lauw, Mandy N; Vanassche, Thomas; Weitz, Jeffrey I; Hirsh, Jack

    2014-07-31

    The P2Y12 inhibitors, clopidogrel, prasugrel, and ticagrelor, are administered in fixed doses without laboratory monitoring. Randomized trials in acute coronary syndrome have shown that prasugrel and ticagrelor are more effective than standard-dose clopidogrel. Nonetheless, standard-dose clopidogrel remains widely used because it causes less bleeding and is less expensive. Patients treated with standard-dose clopidogrel have substantial variability in platelet inhibition, which is partly explained by genetic polymorphisms encoding CYP2C19, the hepatic enzyme involved in biotransformation of clopidogrel to its active metabolite. Some advocate tailoring P2Y12 inhibitor therapy according to the results of routine laboratory testing. Although there is good evidence for analytic, biological, and clinical validity of several phenotypic and genotypic biomarkers, the benefit of a management strategy that incorporates routine biomarker testing over standard of care without such testing remains unproven. Appropriately designed, adequately powered trials are needed but face the challenges of feasibility, cost, and the progressive switch from clopidogrel to prasugrel or ticagrelor.

  14. Aspirin resistance or variable response or both?

    PubMed

    Cheng, Xi; Chen, Wai-Hong; Simon, Daniel I

    2006-11-20

    Numerous clinical trials have demonstrated that aspirin is effective in secondary prevention and in high-risk primary prevention of adverse cardiovascular events. However, a constellation of clinical and laboratory evidence exists that demonstrates diminished or absent response to aspirin in some patients. This has led to the concept of "aspirin resistance," which is a poorly defined, somewhat misleading term. The mechanism for aspirin resistance has not been fully established, but it is almost certainly due to a combination of clinical, biological, and genetic properties affecting platelet function. There are no criteria for distinguishing true resistance from treatment failure, and there is no consensus on whether the definition of aspirin resistance should be based on clinical outcomes, laboratory evidence, or both. Studies in large populations are needed to define antiplatelet resistance using consistent and reproducible assays and correlate the measurements with clinical outcomes. One such prospective randomized trial is completed, and 2 others are under way: the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial compared clopidogrel and aspirin with placebo and aspirin for high-risk primary or secondary prevention, and the Aspirin Nonresponsiveness and Clopidogrel Endpoint Trial (ASCET) is evaluating whether switching to clopidogrel will be superior to continued aspirin therapy in improving clinical outcomes in aspirin-resistant patients with angiographically documented coronary artery disease. The Research Evaluation to Study Individuals Who Show Thromboxane or P2Y(12) Receptor Resistance (RESISTOR) trial is investigating whether modifying antiplatelet regimens could prevent myonecrosis after percutaneous coronary intervention in patients with aspirin and clopidogrel resistance. PMID:17097412

  15. [Clopidogrel- induced hepatotoxicity in hemodialyzed patient: a case report].

    PubMed

    Papagni, Sergio; Bonifati, Carmen; Dagostino, Filippo; Murgo, Angelo Marco

    2016-01-01

    Drug-induced liver injury is a frequent cause of acute liver failure. It may cause clinical manifestations ranging from simple alteration of the common liver function tests until more severe manifestations including encephalopathy, coagulopathy, and in many cases progressive multi-organ dysfunction. The condition, therefore, may be associated with higher morbidity and mortality as well as higher consumption of economic resources. In this paper, we present the case of a 71-year-old patient treated with hemodialysis, diabetic, with ischemic cardiopathy and severe peripheral vascular disease. The patient presented a progressive clinical deterioration with the development of ascites, jaundice and significant deterioration of liver function. Diagnostic studies have ruled out viral and immunological diseases and, in agreement with the score obtained from the Maria and Victorino scale, clopidogrel was identified as the major factor responsible for the damage. After the suspension of the drug, the follow-up has led to the complete and stable recovery of liver function. PMID:26913747

  16. Delayed clopidogrel transit during myocardial infarction evident on angiography.

    PubMed

    Ghobrial, Joanna; Gibson, C Michael; Pinto, Duane S

    2015-05-01

    We describe the case of a patient with non-ST segment elevation myocardial infarction (NSTEMI) where a limitation of oral clopidogrel loading prior to percutaneous coronary intervention (PCI) was directly visualized on angiography. Clopidogrel is a thienopyridine antiplatelet agent used in acute coronary syndromes. It reduces platelet aggregation via inhibition of the P2Y12 receptor. Clopidogrel is an inactive metabolite that is metabolized into the active metabolite by the cytochrome P450 isoenzymes located mostly in the liver and partly in the gastrointestinal system. As such, it requires at least 2 hours to reach maximal effect. A 63-year-old female went to an outside facility where she was diagnosed with NSTEMI and underwent angiography. She was administered 324 mg of aspirin and 600 mg of clopidogrel, and was transferred to our facility. Upon arrival, approximately 1.5 hours after the oral loading dose, the clopidogrel tablets were visualized intact in the stomach during angiography, implying a very low likelihood of adequate absorption or antiplatelet effect. This observation raises the concern that delayed gastrointestinal transit, apart from other metabolic derangements, may be a factor in achieving optimal platelet inhibition using oral agents. PMID:25929306

  17. Clopidogrel Enhances Mesenchymal Stem Cell Proliferation Following Periodontitis.

    PubMed

    Coimbra, L S; Steffens, J P; Alsadun, S; Albiero, M L; Rossa, C; Pignolo, R J; Spolidorio, L C; Graves, D T

    2015-12-01

    Bone formation is dependent on the differentiation of osteoblasts from mesenchymal stem cells (MSCs). In addition to serving as progenitors, MSCs reduce inflammation and produce factors that stimulate tissue formation. Upon injury, MSCs migrate to the periodontium, where they contribute to regeneration. We examined the effect of clopidogrel and aspirin on MSCs following induction of periodontitis in rats by placement of ligatures. We showed that after the removal of ligatures, which induces resolution of periodontal inflammation, clopidogrel had a significant effect on reducing the inflammatory infiltrate. It also increased the number of osteoblasts and MSCs. Mechanistically, the latter was linked to increased proliferation of MSCs in vivo and in vitro. When given prior to inducing periodontitis, clopidogrel had little effect on MSC or osteoblasts numbers. Applying aspirin before or after induction of periodontitis did not have a significant effect on the parameters measured. These results suggest that clopidogrel may have a positive effect on MSCs in conditions where a reparative process has been initiated.

  18. Actively using clopidogrel correlates with an increased risk of acute pancreatitis in Taiwan.

    PubMed

    Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

    2015-03-15

    The aim of this study is to assess whether there is an association between clopidogrel use and risk of acute pancreatitis in Taiwan. We conducted a case-control study using the database of the Taiwan National Health Insurance Program from 2000 to 2011. There were 5644 subjects aged 20-84 years with a first-time attack of acute pancreatitis as the case group and 22,576 randomly selected sex-matched and age-matched subjects without acute pancreatitis as the control group. We defined clopidogrel use as "actively using" if the final clopidogrel prescription was filled between 0 and 7 days before the date of diagnosing acute pancreatitis, or "not actively using" if the final clopidogrel prescription was filled ≧ 8 days before the date of diagnosing acute pancreatitis. Subjects who never used clopidogrel were defined as never used. The multivariable logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of acute pancreatitis associated with clopidogrel use. Comparing the subjects actively using clopidogrel to those who never used clopidogrel, the adjusted OR of acute pancreatitis was 8.46 (95%CI 5.25, 13.7). The adjusted OR decreased to 1.16 among subjects not actively using clopidogrel (95%CI 0.95, 1.43). Persons actively using clopidogrel are at an increased risk of acute pancreatitis. Further studies are necessary to prove the causal relationship.

  19. Changing CS Features Alters Evaluative Responses in Evaluative Conditioning

    ERIC Educational Resources Information Center

    Unkelbach, Christian; Stahl, Christoph; Forderer, Sabine

    2012-01-01

    Evaluative conditioning (EC) refers to changes in people's evaluative responses toward initially neutral stimuli (CSs) by mere spatial and temporal contiguity with other positive or negative stimuli (USs). We investigate whether changing CS features from conditioning to evaluation also changes people's evaluative response toward these CSs. We used…

  20. Aligning collaborative and culturally responsive evaluation approaches.

    PubMed

    Askew, Karyl; Beverly, Monifa Green; Jay, Michelle L

    2012-11-01

    The authors, three African-American women trained as collaborative evaluators, offer a comparative analysis of collaborative evaluation (O'Sullivan, 2004) and culturally responsive evaluation approaches (Frierson, Hood, & Hughes, 2002; Kirkhart & Hopson, 2010). Collaborative evaluation techniques immerse evaluators in the cultural milieu of the program, systematically engage stakeholders and integrate their program expertise throughout the evaluation, build evaluation capacity, and facilitate the co-creation of a more complex understanding of programs. However, the authors note that without explicit attention to considerations raised in culturally responsive evaluation approaches (for example, issues of race, power, and privilege), the voices and concerns of marginalized and underserved populations may be acknowledged, but not explicitly or adequately addressed. The intentional application of collaborative evaluation techniques coupled with a culturally responsive stance enhances the responsiveness, validity and utility of evaluations, as well as the cultural competence of evaluators.

  1. Clopidogrel plus Aspirin for Symptomatic Intracranial Atherosclerotic Stenosis: A Pilot Study

    PubMed Central

    Kass-Hout, Tareq; Winningham, Melanie; Kass-Hout, Omar; Henriquez, Laura; Tong, Frank; Dion, Jacques; Cawley, Michael; Belagaje, Samir; Frankel, Michael; Anderson, Aaron; Nahab, Fadi

    2016-01-01

    Background and Purpose There are limited data on the optimal duration of dual antiplatelet therapy for secondary stroke prevention in patients with symptomatic intracranial atherosclerotic disease. Methods Consecutive patients presenting with high-grade (70–99%) symptomatic intracranial stenosis from January 1, 2011, to December 31, 2013, and evaluated within 30 days of the index event were eligible for this analysis. All patients underwent treatment with aspirin plus clopidogrel for a target duration of 12 months along with aggressive medical management based on the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) protocol; all patients were given gastrointestinal prophylaxis for the duration of their aspirin and clopidogrel treatment. Clinical and safety outcomes of our cohort were compared with the medical arm of the SAMMPRIS trial cohort (n = 227). Results Our cohort included 25 patients that met the inclusion criteria. Achievement of blood pressure and LDL cholesterol targets were similar between our cohort and the SAMMPRIS cohort. At 1 year, the rates of stroke, myocardial infarction or vascular death were 0% in our cohort and 16% in the SAMMPRIS cohort (p = 0.03). At 1 year, major bleeding rates were similar between our cohort and the SAMMPRIS cohort (4 vs. 2.2%, p = 1.0). Conclusion A prolonged course of dual antiplatelet therapy for symptomatic intracranial atherosclerotic disease may be associated with less vascular events with no increase in hemorrhagic complications. PMID:27781044

  2. Educational Evaluation: Analysis and Responsibility.

    ERIC Educational Resources Information Center

    Apple, Michael W., Ed.; And Others

    This book presents controversial aspects of evaluation and aims at broadening perspectives and insights in the evaluation field. Chapter 1 criticizes modes of evaluation and the basic rationality behind them and focuses on assumptions that have problematic consequences. Chapter 2 introduces concepts of evaluation and examines methods of grading…

  3. Aligning Collaborative and Culturally Responsive Evaluation Approaches

    ERIC Educational Resources Information Center

    Askew, Karyl; Beverly, Monifa Green; Jay, Michelle L.

    2012-01-01

    The authors, three African-American women trained as collaborative evaluators, offer a comparative analysis of collaborative evaluation (O'Sullivan, 2004) and culturally responsive evaluation approaches (Frierson, Hood, & Hughes, 2002; Kirkhart & Hopson, 2010). Collaborative evaluation techniques immerse evaluators in the cultural milieu of the…

  4. A Summary: Responsive Evaluation and Family Practice

    ERIC Educational Resources Information Center

    Rakel, Robert E.

    1976-01-01

    The author feels that both responsive and preordinate methods would be useful in evaluating the family practice residency program at a medical school. Appropriate uses of both evaluation methods are suggested. (GDC)

  5. Clopidogrel treatment on the incidence and severity of community acquired pneumonia in a cohort study and meta-analysis of antiplatelet therapy in pneumonia and critical illness

    PubMed Central

    Gross, A. Kendall; Dunn, Steven P.; Feola, David J.; Martin, Craig A.; Charnigo, Richard; Li, Zhenyu; Abdel-Latif, Ahmed; Smyth, Susan S.

    2013-01-01

    Background Platelet activation results in the release and upregulation of mediators responsible for immune cell activation and recruitment, suggesting that platelets play an active role in immunity. Animal models and retrospective data have demonstrated benefit of antiplatelet therapy on inflammatory mediator expression and clinical outcomes. This study sought to characterize effects of clopidogrel on the incidence and severity of community-acquired pneumonia (CAP). Methods A retrospective cohort study was conducted of Kentucky Medicaid patients (2001-2005). The exposed cohort consisted of patients receiving at least six consecutive clopidogrel prescriptions; the non-exposed cohort was comprised of patients not prescribed clopidogrel. Primary endpoints included incidence of CAP and inpatient treatment. Secondary severity endpoints included mortality, intensive care unit admission, mechanical ventilation, sepsis, and acute respiratory distress syndrome/acute lung injury. Results CAP incidence was significantly greater in the exposed cohort (OR 3.39, 95% CI 3.27-3.51, p < 0.0001) that remained after adjustment (OR 1.48, 95% CI 1.41-1.55, p < 0.0001). Inpatient treatment was more common in the exposed cohort (OR 1.96, 95% CI 1.85-2.07, p < 0.0001), but no significant difference remained after adjustment. Trends favoring the exposed cohort were found for the secondary severity endpoints of mechanical ventilation (p = 0.07) and mortality (p = 0.10). Pooled analysis of published studies supports these findings. Conclusions While clopidogrel use may be associated with increased CAP incidence, clopidogrel does not appear to increase – and may reduce – its severity among inpatients. Because this study was retrospective and could not quantify all variables (e.g., aspirin use), these findings should be explored prospectively. PMID:23124575

  6. Cost-effectiveness of clopidogrel, prasugrel and ticagrelor for dual antiplatelet therapy after acute coronary syndrome: a decision-analytic model

    PubMed Central

    Abdel-Qadir, Husam; Roifman, Idan; Wijeysundera, Harindra C.

    2015-01-01

    Background: The use of prasugrel or ticagrelor as part of dual antiplatelet therapy with acetylsalicylic acid after acute coronary syndrome (ACS) improves clinical outcomes relative to clopidogrel. The relative cost-effectiveness of these agents are unknown. We conducted an economic analysis evaluating 12 months of treatment with clopidogrel, prasugrel or ticagrelor after ACS. Methods: We developed a fully probabilistic Markov cohort decision-analytic model using a lifetime horizon, from the perspective of the Ontario Ministry of Health and Long-Term Care. The model incorporated risks of death, recurrent ACS, heart failure, major bleeding and other adverse effects of treatment. Data on probabilities and utilities were obtained from the published literature where available. The primary outcome was quality-adjusted life-years (QALYs). Results: Treatment with clopidogrel was associated with the lowest effectiveness (7.41 QALYs, 95% confidence interval [CI] 1.05-14.79) and the lowest cost ($39 601, 95% CI $8434-$111 186). Ticagrelor treatment had an effectiveness of 7.50 QALYs (95% CI 1.13-14.84) at a cost of $40 649 (95% CI $9327-$111 881). The incremental cost-effectiveness ratio (ICER) for ticagrelor relative to clopidogrel was $12 205 per QALY gained. Prasugrel had an ICER of $57 630 per QALY gained relative to clopidogrel. Ticagrelor was the preferred option in 90% of simulations at a willingness-to-pay threshold of $50 000 per QALY gained. Interpretation: Ticagrelor was the most cost-effective agent when used as part of dual antiplatelet therapy after ACS. This conclusion was robust to wide variations in model parameters. PMID:26770967

  7. Cost-effectiveness analysis of short-term clopidogrel therapy for ST elevation myocardial infarction.

    PubMed

    Gibler, Kyle B; Huskamp, Haiden A; Sabatine, Marc S; Murphy, Sabina A; Cohen, David J; Cannon, Christopher P

    2010-03-01

    Clopidogrel improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and is recommended in the guidelines. We sought to determine the incremental cost-effectiveness of clopidogrel therapy in this patient population. We used primary patient-level resource use and clinical outcomes data from 3491 STEMI patients treated with fibrinolysis and either clopidogrel or placebo prior to a diagnostic coronary angiogram in the Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial. Costs for each patient were calculated based on diagnosis-related groups-specific Medicare reimbursement rates for all hospitalizations and the average wholesale price of clopidogrel. Cost per event prevented and cost per life year gained (LYG) were calculated using standard methods. The estimate of LYG due to clopidogrel therapy was based on recurrent myocardial infarction and death outcomes. The bootstrap method was used to produce bias-corrected confidence intervals for cost and efficacy estimates as well as the cost per LYG ratio. Total costs and resource use were not significantly different for the clopidogrel and placebo groups ($8128 vs. $8134), indicating that short-term clopidogrel therapy is an economically dominant treatment strategy. Even in a sensitivity analysis accounting for higher long-term medical costs due to greater life expectancy, clopidogrel remained under $6000 per LYG. Clopidogrel therapy was dominant in 35% of the bootstrap simulations and cost less than $50,000 per LYG in 67% of simulations. In conclusion, this analysis finds short-term clopidogrel therapy to be a highly economically attractive therapy, improving patient outcomes at no increase in costs. PMID:20215905

  8. A Ranking Method for Evaluating Constructed Responses

    ERIC Educational Resources Information Center

    Attali, Yigal

    2014-01-01

    This article presents a comparative judgment approach for holistically scored constructed response tasks. In this approach, the grader rank orders (rather than rate) the quality of a small set of responses. A prior automated evaluation of responses guides both set formation and scaling of rankings. Sets are formed to have similar prior scores and…

  9. Clopidogrel-Induced Severe Hepatitis: A Case Report and Literature Review

    PubMed Central

    Keshmiri, Hesam; Behal, Anuj; Shroff, Shawn

    2016-01-01

    Clopidogrel is a commonly prescribed antiplatelet agent that carries a rare risk of hepatotoxicity. We describe a case of severe clopidogrel-induced hepatitis with liver biopsy assessment. Prompt recognition and withdrawal of the offending agent are imperative to prevent progression and potentially fatal liver injury. PMID:27429813

  10. [Spinal cord ischaemia and preoperative clopidogrel withdrawal in an arteriosclerotic patient].

    PubMed

    Murat, O; Durand, E; Delépine, G; Nguyen, P; Malinovsky, J-M

    2008-04-01

    We report the case of a motor impairment associated with bladder dysfunction several days after clopidogrel withdrawal in an arteriosclerotic woman scheduled for thoracotomy under general and thoracic epidural anaesthesia. Even if spinal artery syndrome may have a lot of aetiologies, we believe in a direct link between clopidogrel withdrawal and medulla ischaemia. PMID:18378112

  11. The Pros and Cons of Responsive Evaluation.

    ERIC Educational Resources Information Center

    Hurteau, Marthe; Nadeau, Marc-Andre.

    The responsive model of evaluation has been seen as an alternative to formal evaluation models. This model was used for the evaluation of a Certificate in Industrial Relations program in a Quebec French university. This study focused on two main objectives: first, the local utility of the program being assessed, along with the major problems…

  12. Aspirin and Clopidogrel Alter Core Temperature and Skin Blood Flow during Heat Stress

    PubMed Central

    Bruning, Rebecca S.; Dahmus, Jessica D.; Kenney, W. Larry; Holowatz, Lacy A.

    2012-01-01

    Antithrombotic therapy with oral aspirin or clopidogrel (PlavixR) is associated with an attenuated skin vasodilator response and a greater rate of rise in core temperature in healthy, middle-aged individuals during passive heating in a water perfused suit. Purpose The present double-blind, crossover study examined the functional consequences of 7 days of low-dose aspirin (ASA, 81 mg/day) vs. clopidogrel (CLO, 75 mg/day) treatment in 14 healthy, middle-aged (50–65 yrs) men and women during passive heating in air (40 min at 30°C, 40% rh) followed by exercise (60% V̇O2peak). Methods Oral temperature (Tor) was measured in the antechamber (23.0 ± 0.1°C) before entering a warm environmental chamber. After 40 minutes of rest subjects cycled on a recumbent cycle ergometer for up to 120 minutes. Esophageal temperature (Tes) and laser Doppler flux were measured continuously, and the latter was normalized to maximal cutaneous vascular conductance (%CVCmax). Results Prior to entry into the environmental chamber there were no differences in Tor among treatments; however, after 40 minutes of rest in the heat, Tes was significantly higher for ASA and CLO vs. placebo (37.2±0.1°C, 37.3±0.1°C, vs. 37.0±0.1°C, both P<0.001), a difference that persisted throughout exercise (P<0.001 vs. placebo). The mean body temperature thresholds for the onset of cutaneous vasodilation were shifted to the right for both ASA and CLO during exercise (P<0.05). Conclusion ASA and CLO resulted in elevated core temperatures during passive heat stress and shifted the onset of peripheral thermoeffector mechanisms toward higher body temperatures during exercise heat stress. PMID:23135368

  13. Use of Responsive Evaluation in Statewide Program Evaluation

    ERIC Educational Resources Information Center

    Kalman, Marjorie

    1976-01-01

    A summer school program stressing basic skills for migrant children in a rural Illinois community was assessed according to Stake's responsive evaluation model. Informal communication, program activities, audience needs, and participant values were emphasized in this case study. This evaluation method provided useful information for the state's…

  14. Use of Responsive Evaluation in Statewide Program Evaluation.

    ERIC Educational Resources Information Center

    Kalman, Marjorie

    The objective of this paper is to discuss the utilization of Stake's theory of responsive evaluation by a unit in state government charged with the evaluation of the Illinois Migrant Program. Through interviews with state and local Title I staff, we were able to discover program purposes and concerns and to later conceptualize these concerns into…

  15. Combination of clopidogrel and everolimus dramatically reduced the development of transplant arteriosclerosis in murine aortic allografts.

    PubMed

    Eckl, Sebastian; Heim, Christian; Abele-Ohl, Silke; Hoffmann, Julia; Ramsperger-Gleixner, Martina; Weyand, Michael; Ensminger, Stephan M

    2010-09-01

    Our group has shown that platelet inhibition with clopidogrel, an antagonist of the P2Y12 adenosine diphosphate receptor on platelets, reduced the formation of transplant arteriosclerosis. The aim of this study was to investigate whether a combination of cyclosporin or everolimus with clopidogrel has a beneficial effect on the development of transplant arteriosclerosis. Fully MHC mismatched C57Bl/6 (H2(b)) donor aortas were transplanted into CBA.J (H2(k)) recipients and mice received either clopidogrel alone (1 mg/kg/day) or in combination with cyclosporin (2 mg/kg/day) or everolimus (0.05 mg/kg/day). Grafts were analysed by histology and morphometry on day 30 after transplantation. In mice treated with clopidogrel alone, transplant arteriosclerosis was significantly reduced [intima proliferation 56 +/- 11% vs. 81 +/- 7% (control)/n = 7]. Daily application of everolimus reduced the development of transplant arteriosclerosis compared with untreated controls [intima proliferation of 29 +/- 9% vs. 81 +/- 7% (control)/n = 7]. Strikingly, combination of clopidogrel and everolimus almost abolished the formation of transplant arteriosclerosis [intima proliferation: 11 +/- 8% vs. 81 +/- 7% (control)/n = 7]. By contrast, combination of cyclosporin and clopidogrel compared with clopidogrel alone showed no additive effect. These results demonstrate that combination of platelet- and mammalian target of Rapamycin-inhibition can dramatically reduce the development of transplant arteriosclerosis.

  16. Perioperative Management of Patients on Clopidogrel (Plavix) Undergoing Major Lung Resection

    PubMed Central

    Ceppa, DuyKhanh P.; Welsby, Ian J.; Wang, Tracy Y.; Onaitis, Mark W.; Tong, Betty C.; Harpole, David H.; D’Amico, Thomas A.; Berry, Mark F.

    2014-01-01

    BACKGROUND Management of patients requiring antiplatelet therapy with clopidogrel (Plavix) and major lung resection must balance the risks of bleeding and cardiovascular events. We reviewed our experience with patients treated with clopidogrel perioperatively to examine outcomes, including results of a new strategy for high-risk patients. METHODS Patients who underwent major lung resection and received perioperative clopidogrel between January 2005 and September 2010 were reviewed. Initially, clopidogrel management consisted of discontinuation approximately 5 days before surgery and resumption immediately after surgery. Following July 2010, high-risk patients (drug-eluting coronary stent placement within prior year or previous coronary event after clopidogrel discontinuation) were admitted 2–3 days preoperatively and bridged with the intravenous GP IIb/IIIa receptor inhibitor eptifibatide (Integrilin) according to a multidisciplinary cardiology/anesthesiology/thoracic surgery protocol. Outcomes were compared to control patients (matched for preoperative risk factors and extent of pulmonary resection) who did not receive perioperative clopidogrel. RESULTS Fifty-four patients who had major lung resection between January 2005 and September 2010 and received clopidogrel perioperatively were matched with 108 controls. Both groups had similar mortality, postoperative length of stay, and no differences in the rates of perioperative transfusions, reoperations for bleeding, myocardial infarctions, and strokes. Seven of the 54 clopidogrel patients were admitted preoperatively for an eptifibatide bridge. Two of these patients received perioperative transfusions, but there were no mortalities, reoperations, myocardial infarctions, or stroke. CONCLUSIONS Patients taking clopidogrel can safely undergo major lung resection. Treatment with an eptifibatide bridge may minimize the risk of cardiovascular events in higher risk patients. PMID:21978871

  17. The evolution of dual antiplatelet therapy in the setting of acute coronary syndrome: ticagrelor versus clopidogrel.

    PubMed

    Amico, Frank; Amico, Angela; Mazzoni, Jennifer; Moshiyakhov, Mark; Tamparo, William

    2016-01-01

    Review of: Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Eng J Med 2009; 361(11): 1045-1057. For acute coronary syndrome (ACS), a dual antiplatelet regimen comprised of treatment with aspirin and either P2Y12 adenosine diphosphate receptor antagonists, clopidogrel, prasugrel or ticagrelor is usually employed. This article compares clopidogrel with ticagrelor for the prevention of vascular events and death in broad population of ACS patients ranging from UA, NSTEMI to STEMI, utilizing planned strategies of medical or invasive treatment strategy. PMID:26560350

  18. Clopidogrel-Associated Thrombotic Thrombocytopenic Purpura following Endovascular Treatment of Spontaneous Carotid Artery Dissection

    PubMed Central

    Rubano, Jerry A.; Chen, Kwan; Sullivan, Brianne; Vosswinkel, James A.; Jawa, Randeep S.

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disease secondary to platelet aggregation. We present a patient who developed profound thrombocytopenia and anemia 8 days following initiation of therapy with clopidogrel after stent placement for carotid artery dissection. She did not have a disintegrin and metalloproteinase with thrombospondin domain 13 (ADAMTS 13) deficiency. Management included steroids and therapeutic plasma exchange. Clopidogrel has rarely been associated with TTP. Unlike other causes of acquired TTP, the diagnosis of early clopidogrel-associated TTP is largely clinical given the infrequent reduction in ADAMTS 13 activity. PMID:26623244

  19. Platelet factor XIIIa release during platelet aggregation and plasma clot strength measured by thrombelastography in patients with coronary artery disease treated with clopidogrel.

    PubMed

    Kreutz, Rolf P; Owens, Janelle; Lu, Deshun; Nystrom, Perry; Jin, Yan; Kreutz, Yvonne; Desta, Zeruesenay; Flockhart, David A

    2015-01-01

    It has been estimated that up to half of circulating factor XIIIa (FXIIIa) is stored in platelets. The release of FXIIIa from platelets upon stimulation with adenosine diphosphate (ADP) in patients with coronary artery disease treated with dual antiplatelet therapy has not been previously examined. Samples from 96 patients with established coronary artery disease treated with aspirin and clopidogrel were examined. Platelet aggregation was performed by light transmittance aggregometry in platelet-rich plasma (PRP), with platelet-poor plasma (PPP) as reference, and ADP 5 µM as agonist. Kaolin-activated thrombelastography (TEG) was performed in citrate PPP. PRP after aggregation was centrifuged and plasma supernatant (PSN) collected. FXIIIa was measured in PPP and PSN. Platelet aggregation after stimulation with ADP 5 µM resulted in 24% additional FXIIIa release in PSN as compared to PPP (99.3 ± 27 vs. 80.3 ± 24%, p < 0.0001). FXIIIa concentration in PSN correlated with maximal plasma clot strength (TEG-G) (r = 0.48, p < 0.0001), but not in PPP (r = 0.15, p = 0.14). Increasing quartiles of platelet-derived FXIIIa were associated with incrementally higher TEG-G (p = 0.012). FXIIIa release was similar between clopidogrel responders and non-responders (p = 0.18). In summary, platelets treated with aspirin and clopidogrel release a significant amount of FXIIIa upon aggregation by ADP. Platelet-derived FXIIIa may contribute to differences in plasma TEG-G, and thus, in part, provide a mechanistic explanation for high clot strength observed as a consequence of platelet activation. Variability in clopidogrel response does not significantly influence FXIIIa release from platelets. PMID:24833046

  20. Implementation of Cell Samples as Controls in National Proficiency Testing for Clopidogrel Therapy-Related CYP2C19 Genotyping in China: A Novel Approach

    PubMed Central

    Zhang, Kuo; Wang, Lunan; Zhang, Rui; Xie, Jiehong; Li, Jinming

    2015-01-01

    Laboratories are increasingly requested to perform CYP2C19 genetic testing when managing clopidogrel therapy, especially in patients with acute coronary syndrome undergoing percutaneous coronary intervention. To ensure high quality molecular testing and ascertain that the referring clinician has the correct information for CYP2C19 genotype–directed antiplatelet therapy, a proficiency testing scheme was set up to evaluate the laboratory performance for the entire testing process. Proficiency panels of 10 cell samples encompassing the common CYP2C19 genetic polymorphisms were distributed to 62 participating laboratories for routine molecular testing and the responses were analyzed for accuracy of genotyping and the reporting of results. Data including the number of samples tested, the accreditation/certification status, and test methodology of each individual laboratory were also reviewed. Fifty-seven of the 62 participants correctly identified the CYP2C19 variants in all samples. There were six genotyping errors, with a corresponding analytical sensitivity of 98.5% (333/338 challenges; 95% confidence interval: 96.5–99.5%) and an analytic specificity of 99.6% (281/282; 95% confidence interval: 98.0–99.9%). Reports of the CYP2C19 genotyping results often lacked essential information. In conclusion, clinical laboratories demonstrated good analytical sensitivity and specificity; however, the pharmacogenetic testing community requires additional education regarding the correct reporting of CYP2C19 genetic test results. PMID:26218263

  1. Pre-treatment with puerarin affects pharmacokinetics of warfarin, but not clopidogrel, in experimental rats.

    PubMed

    Liu, An-Chang; Zhao, Li-Xia; Yu, Shu-Wen; Lou, Hong-Xiang

    2015-04-01

    The present study was designed to determine the effects of puerarin pre-treatment on the pharmacokinetics of the oral anticoagulant agent warfarin and the antiplatelet agent clopidogrel in rats. In the treatment group, rats was gavaged with warfarin or clopidogrel after repeated treatment with puerarin at intraperitoneal doses of 20, 60, or 200 mg·kg(-1) for 7 days, while rats in the control group were administrated only with the same dose warfarin or clopidogrel. Plasma samples were obtained at the prescribed times and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The results showed that rats treated with puerarin at all the test doses of 20, 60 and 200 mg·kg(-1) were found to affect the pharmacokinetics of warfarin, but not clopidogrel, suggesting a potential herb-drug interaction between puerarin and warfarin. PMID:25908622

  2. Bleeding Outcomes in Patients Given Clopidogrel Within 5 Days of Robotic Coronary Artery Bypass Graft Procedure

    PubMed Central

    Vainrub, Sophia; Patanwala, Asad E.; Cosgrove, Richard; Poston, Robert; Nolan, Paul E.

    2014-01-01

    Background Current guidelines recommend that clopidogrel should be held for 5 days prior to coronary artery bypass graft (CABG) procedure. However, it is unknown if this recommendation should apply to robotic-assisted (rCABG), which is less invasive because it does not involve sternotomy and thus reduces the risk of bleeding. Objective To compare postoperative bleeding for rCABG patients who were taking clopidogrel within 5 days of the procedure with those who were not taking clopidogrel. Methods This was a retrospective cohort study conducted between January 1, 2012 and December 31, 2012 of consecutive patients undergoing rCABG. Patients were categorized into 2 groups based on whether or not clopidogrel was administered within 5 days prior to the date of surgery. The primary outcome measure was the occurrence of the Bleeding Academic Research Consortium (BARC) definition for CABG-related bleeding. The secondary outcome measure was a comparison of chest tube output during the first 24-hour postoperative period. Results A total of 136 rCABG patients were included in the final analyses. Of these, 39 (29%) received clopidogrel within 5 days of surgery. CABG-related bleeding using the BARC definition occurred in 26% of patients who received clopidogrel and 8% of patients who did not (P = .011). Median chest tube output during the first 24-hour postoperative period was also greater in patients who received clopidogrel (900 vs 735 mL, P = .002). Conclusions The use of clopidogrel within 5 days of rCABG is associated with greater postoperative bleeding and chest tube output, as defined by the BARC criteria. PMID:24259636

  3. Comparative risk of ischemic stroke among users of clopidogrel together with individual proton pump inhibitors

    PubMed Central

    Bilker, Warren B.; Brensinger, Colleen M.; Flockhart, David A.; Freeman, Cristin P.; Kasner, Scott E.; Kimmel, Stephen E.; Hennessy, Sean

    2015-01-01

    Background and Purpose There is controversy and little information concerning whether individual proton pump inhibitors (PPIs) differentially alter the effectiveness of clopidogrel in reducing ischemic stroke risk. We therefore aimed to elucidate the risk of ischemic stroke among concomitant users of clopidogrel and individual PPIs. Methods We conducted a propensity score-adjusted cohort study of adult new users of clopidogrel, using 1999–2009 Medicaid claims from 5 large states. Exposures were defined by prescriptions for esomeprazole, lansoprazole, omeprazole, rabeprazole and pantoprazole—with pantoprazole serving as the referent. The endpoint was hospitalization for acute ischemic stroke, defined by International Classification of Diseases 9th Revision Clinical Modification codes in the principal position on inpatient claims, within 180 days of concomitant therapy initiation. Results Among 325,559 concomitant users of clopidogrel and a PPI, we identified 1,667 ischemic strokes for an annual incidence of 2.4% (95% confidence interval: 2.3–2.5). Adjusted hazard ratios for ischemic stroke vs. pantoprazole were: 0.98 (0.82–1.17) for esomeprazole; 1.06 (0.92–1.21) for lansoprazole; 0.98 (0.85–1.15) for omeprazole; and 0.85 (0.63–1.13) for rabeprazole. Conclusions PPIs of interest did not increase the rate of ischemic stroke among clopidogrel users when compared to pantoprazole, a PPI thought to be devoid of the potential to interact with clopidogrel. PMID:25657176

  4. Reticulated platelets and antiplatelet therapy response in diabetic patients.

    PubMed

    Mijovic, Romana; Kovacevic, Nada; Zarkov, Marija; Stosic, Zoran; Cabarkapa, Velibor; Mitic, Gorana

    2015-08-01

    Increased platelet turnover and high level of reticulated platelets are associated with low response to antiplatelet therapy in diabetes mellitus type 2. This study evaluated association between percentage of reticulated platelets (%RP) and the response to antiplatelet therapy in patients with type 2 diabetes mellitus (T2DM). This prospective, pilot, case-control, clinical trial included 79 subjects stratified in three groups: group I included 30 patients with T2DM, group II included 34 non-diabetic patients and 15 healthy age and sex matched healthy volunteers were enrolled in control group. Platelet response to clopidogrel and aspirin was assessed by Multiplate(®) aggregometry analyzer. Individual response to dual antiplatelet therapy was estimated by the percentage of decrease in overall platelet aggregability (%DPA) obtained after antiplatelet therapy, calculated by presented formulas: %DPAadp = 100 × (1 - ADP/TRAP) and %DPAaspi = 100 × (1 - ASPI/TRAP). %RP was significantly higher in diabetics, than in non-diabetics, (3.17 ± 1.26 vs. 2.39 ± 1.56; p < 0.05). Significantly lower response to clopidogrel (31.55 ± 13.02 vs. 50.24 ± 11.38; p < 0.001) and aspirin (52.33 ± 22.67 vs. 64.31 ± 16.47; p < 0.05) therapy was observed in diabetics. %RP negatively correlated with response to clopidogrel therapy, but positively with metabolic profile indicators in diabetics (p < 0.05, all). Correlation of %RP with metabolic profile indicators and poor response to antiplatelet therapy suggest that altered metabolic profile can affect platelet turnover in T2DM leading to low responsiveness to antiplatelet therapy in these patients.

  5. Results of the Ticlid or Plavix Post-Stents (TOPPS) trial: do they justify the switch from ticlopidine to clopidogrel after coronary stent placement?

    PubMed

    Berger, Peter B

    2000-01-01

    In the Ticlid or Plavix Post-Stents (TOPPS) trial, 1016 patients undergoing successful coronary stent placement were randomized to receive aspirin and either ticlopidine or clopidogrel. In this trial, the dosages and regimens of ticlopidine and clopidogrel resembled more closely those used in most catheterization laboratories than did the two previous randomized trials comparing ticlopidine and clopidogrel. The results of the TOPPS trial support the current practice of substituting ticlopidine for clopidogrel in stent patients.

  6. How to test the effect of aspirin and clopidogrel in patients on dual antiplatelet therapy?

    PubMed

    Bagoly, Zsuzsa; Homoródi, Nóra; Kovács, Emese Gyöngyvér; Sarkady, Ferenc; Csiba, László; Édes, István; Muszbek, László

    2016-01-01

    Dual antiplatelet therapy with clopidogrel and aspirin is frequently used for the prevention of recurrent ischemic events. Various laboratory methods are used to detect the effect of these drugs administered in monotherapy, however their value in dual therapy has not been explored. Here, we determined which methods used for testing the effect of clopidogrel or aspirin are influenced by the other antiplatelet agent. One arm of the study included 53 ischemic stroke patients being on clopidogrel monotherapy showing effective inhibition of the P2Y12 ADP receptor. Laboratory tests routinely used for the detection of aspirin resistance (arachidonic acid (AA)-induced platelet aggregation/secretion, AA-induced thromboxane B2 (TXB2) production in platelet-rich plasma and VerifyNow Aspirin assay) were carried out on samples obtained from these patients. The other arm of the study involved 52 patients with coronary artery disease being on aspirin monotherapy. Methods used for testing the effect of clopidogrel (ADP-induced platelet aggregation and secretion, flow cytometric analysis of vasodilator-stimulated phosphoprotein (VASP) phosphorylation and a newly developed P2Y12-specific platelet aggregation (ADP[PGE1] test)) were performed on samples obtained from these patients. Clopidogrel monotherapy significantly inhibited AA-induced platelet aggregation and secretion, moreover, AA-induced TXB2 production was also significantly decreased. VASP phosphorylation and AA-induced platelet aggregation showed fair correlation in patients taking clopidogrel only. Clopidogrel did not inhibit the VerifyNow Aspirin test significantly. Aspirin monotherapy influenced ADP-induced platelet aggregation and secretion, but did not have an effect on VASP phosphorylation and on the ADP[PGE1] platelet aggregation test.

  7. Peribulbar block in patients scheduled for eye procedures and treated with clopidogrel.

    PubMed

    Calenda, Emile; Lamothe, Laure; Genevois, Olivier; Cardon, Annie; Muraine, Marc

    2012-10-01

    Our hypothesis was that the continuation of clopidogrel does not increase the risk of eye hemorrhage, compared to patients not treated with clopidogrel, when a peribulbar anesthesia is required. Our prospective case-control study enrolled two groups of 1,000 patients scheduled for intraocular eye surgery requiring a peribulbar block. Patients treated with clopidogrel were included in group A (1,000 patients). Patients who had never been treated with clopidogrel constituted the control group (group B, 1,000 patients). Hemorrhages were graded as follows: 1 = spot ecchymosis of eyelid and or subconjunctival hemorrhage; 2 = eyelid ecchymosis involving half the lid surface area; 3 = eyelid ecchymosis all around the eye, no increase in intraocular pressure; 4 = retrobulbar hemorrhage with increased intraocular pressure. Grade 1 hemorrhages were observed in 30 patients (3.0 %) in group A and in 20 patients (2.0 %) in group B. No grade 2, 3, or 4 hemorrhage was encountered. There was no significant difference in the grading of hemorrhage between the groups (p = 0.017). Clopidogrel was not associated with a significant increase in potentially sight-threatening local anesthetic complications. PMID:22581096

  8. Peribulbar block in patients scheduled for eye procedures and treated with clopidogrel.

    PubMed

    Calenda, Emile; Lamothe, Laure; Genevois, Olivier; Cardon, Annie; Muraine, Marc

    2012-10-01

    Our hypothesis was that the continuation of clopidogrel does not increase the risk of eye hemorrhage, compared to patients not treated with clopidogrel, when a peribulbar anesthesia is required. Our prospective case-control study enrolled two groups of 1,000 patients scheduled for intraocular eye surgery requiring a peribulbar block. Patients treated with clopidogrel were included in group A (1,000 patients). Patients who had never been treated with clopidogrel constituted the control group (group B, 1,000 patients). Hemorrhages were graded as follows: 1 = spot ecchymosis of eyelid and or subconjunctival hemorrhage; 2 = eyelid ecchymosis involving half the lid surface area; 3 = eyelid ecchymosis all around the eye, no increase in intraocular pressure; 4 = retrobulbar hemorrhage with increased intraocular pressure. Grade 1 hemorrhages were observed in 30 patients (3.0 %) in group A and in 20 patients (2.0 %) in group B. No grade 2, 3, or 4 hemorrhage was encountered. There was no significant difference in the grading of hemorrhage between the groups (p = 0.017). Clopidogrel was not associated with a significant increase in potentially sight-threatening local anesthetic complications.

  9. A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension.

    PubMed

    Robbins, I M; Kawut, S M; Yung, D; Reilly, M P; Lloyd, W; Cunningham, G; Loscalzo, J; Kimmel, S E; Christman, B W; Barst, R J

    2006-03-01

    Idiopathic pulmonary arterial hypertension (IPAH) is characterised by in situ thrombosis and increased thromboxane (Tx) A2 synthesis; however, there are no studies of antiplatelet therapy in IPAH. The aim of the current study was to determine the biochemical effects of aspirin (ASA) and clopidogrel on platelet function and eicosanoid metabolism in patients with IPAH. A randomised, double-blind, placebo-controlled crossover study of ASA 81 mg once daily and clopidogrel 75 mg once daily was performed. Plasma P-selectin levels and aggregometry were measured after exposure to adenosine diphosphate, arachidonic acid and collagen. Serum levels of TxB2 and urinary metabolites of TxA2 and prostaglandin I2 (Tx-M and PGI-M, respectively) were assessed. A total of 19 IPAH patients were enrolled, of whom nine were being treated with continuous intravenous epoprostenol. ASA and clopidogrel significantly reduced platelet aggregation to arachidonic acid and adenosine diphosphate, respectively. ASA significantly decreased serum TxB2, urinary Tx-M levels and the Tx-M/PGI-M ratio, whereas clopidogrel had no effect on eicosanoid levels. Neither drug significantly lowered plasma P-selectin levels. Epoprostenol use did not affect the results. In conclusion, aspirin and clopidogrel inhibited platelet aggregation, and aspirin reduced thromboxane metabolite production without affecting prostaglandin I2 metabolite synthesis. Further clinical trials of aspirin in patients with idiopathic pulmonary arterial hypertension should be performed. PMID:16507859

  10. Management of low-dose aspirin and clopidogrel in clinical practice: a gastrointestinal perspective.

    PubMed

    Lanas, Angel; Gargallo, Carla J

    2015-06-01

    Low-dose aspirin, alone or combined with other antiplatelet agents, is increasingly prescribed for cardiovascular prevention. However, the cardiovascular benefits should be evaluated together with the gastrointestinal risks. Low-dose aspirin is associated with upper and lower gastrointestinal injury, although lower gastrointestinal effects are poorly characterized. This gastrointestinal risk differs among antiplatelets drugs users. The most important risk factors are history of peptic ulcer, older age, and concomitant use of non-steroidal anti-inflammatory drugs or dual antiplatelet therapy. Effective upper gastrointestinal prevention strategies are available and should be used in at-risk patients taking low-dose aspirin or clopidogrel. Proton pump inhibitors seem to be the best gastroprotective agents, whereas the benefits of Helicobacter pylori eradication are still unclear. Low-dose aspirin has additional effects in the gastrointestinal tract. A large body of evidence indicates that it can protect against different cancers, in particular colorectal cancer. This effect could modify the future indications for use of low-dose aspirin and the risk-benefit balance. PMID:25595209

  11. Evaluation of allergic response using dynamic thermography

    NASA Astrophysics Data System (ADS)

    Rokita, E.; Rok, T.; Tatoń, G.

    2015-03-01

    Skin dynamic termography supplemented by a mathematical model is presented as an objective and sensitive indicator of the skin prick test result. Termographic measurements were performed simultaneously with routine skin prick tests. The IR images were acquired every 70 s up to 910 s after skin prick. In the model histamine is treated as the principal mediator of the allergic reaction. Histamine produces vasolidation and the engorged vessels are responsible for an increase in skin temperature. The model parameters were determined by fitting the analytical solutions to the spatio-temporal distributions of the differences between measured and baseline temperatures. The model reproduces experimental data very well (coefficient of determination = 0.805÷0.995). The method offers a set of parameters to describe separately skin allergic reaction and skin reactivity. The release of histamine after allergen injection is the best indicator of allergic response. The diagnostic parameter better correlates with the standard evaluation of a skin prick test (correlation coefficient = 0.98) than the result of the thermographic planimetric method based on temperature and heated area determination (0.81). The high sensitivity of the method allows for determination of the allergic response in patients with the reduced skin reactivity.

  12. Simultaneous administration of high-dose atorvastatin and clopidogrel does not interfere with platelet inhibition during percutaneous coronary intervention

    PubMed Central

    Kreutz, Rolf P; Breall, Jeffrey A; Sinha, Anjan; von der Lohe, Elisabeth; Kovacs, Richard J; Flockhart, David A

    2016-01-01

    Background Reloading with high-dose atorvastatin shortly before percutaneous coronary interventions (PCIs) has been proposed as a strategy to reduce periprocedural myonecrosis. There has been a concern that statins that are metabolized by cytochrome P450 3A4 may interfere with clopidogrel metabolism at high doses. The impact of simultaneous administration of high doses of atorvastatin and clopidogrel on the efficacy of platelet inhibition has not been established. Methods Subjects (n=60) were randomized to receive atorvastatin 80 mg together with clopidogrel 600 mg loading dose (n=28) versus clopidogrel 600 mg alone (n=32) at the time of PCI. Platelet aggregation was measured at baseline, 4 hours after clopidogrel loading dose, and 16–24 hours after clopidogrel loading dose by light transmittance aggregometry using adenosine diphosphate as agonist. Results Platelet aggregation was similar at baseline in both the atorvastatin and the control groups (adenosine diphosphate 10 µM: 57%±19% vs 61%±21%; P=0.52). There was no significant difference in platelet aggregation between the atorvastatin and the control groups at 4 hours (37%±18% vs 39%±21%; P=0.72) and 16–24 hours post-clopidogrel loading dose (35%±17% vs 37%±18%; P=0.75). No significant difference in incidence of periprocedural myonecrosis was observed between the atorvastatin and control groups (odds ratio: 1.02; 95% confidence interval 0.37–2.8). Conclusion High-dose atorvastatin given simultaneously with clopidogrel loading dose at the time of PCI does not significantly alter platelet inhibition by clopidogrel. Statin reloading with high doses of atorvastatin at the time of PCI appears to be safe without adverse effects on platelet inhibition by clopidogrel (ClinicalTrials.gov: NCT00979940). PMID:27350760

  13. Predictive value of high residual platelet reactivity by flow cytometry for outcomes of ischemic stroke patients on clopidogrel therapy.

    PubMed

    Qiu, Li-Na; Wang, Lin; Li, Xin; Han, Rui-Fa; Xia, Xiao-Shuang; Liu, Jie

    2015-06-01

    High residual platelet reactivity (HRPR) assessed by multiple tests has been associated with worse clinical outcomes. However, the clinical impact of HRPR assessed by flow cytometry is unknown. The aim of this study was to validate the predictive value of HRPR measured by flow cytometry for clinical outcomes in ischemic stroke patients during clopidogrel therapy. Overall, 198 consecutive patients with ischemic stroke taking clopidogrel underwent platelet function testing on flow cytometer including adenosine diphosphate (ADP)-induced platelet aggregation (PAg) and platelet activation markers (CD62P, CD63, and PAC-1). Poor outcome was defined as poor prognosis and ischemic events during 12-month follow-up. By receiver operating characteristic curve analysis, residual platelet reactivity assessed by flow cytometry was able to distinguish between patients with and without poor outcomes, when platelet inhibition was evaluated with ADP-PAg (area under the curve [AUC], .77; 95% confidence interval [CI], .69-.84; P < .001), CD62P (AUC, .73; 95% CI, .64-.81; P < .001), CD63 (AUC, .72; 95% CI, .64-.80; P < .001), and PAC-1 (AUC, .70; 95% CI, .62-.78; P < .001). The prevalence of HRPR was 25.8% for ADP-PAg, 32.8% for CD62P, 41.4% for CD63, and 56.1% for PAC-1. The multiple logical regression analysis demonstrated that HRPR was an independent predictor of poor outcomes (ADP-PAg: odds ratio [OR] 13.03, 95% CI 5.66-29.98, P < .001; CD62P: OR 8.55, 95% CI 3.94-18.57, P < .001; CD63: OR 8.74, 95% CI 3.89-19.64, P < .001; PAC-1: OR 4.23, 95% CI 1.98-9.08). In conclusion, HRPR, assessed by flow cytometry, is able to detect ischemic stroke patients at increased risk of 12-month poor outcomes on clopidogrel treatment.

  14. CYP-independent inhibition of platelet aggregation in rabbits by a mixed disulfide conjugate of clopidogrel.

    PubMed

    Zhang, H; Lauver, D A; Hollenberg, P F

    2014-12-01

    Dual antiplatelet therapy with clopidogrel and aspirin has been the standard of care in the United States for patients with acute coronary syndromes (ACS) and/or undergoing percutaneous coronary interventions (PCI). However, the effectiveness of clopidogrel varies significantly among different sub-populations due to inter-individual variability. In this study we examined the antiplatelet potential of a novel mixed disulfide conjugate of clopidogrel with the aim to overcome the inter-individual variability. In the metabolic studies using human liver microsomes and cDNA-expressed P450s, we confirmed that multiple P450s are involved in the bioactivation of 2-oxoclopidogrel to H4, one of the diastereomers of the pharmacologically active metabolite (AM) possessing antiplatelet activity. Results from kinetic studies demonstrated that 2C19 is the most active in converting 2-oxoclopidogrel to H4 with a catalytic efficiency of 0.027 µM⁻¹min⁻¹ in the reconstituted system. On the basis of this finding, we were able to biosynthesise the conjugate of clopidogrel with 3-nitropyridine-2-thiol, referred to as clopNPT, and examined its antiplatelet activity in male New Zealand white rabbits. After administration as intravenous bolus at 2 mg/kg, the clopNPT conjugate was rapidly converted to the AM leading to the inhibition of platelet aggregation (IPA). Analyses of the blood samples drawn at various time points showed that intravenous administration of clopNPT led to ~70% IPA within 1 hour and the IPA persisted for more than 3 hours. Since the antiplatelet activity of clopNPT does not require bioactivation by P450s, the mixed disulfide conjugate of clopidogrel has the potential to overcome the inter-individual variability in clopidogrel therapy. PMID:25230737

  15. Safety and Efficacy of Acute Clopidogrel Load in Patients with Moderate and Severe Ischemic Strokes

    PubMed Central

    Monlezun, Dominique J.; Rincon, Natalia; Tiu, Jonathan; Valmoria, Melisa

    2016-01-01

    Objective. To study the safety and efficacy of a clopidogrel loading dose in patients with moderate and severe acute ischemic strokes. Background. The safety of clopidogrel loading has been extensively investigated in patients with minor strokes and transient ischemic attacks. Methods. Acute ischemic stroke patients presenting consecutively to our center from 07/01/08 to 07/31/13 were screened. Clopidogrel loading was defined as at least 300 mg dose (with or without aspirin) given within 6 hours of admission. We compared outcomes in patients with baseline NIHSS > 3 with and without clopidogrel loading. Results. Inclusion criteria were met for 1011 patients (43.6% females, 69.1% black, median age 63). Patients with clopidogrel loading had lower baseline NIHSS than patients who were not loaded (8 versus 9, p = 0.005). The two groups had similar risk for hemorrhagic transformation (p = 0.918) and symptomatic hemorrhage (p = 0.599). Patients who were loaded had a lower rate of neurological worsening (38.9% versus 48.3%, p = 0.031) and less in-hospital mortality (4.3% versus 13.4%, p = 0.001) compared to those who were not loaded. The likelihood of having a poor functional outcome did not differ between the two groups after adjusting for NIHSS on admission (OR = 0.71, 95% CI 0.4633–1.0906, p = 0.118). Conclusion. Clopidogrel loading dose was not associated with increased risk for hemorrhagic transformation or symptomatic intracranial hemorrhage in our retrospective study and was associated with reduced rates of neuroworsening following moderate and severe stroke.

  16. CYP2C19 polymorphisms in acute coronary syndrome patients undergoing clopidogrel therapy in Zhengzhou population.

    PubMed

    Guo, Y M; Zhao, Z C; Zhang, L; Li, H Z; Li, Z; Sun, H L

    2016-01-01

    The goal of this study was to explore the polymorphisms of CYP2C19 (CYP2C19*2, CYP2C19*3) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) on clopidogrel therapy in Zhengzhou city for guidance on clinical medication and reduction in the incidence of thromboembolic events. Two hundred and thirty-four ACS patients undergoing PCI were included in the study, including 171 males (average age = 64.13 ± 12 years) and 63 females (average age = 67.86 ± 10.20 years). Pyrosequencing analysis detected CYP2C19*2/*3 genotypes, which were divided into wild-type homozygous C/C, mutant heterozygous C/T, and mutant homozygous T/T. This study further explored the relationship between CYP2C19 polymorphisms and clopidogrel resistance in ACS patients. Gene frequencies of C/C, C/T, and T/T for CYP2C19*2 were 39.74, 50, and 10.26%, respectively, while the frequencies of C/C, C/T, and T/T for CYP2C19*3 were 94.02, 5.55, and 0.43%, respectively. According to platelet aggregation analysis, 203 cases normally responded to clopidogrel (86.8%) and 31 cases were clopidogrel resistant (13.2%). There was a correlation between gender and genotype distribution but none between age and genotype. In addition, patients with clopidogrel resistance were treated with ticagrelor antiplatelet therapy instead of clopidogrel, and only 1 case in all patients suffered thrombotic events during a 3-12 month follow-up. In conclusion, CYP2C19*2/*3 polymorphisms may be associated with clopidogrel resistance. Wild-type homozygote and single mutant heterozygote of CYP2C19*2/*3 can be given a normal dose of clopidogrel, while carriers with single mutant homozygote or double mutant heterozygote require ticagrelor antiplatelet therapy as an alternative. PMID:27323099

  17. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel.

    PubMed

    Payne, Christopher D; Li, Ying Grace; Small, David S; Ernest, C Steven; Farid, Nagy A; Jakubowski, Joseph A; Brandt, John T; Salazar, Daniel E; Winters, Kenneth J

    2007-11-01

    Prasugrel pharmacodynamics and pharmacokinetics after a 60-mg loading dose (LD) and daily 10-mg maintenance doses (MD) were compared in a 3-way crossover study to clopidogrel 600-mg/75-mg and 300-mg/75-mg LD/MD in 41 healthy, aspirin-free subjects. Each LD was followed by 7 days of daily MD and a 14-day washout period. Inhibition of platelet aggregation (IPA) was assessed by turbidometric aggregometry (20 and 5 microM ADP). Prasugrel 60-mg achieved higher mean IPA (54%) 30 minutes post-LD than clopidogrel 300-mg (3%) or 600-mg (6%) (P < 0.001) and greater IPA by 1 hour (82%) and 2 hours (91%) than the 6-hour IPA for clopidogrel 300-mg (51%) or 600-mg (69%) (P < 0.01). During MD, IPA for prasugrel 10-mg (78%) exceeded that of clopidogrel (300-mg/75-mg, 56%; 600-mg/75-mg, 52%; P < 0.001). Active metabolite area under the concentration-time curve (AUC0-tlast) after prasugrel 60-mg (594 ng.hr/mL) was 2.2 times that after clopidogrel 600-mg. Prasugrel active metabolite AUC0-tlast was consistent with dose-proportionality from 10-mg to 60-mg, while clopidogrel active metabolite AUC0-tlast exhibited saturable absorption and/or metabolism. In conclusion, greater exposure to prasugrel's active metabolite results in faster onset, higher levels, and less variability of platelet inhibition compared with high-dose clopidogrel in healthy subjects. PMID:18030066

  18. Antiplatelet Therapy of Cilostazol or Sarpogrelate with Aspirin and Clopidogrel after Percutaneous Coronary Intervention: A Retrospective Cohort Study Using the Korean National Health Insurance Claim Database

    PubMed Central

    Noh, Yoojin; Lee, Jimin; Shin, Sooyoung; Lim, Hong-Seok; Bae, Soo Kyung; Oh, Euichul; Kim, Grace Juyun; Kim, Ju Han; Lee, Sukhyang

    2016-01-01

    Background/Objectives Addition of cilostazol or sarpogrelate to the standard dual antiplatelet therapy of aspirin and clopidogrel has been implemented in patients that underwent percutaneous coronary intervention (PCI) with stents in Korea. This study aimed to evaluate the efficacy and safety of triple antiplatelet therapies. Methods This retrospective cohort study was performed using the Korean National Insurance Claim Data of the Health Insurance Review and Assessment Service from January 1, 2009 to December 31, 2014. The study cohort population consisted of patients with ischemic heart diseases and a history of PCI. They were treated with antiplatelet therapy of aspirin, clopidogrel (AC); aspirin, clopidogrel, cilostazol (ACCi); or aspirin, clopidogrel, sarpogrelate (ACSa) during the index period from January 1, 2010 to December 31, 2011. During the follow-up period up to December 31, 2014, the major adverse cardiac or cerebral events (MACCE) including death, myocardial infarction, target lesion revascularization, and ischemic stroke were assessed. Bleeding complications were also evaluated as adverse drug events. Results Out of 93,876 patients with PCI during the index period, 69,491 patients started dual (AC) or triple therapy (ACSa or ACCi). The clinical outcomes of comparing ACSa and ACCi therapy showed beneficial effects in the ACSa group in the prevention of subsequent cardiac or cerebral events. After Propensity score-matching between ACSa and ACCi groups, there were significant differences in MI and revascularization, with corresponding HR of 0.38 (95% CI, 0.20–0.73) and 0.66 (95% CI, 0.53–0.82) in ACSa vs. ACCi at 12 months, respectively. At the 24-month follow-up, the triple therapy groups (ACS or ACC) had a higher incidence of MACCE compared to the dual therapy (AC) group; ACSa vs. AC HR of 1.69 (95% CI, 1.62–1.77); ACC vs. AC HR of 1.22 (95% CI, 1.06–1.41). There was no significant difference in severe or life-threatening bleeding risk among

  19. Physiologically based pharmacokinetic modeling for sequential metabolism: effect of CYP2C19 genetic polymorphism on clopidogrel and clopidogrel active metabolite pharmacokinetics.

    PubMed

    Djebli, Nassim; Fabre, David; Boulenc, Xavier; Fabre, Gérard; Sultan, Eric; Hurbin, Fabrice

    2015-04-01

    Clopidogrel is a prodrug that needs to be converted to its active metabolite (clopi-H4) in two sequential cytochrome P450 (P450)-dependent steps. In the present study, a dynamic physiologically based pharmacokinetic (PBPK) model was developed in Simcyp for clopidogrel and clopi-H4 using a specific sequential metabolite module in four populations with phenotypically different CYP2C19 activity (poor, intermediate, extensive, and ultrarapid metabolizers) receiving a loading dose of 300 mg followed by a maintenance dose of 75 mg. This model was validated using several approaches. First, a comparison of predicted-to-observed area under the curve (AUC)0-24 obtained from a randomized crossover study conducted in four balanced CYP2C19-phenotype metabolizer groups was performed using a visual predictive check method. Second, the interindividual and intertrial variability (on the basis of AUC0-24 comparisons) between the predicted trials and the observed trial of individuals, for each phenotypic group, were compared. Finally, a further validation, on the basis of drug-drug-interaction prediction, was performed by comparing observed values of clopidogrel and clopi-H4 with or without dronedarone (moderate CYP3A4 inhibitor) coadministration using a previously developed and validated physiologically based PBPK dronedarone model. The PBPK model was well validated for both clopidogrel and its active metabolite clopi-H4, in each CYP2C19-phenotypic group, whatever the treatment period (300-mg loading dose and 75-mg last maintenance dose). This is the first study proposing a full dynamic PBPK model able to accurately predict simultaneously the pharmacokinetics of the parent drug and of its primary and secondary metabolites in populations with genetically different activity for a metabolizing enzyme.

  20. Higher body weight patients on clopidogrel maintenance therapy have lower active metabolite concentrations, lower levels of platelet inhibition, and higher rates of poor responders than low body weight patients.

    PubMed

    Wagner, Henrik; Angiolillo, Dominick J; Ten Berg, Jurrien M; Bergmeijer, Thomas O; Jakubowski, Joseph A; Small, David S; Moser, Brian A; Zhou, Chunmei; Brown, Patricia; James, Stefan; Winters, Kenneth J; Erlinge, David

    2014-01-01

    Body weight is a predictor of clopidogrel response. However, no prospective studies have compared pharmacodynamic (PD) and pharmacokinetic (PK) data based on body weight. We compared PD and PK effects of clopidogrel 75 mg in low body weight (LBW, <60 kg) and higher body weight (HBW, ≥60 kg) patients with stable coronary artery disease. LBW (n = 34, 56.4 ± 3.7 kg) and HBW (n = 38, 84.7 ± 14.9 kg) aspirin-treated patients received clopidogrel 75 mg for 10-14 days. The area under the concentration-time curve of active metabolite (Clop-AM) calculated through the last quantifiable concentration up to 4 h postdose, AUC(0-tlast), was calculated by noncompartmental methods. Light transmission aggregometry (LTA) (maximum platelet aggregation and inhibition of platelet aggregation to 20 μM adenosine diphosphate (ADP), and residual platelet aggregation to 5 μM ADP), VerifyNow(®) P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein phosphorylation platelet reactivity index (VASP-PRI) were performed. Mean AUC(0-tlast) was lower in HBW than LBW patients: 12.8 versus 17.9 ng h/mL. HBW patients had higher platelet reactivity as measured by LTA (all p ≤ 0.01), PRU (207 ± 68 vs. 152 ± 57, p < 0.001), and VASP-PRI (56 ± 18 vs. 39 ± 17, p < 0.001). More HBW patients exhibited high on-treatment platelet reactivity (HPR) using PRU (35 vs. 9%) and VASP-PRI (65 vs. 27%). Body weight correlated with PRU and VASP-PRI (both p < 0.001), and inversely with log transformed AUC(0-tlast) (p < 0.001). In conclusion, HBW patients had lower levels of Clop-AM, and higher platelet reactivity and rates of HPR than LBW subjects, contributing to their suboptimal response to clopidogrel. PMID:24043374

  1. Identification of alcohol-dependent clopidogrel metabolites using conventional liquid chromatography/triple quadrupole mass spectrometry

    PubMed Central

    Hu, Zhe-Yi; Laizure, S. Casey; Herring, Vanessa L.; Parker, Robert B.

    2014-01-01

    RATIONALE Clopidogrel (CLO) is a prodrug used to prevent ischemic events in patients undergoing percutaneous coronary intervention or with myocardial infarction. A previous study found ethyl clopidogrel (ECLO) is formed by transesterification of CLO when incubated with alcohol in human liver microsomes. We hypothesize that ECLO will be subject to further metabolism and developed an assay to identify its metabolites. METHODS A liquid chromatography/triple quadrupole mass spectrometry (LC-MS/MS) method was developed to identify metabolites of ECLO. According to the predicted metabolic pathway of ECLO, precursor–product ion pairs were used to screen the possible metabolites of ECLO in human liver S9 fractions. Subsequently, the detected metabolites were characterized by the results of product ion scan. RESULTS In the presence of alcohol, CLO was tranesterified to ECLO, which was further oxidized to form ethylated 2-oxo-clopidogrel and several ethylated thiol metabolites including the ethylated form of the H4 active metabolite. CONCLUSIONS The ECLO formed by transesterification with alcohol is subject to metabolism by CYP450 enzymes producing ethylated forms of 2-oxo-clopidogrel and the active H4 thiol metabolite. PMID:24760569

  2. St. John's Wort in patients non-responders to clopidogrel undergoing percutaneous coronary intervention: a single-center randomized open-label trial (St. John's Trial).

    PubMed

    Trana, Catalina; Toth, Gabor; Wijns, William; Barbato, Emanuele

    2013-06-01

    We assessed if St. John's Wort (SJW) improves platelet response in patients (pts) resistant to clopidogrel after percutaneous coronary intervention (PCI). Stable angina pts non-responders to 600 mg clopidogrel (P2Y12 reaction units (PRU) >240) were randomized (2:1) to SJW (n = 15) or placebo (n = 8). SJW (300 mg × 3/day) was administrated for 2 weeks after PCI. Platelet reactivity was assessed by VerifyNowTM before (BL), 2 (T1), and 4 weeks (T2) after PCI. PRU significantly changed during protocol in SJW (BL (316 ± 60) vs. T1 (170 ± 87) vs. T2 (220 ± 96), p < 0.0001) and placebo group (BL (288 ± 36) vs. T1 (236 ± 31) vs. T2 (236 ± 62), p = 0.046). Yet, PRU changes from BL were higher at T1 in SJW than in placebo group (Δ%, -47 ± 24 vs. -16 ± 15, p = 0.0033), with no differences at T2 between the groups (Δ%, -30 ± 29 vs. -17 ± 24, p = 0.30). Residual platelet reactivity improved with SJW during the first month post-PCI.

  3. Politics in evaluation: Politically responsive evaluation in high stakes environments.

    PubMed

    Azzam, Tarek; Levine, Bret

    2015-12-01

    The role of politics has often been discussed in evaluation theory and practice. The political influence of the situation can have major effects on the evaluation design, approach and methods. Politics also has the potential to influence the decisions made from the evaluation findings. The current study focuses on the influence of the political context on stakeholder decision making. Utilizing a simulation scenario, this study compares stakeholder decision making in high and low stakes evaluation contexts. Findings suggest that high stakes political environments are more likely than low stakes environments to lead to reduced reliance on technically appropriate measures and increased dependence on measures better reflect the broader political environment. PMID:26283476

  4. Politics in evaluation: Politically responsive evaluation in high stakes environments.

    PubMed

    Azzam, Tarek; Levine, Bret

    2015-12-01

    The role of politics has often been discussed in evaluation theory and practice. The political influence of the situation can have major effects on the evaluation design, approach and methods. Politics also has the potential to influence the decisions made from the evaluation findings. The current study focuses on the influence of the political context on stakeholder decision making. Utilizing a simulation scenario, this study compares stakeholder decision making in high and low stakes evaluation contexts. Findings suggest that high stakes political environments are more likely than low stakes environments to lead to reduced reliance on technically appropriate measures and increased dependence on measures better reflect the broader political environment.

  5. Efficacy and safety outcomes of ticagrelor compared with clopidogrel in elderly Chinese patients with acute coronary syndrome

    PubMed Central

    Wang, Huidong; Wang, Xin

    2016-01-01

    Objective This study was designed to investigate the efficacy and safety outcomes of ticagrelor in comparison with clopidogrel on a background of aspirin in elderly Chinese patients with acute coronary syndrome (ACS). Patients and methods A double-blinded, randomized controlled study was conducted, and 200 patients older than 65 years with the diagnosis of ACS were assigned 1:1 to take ticagrelor or clopidogrel. The course of treatment was required to continue for 12 months. Results The median age of the whole cohort was 79 years (range: 65–93 years), and females accounted for 32.5% (65 patients). Baseline characteristics and clinical diagnosis had no significant difference between patients taking ticagrelor and clopidogrel; they were also balanced with respect to other treatments (P>0.05 for all). The risk of cardiovascular death was significantly lower in patients taking ticagrelor compared with clopidogrel, as was the risk of myocardial infarction (P<0.05 for all); there was no difference in the risk of stroke (P>0.05). Ticagrelor was more effective than clopidogrel in decreasing the primary efficacy end point (cardiovascular death, myocardial infarction, and stroke, P<0.05). The all-cause mortality was not significantly different between patients taking ticagrelor and clopidogrel (P>0.05). The difference in the risk of bleeding, platelet inhibition and patient outcomes major bleeding (life-threatening bleeding and others), and platelet inhibition and patient outcomes minor bleeding was not evident between patients taking ticagrelor and clopidogrel (P>0.05 for all). Conclusion The current study in elderly Chinese patients with ACS demonstrated that ticagrelor reduced the primary efficacy end point at no expense of increased bleeding risk compared with clopidogrel, suggesting that ticagrelor is a suitable alternative for use in elderly Chinese patients with ACS. PMID:27471389

  6. Response Style Contamination of Student Evaluation Data

    ERIC Educational Resources Information Center

    Dolnicar, Sara; Grun, Bettina

    2009-01-01

    Student evaluation surveys provide instructors with feedback regarding development opportunities and they form the basis of promotion and tenure decisions. Student evaluations have been extensively studied, but one dimension hitherto neglected is the actual measurement aspect: which questions to ask, how to ask them, and what answer options to…

  7. Oral clopidogrel improves cutaneous microvascular function through EDHF-dependent mechanisms in middle-aged humans.

    PubMed

    Dahmus, Jessica D; Bruning, Rebecca S; Kenney, W Larry; Alexander, Lacy M

    2013-08-15

    Platelet P₂Y₁₂-ADP and COX-1 receptor inhibition with oral clopidogrel (CLO) and low-dose aspirin (ASA), respectively, attenuates reflex-mediated cutaneous vasodilation, but little is known about how these medications affect local vasodilatory signaling. Reactive hyperemia (RH) results in vasodilation that is mediated by sensory nerves and endothelium-derived hyperpolarization factors (EDHF) through large-conductance calcium-activated potassium channels, whereas slow local heating (LH) elicits vasodilation largely through the production of nitric oxide (NO). We hypothesized that CLO and ASA would attenuate locally mediated cutaneous vasodilation assessed by RH and LH (0.5°C/min). In a randomized, cross-over, double-blind placebo-controlled study, nine healthy men and women (56 ± 1 yr) took CLO (75 mg), ASA (81 mg), and placebo for 7 days. Skin blood flow was measured (laser-Doppler flowmetry, LDF) and cutaneous vascular conductance (CVC) was calculated (LDF/mean arterial pressure) and normalized to maximal CVC (%CVCmax: 43°C and 28 mM sodium nitroprusside). RH response parameters, including area under the curve (AUC), total hyperemic response (THR), and the decay constant tau (λ) were calculated. NO-dependent vasodilation during LH was assessed by calculating the difference in %CVCmax between a control site and an NO synthase-inhibited site (10 mM l-NAME: intradermal microdialysis). CLO augmented the AUC and THR (AUCclo = 3,783 ± 342; THRclo = 2,306 ± 266% CVCmax/s) of the RH response compared with ASA (AUCASA = 3,101 ± 325; THRASA = 1,695 ± 197% CVCmax/s) and placebo (AUCPlacebo = 3,000 ± 283; THRPlacebo = 1,675 ± 170% CVCmax/s; all P < 0.0001 vs. CLO). There was no difference in the LH response or calculated NO-dependent vasodilation among treatments (all P > 0.05). Oral CLO treatment augments vasodilation during RH but not LH, suggesting that CLO may improve cutaneous microvascular function.

  8. Curcumin alters the pharmacokinetics of warfarin and clopidogrel in Wistar rats but has no effect on anticoagulation or antiplatelet aggregation.

    PubMed

    Liu, An-Chang; Zhao, Li-Xia; Lou, Hong-Xiang

    2013-07-01

    This study examined the effects of curcumin on the pharmacokinetic and pharmacodynamic properties of warfarin and clopidogrel in Wistar rats. Results showed that oral administration of curcumin at 25 mg/kg, 50 mg/kg, and 100 mg/kg for 7 days had no substantial effects on the pharmacodynamics of warfarin and clopidogrel in this animal model. However, oral administration of 100 mg/kg curcumin for 7 days significantly increased the AUC0-∞ and Cmax of the two drugs (by × 1.6 and × 1.5, respectively, for warfarin, and × 1.61 and × 1.81, respectively, for clopidogrel carboxylic acid). However, compared to warfarin alone, different doses of curcumin combined with warfarin had no effects on the prothrombin time in rats. Similarly, a combination of curcumin and clopidogrel had no significant effect on the maximum platelet aggregation rate of rats compared with the use of clopidogrel alone. This work demonstrated that preadministration of 100 mg/kg curcumin affected the pharmacokinetics of warfarin and clopidogrel but had no effect on pharmacodynamic parameters such as anticoagulation rate and antiplatelet aggregation. PMID:23807811

  9. Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke

    PubMed Central

    Sacco, Ralph L.; Diener, Hans-Christoph; Yusuf, Salim; Cotton, Daniel; Ôunpuu, Stephanie; Lawton, William A.; Palesch, Yuko; Martin, Reneé H.; Albers, Gregory W.; Bath, Philip; Bornstein, Natan; Chan, Bernard P.L.; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A.; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

    2009-01-01

    BACKGROUND Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens — aspirin plus extendedrelease dipyridamole (ASA–ERDP) versus clopidogrel. METHODS In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA–ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA–ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA–ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA–ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA–ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. PMID:18753638

  10. Head to Head Comparison of Two Point-of-care Platelet Function Tests Used for Assessment of On-clopidogrel Platelet Reactivity in Chinese Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Yao, Yi; Zhang, Jia-Hui; Tang, Xiao-Fang; He, Chen; Ma, Yuan-Liang; Xu, Jing-Jing; Song, Ying; Liu, Ru; Meng, Xian-Min; Song, Lei; Wang, Miao; Gao, Run-Lin; Yuan, Jin-Qing

    2016-01-01

    Background: Platelet function tests are widely used in clinical practice to guide personalized antiplatelet therapy. In China, the thromboelastography (TEG) test has been well accepted in clinics, whereas VerifyNow, mainly used for scientific research, has not been used in routine clinical practice. The aim of the current study was to compare these two point-of-care platelet function tests and to analyze the consistency between the two tests for evaluating on-clopidogrel platelet reactivity in Chinese acute myocardial infarction patients undergoing percutaneous coronary intervention (PCI). Methods: A total of 184 patients admitted to Fuwai Hospital between August 2014 and May 2015 were enrolled in the study. On-clopidogrel platelet reactivity was assessed 3 days after PCI by TEG and VerifyNow using adenosine diphosphate as an agonist. Based on the previous reports, an inhibition of platelet aggregation (IPA) <30% for TEG or a P2Y12 reaction unit (PRU) >230 for VerifyNow was defined as high on-clopidogrel platelet reactivity (HPR). An IPA >70% or a PRU <178 was defined as low on-clopidogrel platelet reactivity (LPR). Correlation and agreement between the two methods were analyzed using the Spearman correlation coefficient (r) and kappa value (κ), respectively. Results: Our results showed that VerifyNow and TEG had a moderate but significant correlation in evaluating platelet reactivity (r = −0.511). A significant although poor agreement (κ = 0.225) in identifying HPR and a significantly moderate agreement in identifying LPR (κ = 0.412) were observed between TEG and VerifyNow. By using TEG as the reference for comparison, the cutoff values of VerifyNow for the Chinese patients in this study were identified as PRU >205 for HPR and PRU <169 for LPR. Conclusions: By comparing VerifyNow to TEG which has been widely used in clinics, VerifyNow could be an attractive alternative to TEG for monitoring on-clopidogrel platelet reactivity in Chinese patients. PMID:27647183

  11. Measurement and evaluation techniques for automated demand response demonstration

    SciTech Connect

    Motegi, Naoya; Piette, Mary Ann; Watson, David S.; Sezgen, Osman; ten Hope, Laurie

    2004-08-01

    The recent electricity crisis in California and elsewhere has prompted new research to evaluate demand response strategies in large facilities. This paper describes an evaluation of fully automated demand response technologies (Auto-DR) in five large facilities. Auto-DR does not involve human intervention, but is initiated at a facility through receipt of an external communications signal. This paper summarizes the measurement and evaluation of the performance of demand response technologies and strategies in five large facilities. All the sites have data trending systems such as energy management and control systems (EMCS) and/or energy information systems (EIS). Additional sub-metering was applied where necessary to evaluate the facility's demand response performance. This paper reviews the control responses during the test period, and analyzes demand savings achieved at each site. Occupant comfort issues are investigated where data are available. This paper discusses methods to estimate demand savings and results from demand response strategies at five large facilities.

  12. Aspirin and clopidogrel resistance: possible mechanisms and clinical relevance. Part II: Potential causes and laboratory tests.

    PubMed

    Vadász, Dávid; Sztriha, László K; Sas, Katalin; Vécsei, László

    2013-01-30

    Recent meta-analyses have indicated that patients with vascular disease demonstrated by laboratory tests to be aspirin or clopidogrel-resistant are at an increased risk of major vascular events. The suggested mechanisms of aspirin resistance include genetic polymorphism, alternative pathways of platelet activation, aspirin-insensitive thromboxane biosynthesis, drug interactions, or a low aspirin dose. Clopidogrel resistance is likely to develop as a result of a decreased bioavailability of the active metabolite, due to genetic variation or concomitant drug treatment. Additional work is required to improve and validate laboratory tests of platelet function, so that they may become useful tools for selection of the most appropriate antiplatelet therapy for an individual patient. Improvements in antiplatelet treatment strategies in the future should lead to a reduction in premature vascular events. PMID:23607225

  13. Genetics of response to antiplatelet therapy.

    PubMed

    Thomas, Mark R; Storey, Robert F

    2014-01-01

    Dual antiplatelet therapy has a major role in the management of acute coronary syndromes (ACS) and following percutaneous coronary intervention (PCI). However, significant variation in pharmacodynamic response to antiplatelet therapy has been demonstrated, especially to clopidogrel. Single nucleotide polymorphisms, particularly those affecting the metabolism of antiplatelet therapy, account for some, but not all, of this variability in response. Loss-of-function polymorphisms of CYP2C19, the gene encoding for the key enzyme in the metabolism of clopidogrel, are associated with reduced formation of the active metabolite of clopidogrel, a lower pharmacodynamic effect of the drug and a corresponding increase in adverse cardiovascular events. Conversely, gain-of-function polymorphisms of CYP2C19 are associated with an increased pharmacodynamic response to the drug and therefore an increase in bleeding. The clinical relevance of other polymorphisms that affect antiplatelet therapy has not been clearly established. PMID:24751429

  14. Species Comparison of Pre-systemic Bioactivation of Vicagrel, a New Acetate Derivative of Clopidogrel

    PubMed Central

    Qiu, Zhi-xia; Gao, Wen-chao; Dai, Yu; Zhou, Su-feng; Zhao, Jie; Lu, Yang; Chen, Xi-jing; Li, Ning

    2016-01-01

    Previously we have found vicagrel, a new acetate derivative of clopidogrel, underwent hydrolysis to 2-oxo-clopidogrel and subsequent conversions to its pharmacological active metabolite (AM) and inactive carboxylic acid metabolite (CAM). This study demonstrated the interspecies differences of the vicagrel bioactivation by comparing the critical vicagrel metabolites formation in rats, dogs and human. The pharmacokinetic studies with rats and dogs were conducted after intragastric administration of vicagrel, followed by in vitro metabolism investigation in venous system, intestinal/hepatic microsomes from rats, dogs and human. An obvious disparity was observed in system exposure to AM (99.0 vs. 635.1 μg⋅h/L, p < 0.05) and CAM (10119 vs. 2634 μg⋅h/L, p < 0.05) in rats and dogs. It was shown that the cleavage of vicagrel was almost completed in intestine with great different clearance (53.28 vs. 3.643 L⋅h-1⋅kg-1, p < 0.05) in rats and dogs. With no further hydrolysis to CAM, the greatest clearance of AM (3.26 mL⋅h-1⋅kg-1) was found in dog intestine. In rat plasma, 2-oxo-clopidogrel was much more extensively hydrolyzed to CAM than in dog and human. Albeit similar hydrolysis clearance and AM production was observed among hepatic microsomes of the three species, the production velocity of CAM ranked highest in dogs (7.55 pmol/min/mg protein). Therefore, the unconformity of AM and CAM exposure cross species mainly came from the metabolism of 2-oxo-clopidogrel associated largely with tissue specificity and interspecies differences of esterases. In human, the pharmacokinetics of vicagrel might be more optimistic due to less inactivation hydrolysis before reaching liver. PMID:27774067

  15. Decision making on timing of surgery for hip fracture patients on clopidogrel.

    PubMed

    Purushothaman, B; Webb, M; Weusten, A; Bonczek, S; Ramaskandhan, J; Nanu, A

    2016-02-01

    Patients taking clopidogrel who sustain a fractured neck of femur pose a challenge to orthopaedic surgeons. The aim of this study was to determine whether delay to theatre for these patients affects drop in haemoglobin levels, need for blood transfusion, length of hospital stay and 30-day mortality. A retrospective review of all neck of femur patients admitted at two centres in the North East of England over 3 years revealed 85 patients. Patients were divided into two groups depending on whether they were taking clopidogrel alone (C) or with aspirin (CA). Haemoglobin drop was significantly different in the CA group that was operated on early (CA1) versus the group for which surgery was delayed by over 48 hours (CA2): 3.3g/dl and 1.9g/dl respectively (p=0.01). The mean inpatient stay in group C was 35.9 days while in group CA it was 19.9 days (p=0.002). The mean length of stay in group CA2 (26.7 days) was significantly longer than for CA1 patients (14.1 days) (p=0.01). There were no significant differences in mortality or wound complications. Hip fracture patients on clopidogrel can be safely operated on early provided they are medically stable. Bleeding risk should be borne in mind in those patients on dual therapy with aspirin. PMID:26829666

  16. Thrombotic Thrombocytopenic Purpura associated with Clopidogrel: a case report and review of the literature

    PubMed Central

    Azarm, Taleb; Sohrabi, Ayatollah; Mohajer, Hamid; Azarm, Arezou

    2011-01-01

    Thrombotic Thrombocytopenic Purpura (TTP) is a life threatening, multisystem disease characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurological changes, renal failure, and fever. These signs and symptoms are thought to be caused by microthrombi, composed of agglutinated platelets and fibrin, which deposit in the arterioles and capillaries without mediation by an inflammatory process. TTP can occur in the first two weeks of initiation of Clopidogrel therapy. Early signs of TTP may be a skin reaction, which may precede the onset of TTP or it may be other type of purpura or neurological changes. We report the clinical and laboratory findings in a 67 years old female patient in whom TTP developed soon after treatment with 40 mg/day oral Clopidogrel after 8 days. She developed thrombocytopenia (platelets count 12000 /mm3). Her clinical signs and symptoms were fever (39.6C), bleeding from the nose and gum, large skin bruises (purpura and ecchymoses), neurological changes including hallucinations, bizarre behavior, altered mental status (fluctuating), headache, and renal dysfunction. Physicians should be aware of the possibility early onset of this syndrome when initiate Clopidogrel treatment. PMID:22091257

  17. Clopidogrel Has No Clinically Meaningful Effect on the Pharmacokinetics of the Organic Anion Transporting Polypeptide 1B1 and Cytochrome P450 3A4 Substrate Simvastatin.

    PubMed

    Itkonen, Matti K; Tornio, Aleksi; Neuvonen, Mikko; Neuvonen, Pertti J; Niemi, Mikko; Backman, Janne T

    2015-11-01

    Simvastatin and clopidogrel are commonly used together in the treatment of cardiovascular diseases. Organic anion transporting polypeptide (OATP) 1B1 activity markedly affects the hepatic uptake of simvastatin acid, whereas both simvastatin and simvastatin acid are sensitive to changes in cytochrome P450 3A4 activity. Clopidogrel and its metabolites inhibit OATP1B1 and CYP3A4 in vitro. We studied the effect of clopidogrel on the pharmacokinetics of simvastatin in a randomized crossover study. Twelve healthy volunteers ingested either a dose of placebo (control) or 300 mg of clopidogrel on day 1 and 75 mg on days 2 and 3. Simvastatin 40 mg was administered 1 hour after placebo and after clopidogrel on days 1 and 3. Plasma drug concentrations were measured for up to 12 hours. Clopidogrel 300 mg (day 1) increased the concentrations of simvastatin and simvastatin acid during the absorption phase. After clopidogrel 300 mg, the area under the concentration time curve (AUC) of simvastatin from 0 to 2 hours was 156% (P = 0.02) and its AUC(0-12 hours) was 132% (P = 0.08) of that during placebo, whereas the AUC(0-2 hours) and the AUC(0-12 hours) of simvastatin acid were 148% (P = 0.04) and 112% (P = 0.52) of control. Clopidogrel 75 mg (day 3) had no significant effect on the pharmacokinetic variables of simvastatin or simvastatin acid compared with placebo. The effect of clopidogrel seemed independent of the SLCO1B1 c.521T>C genotype. In conclusion, as clopidogrel did not have significant effects on the total exposure to simvastatin or simvastatin acid, clopidogrel does not seem to inhibit OATP1B1 or CYP3A4 to a clinically relevant extent.

  18. Evaluation of riser 14 temperature response

    SciTech Connect

    OGDEN, D.M.

    1999-03-08

    The initial sluicing activities of Project WRSS resulted in a two month increase in temperatures as measured by the Riser 14 thermocouple tree of tank 241-C-106. While this increase was anticipated, the maximum temperature was higher than expected. An evaluation was performed to determine if adequate subcooling exists in the waste to continue sluicing activities. It was determined that a minimum of 10 F subcooling exists in the waste and that the higher Riser 14 temperatures were the result of higher than assumed waste saturation temperature.

  19. Cytochrome P450 Gene Variants, Race, and Mortality Among Clopidogrel Treated Patients Following Acute Myocardial Infarction

    PubMed Central

    Cresci, Sharon; Depta, Jeremiah P.; Lenzini, Petra A.; Li, Allie Y.; Lanfear, David E.; Province, Michael A.; Spertus, John A.; Bach, Richard G.

    2014-01-01

    Background Clopidogrel is recommended after acute myocardial infarction (AMI) but has variable efficacy and safety, in part related to the effect of cytochrome P450 (CYP) polymorphisms on its metabolism. The effect of CYP polymorphisms on cardiovascular events among clopidogrel-treated patients after AMI remains controversial, and no studies to date have investigated the association of CYP variants with outcomes in African American patients. Methods and Results 2732 subjects (2062 Caucasians; 670 African Americans) hospitalized with AMI enrolled in the prospective, multicenter TRIUMPH study were genotyped for CYP polymorphisms. The majority of Caucasians (79%) and African Americans (64.4%) were discharged on clopidogrel. Among Caucasians, carriers of the loss-of-function CYP2C19*2 allele had significantly increased 1-year mortality (adjusted HR: 1.70; CI: 1.01 to 2.86; p=0.046), and a trend toward increased rate of recurrent MI (adjusted HR: 2.10; CI 0.95 to 4.63; p= 0.066). Among African Americans, increased 1-year mortality was associated with the gain of function CYP2C19*17 allele (adjusted HR for *1/*17 vs. *1/*1: 2.02; CI: 0.92 to 4.44; *17/*17 vs. *1/*1: 8.97; CI: 3.34 to 24.10; p< 0.0001) and the CYP1A2*1C allele (adjusted HR for *1/*1C vs. *1/*1: 1.89; CI: 0.85 to 4.22; *1C/*1C vs. *1/*1: 4.96; CI: 1.69 to 14.56; p= 0.014). Bleeding events were significantly more common among African American carriers of CYP2C19*17 or CYP1A2*1C. Conclusions Both loss of function and gain of function CYP polymorphisms affecting clopidogrel metabolism are associated with increased mortality among clopidogrel treated patients following AMI; the specific polymorphism and the putative mechanism vary according to race. PMID:24762860

  20. Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment.

    PubMed

    Abou-Abbass, Hussein; Bahmad, Hisham; Abou-El-Hassan, Hadi; Zhu, Rui; Zhou, Shiyue; Dong, Xue; Hamade, Eva; Mallah, Khalil; Zebian, Abir; Ramadan, Naify; Mondello, Stefania; Fares, Jawad; Comair, Youssef; Atweh, Samir; Darwish, Hala; Zibara, Kazem; Mechref, Yehia; Kobeissy, Firas

    2016-06-01

    As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitantly receiving preinjury antiplatelet therapy such as aspirin (ASA) and clopidogrel (CLOP) is rising. These drugs have been linked with unfavorable clinical outcomes following TBI, where the exact mechanism(s) involved are still unknown. In this novel work, we aimed to identify and compare the altered proteome profile imposed by ASA and CLOP when administered alone or in combination, prior to experimental TBI. Furthermore, we assessed differential glycosylation PTM patterns following experimental controlled cortical impact model of TBI, ASA, CLOP, and ASA + CLOP. Ipsilateral cortical brain tissues were harvested 48 h postinjury and were analyzed using an advanced neuroproteomics LC-MS/MS platform to assess proteomic and glycoproteins alterations. Of interest, differential proteins pertaining to each group (22 in TBI, 41 in TBI + ASA, 44 in TBI + CLOP, and 34 in TBI + ASA + CLOP) were revealed. Advanced bioinformatics/systems biology and clustering analyses were performed to evaluate biological networks and protein interaction maps illustrating molecular pathways involved in the experimental conditions. Results have indicated that proteins involved in neuroprotective cellular pathways were upregulated in the ASA and CLOP groups when given separately. However, ASA + CLOP administration revealed enrichment in biological pathways relevant to inflammation and proinjury mechanisms. Moreover, results showed differential upregulation of glycoproteins levels in the sialylated N-glycans PTMs that can be implicated in pathological changes. Omics data obtained have provided molecular insights of the underlying mechanisms that can be translated into clinical bedside settings. PMID:27249377

  1. Evaluation Responsibility and Leadership in the Face of Failing Democracies

    ERIC Educational Resources Information Center

    McKegg, Kate

    2013-01-01

    In a world faced with unprecedented rising levels of inequality and injustice, is there a responsibility for our evaluation organizations to take on a leadership role in promoting inclusive, evaluative dialog and deliberation about the state of our democracies in relation to key democratic principles and ideals? In this forum, I question whether…

  2. High On-Aspirin Platelet Reactivity and Clinical Outcome in Patients With Stable Coronary Artery Disease: Results From ASCET (Aspirin Nonresponsiveness and Clopidogrel Endpoint Trial)

    PubMed Central

    Pettersen, Alf-Åge R.; Seljeflot, Ingebjørg; Abdelnoor, Michael; Arnesen, Harald

    2012-01-01

    Background Patients with stable coronary artery disease on single-antiplatelet therapy with aspirin are still at risk for atherothrombotic events, and high on-aspirin residual platelet reactivity (RPR) has been suggested as a risk factor. Methods and Results In this randomized trial, the association between platelet function determined by the PFA100 platelet function analyzer system (Siemens Healthcare Diagnostics, Germany) and clinical outcome in 1001 patients, all on single-antiplatelet therapy with aspirin (160 mg/d) was studied. Patients were randomized to continue with aspirin 160 mg/d or change to clopidogrel 75 mg/d. A composite end point of death, myocardial infarction, ischemic stroke, and unstable angina was used. At 2-year follow-up, 106 primary end points were registered. The prevalence of high RPR was 25.9%. High on-aspirin RPR did not significantly influence the primary end point in the aspirin group (13.3% versus 9.9%, P=0.31). However, in post hoc analysis, patients with von Willebrand factor levels or platelet count below median values and high on-aspirin RPR had a statistically significant higher end point rate than that of patients with low RPR (20% versus 7.5%, P=0.014, and 18.2% versus 10.8%, P=0.039, respectively). The composite end point rate in patients with high on-aspirin RPR treated with clopidogrel was not different from that of patients treated with aspirin (7.6% versus 13.3%, P=0.16). Conclusions In stable, aspirin-treated patients with coronary artery disease, high on-aspirin RPR did not relate to clinical outcome and did not identify a group responsive to clopidogrel. Post hoc subgroup analysis raised the possibility that high on-aspirin RPR might be predictive in patients with low von Willebrand factor or platelet count, but these findings will require confirmation in future studies. Clinical Trial Registration URL: http://www.clinicaltrials.gov Unique identifier: NCT00222261. (J Am Heart Assoc. 2012;1:e000703 doi: 10.1161/JAHA.112

  3. A Method to Evaluate Hormesis in Nanoparticle Dose-Responses

    PubMed Central

    Nascarella, Marc A.; Calabrese, Edward J.

    2012-01-01

    The term hormesis describes a dose-response relationship that is characterized by a response that is opposite above and below the toxicological or pharmacological threshold. Previous reports have shown that this relationship is ubiquitous in the response of pharmaceuticals, metals, organic chemicals, radiation, and physical stressor agents. Recent reports have also indicated that certain nanoparticles (NPs) may also exhibit a hormetic dose-response. We describe the application of three previously described methods to quantify the magnitude of the hormetic biphasic dose-responses in nanotoxicology studies. This methodology is useful in screening assays that attempt to parse the observed toxicological dose-response data into categories based on the magnitude of hormesis in the evaluation of NPs. For example, these methods may be used to quickly identify NP induced hormetic responses that are either desirably enhanced (e.g., neuronal cell viability) or undesirably stimulated (e.g., low dose stimulation of tumor cells). PMID:22942868

  4. Simultaneous Two-Vessel Subacute Stent Thrombosis Caused by Clopidogrel Resistance from CYP2C19 Polymorphism.

    PubMed

    Afzal, Ashwad; Patel, Bimal; Patel, Neel; Sattur, Sudhakar; Patel, Vinod

    2016-01-01

    Clopidogrel resistance from CYP2C19 polymorphism has been associated with stent thrombosis in patients undergoing percutaneous coronary intervention with drug-eluting stents. We present a case of a 76-year-old male who received drug-eluting stents to the right coronary artery and left anterior descending artery for non-ST elevation myocardial infarction and was discharged on dual antiplatelet therapy with aspirin and clopidogrel. He subsequently presented with chest pain from anterior, anteroseptal, and inferior ST segment elevation myocardial infarction. An emergent coronary angiogram revealed acute stent thrombosis with 100% occlusion of RCA and LAD that was successfully treated with thrombus aspiration and angioplasty. Although he was compliant with his dual antiplatelet therapy, he developed stent thrombosis, which was confirmed as clopidogrel resistance from homozygous CYP2C19 polymorphism. PMID:27555873

  5. Simultaneous Two-Vessel Subacute Stent Thrombosis Caused by Clopidogrel Resistance from CYP2C19 Polymorphism

    PubMed Central

    Patel, Bimal; Patel, Neel; Sattur, Sudhakar; Patel, Vinod

    2016-01-01

    Clopidogrel resistance from CYP2C19 polymorphism has been associated with stent thrombosis in patients undergoing percutaneous coronary intervention with drug-eluting stents. We present a case of a 76-year-old male who received drug-eluting stents to the right coronary artery and left anterior descending artery for non-ST elevation myocardial infarction and was discharged on dual antiplatelet therapy with aspirin and clopidogrel. He subsequently presented with chest pain from anterior, anteroseptal, and inferior ST segment elevation myocardial infarction. An emergent coronary angiogram revealed acute stent thrombosis with 100% occlusion of RCA and LAD that was successfully treated with thrombus aspiration and angioplasty. Although he was compliant with his dual antiplatelet therapy, he developed stent thrombosis, which was confirmed as clopidogrel resistance from homozygous CYP2C19 polymorphism. PMID:27555873

  6. Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate thrombotic responses.

    PubMed

    Gould, W R; Baxi, S M; Schroeder, R; Peng, Y W; Leadley, R J; Peterson, J T; Perrin, L A

    2005-04-01

    Gas6 (encoded by growth arrest-specific gene 6) is a vitamin-K dependent protein highly homologous to coagulation protein S that is secreted from platelet alpha-granules and has recently been demonstrated to participate in platelet thrombus formation. The current study evaluated the contribution of each of the three known Gas6 receptors (Axl, Sky and Mer) in human and mouse platelet function. Flow cytometry analyses confirmed that all three receptors are present on both human and mouse platelets. Pre-incubation of human platelets with either an anti-Gas6 antibody or blocking antibodies to Sky or Mer inhibited platelet aggregation and degranulation responses to both ADP and the PAR-1 activating peptide, SFLLRN, by more than 80%. In contrast, a stimulatory anti-Axl antibody increased activation responses to these agonists, suggesting a potentiating role for Gas6 in platelet activation. Moreover, in a mouse model of thrombosis, administration of Gas6 or Sky blocking antibodies resulted in a decrease in thrombus weight similar to clopidogrel but, unlike clopidogrel, produced no increase in template bleeding. Thus, Gas6 enhances platelet degranulation and aggregation responses through its known receptors, promoting platelet activation and mediating thrombus formation such that its inhibition prevents thrombosis without increasing bleeding. PMID:15733062

  7. Functional impact of high clopidogrel maintenance dosing in patients undergoing elective percutaneous coronary interventions. Results of a randomized study.

    PubMed

    Angiolillo, Dominick J; Bernardo, Esther; Palazuelos, Jorge; Desai, Bhaloo; Weisberg, Ian; Alfonso, Fernando; Guzman, Luis A; Hernández-Antolin, Rosana; Zenni, Martin Z; Macaya, Carlos; Fernandez-Ortiz, Antonio; Bass, Theodore A

    2008-01-01

    The currently recommended maintenance dose of clopidogrel is often associated with inadequate platelet inhibition, suggesting the need for a higher dose. The aim of this pilot study was to assess the functional impact of a high (150 mg/day) maintenance dose of clopidogrel in patients undergoing elective percutaneous coronary intervention (PCI). This is a prospective, randomized, platelet function study which was performed in elective PCI patients assigned to treatment with either a 75 mg (n = 20) or 150 mg (n = 20) daily maintenance dose of clopidogrel for 30 days; afterwards, all patients resumed standard dosing. Platelet aggregation was performed using light transmittance aggregometry following 20 microM and 5 microM adenosine diphosphate (ADP) stimuli 30 days after randomization and 30 days after resuming standard dosing. Patients treated with 150 mg/day clopidogrel had lower 20 microM ADP-induced platelet aggregation compared to patients on 75 mg/day (52.1 +/- 9% vs. 64.0 +/- 8%; p < 0.001; primary endpoint). The dose-dependent effect was confirmed by the absolute and relative increase in platelet aggregation after resuming standard dosing (p < 0.001). No changes were observed in patients randomized to standard dosing. Parallel findings were observed following 5 microM ADP stimuli for all assessments. A broad variability in clopidogrel-induced antiplatelet effects was observed irrespective of dosing. In conclusion, a 150 mg/day maintenance dose regimen of clopidogrel is associated with reduced platelet reactivity and enhanced platelet inhibition compared to that achieved with the currently recommended 75 mg/day in patients undergoing elective PCI.

  8. Cytochromes P450 catalyze both steps of the major pathway of clopidogrel bioactivation, whereas paraoxonase catalyzes the formation of a minor thiol metabolite isomer.

    PubMed

    Dansette, Patrick M; Rosi, Julien; Bertho, Gildas; Mansuy, Daniel

    2012-02-20

    The mechanism generally admitted for the bioactivation of the antithrombotic prodrug, clopidogrel, is its two-step enzymatic conversion into a biologically active thiol metabolite. The first step is a classical cytochrome P450 (P450)-dependent monooxygenation of its thiophene ring leading to 2-oxo-clopidogrel, a thiolactone metabolite. The second step was described as a P450-dependent oxidative opening of the thiolactone ring of 2-oxo-clopidogrel, with intermediate formation of a reactive sulfenic acid metabolite that is eventually reduced to the corresponding thiol 4b. A very recent paper published in Nat. Med. (Bouman et al., (2011) 17, 110) reported that the second step of clopidogrel bioactivation was not catalyzed by P450 enzymes but by paraoxonase-1(PON-1) and that PON-1 was a major determinant of clopidogrel efficacy. The results described in the present article show that there are two metabolic pathways for the opening of the thiolactone ring of 2-oxo-clopidogrel. The major one, that was previously described, results from a P450-dependent redox bioactivation of 2-oxo-clopidogrel and leads to 4b cis, two previously reported thiol diastereomers bearing an exocyclic double bond. The second, minor one, results from a hydrolysis of 2-oxo-clopidogrel, which seems to be dependent on PON-1, and leads to an isomer of 4b cis, 4b "endo", in which the double bond has migrated from an exocyclic to an endocyclic position in the piperidine ring. These results were obtained from a detailed study of the metabolism of 2-oxo-clopidogrel by human liver microsomes and human sera and analysis by HPLC-MS under conditions allowing a complete separation of the thiol metabolite isomers, either as such or after derivatization with 3'-methoxy phenacyl bromide or N-ethyl maleimide (NEM). These results also show that the major bioactive thiol isomer found in the plasma of clopidogrel-treated patients derives from 2-oxo-clopidogrel by the P450-dependent pathway. Finally, chemical

  9. Formation of the Thiol Conjugates and Active Metabolite of Clopidogrel by Human Liver Microsomes

    PubMed Central

    Lau, Wei C.; Hollenberg, Paul F.

    2012-01-01

    We reported previously the formation of a glutathionyl conjugate of the active metabolite (AM) of clopidogrel and the covalent modification of a cysteinyl residue of human cytochrome P450 2B6 in a reconstituted system (Mol Pharmacol 80:839–847, 2011). In this work, we extended our studies of the metabolism of clopidogrel to human liver microsomes in the presence of four reductants, namely, GSH, l-Cys, N-acetyl-l-cysteine (NAC), and ascorbic acid. Our results demonstrated that formation of the AM was greatly affected by the reductant used and the relative amounts of the AM formed were increased in the following order: NAC (17%) < l-Cys (53%) < ascorbic acid (61%) < GSH (100%). AM-thiol conjugates were observed in the presence of NAC, l-Cys, and GSH. In the case of GSH, the formation of both the AM and the glutathionyl conjugate was dependent on the GSH concentrations, with similar Km values of ∼0.5 mM, which indicates that formation of the thiol conjugates constitutes an integral part of the bioactivation processes for clopidogrel. It was observed that the AM was slowly converted to the thiol conjugate, with a half-life of ∼10 h. Addition of dithiothreitol to the reaction mixture reversed the conversion, which resulted in a decrease in AM-thiol conjugate levels and a concomitant increase in AM levels, whereas addition of NAC led to the formation of AM-NAC and a concomitant decrease in AM-GSH levels. These results not only confirm that the AM is formed through oxidative opening of the thiolactone ring but also suggest the existence of an equilibrium between the AM, the thiol conjugates, and the reductants. These factors may affect the effective concentrations of the AM in vivo. PMID:22584220

  10. Evaluation of the Emergency Response Dose Assessment System(ERDAS)

    NASA Technical Reports Server (NTRS)

    Evans, Randolph J.; Lambert, Winifred C.; Manobianco, John T.; Taylor, Gregory E.; Wheeler, Mark M.; Yersavich, Ann M.

    1996-01-01

    The emergency response dose assessment system (ERDAS) is a protype software and hardware system configured to produce routine mesoscale meteorological forecasts and enhanced dispersion estimates on an operational basis for the Kennedy Space Center (KSC)/Cape Canaveral Air Station (CCAS) region. ERDAS provides emergency response guidance to operations at KSC/CCAS in the case of an accidental hazardous material release or an aborted vehicle launch. This report describes the evaluation of ERDAS including: evaluation of sea breeze predictions, comparison of launch plume location and concentration predictions, case study of a toxic release, evaluation of model sensitivity to varying input parameters, evaluation of the user interface, assessment of ERDA's operational capabilities, and a comparison of ERDAS models to the ocean breeze dry gultch diffusion model.

  11. Metabolic activation of clopidogrel: in vitro data provide conflicting evidence for the contributions of CYP2C19 and PON1.

    PubMed

    Polasek, Thomas M; Doogue, Matthew P; Miners, John O

    2011-12-01

    The recent report that clopidogrel efficacy may be more dependent on paraoxonase-1 (PON1) than on cytochrome P450 2C19 (CYP2C19) activity raises questions about the roles of these and other enzymes in clopidogrel activation. To provide insight into the emerging PON1 versus CYP2C19 debate, this commentary summarizes the clinical evidence on the pharmacokinetic determinants of clopidogrel efficacy. We then review the in vitro studies investigating the enzymes involved in clopidogrel activation, and comment on their strengths and limitations. There is agreement amongst in vitro studies regarding the involvement of CYP1A2 and CYP2B6 in the metabolism of clopidogrel to 2-oxo-clopidogrel. However, the evidence for other CYP enzymes in the first activation step (e.g. CYP2C19 and CYP3A4) is inconsistent and dependent on the in vitro test system and laboratory. All major drug metabolizing CYP enzymes are capable of converting 2-oxo-clopidogrel to sulfenic acid intermediates that subsequently form the active thiol metabolite. However, the extent of CYP involvement in this second step has been challenged, and new evidence suggests that CYP-independent hydrolytic cleavage of the thioester bond may be more important than oxidative metabolism.

  12. 5 CFR 410.202 - Responsibilities for evaluating training.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Responsibilities for evaluating training. 410.202 Section 410.202 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE... contribute to mission accomplishment and meet organizational performance goals....

  13. 5 CFR 410.202 - Responsibilities for evaluating training.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Responsibilities for evaluating training. 410.202 Section 410.202 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE... contribute to mission accomplishment and meet organizational performance goals....

  14. 5 CFR 410.202 - Responsibilities for evaluating training.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Responsibilities for evaluating training. 410.202 Section 410.202 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE... contribute to mission accomplishment and meet organizational performance goals....

  15. 5 CFR 410.202 - Responsibilities for evaluating training.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Responsibilities for evaluating training. 410.202 Section 410.202 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE... contribute to mission accomplishment and meet organizational performance goals....

  16. Evaluating Item Fit for Multidimensional Item Response Models

    ERIC Educational Resources Information Center

    Zhang, Bo; Stone, Clement A.

    2008-01-01

    This research examines the utility of the s-x[superscript 2] statistic proposed by Orlando and Thissen (2000) in evaluating item fit for multidimensional item response models. Monte Carlo simulation was conducted to investigate both the Type I error and statistical power of this fit statistic in analyzing two kinds of multidimensional test…

  17. 40 CFR 265.93 - Preparation, evaluation, and response.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., STORAGE, AND DISPOSAL FACILITIES Ground-Water Monitoring § 265.93 Preparation, evaluation, and response... an outline of a ground-water quality assessment program. The outline must describe a more comprehensive ground-water monitoring program (than that described in §§ 265.91 and 265.92) capable...

  18. 40 CFR 265.93 - Preparation, evaluation, and response.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., STORAGE, AND DISPOSAL FACILITIES Ground-Water Monitoring § 265.93 Preparation, evaluation, and response... an outline of a ground-water quality assessment program. The outline must describe a more comprehensive ground-water monitoring program (than that described in §§ 265.91 and 265.92) capable...

  19. Clinical parameters for evaluating biological response modifier therapy.

    PubMed

    Hamblin, T J

    1989-01-01

    Evaluating response in cancer is a well established practice, depending on the recognition of complete response, partial response, stable disease and progressive disease. For chemotherapeutic drugs, only those patients achieving a complete response experience an increase in survival. Partial response merely indicates that the drug has some activity in that disease. What the patient wants is not active drugs but prolonged survival with good quality of life. It is well recognised that tumours may remain dormant for many years, and that even those patients with complete responses to chemotherapy usually have minimal residual disease. It is assumed that such minimal disease is controlled and held in check by a biological process. The principal aim of biological response modifiers is to enhance this effect so as to control an even larger tumour load. It therefore follows that removal of all tumour is not the only benefit, and that stable disease and even slower progression might translate to longer survival. Survival curves are the acid test and we should expect longer survival even for those patients failing to achieve complete response if we are to establish that life imprisonment is as effective in cancer treatment as capital punishment.

  20. Moral Knowledge and Responsibilities in Evaluation Implementation: When Critical Theory and Responsive Evaluation Collide

    ERIC Educational Resources Information Center

    Freeman, Melissa; Preissle, Judith; Havick, Steven

    2010-01-01

    An external evaluation documented what occurred in an inaugural summer camp to teach high school students how to preserve religious freedom by learning about and acting on the history and current state of church-state separation and other first amendment issues. Camp designers hoped to promote religious diversity values and civic engagement in…

  1. [Argatroban, Aspirin, and Clopidogrel Combination Therapy for Acute Penetrating Artery Infarction: A Pilot Study].

    PubMed

    Nishi, Ryoji; Mano, Tomoo; Kobayashi, Yosuke; Matsuo, Koji; Kobayashi, Yasushi

    2016-02-01

    Treatment to prevent progressive neurological deficits in acute penetrating artery infarction (API) is clinically important, but has not yet been established. This study aims to investigate the efficacy and safety of argatroban, aspirin, and clopidogrel combination therapy for API. Patients with API (lacunar infarcts or branch atheromatous disease) admitted within 48 hours after onset were enrolled. We assigned them to argatroban, aspirin, and clopidogrel (AAC) group or argatroban and aspirin (AA) group. In both groups, blood pressure was controlled to near or below 180/105 mmHg in the admission period. We defined progressing stroke as a worsening of two or more points in the National Institutes of Health Stroke Scale score on the seventh day of admission. Fifty-four patients were enrolled. We assigned 28 patients to the AAC group, and 26 patients to the AA group. There were no significant differences in background factors between the two groups. The incidence of progressing stroke was significantly higher in the AA group (P<0.05). Intracranial hemorrhage or any other bleeding was not seen in the admission period in either group. Our findings suggest that the AAC combination therapy may positively affect progressive neurological deficits in API patients.

  2. Modern role for clopidogrel in management of atrial fibrillation and stroke reduction

    PubMed Central

    Maegdefessel, Lars; Azuma, Junya; Tsao, Philip S

    2010-01-01

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The prevalence of AF increases sharply in old age (prevalence approximately 10% among persons 80 years of age and older). The expected risk for ischemic stroke is increased five-fold by the presence of AF, primarily as a result of cardiogenic embolism. Multiple large-scale, randomized trials have been completed or are still underway to find optimal, efficacious, and relatively safe ways to reduce the risk of ischemic stroke and other systemic thromboembolic events related to AF. Antithrombotic strategies are accompanied by serious bleeding complications that threaten patients in need of medical stroke prevention. Treatment regimens for preventing thromboembolism in AF patients range from vitamin K antagonists such as warfarin or coumadins, antiplatelet drugs like aspirin or clopidogrel, to newly developed orally available antithrombotics like the direct thrombin inhibitor dabigatran, or the Factor Xa-inhibitor rivaroxaban. The available anticoagulant and antiplatelet drugs have different advantages and disadvantages. This review attempts to delineate the specific role of clopidogrel in patients with AF and at risk of stroke, taking into consideration new and ongoing trials in this important field of medical practice. PMID:20234784

  3. Response variables for evaluation of the effectiveness of conservation corridors.

    PubMed

    Gregory, Andrew J; Beier, Paul

    2014-06-01

    Many studies have evaluated effectiveness of corridors by measuring species presence in and movement through small structural corridors. However, few studies have assessed whether these response variables are adequate for assessing whether the conservation goals of the corridors have been achieved or considered the costs or lag times involved in measuring the response variables. We examined 4 response variables-presence of the focal species in the corridor, interpatch movement via the corridor, gene flow, and patch occupancy--with respect to 3 criteria--relevance to conservation goals, lag time (fewest generations at which a positive response to the corridor might be evident with a particular variable), and the cost of a study when applying a particular variable. The presence variable had the least relevance to conservation goals, no lag time advantage compared with interpatch movement, and only a moderate cost advantage over interpatch movement or gene flow. Movement of individual animals between patches was the most appropriate response variable for a corridor intended to provide seasonal migration, but it was not an appropriate response variable for corridor dwellers, and for passage species it was only moderately relevant to the goals of gene flow, demographic rescue, and recolonization. Response variables related to gene flow provided a good trade-off among cost, relevance to conservation goals, and lag time. Nonetheless, the lag time of 10-20 generations means that evaluation of conservation corridors cannot occur until a few decades after a corridor has been established. Response variables related to occupancy were most relevant to conservation goals, but the lag time and costs to detect corridor effects on occupancy were much greater than the lag time and costs to detect corridor effects on gene flow. PMID:24606549

  4. In Vitro Evaluation of Fluorescence Glucose Biosensor Response

    PubMed Central

    Aloraefy, Mamdouh; Pfefer, T. Joshua; Ramella-Roman, Jessica C.; Sapsford, Kim E.

    2014-01-01

    Rapid, accurate, and minimally-invasive glucose biosensors based on Förster Resonance Energy Transfer (FRET) for glucose measurement have the potential to enhance diabetes control. However, a standard set of in vitro approaches for evaluating optical glucose biosensor response under controlled conditions would facilitate technological innovation and clinical translation. Towards this end, we have identified key characteristics and response test methods, fabricated FRET-based glucose biosensors, and characterized biosensor performance using these test methods. The biosensors were based on competitive binding between dextran and glucose to concanavalin A and incorporated long-wavelength fluorescence dye pairs. Testing characteristics included spectral response, linearity, sensitivity, limit of detection, kinetic response, reversibility, stability, precision, and accuracy. The biosensor demonstrated a fluorescence change of 45% in the presence of 400 mg/dL glucose, a mean absolute relative difference of less than 11%, a limit of detection of 25 mg/dL, a response time of 15 min, and a decay in fluorescence intensity of 72% over 30 days. The battery of tests presented here for objective, quantitative in vitro evaluation of FRET glucose biosensors performance have the potential to form the basis of future consensus standards. By implementing these test methods for a long-visible-wavelength biosensor, we were able to demonstrate strengths and weaknesses with a new level of thoroughness and rigor. PMID:25006996

  5. Evaluation of Piloted Inputs for Onboard Frequency Response Estimation

    NASA Technical Reports Server (NTRS)

    Grauer, Jared A.; Martos, Borja

    2013-01-01

    Frequency response estimation results are presented using piloted inputs and a real-time estimation method recently developed for multisine inputs. A nonlinear simulation of the F-16 and a Piper Saratoga research aircraft were subjected to different piloted test inputs while the short period stabilator/elevator to pitch rate frequency response was estimated. Results show that the method can produce accurate results using wide-band piloted inputs instead of multisines. A new metric is introduced for evaluating which data points to include in the analysis and recommendations are provided for applying this method with piloted inputs.

  6. Therapy response evaluation with positron emission tomography-computed tomography.

    PubMed

    Segall, George M

    2010-12-01

    Positron emission tomography-computed tomography with F-18-fluorodeoxyglucose is widely used for evaluation of therapy response in patients with solid tumors but has not been as readily adopted in clinical trials because of the variability of acquisition and processing protocols and the absence of universal response criteria. Criteria proposed for clinical trials are difficult to apply in clinical practice, and gestalt impression is probably accurate in individual patients, especially with respect to the presence of progressive disease and complete response. Semiquantitative methods of determining tissue glucose metabolism, such as standard uptake value, can be a useful descriptor for levels of tissue glucose metabolism and changes in response to therapy if technical quality control measures are carefully maintained. The terms partial response, complete response, and progressive disease are best used in clinical trials in which the terms have specific meanings and precise definitions. In clinical practice, it may be better to use descriptive terminology agreed upon by imaging physicians and clinicians in their own practice. PMID:21147376

  7. Evaluation of the Adaptive Immune Response to Respiratory Syncytial Virus.

    PubMed

    Knudson, Cory J; Weiss, Kayla A; Stoley, Megan E; Varga, Steven M

    2016-01-01

    Evaluation of the adaptive immune response is critical to the advancement of our basic knowledge and understanding of respiratory syncytial virus (RSV). The cellular composition in the lung following RSV infection is often evaluated using flow cytometry. However, a limitation of this approach has been the inability to readily distinguish cells that are within the lung parenchyma from cells that remain in the pulmonary blood vessels. Herein, we detail a procedure to evaluate the adaptive immune response via flow cytometric analysis that incorporates an in vivo intravascular staining technique. This technique allows for discrimination of immune cells in the lung tissue from cells that remain in the pulmonary vasculature following perfusion. Therefore at any given time point following an RSV infection, the leukocytic populations in the lung parenchyma can be quantified and phenotypically assessed with high resolution. While we focus on the T lymphocyte response in the lung, this technique can be readily adapted to examine various leukocytic cell types in the lung following RSV infection. PMID:27464699

  8. Clopidogrel, prasugrel, ticagrelor or vorapaxar in patients with renal impairment: do we have a winner?

    PubMed

    Serebruany, Victor L; Tomek, Ales; Pokov, Alex N; Kim, Moo Hyun

    2015-12-01

    The optimal utilization of antiplatelet therapy in patients with renal impairment (RI) following acute coronary syndromes (ACS) represents an urgent, unmet and yet unsolved need with regards to the choice of agents, duration of treatment and potential dose/regimen adjustment. The lack of any large randomized trials designed and powered specifically in such high-risk patients, absence of the uniformed efficacy and safety data reporting policy to the FDA and endless overoptimistic publications based on post hoc analyses of primary trials sometimes exaggerating benefits and hiding risks, clouds reality. In addition, triaging RI patients is problematic due to ongoing kidney deterioration and the fact that such patients are prone to both vascular occlusions and bleeding. The authors summarize available FDA-confirmed evidence from the latest trials with approved antiplatelet agents, namely clopidogrel (CAPRIE, CURE, CREDO, CLARITY, CHARISMA); prasugrel (TRITON, TRILOGY); ticagrelor (PLATO, and PEGASUS); and vorapaxar (TRACER and TRA2P) in RI patient cohorts on top of aspirin as part of dual antiplatelet therapy (DAPT). We deliberately avoided any results unless they were verified by the FDA, with the exception of the recent PEGASUS, since Agency reviews are not yet available. Despite differences among the trials and DAPT choices, RI patients universally experience much higher (HR = 1.3-3.1) rates of primary endpoint events, and bleeding risks (HR = 1.7-3.6). However, only ticagrelor increases creatinine and uric acid levels above that of clopidogrel; has the worst incidence of serious adverse events, more adverse events, and inferior outcomes in patients with severe (eGFR <30 ml/min), especially in the lowest (eGFR <15 ml/min) RI subsets. Clopidogrel, prasugrel and vorapaxar appear safer. Moreover, less aggressive half dose (5 mg/daily) prasugrel and strict DAPT, are well justified in RI, but not predominantly triple strategies with vorapaxar as tested in TRA2P and

  9. Six Versus Twelve Months Clopidogrel Therapy After Drug-Eluting Stenting in Patients With Acute Coronary Syndrome: An ISAR-SAFE Study Subgroup Analysis.

    PubMed

    Lohaus, Raphaela; Michel, Jonathan; Mayer, Katharina; Lahmann, Anna Lena; Byrne, Robert A; Wolk, Annabelle; Ten Berg, Jurrien M; Neumann, Franz-Josef; Han, Yaling; Adriaenssens, Tom; Tölg, Ralph; Seyfarth, Melchior; Maeng, Michael; Zrenner, Bernhard; Jacobshagen, Claudius; Wöhrle, Jochen; Kufner, Sebastian; Morath, Tanja; Ibrahim, Tareq; Bernlochner, Isabell; Fischer, Marcus; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Mehilli, Julinda; Kastrati, Adnan; Schulz-Schüpke, Stefanie

    2016-01-01

    In patients presenting with acute coronary syndrome (ACS) the optimal duration of dual-antiplatelet therapy after drug-eluting stent (DES) implantation remains unclear. At 6 months after intervention, patients receiving clopidogrel were randomly assigned to either a further 6-month period of placebo or clopidogrel. The primary composite endpoint was death, myocardial infarction, stent thrombosis, stroke, or major bleeding 9 months after randomization. The ISAR-SAFE trial was terminated early due to low event rates and slow recruitment. 1601/4000 (40.0%) patients presented with ACS and were randomized to 6 (n = 794) or 12 months (n = 807) clopidogrel. The primary endpoint occurred in 14 patients (1.8%) receiving 6 months of clopidogrel and 17 patients (2.2%) receiving 12 months; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.41-1.68, P = 0.60. There were 2 (0.3%) cases of stent thrombosis in each group; HR 1.00, 95% CI 0.14-7.09, P = >0.99. Major bleeding occurred in 3 patients (0.4%) receiving 6 months clopidogrel and 5 (0.6%) receiving 12 months; HR 0.60, 95% CI 0.15-2.49, P = 0.49. There was no significant difference in net clinical outcomes after DES implantation in ACS patients treated with 6 versus 12 months clopidogrel. Ischaemic and bleeding events were low beyond 6-months. PMID:27624287

  10. Six Versus Twelve Months Clopidogrel Therapy After Drug-Eluting Stenting in Patients With Acute Coronary Syndrome: An ISAR-SAFE Study Subgroup Analysis.

    PubMed

    Lohaus, Raphaela; Michel, Jonathan; Mayer, Katharina; Lahmann, Anna Lena; Byrne, Robert A; Wolk, Annabelle; Ten Berg, Jurrien M; Neumann, Franz-Josef; Han, Yaling; Adriaenssens, Tom; Tölg, Ralph; Seyfarth, Melchior; Maeng, Michael; Zrenner, Bernhard; Jacobshagen, Claudius; Wöhrle, Jochen; Kufner, Sebastian; Morath, Tanja; Ibrahim, Tareq; Bernlochner, Isabell; Fischer, Marcus; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Mehilli, Julinda; Kastrati, Adnan; Schulz-Schüpke, Stefanie

    2016-09-14

    In patients presenting with acute coronary syndrome (ACS) the optimal duration of dual-antiplatelet therapy after drug-eluting stent (DES) implantation remains unclear. At 6 months after intervention, patients receiving clopidogrel were randomly assigned to either a further 6-month period of placebo or clopidogrel. The primary composite endpoint was death, myocardial infarction, stent thrombosis, stroke, or major bleeding 9 months after randomization. The ISAR-SAFE trial was terminated early due to low event rates and slow recruitment. 1601/4000 (40.0%) patients presented with ACS and were randomized to 6 (n = 794) or 12 months (n = 807) clopidogrel. The primary endpoint occurred in 14 patients (1.8%) receiving 6 months of clopidogrel and 17 patients (2.2%) receiving 12 months; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.41-1.68, P = 0.60. There were 2 (0.3%) cases of stent thrombosis in each group; HR 1.00, 95% CI 0.14-7.09, P = >0.99. Major bleeding occurred in 3 patients (0.4%) receiving 6 months clopidogrel and 5 (0.6%) receiving 12 months; HR 0.60, 95% CI 0.15-2.49, P = 0.49. There was no significant difference in net clinical outcomes after DES implantation in ACS patients treated with 6 versus 12 months clopidogrel. Ischaemic and bleeding events were low beyond 6-months.

  11. Clopidogrel-induced refractory thrombotic thrombocytopenic purpura successfully treated with rituximab.

    PubMed

    Khodor, Sara; Castro, Miguel; McNamara, Colin; Chaulagain, Chakra P

    2016-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by microvascular aggregation of platelets and fibrin strands causing thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction. TTP can develop as a result of a deficiency in ADAMTS13 enzyme activity due to either a genetic defect or, more commonly, the development of anti-ADAMTS13 autoantibodies. TTP can also be associated with pregnancy, organ transplant, lupus, infections, and drugs. Here, we present a case of TTP that developed shortly after the start of clopidogrel treatment for acute ischemic stroke and acute myocardial infarction, and describe the clinical presentation, refractory course of the disease, and successful induction of remission through the use of rituximab in a setting of pre-existing autoimmune diseases. PMID:26684918

  12. CYP2C19 Metabolizer Status and Clopidogrel Efficacy in the Secondary Prevention of Small Subcortical Strokes (SPS3) Study

    PubMed Central

    McDonough, Caitrin W; McClure, Leslie A; Mitchell, Braxton D; Gong, Yan; Horenstein, Richard B; Lewis, Joshua P; Field, Thalia S; Talbert, Robert L; Benavente, Oscar R; Johnson, Julie A; Shuldiner, Alan R

    2015-01-01

    Background The role of the CYP2C19 genotype on clopidogrel efficacy has been studied widely, with data suggesting reduced clopidogrel efficacy in loss-of-function variant carriers taking clopidogrel after percutaneous coronary intervention; however, data are limited regarding the association between CYP2C19 genetic variants and outcomes in stroke patients. We investigated whether CYP2C19 metabolizer status affects the risk of recurrent stroke or major bleeding in subcortical stroke patients taking dual antiplatelet therapy with aspirin and clopidogrel. Methods and Results CYP2C19*2 and CYP2C19*17 were genotyped in 522 patients treated with dual antiplatelet therapy from the Secondary Prevention of Small Subcortical Strokes (SPS3) study. CYP2C19 metabolizer status was inferred from genotype, and associations with the risk of recurrent stroke and major bleeding were assessed in the overall cohort and by race/ethnic group with logistic regression modeling. In the overall cohort, there were no differences in outcomes by CYP2C19 metabolizer status (recurrent stroke, odds ratio 1.81 [95% CI 0.76 to 4.30]; major bleeding, odds ratio 0.67 [95% CI 0.22 to 2.03]). In white participants, those with CYP2C19 intermediate or poor metabolizer status had higher odds of recurrent stroke (odds ratio 5.19 [95% CI 1.08 to 24.90]) than those with extensive or ultrarapid metabolizer status, but there was no evidence of difference in major bleeding. Conclusions There were significant differences in recurrent stroke by CYP2C19 genotype-inferred metabolizer status in white subcortical stroke patients receiving dual antiplatelet therapy with aspirin and clopidogrel, consistent with cardiovascular studies on CYP2C19 and clopidogrel; however, the bleeding risk that led to early termination of the antiplatelet arm of the SPS3 trial does not appear to be explained by CYP2C19 genotype. This study was relatively underpowered; therefore, these findings should be interpreted with caution and

  13. [Platelet aggregation upon acetylsalicylic acid and clopidogrel treatment and glycoprotein IIb/IIIa content in patients with acute coronary syndrome].

    PubMed

    Khaspekova, S G; Ziuriaev, I T; Iakushkin, V V; Golubeva, N V; Ruda, M Ia; Mazurov, A V

    2011-01-01

    Interaction between aggregating activity of platelets and glycoprotein (GP) IIb/IIIa (fibrinogen receptor) content on their surface was investigated in patients with acute coronary syndrome (ACS). Eighty nine ACS patients were included into the study - 69 with and 20 without elevation of ST segment. Blood was collected within the first hour of admission to the clinic (1 day), and then at 3-5 and 8-12 days. All patients received standard antiaggregant therapy - acetylsalicylic acid - ASA (thromboxane A2 synthesis inhibitor) and clopidogrel (ADP receptor antagonist). Platelet aggregation was analyzed at the first time point when patients had already taken ASA but not clopidogrel, and then (3-5 and 8- 12 days) upon combined therapy with both preparations. Aggregation was induced by 5 and 20 uM ADP and measured by turbidimetric method. In comparison with the initial level (1 day, ASA) at days 3-5, i.e. after development of clopidogrel effect, platelet aggregation was decreased by 54 and 40% upon its stimulation with 5 and 20 uM ADP, and was not further changed at days 8-12. GP IIb/IIIa content on platelet surface was determined by binding of 125I-labelled monoclonal antibody CRC64. GP IIb/IIIa number varied from 31100 to 73000 per platelet with the mean level of 48500 +/- 8400 (mean +/- standard deviation). No differences were detected between mean GP IIb/IIIa number at 1, 3-5 and 8-12 days after ACS onset. Upon repeat GP IIb/IIIa measurement coefficient of variation was 6.1% demonstrating the stability of this parameter in each patient. Positive correlation between platelet aggregation and GP IIb/IIIa content was detected at the first day - correlation coefficients (r) 0.425 and 0.470 for 5 and 20 uM ADP (n=57, p<0.001). However positive association between these parameters was not revealed at 3-5 and 8-12 days, when patients received not only ASA but clopidogrel as well (r from -0.054 to -0.237, p>0.05). These results indicates that variations of GP IIb/IIIa content

  14. Optimal Anticoagulation during Off Pump Coronary Artery Bypass in Patients Recently Exposed to Clopidogrel

    PubMed Central

    Song, Young; Song, Jong Wook; Shim, Jae Kwang

    2013-01-01

    Purpose The aim of this study was to find an optimal range of activated clotting time (ACT) during off-pump coronary artery bypass surgery (OPCAB) yielding ischemic protection without the risk of hemorrhagic complications in patients with recent exposure to dual antiplatelet therapy. Materials and Methods Three hundred and five patients who received aspirin and clopidogrel within 7 days of isolated multi-vessel OPCAB were retrospectively studied. Combined hemorrhagic and ischemic outcome was defined as the occurrence of 1 of the following: significant perioperative bleeding (>30% of estimated blood volume), transfusion of packed red blood cell (pRBC) ≥2 U, or myocardial infarction (MI). This was compared in relation to the tertile distribution of the time-weighted average ACT-212-291 sec (first tertile), 292-334 sec (second tertile), 335-485 sec (third tertile). Results The amount of perioperative blood loss was 937±313 mL, 1014±340 mL, and 1076±383 mL, respectively (p=0.022). Significantly more patients in the third tertile developed MI (4%, 4%, and 12%, respectively, p=0.034). The incidence of significant perioperative blood loss and transfusion of pRBC ≥2 U were lower in the first tertile than those of other tertiles without statistical significance. In the multivariate analysis, the first tertile was associated with a 52% risk reduction of combined hemorrhagic and ischemic outcomes (95% confidence interval: 0.25-0.92, p=0.027). Conclusion A lower degree of anticoagulation with a reduced initial heparin loading dose should be carefully considered for patients undergoing OPCAB who have recently been exposed to clopidogrel. PMID:23918560

  15. Cancer Education Program Evaluation: A Responsive Approach to Planning an Evaluation and Initial Results.

    ERIC Educational Resources Information Center

    Pearsol, James A.

    This paper describes evaluation planning for the Cancer Education Program (CEP) at Ohio State University (OSU). The three-year OSU CEP project was designed as a multidisciplinary cancer education program. A responsive method, which trades off some measurement precision in order to increase the usefulness of the findings, was employed in the…

  16. Probability effects on stimulus evaluation and response processes

    NASA Technical Reports Server (NTRS)

    Gehring, W. J.; Gratton, G.; Coles, M. G.; Donchin, E.

    1992-01-01

    This study investigated the effects of probability information on response preparation and stimulus evaluation. Eight subjects responded with one hand to the target letter H and with the other to the target letter S. The target letter was surrounded by noise letters that were either the same as or different from the target letter. In 2 conditions, the targets were preceded by a warning stimulus unrelated to the target letter. In 2 other conditions, a warning letter predicted that the same letter or the opposite letter would appear as the imperative stimulus with .80 probability. Correct reaction times were faster and error rates were lower when imperative stimuli confirmed the predictions of the warning stimulus. Probability information affected (a) the preparation of motor responses during the foreperiod, (b) the development of expectancies for a particular target letter, and (c) a process sensitive to the identities of letter stimuli but not to their locations.

  17. Clopidogrel (Plavix)

    MedlinePlus

    ... 2007;116:2762-2772. Kushner FG, Hand M, Smith SC Jr, King SB 3rd, Anderson JL, Antman ... Clinical Practice Guidelines. Chest . 2012;141:e601S-e36S. Smith SC Jr, Benjamin EJ, Bonow RO, Braun LT, ...

  18. Evaluation of a hospice rapid response community service: a controlled evaluation

    PubMed Central

    2012-01-01

    Background While most people faced with a terminal illness would prefer to die at home, less than a third in England are enabled to do so with many dying in National Health Service hospitals. Patients are more likely to die at home if their carers receive professional support. Hospice rapid response teams, which provide specialist palliative care at home on a 24/7 on-call basis, are proposed as an effective way to help terminally ill patients die in their preferred place, usually at home. However, the effectiveness of rapid response teams has not been rigorously evaluated in terms of patient, carer and cost outcomes. Methods/Design The study is a pragmatic quasi-experimental controlled trial. The primary outcome for the quantitative evaluation for patients is dying in their preferred place of death. Carers’ quality of life will be evaluated using postal questionnaires sent at patient intake to the hospice service and eight months later. Carers’ perceptions of care received and the patient’s death will be assessed in one to one interviews at 6 to 8 months post bereavement. Service utilisation costs including the rapid response intervention will be compared to those of usual care. Discussion The study will contribute to the development of the evidence base on outcomes for patients and carers and costs of hospice rapid response teams operating in the community. Trial registration: Current controlled trials ISRCTN32119670. PMID:22846107

  19. Neural attention and evaluative responses to gay and lesbian couples.

    PubMed

    Dickter, Cheryl L; Forestell, Catherine A; Mulder, Blakely E

    2015-01-01

    The goal of the current study was to examine whether differential neural attentional capture and evaluative responses for out-group homosexual relative to in-group heterosexual targets occur during social categorization. To this end, 36 heterosexual participants were presented with pictures of heterosexual and homosexual couples in a picture-viewing task that was designed to assess implicit levels of discomfort toward homosexuality and explicit evaluations of pleasantness toward the images. Neural activity in the form of electroencephalogram was recorded during the presentation of the pictures, and event-related potentials resulting from these stimuli were examined. Participants also completed questionnaires that assessed the degree to which they socialized with gays and lesbians. Results demonstrated that relative to straight couples, larger P2 amplitude was observed in response to gay but not to lesbian couples. However, both gay and lesbian couples yielded a larger late positive potential than straight couples. Moreover, the degree to which participants differentially directed early neural attention to out-group lesbian versus in-group straight couples was related to their familiarity with homosexual individuals. This work, which provides an initial understanding of the neural underpinnings of attention toward homosexual couples, suggests that differences in the processing of sexual orientation can occur as early as 200 ms and may be moderated by familiarity. PMID:25574938

  20. Inhibition of platelet function with clopidogrel, as measured with a novel whole blood impedance aggregometer in horses.

    PubMed

    Roscher, Katja A; Failing, Klaus; Moritz, Andreas

    2015-03-01

    This study aimed to validate a loading and maintenance clopidogrel dosing scheme for the inhibition of platelet function, measured by whole blood impedance aggregometry in healthy adult horses. Ten Warmblood horses received oral clopidogrel once daily. Doses were based on 50 kg weight categories and resulted in one loading dose of 6-6.5 mg/kg bodyweight and maintenance doses of 1.2-1.4 mg/kg over the next 4 days. Platelet function was measured via whole blood multiple electrode impedance aggregometry prior to (T0) and at 6, 12, 24, 48, 72, 96, 144, 192 and 240 h following the loading dose. Aggregometries for collagen (COLtest), arachidonic acid (ASPItest), adenosine diphosphate (ADPtest) and ADP with prostaglandin E1 (ADPtestHS) were performed. Statistical analyses included one way repeated measures ANOVAs and subsequent Dunnett's tests. Platelet aggregation induced by collagen remained unchanged. There were significant inhibitions in the ASPItest (P <0.01 at 192 h, and P <0.05 at 240 h) and the ADPtest and ADPtestHS (P < 0.01, with the exception of 240 h). The loading dose of clopidogrel induced rapid inhibition of platelet function within hours, and the low dose was suitable for maintaining the inhibition over the 4 days of therapy. Recovery of platelet function was restored 6 days after the cessation of medication, determined with the ADPtest and ADPtestHS, but remained inhibited with the ASPItest. The prolonged effect of clopidogrel may indicate differences in the activation of platelets between horses and humans that were previously unknown.

  1. Acute Coronary Syndromes, Gastrointestinal Protection, and Recommendations Regarding Concomitant Administration of Proton-Pump Inhibitors (Omeprazol/Esomeprazole) and Clopidogrel.

    PubMed

    Lozano, Iñigo; Sanchez-Insa, Esther; de Leiras, Sergio Rodríguez; Carrillo, Pilar; Ruiz-Quevedo, Valeriano; Pinar, Eduardo; Gopar-Gopar, Silvia; Bayon, Jeremías; Mañas, Pilar; Lasa, Garikoitz; CruzGonzalez, Ignacio; Hernandez, Felipe; Fernandez-Portales, Javier; Fernandez-Fernandez, Javier; Pérez-Serradilla, Ana; de la Torre Hernandez, José M; Gomez-Jaume, Alfredo

    2016-02-01

    The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. The purpose is to know the gastroprotective approach in patients with acute coronary syndrome (ACS) and the level of follow-up of the alert. In 17 hospitals with catheterization laboratory in Spain, 1 per region, we studied 25 consecutive patients per hospital whose diagnosis of discharge since October 1, 2013, had been any type of ACS. We analyzed their baseline clinical profile, the gatroprotective agents at admission and discharge and the antiplatelet therapy at discharge. The number of patients included was 425: age 67.2 ± 12.5 years, women 29.8%, diabetes 36.5%. The patients presented unstable angina in 21.6%, non-ST-elevation myocardial infarction in 35.3% and ST-elevation myocardial infarction in 43.1%. Conservative approach was chosen in 17.9%, bare-metal stents 32.2%, ≥ 1 drug-eluting stent 48.5%, and surgery 1.4%. Aspirin was indicated in 1.9%, aspirin + clopidogrel 73.6%, aspirin + prasugrel 17.6%, and aspririn + ticagrelor 6.8%. Gastroprotective agents were present in 40.2% patients at admission and this percentage increased to 93.7% at discharge. Of the 313 (73.6%) on clopidogrel in 96 (30.6%) was combined with omeprazole and 3 (0.95%) with esomeprazole, whereas the most commonly used was pantoprazole with 190 patients (44.7%). In conclusion, almost the totality of the patients with an ACS receive gastroprotective agents at the moment of discharge, most of them with proton-pump inhibitors. In one every 3 cases of the patients who are on clopidogrel, the recommendation of the Food and Drug Administration and the European Medicines Agency is not followed.

  2. Edoxaban versus placebo, aspirin, or aspirin plus clopidogrel for stroke prevention in atrial fibrillation. An indirect comparison analysis.

    PubMed

    Blann, A D; Skjøth, F; Rasmussen, L H; Larsen, T B; Lip, G Y H

    2015-08-01

    As non-valvular atrial fibrillation (AF) brings a risk of stroke, oral anticoagulants (OAC) are recommended. In 'real world' clinical practice, many patients (who may be, or perceived to be, intolerant of OACs) are either untreated or are treated with anti-platelet agents. We hypothesised that edoxaban has a better net clinical benefit (NCB, balancing the reduction in stroke risk vs increased risk of haemorrhage) than no treatment or anti-platelet agents. We performed a network meta-analysis of published data from 24 studies of 203,394 AF patients to indirectly compare edoxaban with aspirin alone, aspirin plus clopidogrel, and placebo. Edoxaban 30 mg once daily significantly reduced the risk of all stroke, ischaemic stroke and mortality compared to placebo and aspirin. Compared to aspirin plus clopidogrel, there was a lower risk of intra-cranial haemorrhage (ICH). Edoxaban 60 mg once-daily had a reduced risk of any stroke and systemic embolism compared to placebo, aspirin, and aspirin plus clopidogrel. Mortality rates for both edoxaban doses were estimated to be lower compared to any anti-platelet, and significantly lower compared to placebo. With overall reduced risk of ischemic stroke and ICH, both edoxaban doses bring a NCB of mean (SD) 1.68 (0.15) saved events per 100 patients per year compared to anti-platelet drugs in a clinical trial population. The NCB was demonstrated to be lower, at 0.77 (0.12) events saved (p< 0.01) when modeled to data from a 'real world' cohort of AF patients. In conclusion, edoxaban is likely to provide even better protection from stroke and ICH than placebo, aspirin alone, or aspirin plus clopidogrel in both clinical trial populations and unselected community populations. Both edoxaban doses would also bring a positive NCB compared to anti-platelet drugs or placebo/non-treatment based on 'real world' data.

  3. Critical Evaluation of Ayurvedic Plants for Stimulating Intrinsic Antioxidant Response

    PubMed Central

    Shukla, Sunil Dutt; Bhatnagar, Maheep; Khurana, Sukant

    2012-01-01

    Oxidative damage caused by free radicals plays an important role in the causation and progression of many diseases, including aging. Free-radical damage is countered by many mechanisms, including both active antioxidant enzymatic activity in our body and passive antioxidants. Antioxidant response of our body can accommodate increased oxidative damage in diseased states to a level but beyond that level, additional antioxidants are required to combat the increased stress. Apart from the regular dietary sources of antioxidants, many traditional herbal medicines demonstrate a potential to boost antioxidant activity. Rasayana chikitsa that deals with rejuvenation and revitalization is a branch of the Indian traditional medical system of ayurveda. We review some select herbs described in rasayana chikitsa that have been assessed by modern means for stimulating intrinsic antioxidant responses in humans. A critical evaluation of rasayana chikitsa will likely provide urgently needed, actual stimulants of our physiological antioxidant responses and not just more passive antioxidants to add to an already large catalog. PMID:22855669

  4. Simultaneous quantitation of acetylsalicylic acid and clopidogrel along with their metabolites in human plasma using liquid chromatography tandem mass spectrometry.

    PubMed

    Chhonker, Yashpal S; Pandey, Chandra P; Chandasana, Hardik; Laxman, Tulsankar Sachin; Prasad, Yarra Durga; Narain, V S; Dikshit, Madhu; Bhatta, Rabi S

    2016-03-01

    The interest in therapeutic drug monitoring has increased over the last few years. Inter- and intra-patient variability in pharmacokinetics, plasma concentration related toxicity and success of therapy have stressed the need of frequent therapeutic drug monitoring of the drugs. A sensitive, selective and rapid liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of acetylsalicylic acid (aspirin), salicylic acid, clopidogrel and carboxylic acid metabolite of clopidogrel in human plasma. The chromatographic separations were achieved on Waters Symmetry Shield(TM) C18 column (150 × 4.6 mm, 5 µm) using 3.5 mm ammonium acetate (pH 3.5)-acetonitrile (10:90, v/v) as mobile phase at a flow rate of 0.75 mL/min. The present method was successfully applied for therapeutic drug monitoring of aspirin and clopidogrel in 67 patients with coronary artery disease.

  5. Simultaneous quantitation of acetylsalicylic acid and clopidogrel along with their metabolites in human plasma using liquid chromatography tandem mass spectrometry.

    PubMed

    Chhonker, Yashpal S; Pandey, Chandra P; Chandasana, Hardik; Laxman, Tulsankar Sachin; Prasad, Yarra Durga; Narain, V S; Dikshit, Madhu; Bhatta, Rabi S

    2016-03-01

    The interest in therapeutic drug monitoring has increased over the last few years. Inter- and intra-patient variability in pharmacokinetics, plasma concentration related toxicity and success of therapy have stressed the need of frequent therapeutic drug monitoring of the drugs. A sensitive, selective and rapid liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of acetylsalicylic acid (aspirin), salicylic acid, clopidogrel and carboxylic acid metabolite of clopidogrel in human plasma. The chromatographic separations were achieved on Waters Symmetry Shield(TM) C18 column (150 × 4.6 mm, 5 µm) using 3.5 mm ammonium acetate (pH 3.5)-acetonitrile (10:90, v/v) as mobile phase at a flow rate of 0.75 mL/min. The present method was successfully applied for therapeutic drug monitoring of aspirin and clopidogrel in 67 patients with coronary artery disease. PMID:26230053

  6. Impact of Cytochrome P450 2C19* 2 and * 3 on Clopidogrel Loading Dose in Saudi Patients with Acute Coronary Syndrome

    PubMed Central

    Khalaf, Hassan; AlMeman, Ahmad AbdulRahman; Rasool, Seemab

    2016-01-01

    Background: Emerging evidence shows that clopidogrel is greatly affected by non-functioning alleles measured by P2Y12 or platelet reactivity units (PRU). Cardiac events during short in-hospital stays have been inconclusively suggested as the main causes of discrepancies. Objectives: Evaluate the impact of CYP2C19 allele * 2 and allele * 3 on PRU and the potential clinical consequences of such interaction. To establish a rough estimation for the safe PRU limits for short in-hospital stay following PCI. Method: A short-term experimental study was conducted with 90 patients who underwent coronary angioplasty with drug eluting stents at the Prince Sultan Cardiac Center, Buraidah. All the patients received an initial loading dose of 300 mg clopidogrel, followed by 75 mg daily. Blood samples were used for DNA extraction for cytochrome P450 (CYP) and real-time polymerase chain reaction (PCR) was used for genotyping. PRU and inhibition rate were tested by Verifynow®. All in-hospital cardiac events were recorded until patients were discharged. Results: Genotypes 1/1, 2/2, and 1/2 were expressed by 60, 28, and two patients (67, 32, and 3%), respectively. The 
PRU of the female patients was significantly higher than that of the male patients was (255.6 ± 68.8 and 177.7 ± 66.6, 
p = 0.000, respectively). There was no significant difference in PRUs (193 ± 79 and 212 ±55.4, respectively, p = 0.349), nor inhibition (17.9 ± 18.80 and 13.88 ± 11.5, p = 0.135) in wild and resistant variants, respectively. We only reported one cardiac in-thrombosis events. Conclusion: Genotype differences may not explain variations in the PRU of patients during short-term in-hospital stays. Although it is difficult to confirm, 117–267 units may be a safe PRU range for such patients, with emphasis on attaining higher PRU values in females.

  7. Fear of negative evaluation modulates electrocortical and behavioral responses when anticipating social evaluative feedback

    PubMed Central

    Van der Molen, Melle J. W.; Poppelaars, Eefje S.; Van Hartingsveldt, Caroline T. A.; Harrewijn, Anita; Gunther Moor, Bregtje; Westenberg, P. Michiel

    2014-01-01

    Cognitive models posit that the fear of negative evaluation (FNE) is a hallmark feature of social anxiety. As such, individuals with high FNE may show biased information processing when faced with social evaluation. The aim of the current study was to examine the neural underpinnings of anticipating and processing social-evaluative feedback, and its correlates with FNE. We used a social judgment paradigm in which female participants (N = 31) were asked to indicate whether they believed to be socially accepted or rejected by their peers. Anticipatory attention was indexed by the stimulus preceding negativity (SPN), while the feedback-related negativity and P3 were used to index the processing of social-evaluative feedback. Results provided evidence of an optimism bias in social peer evaluation, as participants more often predicted to be socially accepted than rejected. Participants with high levels of FNE needed more time to provide their judgments about the social-evaluative outcome. While anticipating social-evaluative feedback, SPN amplitudes were larger for anticipated social acceptance than for social rejection feedback. Interestingly, the SPN during anticipated social acceptance was larger in participants with high levels of FNE. None of the feedback-related brain potentials correlated with the FNE. Together, the results provided evidence of biased information processing in individuals with high levels of FNE when anticipating (rather than processing) social-evaluative feedback. The delayed response times in high FNE individuals were interpreted to reflect augmented vigilance imposed by the upcoming social-evaluative threat. Possibly, the SPN constitutes a neural marker of this vigilance in females with higher FNE levels, particularly when anticipating social acceptance feedback. PMID:24478667

  8. Evaluation of vertigo by auditory brain stem response.

    PubMed

    Welsh, Louis W; Welsh, John J; Rosen, Laurie G

    2002-08-01

    The authors examined the hypothesis that abnormal patterns of the auditory brain stem response (ABR) could supplement the neuro-otological evaluation and assist in localizing the site of vestibulocerebellar dysfunction. This project is based upon the fact that the sources of waves I through V have been regionally identified. Absent or delayed patterns can be referenced to the normal data, and the site of a lesion generating vertigo can be established. We found absence of waves or prolonged interpeak latencies in 25% of the vertiginous subjects with normal hearing and magnetic resonance images of the brain. We conclude that in selected cases, lesions affecting the vestibular system can influence the ABR, and the electrophysiological tests of audition may suggest regionalization of the dysfunction in the hindbrain and midbrain. PMID:12184596

  9. 209-E Building -- Response to ventilation failure evaluation

    SciTech Connect

    Foust, D.J.

    1998-07-27

    This document provides an evaluation and recommendations for radiological workplace air monitoring and response to ventilation failure for the Critical Mass Laboratory, 209-E Building. The Critical Mass Laboratory, part of the 209-E Building, was designed to provide a heavily shielded room where plutonium and uranium liquid solutions could be brought into various critical configurations under readily controlled and monitored conditions. The facility is contained within a one-story L-shaped concrete block and reinforced concrete building. One wing houses offices, a control room, shops, and a common area while the other wing includes an equipment room, the change room, work areas, and the two-story Critical Assembly Room (CAR). Three of the rooms contain radiologically contaminated equipment and materials.

  10. CYP2C19 loss-of-function alleles are not associated with clinical outcome of clopidogrel therapy in patients treated with newer-generation drug-eluting stents

    PubMed Central

    Choi, Ik Jun; Koh, Yoon-Seok; Park, Mahn-Won; Her, Sung Ho; Choi, Yun-Seok; Park, Chul-Soo; Park, Hun-Jun; Kim, Pum-Joon; Chung, Wook-Sung; Kim, Ho-Sook; Shin, Jae-Gook; Seung, Ki-Bae; Chang, Kiyuk

    2016-01-01

    Abstract CYP2C19 loss-of-function (LOF) alleles adversely affect clinical outcome of clopidogrel therapy. Recent introduction of a newer-generation drug-eluting stent (DES) has significantly reduced the occurrence of stent thrombosis. The aim of this study was to evaluate the impact of CYP2C19 LOF alleles on clinical outcome in patients treated with the newer-generation DES. The effects of CYP2C19 genotypes were evaluated on clinical outcome of clopidogrel therapy in 2062 patients treated with percutaneous coronary intervention using either first-generation DES (sirolimus- and paclitaxel-eluting stent, n = 1349) or newer-generation DES (everolimus- and zotarolimus-eluting stent, n = 713). The primary clinical outcome was major cardiac and cerebrovascular event (MACCE) including cardiac death, nonfatal myocardial infarction, stroke, and stent thrombosis during 1 year of follow-up. CYP2C19 LOF alleles were significantly associated with a higher risk of MACCE in patients treated with first-generation DES (hazard ratio [HR] 2.599, 95% confidence interval [CI] 1.047–6.453; P = 0.034). In contrast, CYP2C19 LOF alleles were not associated with primary outcome in newer-generation DES (HR 0.716, 95% CI 0.316–1.622; P = 0.522). In the further multivariate analysis, CYP2C19 LOF alleles were not associated with MACCE in patients receiving newer-generation DES (adjusted HR 0.540, 95% CI 0.226–1.291; P = 0.166), whereas they were demonstrated to be an independent risk factor for MACCE in those implanted with first-generation DES (adjusted HR 3.501, 95% CI 1.194–10.262; P = 0.022). In contradiction to their clinical impact in first-generation DES era, CYP2C19 LOF alleles may not affect clinical outcome of clopidogrel therapy in patients treated with newer-generation DES. PMID:27368038

  11. Molecular structure and vibrational spectroscopic analysis of an antiplatelet drug; clopidogrel hydrogen sulphate (form 2) - A combined experimental and quantum chemical approach

    NASA Astrophysics Data System (ADS)

    Srivastava, Anubha; Mishra, Soni; Tandon, Poonam; Patel, Sarasvatkumar; Ayala, A. P.; Bansal, A. K.; Siesler, H. W.

    2010-02-01

    Clopidogrel hydrogen sulphate which belongs to a class of medicine called antiplatelet drugs. Chemically it is methyl (+)-(S)-α-(2-chlorophenyl)-4,5,6,7-tetrahydrothieno [3,2- c] pyridine-5-acetate hydrogen sulphate having the empirical formula C 16H 17ClNO 2S.HSO 4 and molecular mass 321.82 g/mol. The present study is confined to vibrational spectroscopy of the polymorph identified as form 2 of the clopidogrel hydrogen sulphate. The vibrational analysis of clopidogrel hydrogen sulphate salt (form 2) considering separately the two counterions has been performed. We also report a theoretical and experimental study of the molecular conformation and vibrational dynamics of the independent moieties of the clopidogrel hydrogen sulphate salt. The equilibrium geometry, harmonic vibrational frequencies, infrared intensities and activities of Raman scattering were calculated by ab initio Hartree-Fock and density functional theory employing B3LYP with complete relaxation in the potential energy surface using 6-311++G(d,p) basis set. The calculated wavenumbers after a proper scaling show a very good agreement with the observed values. A complete vibrational assignment is provided for the observed Raman and infrared spectra of clopidogrel hydrogen sulphate form 2.

  12. Comparing the effect of clopidogrel versus ticagrelor on coronary microvascular dysfunction in acute coronary syndrome patients (TIME trial): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Although prompt reperfusion treatment restores normal epicardial flow, microvascular dysfunction may persist in some patients with acute coronary syndrome (ACS). Impaired myocardial perfusion is caused by intraluminal platelets, fibrin thrombi and neutrophil plugging; antiplatelet agents play a significant role in terms of protecting against thrombus microembolization. A novel antiplatelet agent, ticagrelor, is a non-thienopyridine, direct P2Y12 blocker that has shown greater, more rapid and more consistent platelet inhibition than clopidogrel. However, the effects of ticagrelor on the prevention of microvascular dysfunction are uncertain. The present study is a comparison between clopidogrel and ticagrelor use for preventing microvascular dysfunction in patients with ST elevation or non-ST elevation myocardial infarction (STEMI or NSTEMI, respectively). Methods/design The TIME trial is a single-center, randomized, open-label, parallel-arm study designed to demonstrate the superiority of ticagrelor over clopidogrel. A total of 152 patients with a spectrum of STEMI or NSTEMI will undergo prospective random assignment to clopidogrel or ticagrelor (1:1 ratio). The primary endpoint is an index of microcirculatory resistance (IMR) measured after percutaneous coronary intervention (PCI); the secondary endpoint is wall motion score index assessed at 3 months by using echocardiography. Discussion The TIME trial is the first study designed to compare the protective effect of clopidogrel and ticagrelor on coronary microvascular dysfunction in patients with STEMI and NSTEMI. Trial registration ClinicalTrials.gov: NCT02026219. Registration date: 24 December 2013. PMID:24885437

  13. Development and validation of a liquid chromatographic method for purity control of clopidogrel-acetylsalicylic acid in combined oral dosage forms.

    PubMed

    Kahsay, Getu; Van Schepdael, Ann; Adams, Erwin

    2012-03-01

    A reversed phase liquid chromatographic method with UV detection for the simultaneous determination of clopidogrel and acetylsalicylic acid and their related substances in combined oral formulations was developed and validated. Good separation was achieved on a Luna C18 column (150 mm × 4.6 mm, 3 μm) using gradient elution at a flow rate of 1 mL/min and a column temperature of 35 °C. UV detection was performed at 220 nm. The validation was performed according to the ICH guidelines. The method proved to be specific, sensitive (LOQ=0.975 μg/mL and 0.0384 μg/mL for clopidogrel and acetylsalicylic acid, respectively), linear in the concentration range from LOQ to 325 μg/mL for clopidogrel and from LOQ to 650 μg/mL for acetylsalicylic acid, precise (RSD values for intermediate precision <1%) and accurate with mean recovery values of 100.7% and 100.2% for clopidogrel and acetylsalicylic acid, respectively. Moreover, the solution stability and method robustness were examined. The method gives satisfactory separation of impurities of clopidogrel and acetylsalicylic acid and so it is suitable for quantification of the related substances as well as for the assay of the actives. PMID:22226416

  14. Platelet-to-lymphocyte ratio but not neutrophil-to-lymphocyte ratio predicts high on-treatment platelet reactivity in clopidogrel-treated patients with acute coronary syndrome

    PubMed Central

    Efe, Edem; Kocayiğit, Ibrahim; Türker, Pabuccu Mustafa; Murat, Küçükukur; Erkan, Alpaslan; Sedat, Taş; Alper, Çil; Necati, Aksoy Murat; Gökhan, Vural Mustafa; Bahri, Akdeniz

    2016-01-01

    Objectives: Dual antiplatelet therapy (DAPT), consisting of clopidogrel and aspirin, is the main-stay treatment of acute coronary syndromes (ACS). However, major adverse cardiovascular events may occur even in patients undergoing DAPT, and this has been related to the variable pharmacodynamic efficacy of these drugs, especially clopidogrel. Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are novel inflammatory markers for cardiovascular risk stratification, which may reflect an inflammatory state and thus high on-treatment platelet reactivity (HPR). Methods: We investigated the usefulness of PLR and NLR in predicting HPR in clopidogrel-treated patients with ACS. A total of 244 patients were enrolled in this study, and 43 of them were nonresponsive to clopidogrel. Results: Logistic regression analysis indicated that PLR was significantly associated with HPR (P < 0.001). Using a cutoff level of 331, PLR predicted HPR with a sensitivity of 73% and a specificity of 69% (odds ratio: 376.15, 95% confidence interval = 37.813–3741.728 P < 0.001, receiver operating characteristic curve: 0.885). Conclusions: We suggest that more attention should be paid to the PLR values of these patients on admission to identify individuals who may not benefit from clopidogrel during the course of ACS. PMID:27756943

  15. Mechanism-Based Inactivation of Human Cytochrome P450 2B6 by Clopidogrel: Involvement of Both Covalent Modification of Cysteinyl Residue 475 and Loss of HemeS⃞

    PubMed Central

    Zhang, Haoming; Amunugama, Hemali; Ney, Sarah; Cooper, Nyemade

    2011-01-01

    We have investigated the mechanisms by which clopidogrel inactivates human cytochrome P450 2B6 (CYP2B6) in a reconstituted system. It was found that clopidogrel and its thiolactone metabolite, 2-oxo-clopidogrel, both inactivate CYP2B6 in a time- and concentration-dependent manner. On the basis of kinact/KI ratios, clopidogrel is approximately 5 times more efficient than 2-oxo-clopidogrel in inactivating CYP2B6. Analysis of the molecular mass of the CYP2B6 wild-type (WT) protein that had been inactivated by either clopidogrel or 2-oxo-clopidogrel showed an increase in the mass of the protein by ∼350 Da. This increase in the protein mass corresponds to the addition of the active metabolite of clopidogrel to CYP2B6. It is noteworthy that this adduct can be cleaved from the protein matrix by incubation with dithiothreitol, confirming that the active metabolite is linked to a cysteinyl residue of CYP2B6 via a disulfide bond. Peptide mapping of tryptic digests of the inactivated CYP2B6 using electrospray ionization liquid chromatography-tandem mass spectrometry identified Cys475 as the site of covalent modification by the active metabolite. This was further confirmed by the observation that mutation of Cys475 to a serine residue eliminates the formation of the protein adduct and prevents the C475S variant from mechanism-based inactivation by 2-oxo-clopidogrel. However, this mutation did not prevent the C475S variant from being inactivated by clopidogrel. Furthermore, inactivation of both CYP2B6 WT and C475S by clopidogrel, but not by 2-oxo-clopidogrel, led to the loss of the heme, which accounts for most of the loss of the catalytic activity. Collectively, these results suggest that clopidogrel inactivates CYP2B6 primarily through destruction of the heme, whereas 2-oxo-clopidogrel inactivates CYP2B6 through covalent modification of Cys475. PMID:21862689

  16. Visualization and quantification of deformation behavior of clopidogrel bisulfate polymorphs during tableting

    NASA Astrophysics Data System (ADS)

    Yin, Xian-Zhen; Wu, Li; Li, Ying; Guo, Tao; Li, Hai-Yan; Xiao, Ti-Qiao; York, Peter; Nangia, Ashwini; Gui, Shuang-Ying; Zhang, Ji-Wen

    2016-02-01

    The deformation behavior of particles under pressure dominates the mechanical properties of solid dosage forms. In this study, the in situ 3D deformation of two polymorphs (I and II) of clopidogrel bisulfate (CLP) was determined to illustrate pressure distribution profiles within the tablet by the deformation of the crystalline particles for the first time. Synchrotron radiation X-ray computed microtomography (SR-μCT) was utilized to visualize and quantify the morphology of thousands crystalline particles of CLP I and CLP II before and after compression. As a result, the deformation was examined across scale dimensions from microns to the size of the final dosage form. Three dimensional parameters such as volume, sphericity, oblate and prolate of individual particle and distributions were computed and analyzed for quantitative comparison to CLP I and CLP II. The different degrees of deformation under the same compression conditions of CLP I and CLP II were observed and characterized quantitatively. The map of deformation degrees within the tablet illustrated the heterogeneous pressure distribution in various regions of the compacted tablet. In conclusion, the polymorph deformation behaviors demonstrated by SR-μCT quantitative structure analysis deepen understanding of tableting across dimensions from microns to millimeters for the macrostrcuture of tablet.

  17. Visualization and quantification of deformation behavior of clopidogrel bisulfate polymorphs during tableting

    PubMed Central

    Yin, Xian-Zhen; Wu, Li; Li, Ying; Guo, Tao; Li, Hai-Yan; Xiao, Ti-Qiao; York, Peter; Nangia, Ashwini; Gui, Shuang-Ying; Zhang, Ji-Wen

    2016-01-01

    The deformation behavior of particles under pressure dominates the mechanical properties of solid dosage forms. In this study, the in situ 3D deformation of two polymorphs (I and II) of clopidogrel bisulfate (CLP) was determined to illustrate pressure distribution profiles within the tablet by the deformation of the crystalline particles for the first time. Synchrotron radiation X-ray computed microtomography (SR-μCT) was utilized to visualize and quantify the morphology of thousands crystalline particles of CLP I and CLP II before and after compression. As a result, the deformation was examined across scale dimensions from microns to the size of the final dosage form. Three dimensional parameters such as volume, sphericity, oblate and prolate of individual particle and distributions were computed and analyzed for quantitative comparison to CLP I and CLP II. The different degrees of deformation under the same compression conditions of CLP I and CLP II were observed and characterized quantitatively. The map of deformation degrees within the tablet illustrated the heterogeneous pressure distribution in various regions of the compacted tablet. In conclusion, the polymorph deformation behaviors demonstrated by SR-μCT quantitative structure analysis deepen understanding of tableting across dimensions from microns to millimeters for the macrostrcuture of tablet. PMID:26911359

  18. Evaluation of acute cardiorespiratory responses to hydraulic resistance exercise.

    PubMed

    Katch, F I; Freedson, P S; Jones, C A

    1985-02-01

    Accurate evaluation of the acute responses to resistance exercise training depends on the stability of the criterion measures. This is particularly true for maximal effort exercise where continuous "all-out" effort for each repetition is encouraged. The present study evaluated reliability of repetition number (repN), respiratory gas parameters (VO2, VCO2, VE), and heart rate (HR) for shoulder (SE), chest (CE), and leg (LE) exercise performed maximally on a single-unit, 3-station hydraulic resistance exercise machine (Hydra-Fitness, Belton, TX). On 2 separate days, 20 college men completed three 20-s bouts of SE, CE, and LE with a 20-s rest between bouts and 5 min between exercise modes. There were no significant differences between bouts or test days for repN, gas measures, or HR. Subjects performed 17, 19, and 21 reps during SE, LE, and CE. VO2 was 1.7 l . min-1 (24.3 ml . kg-1 . min-1) for SE, 1.87 l . min-1 (25.5 ml . kg-1 . min-1) for CE, and 2.1 l . min-1 (28.6 ml . kg-1 . min-1) for LE. These values, averaged, represented 52.8% of the max VO2 determined on a continuous cycle ergometer test. The corresponding HR's during hydraulic exercise averaged 84.6% of HR max. Test-retest reliability coefficients ranged from r = .67 to .87 for repN, r = .41 to .83 for gas measures, and r = .72 to .89 for HR.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Adjunctive treatment with ticagrelor, but not clopidogrel, added to tPA enables sustained coronary artery recanalisation with recovery of myocardium perfusion in a canine coronary thrombosis model.

    PubMed

    Wang, Kai; Zhou, Xiaorong; Huang, Yanming; Khalil, Mazen; Wiktor, Dominik; van Giezen, J J J; Penn, Marc S

    2010-09-01

    Reperfusion therapy for myocardial infarction is limited by significant re-occlusion rates and less-than-optimal myocardial tissue perfusion. It was the objective of this study to assess and compare the effect of ticagrelor, the first reversibly binding oral P2Y12 receptor antagonist, with that of clopidogrel, in conjunction with thrombolytic therapy, on platelet aggregation, thrombus formation, and myocardial perfusion in a canine model. Thrombus formation was induced by electrolytic injury and blood flow was measured with a Doppler ultrasonic flowmeter. All animals received tissue plasminogen activator (tPA) (1 mg/kg over 20 min); 10 animals received clopidogrel (10 mg/kg IV bolus over 5 min), 10 animals received ticagrelor initiated with a 1-min bolus (75 microg/kg/min), followed by continuous infusion (10 microg/kg/min) for 2 h, and 10 animals received IV saline. Re-occlusion rate and cyclic flow variation decreased with ticagrelor compared to saline groups (p<0.05). Adenosine phosphate (ADP)-induced platelet aggregation decreased with ticagrelor (1.9% +/- 2.67) and clopidogrel (1.11% +/- 2.0) vs. saline (26.3% +/- 23.5, p<0.05) at the end of adjunctive therapy. Bleeding time increased in the clopidogrel compared to the ticagrelor group (p=0.01). Infarct size was reduced with ticagrelor compared to the clopidogrel and saline groups (p<0.05). Blood flow remained significantly below baseline values at 20 min after tPA administration in the saline and clopidogrel groups but not in the ticagrelor group. In conclusion, in a dog coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and reduces re-occlusion and cyclic flow variation; and significantly decreases infarct size and rapidly restores myocardial tissue perfusion. PMID:20694285

  20. Prasugrel Results in Higher Decrease in High-Sensitivity C-Reactive Protein Level in Patients Undergoing Percutaneous Coronary Intervention Comparing to Clopidogrel

    PubMed Central

    Hajsadeghi, Shokoufeh; Chitsazan, Mandana; Chitsazan, Mitra; Salehi, Negar; Amin, Ahmad; Bidokhti, Arash Amin; Babaali, Nima; Bordbar, Armin; Hejrati, Maral; Moghadami, Samar

    2016-01-01

    OBJECTIVES A growing body of clinical and laboratory evidence indicates that inflammation plays a crucial role in atherosclerosis. In the present study, we compared the effects of clopidogrel and prasugrel on high-sensitivity C-reactive protein (hs-CRP) in patients undergoing percutaneous coronary intervention (PCI). METHODS The present randomized, double-blind clinical trial included 120 patients who underwent PCI. Eligible patients were randomly assigned 2:1 to one of the two groups: 80 patients in the first group received clopidogrel (Plavix®; loading dose and maintenance dose of 300 and 75 mg daily, respectively) and 40 patients in the second group received prasugrel (Effient®; loading dose and maintenance dose of 60 and 10 mg, respectively) for 12 weeks. The hs-CRP levels between baseline and 12th week were compared. RESULTS Of the 120 patients, 69 patients (57.5%) were male. Pretreatment hs-CRP level was statistically comparable in clopidogrel (median, 15.10 mg/dL; interquartile range [IQR], 9.62–23.75 mg/dL) and prasugrel groups (median, 18 mg/dL; IQR, 14.25–22 mg/dL; P = 0.06). Patients taking clopidogrel showed a significant reduction in hs-CRP level compared with the baseline values (P < 0.001). Prasugrel administration also resulted in a significant reduction in hs-CRP level (P < 0.001). A significant 73% overall reduction in the hs-CRP level was seen with prasugrel compared with 39% overall reduction in hs-CRP level with clopidogrel (P = 0.002). CONCLUSION Prasugrel seems to be superior to clopidogrel in the reduction of hs-CRP in patients undergoing PCI.

  1. Six Versus Twelve Months Clopidogrel Therapy After Drug-Eluting Stenting in Patients With Acute Coronary Syndrome: An ISAR-SAFE Study Subgroup Analysis

    PubMed Central

    Lohaus, Raphaela; Michel, Jonathan; Mayer, Katharina; Lahmann, Anna Lena; Byrne, Robert A.; Wolk, Annabelle; ten Berg, Jurrien M.; Neumann, Franz-Josef; Han, Yaling; Adriaenssens, Tom; Tölg, Ralph; Seyfarth, Melchior; Maeng, Michael; Zrenner, Bernhard; Jacobshagen, Claudius; Wöhrle, Jochen; Kufner, Sebastian; Morath, Tanja; Ibrahim, Tareq; Bernlochner, Isabell; Fischer, Marcus; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Mehilli, Julinda; Kastrati, Adnan; Schulz-Schüpke, Stefanie

    2016-01-01

    In patients presenting with acute coronary syndrome (ACS) the optimal duration of dual-antiplatelet therapy after drug-eluting stent (DES) implantation remains unclear. At 6 months after intervention, patients receiving clopidogrel were randomly assigned to either a further 6-month period of placebo or clopidogrel. The primary composite endpoint was death, myocardial infarction, stent thrombosis, stroke, or major bleeding 9 months after randomization. The ISAR-SAFE trial was terminated early due to low event rates and slow recruitment. 1601/4000 (40.0%) patients presented with ACS and were randomized to 6 (n = 794) or 12 months (n = 807) clopidogrel. The primary endpoint occurred in 14 patients (1.8%) receiving 6 months of clopidogrel and 17 patients (2.2%) receiving 12 months; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.41–1.68, P = 0.60. There were 2 (0.3%) cases of stent thrombosis in each group; HR 1.00, 95% CI 0.14–7.09, P = >0.99. Major bleeding occurred in 3 patients (0.4%) receiving 6 months clopidogrel and 5 (0.6%) receiving 12 months; HR 0.60, 95% CI 0.15–2.49, P = 0.49. There was no significant difference in net clinical outcomes after DES implantation in ACS patients treated with 6 versus 12 months clopidogrel. Ischaemic and bleeding events were low beyond 6-months. PMID:27624287

  2. Prasugrel Results in Higher Decrease in High-Sensitivity C-Reactive Protein Level in Patients Undergoing Percutaneous Coronary Intervention Comparing to Clopidogrel

    PubMed Central

    Hajsadeghi, Shokoufeh; Chitsazan, Mandana; Chitsazan, Mitra; Salehi, Negar; Amin, Ahmad; Bidokhti, Arash Amin; Babaali, Nima; Bordbar, Armin; Hejrati, Maral; Moghadami, Samar

    2016-01-01

    OBJECTIVES A growing body of clinical and laboratory evidence indicates that inflammation plays a crucial role in atherosclerosis. In the present study, we compared the effects of clopidogrel and prasugrel on high-sensitivity C-reactive protein (hs-CRP) in patients undergoing percutaneous coronary intervention (PCI). METHODS The present randomized, double-blind clinical trial included 120 patients who underwent PCI. Eligible patients were randomly assigned 2:1 to one of the two groups: 80 patients in the first group received clopidogrel (Plavix®; loading dose and maintenance dose of 300 and 75 mg daily, respectively) and 40 patients in the second group received prasugrel (Effient®; loading dose and maintenance dose of 60 and 10 mg, respectively) for 12 weeks. The hs-CRP levels between baseline and 12th week were compared. RESULTS Of the 120 patients, 69 patients (57.5%) were male. Pretreatment hs-CRP level was statistically comparable in clopidogrel (median, 15.10 mg/dL; interquartile range [IQR], 9.62–23.75 mg/dL) and prasugrel groups (median, 18 mg/dL; IQR, 14.25–22 mg/dL; P = 0.06). Patients taking clopidogrel showed a significant reduction in hs-CRP level compared with the baseline values (P < 0.001). Prasugrel administration also resulted in a significant reduction in hs-CRP level (P < 0.001). A significant 73% overall reduction in the hs-CRP level was seen with prasugrel compared with 39% overall reduction in hs-CRP level with clopidogrel (P = 0.002). CONCLUSION Prasugrel seems to be superior to clopidogrel in the reduction of hs-CRP in patients undergoing PCI. PMID:27597810

  3. Evaluating Educational Programmes: The Need and the Response.

    ERIC Educational Resources Information Center

    Stake, Robert E.

    This survey of recent developments in educational program evaluation is intended for persons who commission, implement, direct, or carry out evaluation studies. The attitudes of government officials, educators, and researchers toward assessment and their own evaluation needs are discussed. Various approaches to evaluation are briefly described;…

  4. DC photoplethysmography in the evaluation of sympathetic vasomotor responses.

    PubMed

    Barron, S A; Rogowski, Z; Kanter, Y; Hemli, J

    1993-11-01

    The d.c. component of the photoplethsmographic signal was used to determine the response of the finger vasculature to three standard tests of vasomotor function: (1) an inspiratory gasp (IG), (2) immersion of the contralateral hand in ice water (IW), and (3) the Valsalva manoeuvre. The vasoconstrictor response to the first two of these stimuli could be measured in all of 25 normal subjects. The response to the Valsalva manoeuvre could not be detected consistently. Seven patients with known sympathetic autonomic dysfunction showed no response to either IG or IW. In 30 patients with diabetes mellitus of over 10 years duration, 46.7% had no response to IG, and 20% had no response to IW. Absent responses correlated with abnormal autonomic cardiovascular reflexes, with absent sympathetic skin responses and with the severity of peripheral somatic neuropathy. The d.c. photoplethysmographic determination of the vasoconstrictor response in the finger after a deep inspiratory gasp and after ice water immersion offers an additional measure of the function of small (2 mu-6 mu) peripheral nerve fibres. Because of variability in the amplitude of the responses in normals, only an absent response should be accepted as abnormal. PMID:8119051

  5. Solid-state NMR as an effective method of polymorphic analysis: solid dosage forms of clopidogrel hydrogensulfate.

    PubMed

    Pindelska, Edyta; Szeleszczuk, Lukasz; Pisklak, Dariusz Maciej; Mazurek, Andrzej; Kolodziejski, Waclaw

    2015-01-01

    Clopidogrel hydrogensulfate (HSCL) is an antiplatelet agent, one of top-selling drugs in the world. In this paper, we have described a rapid and convenient method of verification which polymorph of HSCL is present in its final solid dosage form. Our methodology based on solid-state NMR spectroscopy and ab initio gauge-including projector-augmented wave calculations of NMR shielding constants is appropriate for currently available commercial solid dosage forms of HSCL. Furthermore, such structural characterization can assist with the development of new pharmaceutical products containing HSCL and also be useful in the identification of counterfeit drugs.

  6. Solid-state NMR as an effective method of polymorphic analysis: solid dosage forms of clopidogrel hydrogensulfate.

    PubMed

    Pindelska, Edyta; Szeleszczuk, Lukasz; Pisklak, Dariusz Maciej; Mazurek, Andrzej; Kolodziejski, Waclaw

    2015-01-01

    Clopidogrel hydrogensulfate (HSCL) is an antiplatelet agent, one of top-selling drugs in the world. In this paper, we have described a rapid and convenient method of verification which polymorph of HSCL is present in its final solid dosage form. Our methodology based on solid-state NMR spectroscopy and ab initio gauge-including projector-augmented wave calculations of NMR shielding constants is appropriate for currently available commercial solid dosage forms of HSCL. Furthermore, such structural characterization can assist with the development of new pharmaceutical products containing HSCL and also be useful in the identification of counterfeit drugs. PMID:25393324

  7. Evaluation and People of Color: A Response to Professor Stanfield.

    ERIC Educational Resources Information Center

    House, Ernest R.

    1999-01-01

    Discusses the inappropriate racial categorizations of minorities that have routinely infected evaluations and social research. By adhering to principles of democracy and including minorities as participants in dialogue, evaluators can avoid such damaging effects in their work. (Author/SLD)

  8. On Messes, Systems Thinking, and Evaluation: A Response to Patton

    ERIC Educational Resources Information Center

    Miller, Robin Lin

    2016-01-01

    To help evaluation professionals better understand what an authentic attempt at Developmental Evaluation (DE) ought to look like and when it is appropriate to use, Michael Patton's provocative essay (this issue) offers evaluators eight sensitizing concepts to call on as guides. Patton states these concepts succinctly define DE and persuasively…

  9. A platelet P-selectin test predicts adverse cardiovascular events in patients with acute coronary syndromes treated with aspirin and clopidogrel.

    PubMed

    Thomas, Mark R; Wijeyeratne, Yanushi D; May, Jane A; Johnson, Andrew; Heptinstall, Stan; Fox, Susan C

    2014-01-01

    There is wide variation in response to antiplatelet therapy and high on-treatment platelet reactivity is associated with adverse cardiovascular events. The objective here was to determine whether the results of a novel strategy for assessing platelet reactivity (based on P-selectin measurement) are associated with clinical outcomes in patients with acute coronary syndromes (ACS). This was a prospective cohort study of 100 ACS patients taking aspirin and clopidogrel. P-selectin tests designed to assess response to P2Y12 antagonists or aspirin were performed alongside light transmission aggregometry. For the P2Y12 P-selectin test, an optimal cutoff for high platelet reactivity was determined by receiver operating characteristic (ROC) curve analysis. Patients were divided into two cohorts based on this value: patients with (n = 42) or without (n = 58) high platelet reactivity. The primary endpoint was defined as the composite of cardiovascular death, myocardial infarction and stent thrombosis. After 12 months, the primary endpoint occurred in 12 patients. ROC curve analysis determined that the P2Y12 P-selectin test results were predictive of the primary endpoint (area under curve = 0.69, p = 0.046). The primary endpoint occurred more frequently in patients with high on-treatment platelet reactivity compared to those without (21.4% vs. 5.2%; hazard ratio (HR) 4.14; p = 0.026). The P2Y12 P-selectin test results correlated with light transmission aggregometry (Spearman p < 0.0001). Using the Aspirin P-selectin test, only two patients demonstrated high on-treatment platelet reactivity. This study suggests that a P2Y12 P-selectin test is capable of detecting high on-treatment platelet reactivity, which is associated with subsequent cardiovascular events.

  10. Crop insurance evaluation in response to extreme events

    NASA Astrophysics Data System (ADS)

    Moriondo, Marco; Ferrise, Roberto; Bindi, Marco

    2013-04-01

    Crop yield insurance has been indicated as a tool to manage the uncertainties of crop yields (Sherrick et al., 2004) but the changes in crop yield variability as expected in the near future should be carefully considered for a better quantitative assessment of farmer's revenue risk and insurance values in a climatic change regime (Moriondo et al., 2011). Under this point of view, mechanistic crop growth models coupled to the output of General/Regional Circulation Models (GCMs, RCMs) offer a valuable tool to evaluate crop responses to climatic change and this approach has been extensively used to describe crop yield distribution in response to climatic change considering changes in both mean climate and variability. In this work, we studied the effect of a warmer climate on crop yield distribution of durum wheat (Triticum turgidum L. subsp durum) in order to assess the economic significance of climatic change in a risk decision context. Specifically, the outputs of 6 RCMs (Tmin, Tmax, Rainfall, Global Radiation) (van der Linden and Mitchell 2009) have been statistically downscaled by a stochastic weather generator over eight sites across the Mediterranean basin and used to feed the crop growth model Sirius Quality. Three time slices were considered i) the present period PP (average of the period 1975-1990, [CO2]=350 ppm), 2020 (average of the period 2010-2030, SRES scenario A1b, [CO2]=415 ppm) and 2040 (average of the period 2030-2050, SRES scenario A1b, [CO2]=480 ppm). The effect of extreme climate events (i.e. heat stress at anthesis stage) was also considered. The outputs of these simulations were used to estimate the expected payout per hectare from insurance triggered when yields fall below a specific threshold defined as "the insured yield". For each site, the threshold was calculated as a fraction (70%) of the median of yield distribution under PP that represents the percentage of median yield above which indemnity payments are triggered. The results

  11. Time/Loss Analysis in the development and evaluation of emergency response procedures

    SciTech Connect

    Francis, A.A.

    1994-08-01

    Time/Loss Analysis (T/LA) provides a standard for conducting technically consistent and objective evaluations of emergency response planning and procedures. T/LA is also a sound tool for evaluating the performance of safeguards and procedures.

  12. Learning about fishery management: evaluation of a contextualized responsive evaluation approach.

    PubMed

    Kouévi, T A; van Mierlo, B; Leeuwis, C

    2013-12-01

    This article discusses the extent to which a responsive evaluation (RE) approach contributed to learning by stakeholders in a case of high complexity. Fishery management in Grand-Popo, Benin is characterized by ambiguity, that is contrasting views among fishery stakeholders about what should be done, why, how, where, and when to resolve fishery problems like the depletion of fish-stock and absence of income alternatives. It was also characterized by great gaps (mismatches) between interventionists' plans and actions, despite generations of interventions and evaluations of their effectiveness. The RE approach aimed at facilitating interactions between interventionists and fishing people to stimulate learning and hence reduce the ambiguity and mismatches. In this article, we take distance and evaluate the results of this action research approach. We found that in the interaction some learning indeed occurred. The fishing people learned among others that intervention resources are limited and that they should organize themselves to lobby for and monitor interventions to solve their problems. Interventionists learned that they could share knowledge about their roles and limited resources with fishing people so that the latter could lobby for more resources. Fishing people however, did not learn to adopt more sustainable fishing practices. Also, interventionists did not learn to influence politicians and financial partners themselves for sufficient resources. Both categories of stakeholders developed ideas for how to collaborate to improve fishery management. We conclude that although some single-loop, double-loop and social learning occurred, the learning was limited and reflect on the related challenges for RE in natural resource management.

  13. Evaluative Priming of Naming and Semantic Categorization Responses Revisited: A Mutual Facilitation Explanation

    ERIC Educational Resources Information Center

    Schmitz, Melanie; Wentura, Dirk

    2012-01-01

    The evaluative priming effect (i.e., faster target responses following evaluatively congruent compared with evaluatively incongruent primes) in nonevaluative priming tasks (such as naming or semantic categorization tasks) is considered important for the question of how evaluative connotations are represented in memory. However, the empirical…

  14. Evaluating School Choice Policies: A Response to Harry Brighouse

    ERIC Educational Resources Information Center

    Giesinger, Johannes

    2009-01-01

    In his writings on school choice and educational justice, Harry Brighouse presents normative evaluations of various choice systems. This paper responds to Brighouse's claim that it is inadequate to criticise these evaluations with reference to empirical data concerning the effects of school choice.

  15. Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the Southern Network on Adverse Reactions (SONAR).

    PubMed

    Jacob, Sony; Dunn, Brianne L; Qureshi, Zaina P; Bandarenko, Nicholas; Kwaan, Hau C; Pandey, Dilip K; McKoy, June M; Barnato, Sara E; Winters, Jeffrey L; Cursio, John F; Weiss, Ivy; Raife, Thomas J; Carey, Patricia M; Sarode, Ravindra; Kiss, Joseph E; Danielson, Constance; Ortel, Thomas L; Clark, William F; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X Long; Chen, Hao; Chen, Fei; Armstrong, John M; Raisch, Dennis W; Bennett, Charles L

    2012-11-01

    Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.

  16. Ticlopidine-, Clopidogrel-, and Prasugrel-Associated Thrombotic Thrombocytopenic Purpura: A 20-Year Review from the Southern Network on Adverse Reactions (SONAR)

    PubMed Central

    Jacob, Sony; Dunn, Brianne L.; Qureshi, Zaina P.; Bandarenko, Nicholas; Kwaan, Hau C.; Pandey, Dilip K.; McKoy, June M.; Barnato, Sara E.; Winters, Jeffrey L.; Cursio, John F.; Weiss, Ivy; Raife, Thomas J.; Carey, Patricia M.; Sarode, Ravindra; Kiss, Joseph E.; Danielson, Constance; Ortel, Thomas L.; Clark, William F.; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X. Long; Chen, Hao; Chen, Fei; Armstrong, John M.; Raisch, Dennis W.; Bennett, Charles L.

    2013-01-01

    Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ. PMID:23111862

  17. Evaluating mechano-transduction and touch responses in plant roots.

    PubMed

    Swanson, Sarah J; Barker, Richard; Ye, Yonggeng; Gilroy, Simon

    2015-01-01

    Mechanical forces can be imposed on plants either from the environment, through factors such as the weather, mechanical properties of the soil and animal movement, or through the internal forces generated by the interplay between turgor-driven growth and the rigid plant cell wall. Such mechanical cues have profound effects on plant growth and development leading to responses ranging from directional growth patterns as seen, e.g., in tendrils coiling around supports, to the reprogramming of entire developmental programs. Thus, assays to assess mechanical sensitivity and response provide important tools for helping understand a wide range of plant physiological and developmental responses. Here, we describe simple assays to monitor mechanical response in the plant root system focusing on the quantification of root skewing, waving and obstacle avoidance.

  18. Evaluation of Histologic Cutpoints for Treatment Response in Eosinophilic Esophagitis

    PubMed Central

    Wolf, W. Asher; Cotton, Cary C.; Green, Daniel J.; Hughes, Julia T.; Woosley, John T.; Shaheen, Nicholas J.; Dellon, Evan S.

    2016-01-01

    Aim No consensus exists on the definition of successful treatment in eosinophilic esophagitis (EoE). The aim of this study was to identify the optimal histologic cutpoint to define successful treatment of EoE by assessing rates of symptomatic and endoscopic improvement. Materials and Methods We performed a retrospective cohort study utilizing the University of North Carolina EoE Clinicopathologic Database between 2006 and 2013. Rates of symptomatic and endoscopic improvement were determined, as were post-treatment eosinophil counts. The area under the receiver operator characteristic curve (AUC) was calculated for symptomatic and endoscopic response at several possible eosinophil count cutpoints (eos/hpf). Predictors of response were also assessed. Results Of 224 treatments in 199 patients, 76% were associated with symptomatic improvement, 68% with endoscopic improvement, and 60% with both. Of treatments that resulted in a post-treatment count of <15 eos/hpf, 90% were associated with an endoscopic response, 88% with a symptomatic response, and 81% with both symptomatic and endoscopic responses. Using a <15 eos/hpf threshold, the area under the curves (AUCs) were 0.70, 0.78, and 0.75 for symptomatic, endoscopic, and symptomatic/endoscopic responses, respectively. Lower histologic cut-points did not result in a substantial gain in response, but decreased the AUC. Conclusion In this large cohort of EoE patients, rates of symptomatic and endoscopic improvement were generally associated with histologic improvement. A histologic cutoff for treatment response of <15 eos/hpf may balance clinical outcomes and test performance. PMID:27110513

  19. Cost-Effectiveness of Cytochrome P450 2C19 Genotype Screening for Selection of Antiplatelet Therapy with Clopidogrel or Prasugrel

    PubMed Central

    Reese, Emily S.; Mullins, C. Daniel; Beitelshees, Amber L.; Onukwugha, Eberechukwu

    2013-01-01

    Study Objective To estimate the cost-effectiveness of genotype-guided selection of antiplatelet therapy compared with selecting clopidogrel or prasugrel irrespective of genotype. Design Decision model based on event occurrence in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38. Patients Simulated cohort of patients with acute coronary syndrome scheduled to undergo percutaneous coronary intervention (PCI), consisting of three arms: those receiving genotype-guided antiplatelet therapy with clopidogrel or prasugrel, those receiving clopidogrel regardless of genotype, and those receiving prasugrel regardless of genotype. Measurements and Main Results All three arms of the model incorporated the probability that patients would experience a cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or non-fatal stroke), a bleeding event (major or minor bleeding), or no event while receiving antiplatelet therapy during the 15 months after the scheduled PCI. The cytochrome P450 (CYP) 2C19 genotype determined antiplatelet drug selection in the genotyping group. Cost-effectiveness was expressed as the incremental cost-effectiveness ratio (ICER) for each event avoided in the genotype-guided therapy arm versus the other two arms. Genotype-guided antiplatelet therapy was dominant, or more effective and less costly, when compared with the selection of clopidogrel (ICER –$6760 [95% confidence interval (CI) –$6720 to –$6790]) or prasugrel (ICER –$11,710 [95% CI –$11,480 to –$11,950]) for all patients with-out regard to genotype. Genotype-guided therapy that included generic clopidogrel was dominant to prasugrel for all patients (ICER –$27,160 [95% CI –$27,890 to –$26,420]). Cost savings were not evident when genotype-guided therapy that included generic clopidogrel was compared with generic clopidogrel for all patients

  20. Platelet Inhibitors in Non-ST-Segment Elevation Acute Coronary Syndromes and Percutaneous Coronary Intervention: Glycoprotein IIb/IIIa Inhibitors, Clopidogrel, or Both?

    PubMed Central

    Silva, Matthew A; Donovan, Jennifer L; Gandhi, Pritesh J; Volturo, Gregory A

    2006-01-01

    The role of glycoprotein (Gp) IIb/IIIa receptor antagonists remains controversial and these agents are infrequently utilized during non-ST-segment elevation acute coronary syndromes (NSTE-ACS) despite American Heart Association/American College of Cardiology guidelines. Despite recommendations, the NRMI-4 (National Registry of Myocardial Infarction 4) and CRUSADE (Can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines?) registries observed that only 25%–32% of eligible patients received early Gp IIb/IIIa therapy, despite a 6.3% absolute mortality reduction in NRMI-4 and a 2% absolute mortality reduction in CRUSADE. A pooled analysis of Gp IIb/IIIa data from these registries suggest a major reduction in mortality (Odds Ratio = 0.43, 95% Confidence Index 0.25–0.74, p = 0.002) with early Gp IIb/IIIa therapy, yet clinicians fail to utilize this option in NSTE-ACS. The evidence-based approach to NSTE-ACS involves aspirin, clopidogrel, low-molecular weight heparins, or unfractionated heparin in concert with Gp IIb/IIIa receptor antagonists, however, newer percutaneous coronary intervention (PCI)-based trials challenge current recommendations. Novel strategies emerging in NSTE-ACS include omitting Gp IIb/IIIa inhibitors altogether or using Gp IIb/IIIa inhibitors with higher doses of clopidogrel in selected patients. The ISAR-REACT (Intracoronary stenting and antithrombotic regimen–Rapid early action for coronary treatment) and ISAR-SWEET (ISAR–Is abciximab a superior way to eliminate elevated thrombotic risk in diabetics) trials question the value of abciximab when 600 mg of clopidogrel concurrently administered during PCI. The CLEAR-PLATELETS (Clopidogrel loading with eptifibatide to arrest the reactivity of platelets) and PEACE (Platelet activity extinction in non-Q-wave MI with ASA, clopidogrel, and eptifibatide) trials suggest more durable platelet inhibition when Gp IIb

  1. Evaluations that Respond: Prescription, Application, and Implications of Responsive Evaluation Theory for Community College Instructional Support Programs

    ERIC Educational Resources Information Center

    Durdella, Nathan R.

    2010-01-01

    This study examines two community college instructional support programs to explore the effectiveness of an evaluation model--responsive evaluation theory--that may ease the tensions between a concern over programs' processes and reporting requirements for program outcomes. The study uses a comparative qualitative case study design and applies…

  2. Evaluation of thermoregulatory response to microwave power deposition

    SciTech Connect

    Stolwijk, J.A.J.

    1981-10-01

    The deposition of electromagnetic energy as heat in all of the human body, or in specific parts of it is one of the specific conditions which lend themselves uniquely to a preliminary evaluation through simulation modeling. In general the use of one of the widely accepted models of thermoregulation to evaluate the thermal effects of exposure to radiofrequency electromagnetic radiation should be seen as a useful tool which should be interpreted with reasonable caution.

  3. Evaluation of oculomotor response in relationship to sports performance.

    PubMed

    Harbin, G; Durst, L; Harbin, D

    1989-06-01

    This study describes a unique testing method which correlates the speed of oculomotor response with athletic performance, injury, and rehabilitation. The test board is a 6 x 6-foot platform with a central 18-inch square panel and four differently colored 18-inch square panels located right, left, fore, and aft. In response to color cues from the computer monitor, the test subject moves to similarly colored squares on the platform returning to the central square as rapidly as possible. On return to this central panel, a new color is generated from a random series. The test subject again moves to the colored platform corresponding to the color indicated on the monitor until a series of 30 repetitions is completed. The groups tested were high school football and basketball, college football and basketball, and professional football teams. No statistically significant differences were noted between football and basketball. There was a significant difference between professional and amateur response times (P = 0.0001). Fifty percent of 180 amateur athletes had a response time greater than 2 SD slower than professional athletes. The response times may, therefore, be useful in determining athletic potential.

  4. Evaluation of Rugged Wireless Mesh Nodes for Use In Emergency Response

    SciTech Connect

    Kevin L Young; Alan M Snyder

    2007-11-01

    During the summer of 2007, engineers at the Idaho National Laboratory (INL) conducted a two-day evaluation of commercially available battery powered, wireless, self-forming mesh nodes for use in emergency response. In this paper, the author describes the fundamentals of this emerging technology, applciations for emergency response and specific results of the technology evaluation conducted at the Idaho National Laboratory.

  5. Multiple Response System (MRS) Evaluation Report to the North Carolina Division of Social Services (NCDSS)

    ERIC Educational Resources Information Center

    Center for Child and Family Policy, Duke University (NJ1), 2004

    2004-01-01

    In response to a request from the North Carolina Division of Social Services (DSS), Center for Child and Family Policy at The Terry Sanford Institute at Duke University evaluated the Multiple Response System reform for families reported for child maltreatment. The North Carolina State Legislature has mandated the evaluation of five key aspects of…

  6. 34 CFR 403.204 - What are the State's responsibilities for program evaluation and improvement?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... responsibilities for program evaluation and improvement? (a) If, one year after an eligible recipient has... 34 Education 3 2013-07-01 2013-07-01 false What are the State's responsibilities for program evaluation and improvement? 403.204 Section 403.204 Education Regulations of the Offices of the Department...

  7. 34 CFR 403.204 - What are the State's responsibilities for program evaluation and improvement?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... responsibilities for program evaluation and improvement? (a) If, one year after an eligible recipient has... 34 Education 3 2014-07-01 2014-07-01 false What are the State's responsibilities for program evaluation and improvement? 403.204 Section 403.204 Education Regulations of the Offices of the Department...

  8. 34 CFR 403.204 - What are the State's responsibilities for program evaluation and improvement?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... responsibilities for program evaluation and improvement? (a) If, one year after an eligible recipient has... 34 Education 3 2012-07-01 2012-07-01 false What are the State's responsibilities for program evaluation and improvement? 403.204 Section 403.204 Education Regulations of the Offices of the Department...

  9. Prasugrel vs clopidogrel in cardiogenic shock patients undergoing primary PCI for acute myocardial infarction. Results of the ISAR-SHOCK registry.

    PubMed

    Orban, M; Mayer, K; Morath, T; Bernlochner, I; Hadamitzky, M; Braun, S; Schulz, S; Hoppmann, P; Hausleiter, J; Tiroch, K; Mehilli, J; Schunkert, H; Massberg, S; Laugwitz, K-L; Sibbing, D; Kastrati, A

    2014-12-01

    There is limited clinical data comparing different P2Y12-receptor inhibitors in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock. The aim of the ISAR-SHOCK registry was to compare the clinical outcome of patients treated with clopidogrel vs prasugrel in this setting. Patients (n=145) with AMI complicated by cardiogenic shock and undergoing primary PCI in two centres (Deutsches Herzzentrum München and Klinikum rechts der Isar, Technical University Munich) between January 2009 and May 2012 were included in this registry. The use of prasugrel for patients within this registry reflected co-morbidities and platelet function testing results during the acute AMI phase. Early outcome at 30-days was reported with regard to all-cause mortality, myocardial infarction (MI), stent thrombosis (ST) and bleeding events. With regard to antiplatelet treatment in the 145 cardiogenic shock patients, 50 patients were initially treated or immediately switched to prasugrel while 95 patients were treated with clopidogrel. All-cause mortality was lower in prasugrel- vs clopidogrel-treated patients (30 % vs 50.5%, HR: 0.51, 95% CI [0.29-0.92], p=0.025). No significant differences in prasugrel- vs clopidogrel-treated patients were observed for the occurrence of MI (p=0.233), ST (p=0.306) or TIMI major bleedings (p=0.571). Results of the ISAR-SHOCK registry suggest that the use of prasugrel in AMI patients complicated by cardiogenic shock might be associated with a lower mortality risk as compared to clopidogrel therapy without increasing the risk of bleeding. These findings, however, need confirmation from specifically designed randomised studies in this high-risk cohort of patients.

  10. Mortality in primary angioplasty patients starting antiplatelet therapy with prehospital prasugrel or clopidogrel: a 1-year follow-up from the European MULTIPRAC Registry

    PubMed Central

    Goldstein, Patrick; Grieco, Niccolò; Ince, Hüseyin; Danchin, Nicolas; Ramos, Yvonne; Goedicke, Jochen; Clemmensen, Peter

    2016-01-01

    Aim MULTIPRAC was designed to provide insights into the use and outcomes associated with prehospital initiation of antiplatelet therapy with either prasugrel or clopidogrel in the context of primary percutaneous coronary intervention. After a previous report on efficacy and safety outcomes during hospitalization, we report here the 1-year follow-up data, including cardiovascular (CV) mortality. Methods and results MULTIPRAC is a multinational, prospective registry of patients with ST-elevation myocardial infarction (STEMI) from 25 hospitals in nine countries, all of which had an established practice of prehospital start of dual antiplatelet therapy in place. The key outcome was CV death at 1 year. Among 2,036 patients followed-up through 1 year, 49 died (2.4%), 10 during the initial hospitalization and 39 within 1 year after hospital discharge. The primary analysis was based on the P2Y12-inhibitor, used from prehospital loading dose through hospital discharge. Prasugrel (n=824) was more commonly used than clopidogrel (n=425). The observed 1-year rates for CV death were 0.5% with prasugrel and 2.6% with clopidogrel. After adjustment for differences in baseline characteristics, treatment with prasugrel was associated with a significantly lower risk of CV death than treatment with clopidogrel (odds ratio 0.248; 95% confidence interval 0.06–0.89). Conclusion In STEMI patients from routine practice undergoing primary angioplasty, who were able to start oral antiplatelet therapy prehospital, treatment with prasugrel as compared to clopidogrel was associated with a lower risk of CV death at 1-year follow-up. PMID:27143908

  11. Evaluation of Representations and Response Models for Polarizable Force Fields

    PubMed Central

    2016-01-01

    For classical simulations of condensed-phase systems, such as organic liquids and biomolecules, to achieve high accuracy, they will probably need to incorporate an accurate, efficient model of conformation-dependent electronic polarization. Thus, it is of interest to understand what determines the accuracy of a polarizable electrostatics model. This study approaches this problem by breaking polarization models down into two main components: the representation of electronic polarization and the response model used for mapping from an inducing field to the polarization within the chosen representation. Among the most common polarization representations are redistribution of atom-centered charges, such as those used in the fluctuating charge model, and atom-centered point dipoles, such as those used in a number of different polarization models. Each of these representations has been combined with one or more response models. The response model of fluctuating charge, for example, is based on the idea of electronegativity equalization in the context of changing electrostatic potentials (ESPs), whereas point-dipole representations typically use a response model based on point polarizabilities whose induced dipoles are computed based on interaction with other charges and dipoles. Here, we decouple polarization representations from their typical response models to analyze the strengths and weaknesses of various polarization approximations. First, we compare the maximal possible accuracies achievable by the charge redistribution and point-dipole model representations, by testing their ability to replicate quantum mechanical (QM) ESPs around small molecules polarized by external inducing charges. Perhaps not surprisingly, the atom-centered dipole model can yield higher accuracy. Next, we test two of the most commonly used response functions used for the point-dipole representations, self-consistent and direct (or first-order) inducible point polarizabilities, where the

  12. Evaluation of Representative Smart Grid Investment Project Technologies: Demand Response

    SciTech Connect

    Fuller, Jason C.; Prakash Kumar, Nirupama; Bonebrake, Christopher A.

    2012-02-14

    This document is one of a series of reports estimating the benefits of deploying technologies similar to those implemented on the Smart Grid Investment Grant (SGIG) projects. Four technical reports cover the various types of technologies deployed in the SGIG projects, distribution automation, demand response, energy storage, and renewables integration. A fifth report in the series examines the benefits of deploying these technologies on a national level. This technical report examines the impacts of a limited number of demand response technologies and implementations deployed in the SGIG projects.

  13. Responsibility-Based Youth Programs Evaluation: Investigating the Investigations.

    ERIC Educational Resources Information Center

    Hellison, Don; Walsh, David

    2002-01-01

    Reviews 26 studies that have investigated the impact of the personal-social responsibility model (RM), a physical activity program model, on underserved and/or at-risk youth since its inception. Results indicate that field research encompasses a wide range of approaches. However, the 26 studies enhance the theoretical and practical potential of RM…

  14. A Systemic Approach to Culturally Responsive Assessment Practices and Evaluation

    ERIC Educational Resources Information Center

    Slee, June

    2010-01-01

    In an earlier paper, Slee and Keenan demonstrated that it was possible for tertiary education institutions to design culturally responsive assessment procedures that complied with standardised assessment policy. The authors' paper described "Growing Our Own," an initiative between Charles Darwin University and Northern Territory Catholic…

  15. Evaluating Where We're at with Differential Response

    ERIC Educational Resources Information Center

    Kyte, Alicia; Trocme, Nico; Chamberland, Claire

    2013-01-01

    Objective: Differential response (DR) models have been implemented internationally since the mid-1990s as an innovative way of responding to child maltreatment. The purpose of the present article is to review the literature on DR and the implications it has for current child welfare research, policy, and practice. Methods: A review of DR studies…

  16. [The application of evaluation tools for criminal responsibility in forensic psychiatric expertise].

    PubMed

    Fu, Pei-Xin; Wang, Jing; Shi, Tian-Tao; Hu, Ji-Nian; Zhu, Ming-Xia

    2010-06-01

    Criminal responsibility is divided into three types: full criminal responsibility, diminished criminal responsibility and criminal irresponsibility in China. In forensic psychiatric expertise, doctors often have different opinions about the responsibility in a given case because of lacking objective criteria. The evaluation of criminal responsibility is always unresolved problem in forensic psychiatric expertise. Application of these evaluation tools in forensic psychiatric expertise were reviewed in this article. The value of the tools were still controversial in the reliability and validity, but it is clear that these tools have the positive roles in ensuring the standardization and the uniformity of the forensic investigation.

  17. White Teachers' Evaluations of Oral Responses Given by White and Negro Ninth Grade Males.

    ERIC Educational Resources Information Center

    Crowl, Thomas Kenneth

    The purpose of this study was to find out if teachers' evaluations of the content of an oral response would change if the content of the response were held constant while the speech characteristics of the student giving the response were varied. A fixed set of 12 answers was established for each of two questions. Tape recordings were made of six…

  18. The Practice of Evaluation in Public Sector Contexts: A Response

    ERIC Educational Resources Information Center

    Chouinard, Jill Anne

    2013-01-01

    In the original paper, it was argued that while there is an array of methods and methodologies available, their use is delimited by the culture of accountability that prevails in public sector institutions, a fact that is particularly problematic given the complexity and diversity of evaluation contexts today. This short rejoinder, to responses…

  19. Test-Based Teacher Evaluations: Accountability vs. Responsibility

    ERIC Educational Resources Information Center

    Bolyard, Chloé

    2015-01-01

    Gert Biesta contends that managerial accountability, which focuses on efficiency and competition, dominates the current political arena in education. Such accountability has influenced states' developments of test-based teacher evaluations in an attempt to quantify teachers' efficacy on student learning. With numerous state policies requiring the…

  20. Evaluation of the stress response of heifers during transportation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To evaluate the stress associated with transportation; 22 heifers (326 ± 47 kg) were randomly assigned to a control (Con) or transport (Tran) group. On d 0, 12 h prior to the transportation, heifers were weighed and fitted with an indwelling rectal temperature (RT) probe, jugular catheters, and hear...

  1. Evaluate Scintillation Response Over a Continuous Energy Region

    SciTech Connect

    Zhang, Yanwen; Elfman, Mikael; Milbrath, Brian D.; Weber, William J.

    2008-06-26

    A recently developed fast analysis technique utilizing a time of flight (TOF) telescope is demonstrated to obtain relevant quantitative data on material scintillation response to energetic He particles. With superior energy resolution and fast response of the TOF telescope, energy of individual particle before impinging on a scintillating crystal can be determined with a high counting rate, which allows quantitative study of material performance over a continuous energy range in a relatively short time. Scintillation performances in terms of light output, nonlinearity and energy resolution in bismuth germinate (BGO) and europium-doped calcium fluoride (CaF2:Eu) Crystals are demonstrated, and the corresponding energy resolution is compared with gamma-ray tests on the same crystals.

  2. Performance evaluation of partial response continuous phase modulation: Discriminator detection

    NASA Astrophysics Data System (ADS)

    Trachtman, Eyal

    1989-09-01

    The principles of continuous phase modulation (CPM) are reviewed and signalling schemes based on it are discussed. The discriminator detector is widely used to detect CPM signals on band limited channels; it is a non-coherent detector which is widely used in mobile communication applications in which fading makes coherent detection difficult; it is suitable for frequency hopping systems. The detector's inferior response to that of a coherent detector can be compensated by suitable design. The performance is compared of various receivers which use the discriminator detector, using an especially written computer simulation. Receiver schemes considered included: Full response signal with integrate and dump filter; Integrate and dump filter with differential symbol detection; zero forcing linear equalization with symbol detection; Decision feedback equalization (DFE); Maximum likelihood sequence estimation; and Tomlinson filter configuration. The Tomlinson filter configuration, which has not previously been used in a CPM communication system, was compared with the other systems with respect to performance and complexity. For all CPM and detection schemes there are optimum values of h, the modulation index and there is no benefit in increasing the value of h and, therefore the bandwidth, beyond this value. Results are presented for various signal schemes, which indicate that detectability performance can be improved and bandwidth reduced by using a partial response CPM. There is a tradeoff between detectability performance and bandwidth, as a function of the baseband pulse duration. It was found that quaternary signal schemes gave better detectability performance than binary schemes, for the same bit-rates. The simulation results indicated that the Tomlinson-DFE configuration was effective for the partial response M-ary CPM channel with discriminator detection; spectral efficiency was not seriously degraded by precoding using the Tomlinson filter, and there was no

  3. Responding to Ambiguity, Responding to Change the Value of a Responsive Approach to Evaluation.

    ERIC Educational Resources Information Center

    Abma, T. A.

    2000-01-01

    Evaluated the success of a palliative health care team in a Dutch health region. Results show that it is more appropriate to acknowledge ambiguity and facilitate its handling as part of dynamic learning processes. Discusses the usefulness of a responsive approach to evaluation, evaluation methodology, and learning experiences. (SLD)

  4. Problems in Being Responsive: Reflections on an Evaluation of a Program for Training Motorcycle Riders.

    ERIC Educational Resources Information Center

    Maxwell, Graham S.

    1985-01-01

    A responsive illuminative approach was used to evaluate a program for training motorcycle riders. This approach provided interaction between evaluators and participants, and attempted to provide a detailed report reflecting stakeholders' views. The design, implementation, and reporting of the evaluation are described, as are implications for…

  5. Evaluating Radiometric Measurements Using a Fixed 45 Degrees Responsivity and Zenith Angle Dependent Responsivities (Poster)

    SciTech Connect

    Dooraghi, M.; Habte, A.; Reda, I.; Sengupta, M.; Gotseff, P.; Andreas, A.; Anderberg, M.

    2014-03-01

    This poster seeks to demonstrate the importance and application of an existing but unused approach that ultimately reduces the uncertainty of radiometric measurements. Current radiometric data is based on a single responsivity value that introduces significant uncertainty to the data, however, through using responsivity as a function of solar zenith angle, the uncertainty could be decreased by 50%.

  6. Target effects on package response: An experimental and analytical evaluation

    SciTech Connect

    Gonzales, A.

    1987-05-01

    Sandia National Laboratories has completed an experimental and analytical evaluation to compare the effects of a simple model transportation cask impacting on targets encompassing a range of stiffnesses. The cylindrical shaped unit was impacted into soil, concrete, and ''unyielding'' targets at velocities varying from 44 ft/s (30 mph) to 110 ft/s (75 mph). The 44 ft/s impact velocity correlates directly to a 30-ft drop height used in regulatory testing. 18 refs., 69 figs., 8 tabs.

  7. A quantitative evaluation of the public response to climate engineering

    NASA Astrophysics Data System (ADS)

    Wright, Malcolm J.; Teagle, Damon A. H.; Feetham, Pamela M.

    2014-02-01

    Atmospheric greenhouse gas concentrations continue to increase, with CO2 passing 400 parts per million in May 2013. To avoid severe climate change and the attendant economic and social dislocation, existing energy efficiency and emissions control initiatives may need support from some form of climate engineering. As climate engineering will be controversial, there is a pressing need to inform the public and understand their concerns before policy decisions are taken. So far, engagement has been exploratory, small-scale or technique-specific. We depart from past research to draw on the associative methods used by corporations to evaluate brands. A systematic, quantitative and comparative approach for evaluating public reaction to climate engineering is developed. Its application reveals that the overall public evaluation of climate engineering is negative. Where there are positive associations they favour carbon dioxide removal (CDR) over solar radiation management (SRM) techniques. Therefore, as SRM techniques become more widely known they are more likely to elicit negative reactions. Two climate engineering techniques, enhanced weathering and cloud brightening, have indistinct concept images and so are less likely to draw public attention than other CDR or SRM techniques.

  8. Dreading the boards: stress response to a competitive audition characterized by social-evaluative threat.

    PubMed

    Boyle, Neil Bernard; Lawton, Clare; Arkbage, Karin; Thorell, Lars; Dye, Louise

    2013-01-01

    The capacity of psychosocial stressors to provoke the hypothalamic-pituitary-adrenal axis has been demonstrated to vary depending upon a number of psychological factors. Laboratory stressors characterized by social-evaluative threat are proposed to be the most efficacious in the elicitation of a cortisol stress response. Salivary cortisol, cardiovascular, and subjective responses of 16 healthy adults facing a naturalistic stressor characterized by social-evaluative threat (competitive performance auditions) were examined. Audition exposure was sufficient to provoke significant cortisol, arterial blood pressure (systolic and diastolic), and subjective stress responses. Cortisol response reactivity (area under the curve with respect to increase [AUCi]) also correlated with participants' subjective rating of social-evaluative threat. The competitive performance audition context is therefore considered a promising context in which to further explore cortisol responsivity to social-evaluative threat. PMID:23394624

  9. Response Evaluation Criteria in Cancer of the Liver (RECICL) (2015 Revised version).

    PubMed

    Kudo, Masatoshi; Ueshima, Kazuomi; Kubo, Shoji; Sakamoto, Michiie; Tanaka, Masatoshi; Ikai, Iwao; Furuse, Junji; Murakami, Takamichi; Kadoya, Masumi; Kokudo, Norihiro

    2016-01-01

    The Response Evaluation Criteria in Solid Tumors (RECIST) is inappropriate to assess the direct effects of treatment on hepatocellular carcinoma (HCC) by locoregional therapies such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE). Therefore, establishment of response evaluation criteria solely devoted to HCC is needed urgently in clinical practice as well as in clinical trials of HCC treatment, such as molecular-targeted therapies, which cause necrosis of the tumor. The Response Evaluation Criteria in Cancer of the Liver (RECICL) was revised in 2015 by the Liver Cancer Study Group of Japan based on the 2009 version of RECICL, which was commonly used in Japan. Major revised points of the RECICL 2015 is to define the target lesions of two lesions per organ or three lesions per liver, up to a maximum of five lesions. The second revised point is that setting the timing at which the overall treatment response has been changed. The third point is that the definition of treatment effect 1 has been changed to more than 50% tumor enlargement, excluding the area of necrosis after treatment. Overall evaluation of treatment response has been amended to make it possible to evaluate the overall response including extrahepatic lesions by systemic therapy, which is similar to RECIST or modified RECIST. We hope this new treatment response criteria, RECICL, proposed by the Liver Cancer Study Group of Japan will benefit HCC treatment response evaluation in the setting of daily clinical practice and clinical trials, not only in Japan, but also internationally.

  10. Automatic contrast: evidence that automatic comparison with the social self affects evaluative responses.

    PubMed

    Ruys, Kirsten I; Spears, Russell; Gordijn, Ernestine H; de Vries, Nanne K

    2007-08-01

    The aim of the present research was to investigate whether unconsciously presented affective information may cause opposite evaluative responses depending on what social category the information originates from. We argue that automatic comparison processes between the self and the unconscious affective information produce this evaluative contrast effect. Consistent with research on automatic behaviour, we propose that when an intergroup context is activated, an automatic comparison to the social self may determine the automatic evaluative responses, at least for highly visible categories (e.g. sex, ethnicity). Contrary to previous research on evaluative priming, we predict automatic contrastive responses to affective information originating from an outgroup category such that the evaluative response to neutral targets is opposite to the valence of the suboptimal primes. Two studies using different intergroup contexts provide support for our hypotheses. PMID:17705936

  11. Evaluation of the impact response of textile composites

    NASA Technical Reports Server (NTRS)

    Portanova, M. A.

    1995-01-01

    An evaluation of the impact damage resistance and impact damage tolerance of stitched and unstitched uniweaves, 2-D braids, and 3-D weaves was conducted. Uniweave laminates were tested at four thicknesses to determine the sensitivity of the tests to this parameter. Several braid and weave parameters were also varied to establish their velocity (large mass) impacts and then loaded in tension or compression to measure residual strength. Experimental results indicate that stitching significantly improves the uniweaves' damage resistance. The 2-D braids and 3-D weaves offered less damage resistance than the stitched materials. Stitching also improved the compression after impact (CAI) and tension after impact (TAI) strengths of the uniweave materials.

  12. Evaluation of an emergency response model for the Rocky Flats Plant: Charter

    SciTech Connect

    Not Available

    1991-01-01

    This Charter provides a basis for a cooperative, interagency effort to evaluate the Terrain-Responsive Atmospheric Code for emergency response and emergency planning for the Rocky Flats Plant. This document establishes the foundation for the project entitled, Evaluation of an Emergency Response Model for the Rocky Flats Plant'' (to be referred to as the Project). This document meets the following objectives: Identify the Project; establish the project management structure, organizational responsibilities, and organizational commitments for reaching the goals of the Project, and identify a process for model revision and revelation for acceptance. 2 figs.

  13. Computerized PET/CT image analysis in the evaluation of tumour response to therapy

    PubMed Central

    Wang, J; Zhang, H H

    2015-01-01

    Current cancer therapy strategy is mostly population based, however, there are large differences in tumour response among patients. It is therefore important for treating physicians to know individual tumour response. In recent years, many studies proposed the use of computerized positron emission tomography/CT image analysis in the evaluation of tumour response. Results showed that computerized analysis overcame some major limitations of current qualitative and semiquantitative analysis and led to improved accuracy. In this review, we summarize these studies in four steps of the analysis: image registration, tumour segmentation, image feature extraction and response evaluation. Future works are proposed and challenges described. PMID:25723599

  14. Dose-Response Evaluation of Braslet-M Occlusion Cuffs

    NASA Technical Reports Server (NTRS)

    Ebert, Douglas; Garcia, Kathleen; Sargsyan, Ashot E.; Ham, David; Hamilton, Douglas; Dulchavsky, Scott A.

    2010-01-01

    Introduction: Braslet-M is a set of special elasticized thigh cuffs used by the Russian space agency to reduce the effects of the head-ward fluid shift during early adaptation to microgravity by sequestering fluid in the lower extremities. Currently, no imaging modalities are used in the calibration of the device, and the pressure required to produce a predictable physiological response is unknown. This investigation intends to relate the pressure exerted by the cuffs to the extent of fluid redistribution and commensurate physiological effects. Materials and Methods: Ten healthy subjects with standardized fluid intake participated in the study. Data collection included femoral and internal jugular vein imaging in two orthogonal planes, pulsed Doppler of cervical and femoral vessels and middle cerebral artery, optic nerve imaging, and echocardiography. Braslet-M cuff pressure was monitored at the skin interface using pre-calibrated pressure sensors. Using 6 and 30 head-down tilt in two separate sessions, the effect of Braslet-M was assessed while incrementally tightening the cuffs. Cuffs were then simultaneously released to document the resulting hemodynamic change. Results: Preliminary analysis shows correlation between physical pressure exerted by the Braslet-M device and several parameters such as jugular and femoral vein cross-sections, resistivity of the lower extremity vascular bed, and others. A number of parameters reflect blood redistribution and will be used to determine the therapeutic range of the device and to prevent unsafe application. Conclusion: Braslet-M exerts a physical effect that can be measured and correlated with many changes in central and peripheral hemodynamics. Analysis of the full data set will be required to make definitive recommendations regarding the range of safe therapeutic application. Objective data and subjective responses suggest that a safer and equally effective use of Braslet can be achieved when compared with the current

  15. Physical dosimetric evaluations in the Apollo 16 microbial response experiment.

    PubMed

    Taylor, G R; Bailey, J V; Benton, E V

    1975-01-01

    Nine biological species, including viruses, bacteria, fungi, and nematodes, were exposed to various combinations of space vacuum, galactic radiation, and solar UV light during the Apollo 16 space flight. No major changes in number of surviving cells occurred, permitting detailed genetic and somatic studies of returned test subjects. To enable dose-response studies, solar UV was employed as a mutagenic source with cells exposed to full sunlight or to components of the UV spectrum at peak wavelengths of 254, 280, and 300 nanometers over a range of energy levels. Proper in-flight UV irradiation monitoring required the development of a potassium ferrioxalate actinometer and an anaerobic photographic emulsion dosimeter which were tested for the first time in space. Studies of the mutagenic activity of cosmic-ray particulate radiation environment required measurement of its components with several lithium fluoride thermoluminescent dosimeters and a package of passive nuclear-track detectors capable of recording high-energy multicharge particles. These detectors included cellulose nitrate, Lexan, Ilford G5, and silver chloride crystals. The nuclear track detectors measured the incident heavy particles with the recorded spherical fluences with LET350,H2O>100 keV x micrometers-1 to be 19.3 +/- 1.8 particles cm-2. This value was found to be lower than that recorded by detectors located in the Biostack and the passive personnel dosimeters worn by the astronauts, suggesting a somewhat greater average shielding.

  16. The role of interpersonal processes in shaping inflammatory responses to social-evaluative threat.

    PubMed

    John-Henderson, Neha A; Stellar, Jennifer E; Mendoza-Denton, Rodolfo; Francis, Darlene D

    2015-09-01

    In response to social-evaluative threat induced in the laboratory, lower (compared to higher) subjective social class of a participant predicts greater increases in the inflammatory cytokine interleukin-6 (IL-6). In spite of the interpersonal nature of social-evaluation, little work has explored whether characteristics of the evaluator shape physiological responses in this context. In the current study, in a sample of 190 college students (male=66), we explored whether one's subjective social class interacts with the perceived social class of an evaluator to predict changes in Oral Mucosal Transudate (OMT) IL-6 in response to the Trier Social Stress Test (TSST). Participants were randomly assigned to be the speaker or the evaluator. Extending past work, we found that while speakers low in subjective social class consistently respond with strong increases in IL-6 regardless of their perception of their evaluator's social class, speakers high in subjective social class responded with greater increases in IL-6 when their evaluator was perceived as high social class compared to when they were perceived as low social class. This finding highlights the importance of perceptions of the evaluator in informing inflammatory responses to a social-evaluative task.

  17. Clinical Evaluation of Tuberculosis Viability Microscopy for Assessing Treatment Response

    PubMed Central

    Datta, Sumona; Sherman, Jonathan M.; Bravard, Marjory A.; Valencia, Teresa; Gilman, Robert H.; Evans, Carlton A.

    2015-01-01

    Background. It is difficult to determine whether early tuberculosis treatment is effective in reducing the infectiousness of patients' sputum, because culture takes weeks and conventional acid-fast sputum microscopy and molecular tests cannot differentiate live from dead tuberculosis. Methods. To assess treatment response, sputum samples (n = 124) from unselected patients (n = 35) with sputum microscopy–positive tuberculosis were tested pretreatment and after 3, 6, and 9 days of empiric first-line therapy. Tuberculosis quantitative viability microscopy with fluorescein diacetate, quantitative culture, and acid-fast auramine microscopy were all performed in triplicate. Results. Tuberculosis quantitative viability microscopy predicted quantitative culture results such that 76% of results agreed within ±1 logarithm (rS = 0.85; P < .0001). In 31 patients with non-multidrug-resistant (MDR) tuberculosis, viability and quantitative culture results approximately halved (both 0.27 log reduction, P < .001) daily. For patients with non-MDR tuberculosis and available data, by treatment day 9 there was a >10-fold reduction in viability in 100% (24/24) of cases and quantitative culture in 95% (19/20) of cases. Four other patients subsequently found to have MDR tuberculosis had no significant changes in viability (P = .4) or quantitative culture (P = .6) results during early treatment. The change in viability and quantitative culture results during early treatment differed significantly between patients with non-MDR tuberculosis and those with MDR tuberculosis (both P < .001). Acid-fast microscopy results changed little during early treatment, and this change was similar for non-MDR tuberculosis vs MDR tuberculosis (P = .6). Conclusions. Tuberculosis quantitative viability microscopy is a simple test that within 1 hour predicted quantitative culture results that became available weeks later, rapidly indicating whether patients were responding to tuberculosis therapy

  18. Evaluating Cognitive Theory: A Joint Modeling Approach Using Responses and Response Times

    ERIC Educational Resources Information Center

    Klein Entink, Rinke H.; Kuhn, Jorg-Tobias; Hornke, Lutz F.; Fox, Jean-Paul

    2009-01-01

    In current psychological research, the analysis of data from computer-based assessments or experiments is often confined to accuracy scores. Response times, although being an important source of additional information, are either neglected or analyzed separately. In this article, a new model is developed that allows the simultaneous analysis of…

  19. Evaluation of the community response to HIV and AIDS: learning from a portfolio approach.

    PubMed

    Rodriguez-García, Rosalía; Wilson, David; York, Nick; Low, Corinne; N'Jie, N'Della; Bonnel, Rene

    2013-01-01

    While communities have played a large role in the HIV/AIDS response, their contributions and innovative approaches to HIV prevention, treatment, care and support have not always been the focus of systematic and rigorous evaluations. To address this gap, the World Bank led an evaluation of the impact of the community response to HIV, including country studies in Burkina Faso, India, Kenya, Lesotho, Nigeria, Senegal, South Africa and Zimbabwe over a three-year period. Due to the complexity and varied nature of community responses, the evaluation attempted to determine the results that investments have produced at the community level by applying a mixed method approach: Randomized Controlled Trials, quasi-experimental studies, qualitative studies and analytical studies including financial data. Specifically, the studies examined a typology of community response and the flow of funds to community-based organizations, while investigating the impact of the community responses on (1) knowledge and behavior, (2) use of services, (3) social transformation, and (4) HIV incidence. This editorial summarizes the results of this evaluation portfolio, finding that investments in communities have produced significant results, including, improved knowledge and behavior, and increased use of health services, and even decreased HIV incidence. Evidence on social transformation was more mixed, with community groups found to be effective only in some settings. Each study in the evaluation provides a partial view of how communities shape the local response; however, taken together they corroborate the common wisdom that communities can be a vital part of the global HIV/AIDS response.

  20. 33 CFR 154.1135 - Response plan development and evaluation criteria.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK... Operating in Prince William Sound, Alaska § 154.1135 Response plan development and evaluation criteria. The following response times must be used in determining the on scene arrival time in Prince William Sound...

  1. 33 CFR 154.1135 - Response plan development and evaluation criteria.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK... Operating in Prince William Sound, Alaska § 154.1135 Response plan development and evaluation criteria. The following response times must be used in determining the on scene arrival time in Prince William Sound...

  2. 33 CFR 154.1135 - Response plan development and evaluation criteria.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK... Operating in Prince William Sound, Alaska § 154.1135 Response plan development and evaluation criteria. The following response times must be used in determining the on scene arrival time in Prince William Sound...

  3. 33 CFR 154.1135 - Response plan development and evaluation criteria.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK... Operating in Prince William Sound, Alaska § 154.1135 Response plan development and evaluation criteria. The following response times must be used in determining the on scene arrival time in Prince William Sound...

  4. 33 CFR 154.1135 - Response plan development and evaluation criteria.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK... Operating in Prince William Sound, Alaska § 154.1135 Response plan development and evaluation criteria. The following response times must be used in determining the on scene arrival time in Prince William Sound...

  5. Evaluating the Effectiveness of a Personal Response System in the Classroom

    ERIC Educational Resources Information Center

    Shaffer, Dennis M.; Collura, Michael J.

    2009-01-01

    We evaluated the effectiveness of the use of an electronic personal response system (or "clickers") during an introductory psychology lecture on perceptual constancy. We graphed and projected student responses to questions during the lecture onto a large-screen display in Microsoft PowerPoint. The distributions of answers corresponded well to…

  6. Tactics to Increase Course Evaluation Response Rates: A Comparison of Effectiveness

    ERIC Educational Resources Information Center

    Jacek, Laura

    2015-01-01

    When an institution decides to move to online teaching evaluations, they often face concerns that their response rates will fall with the change. This fear need never come to pass, however. There are many interventions that can raise response rates. Good communication strategies, improved student and faculty engagement, and grade hold are just a…

  7. Effects of Ethnicity and Gender on Teachers' Evaluation of Students' Spoken Responses

    ERIC Educational Resources Information Center

    Shepherd, Michael A.

    2011-01-01

    To update and extend research on teachers' expectations of students of different sociocultural groups, 57 Black, White, Asian, and Hispanic teachers were asked to evaluate responses spoken by Black, White, and Hispanic 2nd- and 3rd-grade boys and girls. The results show that responses perceived as spoken by minority boys, minority girls, and White…

  8. An Evaluation of the CERES Model Project--Career Education Responsive to Every Student, Ceres, California.

    ERIC Educational Resources Information Center

    Aslanian, Carol B.; Paul, Regina H.

    The CERES (Career Education Responsive to Every Student) Model Project for grades K-12 was evaluated by an outside party as well as internally by project staff (see CE 017 740). The external summative evaluation was limited to assessing project effectiveness based on pre- and posttests for the following objectives: (1) career education knowledge…

  9. Evaluation of the Immediate and Subsequent Effects of Response Interruption and Redirection on Vocal Stereotypy

    ERIC Educational Resources Information Center

    Schumacher, Brittany I.; Rapp, John T.

    2011-01-01

    We evaluated 2 3-component multiple-schedule sequences--a response interruption and redirection (RIRD) treatment sequence and a no-interaction control sequence--using a multielement design. With this design, we were able to evaluate the immediate and subsequent effects of RIRD on 2 participants' vocal stereotypy. For both participants, RIRD…

  10. Nobody Knows my Name: In Praise of African American Evaluators Who Were Responsive.

    ERIC Educational Resources Information Center

    Hood, Stafford

    2001-01-01

    Provides a historical accounting of the work of early African American educational evaluators to show the critical place of race and culture in both historical and contemporary visions of responsive evaluation. Discusses reasons their work has so largely been ignored. (SLD)

  11. Teacher-Course Evaluation: A Longitudinal Study of Response Stability and Instrument Reliability.

    ERIC Educational Resources Information Center

    McCollester, Charles W.; And Others

    The temporal context within which a teacher and course evaluation (TCE) is completed did not appear to be of crucial importance in affecting TCE responses. A sample of students was asked to evaluate, initially as freshmen and retrospectively as seniors, a specific teacher and course. Additional data on the student's academic status characteristics…

  12. Pedagogical Ethical Dilemmas in a Responsive Evaluation of a Leadership Program for Youth

    ERIC Educational Resources Information Center

    Freeman, Melissa; Preissle, Judith

    2010-01-01

    How do responsive evaluators provide input to program planners when competing ethical principles point to different choices of effective feedback? A team of three evaluators used participant observation, individual and focus group interviews, and analysis of documents to provide input on the development and outcome of a summer program for high…

  13. A randomised trial of the pharmacodynamic and pharmacokinetic effects of ticagrelor compared with clopidogrel in Hispanic patients with stable coronary artery disease.

    PubMed

    Price, Matthew J; Clavijo, Leonardo; Angiolillo, Dominick J; Carlson, Glenn; Caplan, Richard; Teng, Renli; Maya, Juan

    2015-01-01

    The objective was to compare the pharmacodynamic (PD) and pharmacokinetic (PK) effects of ticagrelor with clopidogrel among subjects of Hispanic ethnicity, as the PD and PK effects of antiplatelet agents among Hispanics are not specifically known. This was a randomised, open-label, crossover PD/PK study of 40 Hispanic subjects with stable coronary artery disease (CAD). Subjects were allocated to either ticagrelor 180 mg loading dose (LD)/90 mg twice-daily maintenance dose (MD) followed by clopidogrel 600 mg LD/75 mg once-daily MD with an intervening washout period, or vice versa. The primary endpoint was on-treatment reactivity (OTR) at 2 h post-LD according to the VerifyNow P2Y12 test. OTR was significantly lower at 2 h post-LD with ticagrelor compared with clopidogrel (34 PRU vs. 201 PRU, least square means difference = -167 PRU [95 % CI, -197, -137], P < 0.001). OTR was also lower with ticagrelor at 30 min and 8 h post-LD (P < 0.001). The greater magnitude of antiplatelet effect with ticagrelor persisted after 7 days of MD (52 PRU [95 % CI, 30, 73] vs. 182 PRU [95 % CI, 160, 205], P < 0.001). Mean plasma concentration of ticagrelor and its active metabolite were greatest at 2 h post-LD, with similar levels at 2 h post-MD after 7 days of MD. Among Hispanic subjects with stable CAD, ticagrelor provides a more rapid onset of platelet inhibition and a significantly greater antiplatelet effect compared with clopidogrel during both the loading and maintenance phases of treatment. PMID:25305090

  14. Effect of aspirin, clopidogrel and dipyridamole on soluble markers of vascular function in normal volunteers and patients with prior ischaemic stroke.

    PubMed

    Zhao, Lian; Gray, Laura; Leonardi-Bee, Jo; Weaver, Chris S; Heptinstall, Stan; Bath, Philip M W

    2006-03-01

    Although the mechanisms of action by which aspirin, clopidogrel and dipyridamole inhibit platelets are well characterised, their effects on soluble modulators of thrombosis, inflammation, and endothelial function have yet to assessed systematically. In this investigation aspirin (A), clopidogrel (C), and dipyridamole (D) were administered singly and in combination (A, C, D, AC, AD, CD, ACD) in random order for 2 weeks (without washout) to 11 healthy subjects and 11 patients with previous ischaemic stroke. At the end of each treatment period plasma cyclic guanosine monophosphate (cGMP), monocyte chemoattractant pertide-1 (MCP-1), nitric oxide metabolites (NO(x)), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWf); and serum C-reactive protein (CRP) and platelet derived growth factor (PDGF); were measured blinded to treatment. Dipyridamole reduced plasma vWf levels (%) in both volunteers, -10.0 (4.95), and patients, -10.11 (4.34) (p < 0.05). Dipyridamole also lowered CRP (mg/l) in patients, -0.96 (0.47), but not volunteers. Clopidogrel reduced PAI-1 (ng/ml) in volunteers, -5.30 (2.20) (p < 0.05), and patients, -3.61 (2.75) (non-significant trend). Aspirin lowered PDGF (ng/ml) in volunteers, -3.46 (1.55), but not patients. Triple antiplatelet therapy was superior to dual and mono therapy in reducing vWf levels. In conclusion, antiplatelet agents have non-platelet-related effects on soluble modulators of thrombosis, inflammation, and endothelial function. In particular, dipyridamole reduces plasma vWf and clopidogrel lowers plasma PAI-1 levels. These effects may explain, in part, their roles in preventing atherothrombogenesis. PMID:16421011

  15. A randomised trial of the pharmacodynamic and pharmacokinetic effects of ticagrelor compared with clopidogrel in Hispanic patients with stable coronary artery disease.

    PubMed

    Price, Matthew J; Clavijo, Leonardo; Angiolillo, Dominick J; Carlson, Glenn; Caplan, Richard; Teng, Renli; Maya, Juan

    2015-01-01

    The objective was to compare the pharmacodynamic (PD) and pharmacokinetic (PK) effects of ticagrelor with clopidogrel among subjects of Hispanic ethnicity, as the PD and PK effects of antiplatelet agents among Hispanics are not specifically known. This was a randomised, open-label, crossover PD/PK study of 40 Hispanic subjects with stable coronary artery disease (CAD). Subjects were allocated to either ticagrelor 180 mg loading dose (LD)/90 mg twice-daily maintenance dose (MD) followed by clopidogrel 600 mg LD/75 mg once-daily MD with an intervening washout period, or vice versa. The primary endpoint was on-treatment reactivity (OTR) at 2 h post-LD according to the VerifyNow P2Y12 test. OTR was significantly lower at 2 h post-LD with ticagrelor compared with clopidogrel (34 PRU vs. 201 PRU, least square means difference = -167 PRU [95 % CI, -197, -137], P < 0.001). OTR was also lower with ticagrelor at 30 min and 8 h post-LD (P < 0.001). The greater magnitude of antiplatelet effect with ticagrelor persisted after 7 days of MD (52 PRU [95 % CI, 30, 73] vs. 182 PRU [95 % CI, 160, 205], P < 0.001). Mean plasma concentration of ticagrelor and its active metabolite were greatest at 2 h post-LD, with similar levels at 2 h post-MD after 7 days of MD. Among Hispanic subjects with stable CAD, ticagrelor provides a more rapid onset of platelet inhibition and a significantly greater antiplatelet effect compared with clopidogrel during both the loading and maintenance phases of treatment.

  16. Clinical outcomes associated with proton pump inhibitor use among clopidogrel-treated patients within CYP2C19 genotype groups following acute myocardial infarction

    PubMed Central

    Depta, Jeremiah P.; Lenzini, Petra A.; Lanfear, David E.; Wang, Tracy Y.; Spertus, John A.; Bach, Richard G.; Cresci, Sharon

    2014-01-01

    We examined clinical outcomes with proton pump inhibitors (PPI) use within CYP2C19 genotype groups during clopidogrel treatment following acute myocardial infarction (AMI). 2062 patients were genotyped for CYP2C19*2 and *17 variants in TRIUMPH. 12 month clinical outcomes were analyzed among patients discharged on clopidogrel within CYP2C19*2 carrier, CYP2C19*17 carrier, and CYP2C19*1 homozygote genotype groups. PPI use was not associated with a difference in mortality. Among clopidogrel-treated Caucasians following AMI, PPI use was associated with a significantly higher rate of cardiac rehospitalization (HR 1.62, 95% CI 1.19-2.19; p = 0.002) compared with no PPI use. PPI users who were carriers of the CYP2C19*17 variant experienced significantly higher rates of cardiac rehospitalization (HR 2.05, 95% CI 1.26-3.33; p = 0.003), carriers of the CYP2C19*2 variant had a trend toward increased 1-year cardiac rehospitalization (HR 1.69, 95% CI 0.95-2.99; P=0.07) while no significant differences were observed among CYP2C19*1 homozygotes. These results indicate that the risks associated with PPI use among clopidogrel-treated Caucasian post-MI patients are impacted by CYP2C19 genotype, and suggest knowledge of genotype may be useful for personalizing PPI use among patients following AMI to reduce rehospitalization. PMID:25001880

  17. Development and Validation of an HPLC Method for Simultaneous Quantification of Clopidogrel Bisulfate, Its Carboxylic Acid Metabolite, and Atorvastatin in Human Plasma: Application to a Pharmacokinetic Study

    PubMed Central

    Croitoru, Octavian; Spiridon, Adela-Maria; Belu, Ionela; Turcu-Ştiolică, Adina; Neamţu, Johny

    2015-01-01

    A simple, sensitive, and specific reversed phase liquid chromatographic method was developed and validated for simultaneous quantification of clopidogrel, its carboxylic acid metabolite, and atorvastatin in human serum. Plasma samples were deproteinized with acetonitrile and ibuprofen was chosen as internal standard. Chromatographic separation was performed on an BDS Hypersil C18 column (250 × 4.6 mm; 5 μm) via gradient elution with mobile phase consisting of 10 mM phosphoric acid (sodium) buffer solution (pH = 2.6 adjusted with 85% orthophosphoric acid) : acetonitrile : methanol with flow rate of 1 mL·min−1. Detection was achieved with PDA detector at 220 nm. The method was validated in terms of linearity, sensitivity, precision, accuracy, limit of quantification, and stability tests. Calibration curves of the analytes were found to be linear in the range of 0.008–2 μg·mL−1 for clopidogrel, 0.01–4 μg·mL−1 for its carboxylic acid metabolite, and 0.005–2.5 μg·mL−1 for atorvastatin. The results of accuracy (as recovery) with ibuprofen as internal standard were in the range of 96–98% for clopidogrel, 94–98% for its carboxylic acid metabolite, and 90–99% for atorvastatin, respectively. PMID:26839733

  18. Development and Validation of an HPLC Method for Simultaneous Quantification of Clopidogrel Bisulfate, Its Carboxylic Acid Metabolite, and Atorvastatin in Human Plasma: Application to a Pharmacokinetic Study.

    PubMed

    Croitoru, Octavian; Spiridon, Adela-Maria; Belu, Ionela; Turcu-Ştiolică, Adina; Neamţu, Johny

    2015-01-01

    A simple, sensitive, and specific reversed phase liquid chromatographic method was developed and validated for simultaneous quantification of clopidogrel, its carboxylic acid metabolite, and atorvastatin in human serum. Plasma samples were deproteinized with acetonitrile and ibuprofen was chosen as internal standard. Chromatographic separation was performed on an BDS Hypersil C18 column (250 × 4.6 mm; 5 μm) via gradient elution with mobile phase consisting of 10 mM phosphoric acid (sodium) buffer solution (pH = 2.6 adjusted with 85% orthophosphoric acid) : acetonitrile : methanol with flow rate of 1 mL·min(-1). Detection was achieved with PDA detector at 220 nm. The method was validated in terms of linearity, sensitivity, precision, accuracy, limit of quantification, and stability tests. Calibration curves of the analytes were found to be linear in the range of 0.008-2 μg·mL(-1) for clopidogrel, 0.01-4 μg·mL(-1) for its carboxylic acid metabolite, and 0.005-2.5 μg·mL(-1) for atorvastatin. The results of accuracy (as recovery) with ibuprofen as internal standard were in the range of 96-98% for clopidogrel, 94-98% for its carboxylic acid metabolite, and 90-99% for atorvastatin, respectively. PMID:26839733

  19. [Preparedness - decisions in the face of uncertainty. Evaluation of nurses' response readiness in hospital emergency exercises].

    PubMed

    Kupfer, Ramona; Michalzik, Elisabeth; Lenz, Matthias

    2013-01-01

    Events in which the health and life of a large number of people are at stake impose particular challenges to all who are involved in healthcare. An effective response requires prompt decision-making under time pressure, in a context characterised by uncertainty and low routine. The hypothesis is that healthcare staffs' preparedness-related competency increases response quality. An evaluation tool was developed to assess response-relevant competencies of emergency nurses. Competencies relevant to the German healthcare system were systematically defined and operationalised into observable items. Multiple phases of qualitative field studies were employed to develop a conceptual guide to planning and conducting the evaluation. The usability of the evaluation tool was piloted and iteratively optimised. The resulting evaluation approach has the potential to substantiate education and training in the context of curriculum development.

  20. Mastering moral misery: Emotional and coping responses to intragroup morality (vs. competence) evaluations.

    PubMed

    van der Lee, Romy; Ellemers, Naomi; Scheepers, Daan

    2016-01-01

    In social groups, individuals are often confronted with evaluations of their behaviour by other group members and are motivated to adapt their own behaviour accordingly. In two studies we examine emotional responses towards, and perceived coping abilities with, morality vs. competence evaluations individuals receive from other in-group members. In Study 1, we show that evaluations of one's immoral behaviour primarily induce guilt, whereas evaluations of incompetent behaviour raise anger. In Study 2, we elaborate on the psychological process associated with these emotional responses, and demonstrate that evaluations of immorality, compared to incompetence, diminish group members' perceived coping abilities, which in turn intensifies feelings of guilt. However, when anticipating an opportunity to restore one's self-image as a moral group member, perceived coping abilities are increased and the experience of guilt is alleviated. Together these studies demonstrate how group members can overcome their moral misery when restoring their self-image.

  1. PET/CT Imaging for Monitoring Recurrence and Evaluating Response to Treatment in Breast Cancer.

    PubMed

    Lei, Lei; Wang, Xiaojia; Chen, Zhanhong

    2016-01-01

    Monitoring recurrence and evaluating response to therapy are important aspects of clinical decision making in the treatment of breast cancer. In this literature review, the authors highlight several of the key areas where integrated fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) measurements are anticipated to have a significant impact on monitoring recurrence and evaluating response to therapy. These areas include comparing FDG PET/CT with conventional imaging for detecting breast cancer metastases; evaluating the role of FDG PET/CT in the presence of elevated tumor markers during follow-up period after the primary surgery; using FDG PET/CT to assess response to neoadjuvant chemotherapy (NAC), targeted and endocrine therapies; using FDG PET/CT to predict response to NAC according to different molecular phenotypes of breast cancer; and applying PET/CT and some new breast-related PET tracers to evaluate response to anticancer treatment. The authors consider the relative advantages afforded by PET/CT and summarize current evidence as to the likely value of PET/CT in recurrence detection and anticancer treatment response prediction. PMID:27627573

  2. Information Gap Analysis: near real-time evaluation of disaster response

    NASA Astrophysics Data System (ADS)

    Girard, Trevor

    2014-05-01

    Disasters, such as major storm events or earthquakes, trigger an immediate response by the disaster management system of the nation in question. The quality of this response is a large factor in its ability to limit the impacts on the local population. Improving the quality of disaster response therefore reduces disaster impacts. Studying past disasters is a valuable exercise to understand what went wrong, identify measures which could have mitigated these issues, and make recommendations to improve future disaster planning and response. While such ex post evaluations can lead to improvements in the disaster management system, there are limitations. The main limitation that has influenced this research is that ex post evaluations do not have the ability to inform the disaster response being assessed for the obvious reason that they are carried out long after the response phase is over. The result is that lessons learned can only be applied to future disasters. In the field of humanitarian relief, this limitation has led to the development of real time evaluations. The key aspect of real time humanitarian evaluations is that they are completed while the operation is still underway. This results in findings being delivered at a time when they can still make a difference to the humanitarian response. Applying such an approach to the immediate disaster response phase requires an even shorter time-frame, as well as a shift in focus from international actors to the nation in question's government. As such, a pilot study was started and methodology developed, to analyze disaster response in near real-time. The analysis uses the information provided by the disaster management system within the first 0 - 5 days of the response. The data is collected from publicly available sources such as ReliefWeb and sorted under various categories which represent each aspect of disaster response. This process was carried out for 12 disasters. The quantity and timeliness of information

  3. Impact of Dabigatran versus Phenprocoumon on ADP Induced Platelet Aggregation in Patients with Atrial Fibrillation with or without Concomitant Clopidogrel Therapy (the Dabi-ADP-1 and Dabi-ADP-2 Trials)

    PubMed Central

    Martischnig, Amadea M.; Mehilli, Julinda; Pollak, Janina; Petzold, Tobias; Fiedler, Anette K.; Mayer, Katharina; Schulz-Schüpke, Stefanie; Sibbing, Dirk; Massberg, Steffen; Kastrati, Adnan; Sarafoff, Nikolaus

    2015-01-01

    Background. A relevant number of patients receive triple therapy with clopidogrel, aspirin, and oral anticoagulation. Clopidogrel's efficacy on ADP induced platelet function may be influenced by concomitant antithrombotic therapies. Data regarding the effect of dabigatran on platelet function is limited to in vitro studies and healthy individuals. Methods. The “Dabi-ADP-1” and “Dabi-ADP-2” trials randomized patients with atrial fibrillation to either dabigatran or phenprocoumon for a 2-week period. In Dabi-ADP-1 (n = 70) patients with clopidogrel therapy were excluded and in Dabi-ADP-2 (n = 46) patients had to be treated concomitantly with clopidogrel. The primary endpoint was ADP-induced platelet aggregation between dabigatran and phenprocoumon at 14 days. Secondary endpoints were ADPtest HS-, TRAP-, and COL-induced platelet aggregation. Results. There was no significant difference regarding the primary endpoint between both groups in either trial (Dabi-ADP-1: Dabigatran: 846 [650–983] AU × min versus phenprocoumon: 839 [666–1039] AU × min, P = 0.90 and Dabi-ADP-2: 326 [268–462] versus 350 [214–535], P = 0.70) or regarding the secondary endpoints, ADPtest HS-, TRAP-, and COL-induced platelet aggregation. Conclusion. Dabigatran as compared to phenprocoumon has no impact on ADP-induced platelet aggregation in atrial fibrillation patients neither with nor without concomitant clopidogrel therapy. PMID:26229963

  4. Trait Mindfulness Modulates Neuroendocrine and Affective Responses to Social Evaluative Threat

    PubMed Central

    Brown, Kirk Warren; Weinstein, Netta; Creswell, J. David

    2016-01-01

    Background Individual differences in mindfulness have been associated with numerous self-report indicators of stress, but research has not examined how mindfulness may buffer neuroendocrine and psychological stress responses under controlled laboratory conditions. The present study investigated the role of trait mindfulness in buffering cortisol and affective responses to a social evaluative stress challenge versus a control task. Methods Participants completed measures of trait mindfulness, perceived stress, anxiety, and fear of negative evaluation before being randomized to complete the Trier Social Stress Test (TSST; Kirschbaum et al., 1993) or a control task. At points throughout the session, participants provided five saliva samples to assess cortisol response patterns, and completed four self-report measures of anxiety and negative affect to assess psychological responses. Results In accord with hypotheses, higher trait mindfulness predicted lower cortisol responses to the TSST, relative to the control task, as well as lower anxiety and negative affect. These relations remained significant when controlling for the role of other variables that predicted cortisol and affective responses. Conclusions The findings suggest that trait mindfulness modulates cortisol and affective responses to an acute social stressor. Further research is needed to understand the neural pathways through which mindfulness impacts these responses. PMID:22626868

  5. Evaluation of human response to structural vibrations induced by sonic booms

    NASA Technical Reports Server (NTRS)

    Sutherland, Louis C.; Czech, J.

    1992-01-01

    The topic is addressed of building vibration response to sonic boom and the evaluation of the associated human response to this vibration. An attempt is made to reexamine some of the issues addressed previously and to offer fresh insight that may assist in reassessing the potential impact of sonic boom over populated areas. Human response to vibration is reviewed first and a new human vibration response criterion curve is developed as a function of frequency. The difference between response to steady state versus impulsive vibration is addressed and a 'vibration exposure' or 'vibration energy' descriptor is suggested as one possible way to evaluate duration effects on response to transient vibration from sonic booms. New data on the acoustic signature of rattling objects are presented along with a review of existing data on the occurrence of rattle. Structural response to sonic boom is reviewed and a new descriptor, 'Acceleration Exposure Level' is suggested which can be easily determined from the Fourier Spectrum of a sonic boom. A preliminary assessment of potential impact from sonic booms is provided in terms of human response to vibration and detection of rattle based on a synthesis of the preceding material.

  6. Response of osteosarcoma to preoperative intravenous high-dose methotrexate chemotherapy: CT evaluation

    SciTech Connect

    Mail, J.T.; Cohen, M.D.; Mirkin, L.D.; Provisor, A.J.

    1985-01-01

    The histologic response of an osteosarcoma to preamputation high-dose methotrexate therapy can be used to determine the optimum maintenance chemotherapy regimen to be administered after amputation. This study evaluates computed tomography (CT) as a method of assessing the response of the tumor to the methotrexate therapy. Nine patients with nonmetastatic osteosarcoma of an extremity had a CT scan of the tumor at initial presentation. This was compared with a second CT scan after four courses of high-dose intravenous methotrexate. Each set of scans was evaluated for changes in bony destruction, soft-tissue mass, pattern of calcification, and extent of tumor involvement of the marrow cavity. These findings were correlated with the histologic response of the tumor as measured by the degree of tumor necrosis. The changes seen on CT correlated well with the degree of the histologic response in seven of the nine patients.

  7. Non-invasive evaluation of therapeutic response in keloid scar using diffuse reflectance spectroscopy

    PubMed Central

    Hsu, Chao-Kai; Tzeng, Shih-Yu; Yang, Chao-Chun; Lee, Julia Yu-Yun; Huang, Lynn Ling-Huei; Chen, Wan-Rung; Hughes, Michael; Chen, Yu-Wen; Liao, Yu-Kai; Tseng, Sheng-Hao

    2015-01-01

    The pathogenesis and ideal treatment of keloid are still largely unknown, and it is essential to develop an objective assessment of keloid severity to evaluate the therapeutic response. We previously reported that our diffuse reflectance spectroscopy (DRS) system could assist clinicians in understanding the functional and structural condition of keloid scars. The purpose of this study was to understand clinical applicability of our DRS system on evaluating the scar severity and therapeutic response of keloid. We analyzed 228 spectral data from 71 subjects with keloid scars. The scars were classified into mild (0-3), moderate (4-7) and severe (8-11) according to the Vancouver scar scale. We found that as the severity of the scar increased, collagen concentration and water content increased, and the reduced scattering coefficient at 800 nm and oxygen saturation (SaO2) decreased. Using the DRS system, we found that collagen bundles aligned in a specific direction in keloid scars, but not in normal scars. Water content and SaO2 may be utilized as reliable parameters for evaluating the therapeutic response of keloid. In conclusion, the results obtained here suggest that the DRS has potential as an objective technique with which to evaluate keloid scar severity. In addition, it may be useful as a tool with which to track longitudinal response of scars in response to various therapeutic interventions. PMID:25780731

  8. A Comprehensive Evaluation System for Military Hospitals' Response Capability to Bio-terrorism.

    PubMed

    Wang, Hui; Jiang, Nan; Shao, Sicong; Zheng, Tao; Sun, Jianzhong

    2015-05-01

    The objective of this study is to establish a comprehensive evaluation system for military hospitals' response capacity to bio-terrorism. Literature research and Delphi method were utilized to establish the comprehensive evaluation system for military hospitals' response capacity to bio-terrorism. Questionnaires were designed and used to survey the status quo of 134 military hospitals' response capability to bio-terrorism. Survey indicated that factor analysis method was suitable to for analyzing the comprehensive evaluation system for military hospitals' response capacity to bio-terrorism. The constructed evaluation system was consisted of five first-class and 16 second-class indexes. Among them, medical response factor was considered as the most important factor with weight coefficient of 0.660, followed in turn by the emergency management factor with weight coefficient of 0.109, emergency management consciousness factor with weight coefficient of 0.093, hardware support factor with weight coefficient of 0.078, and improvement factor with weight coefficient of 0.059. The constructed comprehensive assessment model and system are scientific and practical.

  9. An evaluation of simultaneous presentation and differential reinforcement with response cost to reduce packing.

    PubMed

    Buckley, Scott D; Newchok, Debra K

    2005-01-01

    We evaluated the effects of multiple treatment procedures, including simultaneous presentation of preferred foods, on the packing behavior of a 9-year-old girl with autism. A reversal design was used to assess the effects of differential reinforcement with response cost alone and with simultaneous presentation. In addition, simultaneous presentation was assessed independent of differential reinforcement with response cost. Results indicated that simultaneous presentation reduced packing and that differential reinforcement with response cost was not necessary to maintain these reductions. Results are discussed in terms of the use of simultaneous presentation for packing as an alternative to consequence manipulations.

  10. Evaluation of human response to structural vibration induced by sonic boom

    NASA Technical Reports Server (NTRS)

    Sutherland, L. C.; Czech, J.

    1992-01-01

    This paper addresses the topic of building vibration response to sonic boom and the evaluation of the associated human response to this vibration. The paper reexamines some of the issues addressed in the previous extensive coverage of the topic, primarily by NASA, and attempts to offer a fresh viewpoint for some of the problems that may assist in reassessing the potential impact of sonic boom over populated areas. The topics addressed are: (1) human response to vibration; (2) criteria for, and acoustic signature of rattle; (3) structural response to shaped booms, including definition of two new descriptors for assessing the structural response to sonic boom; and (4) a detailed review of the previous NASA/FAA Sonic Boom Test Program involving structural response measurements at Edwards AFB and an initial estimate of structural response to sonic booms from possible high speed civil transport configurations. Finally, these estimated vibration responses are shown to be substantially greater than the human response and rattle criteria developed earlier.

  11. Clopidogrel Protects Endothelium by Hindering TNFα-Induced VCAM-1 Expression through CaMKKβ/AMPK/Nrf2 Pathway

    PubMed Central

    Yang, Huabing; Zhao, Pengjun; Tian, Shiliu

    2016-01-01

    Clopidogrel (INN), an oral antiplatelet drug, has been revealed to have a number of biological properties, for instance, anti-inflammation and antioxidation. Oxidative stress plays an imperative role in inflammation, diabetes mellitus, atherosclerosis, and cancer. In the present study, human aortic endothelial cells (HAECs) were employed to explore the anti-inflammatory activity of INN. INN reduced TNFα-induced reactive oxygen species (ROS) generation and time-dependently prompted the expression and activity of heme oxygenase 1 (HO-1). Cellular glutathione (GSH) levels were augmented by INN. shHO-1 blocked the INN suppression of TNFα-induced HL-60 cell adhesion. The CaMKKβ/AMPK pathway and Nrf2 transcriptional factor were implicated in the induction of HO-1 by INN. Additionally, TNFα dramatically augmented VCAM-1 expression at protein and mRNA levels. INN treatment strikingly repressed TNFα-induced expression of VCAM-1 and HL-60 cell adhesion. Compound C, an AMPK inhibitor, and shNrf2 abolished TNFα-induced expression of VCAM-1 and HL-60 cell adhesion. Our data suggest that INN diminishes TNFα-stimulated VCAM-1 expression at least in part via HO-1 induction, which is CaMKKβ/AMPK pathway-dependent. PMID:26824050

  12. Clopidogrel Protects Endothelium by Hindering TNFα-Induced VCAM-1 Expression through CaMKKβ/AMPK/Nrf2 Pathway.

    PubMed

    Yang, Huabing; Zhao, Pengjun; Tian, Shiliu

    2016-01-01

    Clopidogrel (INN), an oral antiplatelet drug, has been revealed to have a number of biological properties, for instance, anti-inflammation and antioxidation. Oxidative stress plays an imperative role in inflammation, diabetes mellitus, atherosclerosis, and cancer. In the present study, human aortic endothelial cells (HAECs) were employed to explore the anti-inflammatory activity of INN. INN reduced TNFα-induced reactive oxygen species (ROS) generation and time-dependently prompted the expression and activity of heme oxygenase 1 (HO-1). Cellular glutathione (GSH) levels were augmented by INN. shHO-1 blocked the INN suppression of TNFα-induced HL-60 cell adhesion. The CaMKKβ/AMPK pathway and Nrf2 transcriptional factor were implicated in the induction of HO-1 by INN. Additionally, TNFα dramatically augmented VCAM-1 expression at protein and mRNA levels. INN treatment strikingly repressed TNFα-induced expression of VCAM-1 and HL-60 cell adhesion. Compound C, an AMPK inhibitor, and shNrf2 abolished TNFα-induced expression of VCAM-1 and HL-60 cell adhesion. Our data suggest that INN diminishes TNFα-stimulated VCAM-1 expression at least in part via HO-1 induction, which is CaMKKβ/AMPK pathway-dependent. PMID:26824050

  13. An Evaluation of the MMPI-2 and MMPI-A True Response Inconsistency (TRIN) Scales

    ERIC Educational Resources Information Center

    Handel, Richard W.; Arnau, Randolph C.; Archer, Robert P.; Dandy, Kristina L.

    2006-01-01

    The Minnesota Multiphasic Personality Inventory--Adolescent (MMPI-A) and Minnesota Multiphasic Personality Inventory--2 (MMPI-2) True Response Inconsistency (TRIN) scales are measures of acquiescence and nonacquiescence included among the standard validity scales on these instruments. The goals of this study were to evaluate the effectiveness of…

  14. Extra Credit Micro-Incentives and Response Rates for Online Course Evaluations: Two Quasi-Experiments

    ERIC Educational Resources Information Center

    Sundstrom, Eric D.; Hardin, Erin E.; Shaffer, Matthew J.

    2016-01-01

    To extend prior findings on the motivational value of tiny, nonfinancial incentives, we conducted two quasi-experiments on the relationship of extra credit micro-incentives (ECMIs, worth =1% of course grade) and response rates for online course evaluations. Study 1 involved two advanced undergraduate psychology courses taught by the same…

  15. 33 CFR 155.1135 - Response plan development and evaluation criteria.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Response plan development and evaluation criteria. 155.1135 Section 155.1135 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION OIL OR HAZARDOUS MATERIAL POLLUTION PREVENTION REGULATIONS...

  16. Evaluation of genotypic variation of broccoli (brassica oleracea var. italic) in response to selenium treatment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Broccoli (Brassica oleracea var. italic) fortified with selenium (Se) has been promoted as a functional food. Here we evaluated 38 broccoli accessions for their capacity to accumulate Se and for their responses to selenate treatment in terms of nutritional qualities and sulfur gene expression. We fo...

  17. Weaving New Meanings: Evaluating Children's Written Responses to a Story Telling Resource Package

    ERIC Educational Resources Information Center

    Brady, Josephine; Millard, Elaine

    2012-01-01

    This paper documents an evaluation of children's written responses to a story telling package used in an intervention project set up by the National Association for the Teaching of English as part of the larger "Inspire Rotherham" literacy campaign. The brief was to provide a group of primary teachers with innovative and inspirational approaches…

  18. EVALUATION OF BIOLOGICALLY BASED DOSE-RESPONSE MODELING FOR DEVELOPMENTAL TOXICITY: A WORKSHOP REPORT

    EPA Science Inventory

    Evaluation of biologically based dose-response modeling for developmental toxicity: a workshop report.

    Lau C, Andersen ME, Crawford-Brown DJ, Kavlock RJ, Kimmel CA, Knudsen TB, Muneoka K, Rogers JM, Setzer RW, Smith G, Tyl R.

    Reproductive Toxicology Division, NHEERL...

  19. The Effects of Audience Interest, Responsiveness, and Evaluation on Public Speaking Anxiety and Related Variables.

    ERIC Educational Resources Information Center

    MacIntyre, Peter D.; Thivierge, Kimly A.; MacDonald, J. Renee

    1997-01-01

    Examines potential sources of public-speaking anxiety among undergraduate students stemming from the audience. Identifies three sources of anxiety: degree of formal evaluation, level of audience interest in the topic, and audience's responsiveness to the speaker. Measures willingness to speak and expected speech quality. Finds interest,…

  20. Evaluation of noise pollution level based upon community exposure and response data

    NASA Technical Reports Server (NTRS)

    Edmiston, R. D.

    1972-01-01

    The results and procedures are reported from an evaluation of noise pollution level as a predictor of annoyance, based on aircraft noise exposure and community response data. The measures of noise exposure presented include composite noise rating, noise exposure forecast, noise and number index. A proposed measure as a universal noise exposure measure for noise pollution level (L sub NP) is discussed.

  1. Preliminary evaluation of the Accident Response Mobile Manipulation System for accident site salvage operations

    SciTech Connect

    Trujillo, J.M.; Morse, W.D.; Jones, D.P.

    1994-10-01

    This paper describes and evaluates operational experiences with the Accident Response Mobile Manipulation System (ARMMS) during simulated accident site salvage operations which might involve nuclear weapons. The ARMMS is based upon a teleoperated mobility platform with two Schilling Titan 7F Manipulators.

  2. Evaluation of the 2006-2007 Students' Creative Response to Conflict Program

    ERIC Educational Resources Information Center

    Yungbluth, Stephen C.

    2008-01-01

    A quasi-experimental pre- and post-test design was used to evaluate the Students' Creative Response to Conflict (SCRC) program, which is based on the principles of conflict resolution education and social-emotional learning. It is predicted that SCRC will influence students to reduce their approval of aggression and associated problem behaviors…

  3. Evaluating Timing of Weaning Stress on Response to BVDV2 Vaccinations in Angus Calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to evaluate the impact of environmental factors and genetic controls on response to vaccination against bovine viral diarrhea virus type 2 (BVDV2) in Purebred American Angus beef cattle. This study utilized 362 Angus calves born in the spring (n = 211) and fall (n = 151) of ...

  4. Student Response to Faculty Instruction (SRFI): An Empirically Derived Instrument to Measure Student Evaluations of Teaching

    ERIC Educational Resources Information Center

    Beitzel, Brian D.

    2013-01-01

    The Student Response to Faculty Instruction (SRFI) is an instrument designed to measure the student perspective on courses in higher education. The SRFI was derived from decades of empirical studies of student evaluations of teaching. This article describes the development of the SRFI and its psychometric attributes demonstrated in two pilot study…

  5. Toward Diversity-Responsive Medical Education: Taking an Intersectionality-Based Approach to a Curriculum Evaluation

    ERIC Educational Resources Information Center

    Muntinga, M. E.; Krajenbrink, V. Q.; Peerdeman, S. M.; Croiset, G.; Verdonk, P.

    2016-01-01

    Recent years have seen a rise in the efforts to implement diversity topics into medical education, using either a "narrow" or a "broad" definition of culture. These developments urge that outcomes of such efforts are systematically evaluated by mapping the curriculum for diversity-responsive content. This study was aimed at…

  6. Evaluation of the endocrine response of cattle during the relocation process

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To evaluate the endocrine responses associated with the relocation process, 22 Holstein heifers (326.4±46.8 kg BW) were randomly assigned to control (CON) or relocation (RELOC) treatment groups. On d 0, all heifers were weighed and fitted with indwelling rectal temperature (RT) probes and jugular ca...

  7. Physiological Response to Social Evaluative Threat in Adolescents with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Edmiston, E. Kale; Jones, Robin M.; Corbett, Blythe A.

    2016-01-01

    The Trier Social Stress Test (TSST) was employed to study response to social evaluative threat in male adolescents with Autism Spectrum Disorder (ASD, n = 21) and typical development (n = 13). Participants wore a mobile electrocardiogram to collect heart rate data. There were significant group effects on respiratory sinus arrhythmia (RSA), a…

  8. Evaluating Student Performance and Attitudes in Response to Videotaped Self-Instruction.

    ERIC Educational Resources Information Center

    Boker, John R.

    This study evaluating an innovative technique for the education of medical students emphasized the measurement of 30 senior medical students' cognitive and affective behaviors in response to their experiences over a period of six weeks with videotaped self-instructional programs. An investigation was made of: (1) the students' gain in knowledge,…

  9. Further Evaluation of Response Interruption and Redirection as Treatment for Stereotypy

    ERIC Educational Resources Information Center

    Ahrens, Erin N.; Lerman, Dorothea C.; Kodak, Tiffany; Worsdell, April S.; Keegan, Courtney

    2011-01-01

    The effects of 2 forms of response interruption and redirection (RIRD)--motor RIRD and vocal RIRD--were examined with 4 boys with autism to evaluate further the effects of this intervention and its potential underlying mechanisms. In Experiment 1, the effects of motor RIRD and vocal RIRD on vocal stereotypy and appropriate vocalizations were…

  10. Appraisal, Coping, Task Performance, and Cardiovascular Responses during the Evaluated Speaking Task.

    ERIC Educational Resources Information Center

    Baggett, H. Lane; And Others

    1996-01-01

    Appraisal, coping, task performance, and cardiovascular responses were examined among men high and low in speech anxiety who prepared and performed a speech under evaluative conditions. Speech-anxious men saw the task as more threatening. They were more stressed, anxious, distracted, and aware of their emotions, focused on the passage of time, and…

  11. An Evaluation of Simultaneous Presentation and Differential Reinforcement with Response Cost to Reduce Packing

    ERIC Educational Resources Information Center

    Buckley, Scott D.; Newchok, Debra K.

    2005-01-01

    We evaluated the effects of multiple treatment procedures, including simultaneous presentation of preferred foods, on the packing behavior of a 9-year-old girl with autism. A reversal design was used to assess the effects of differential reinforcement with response cost alone and with simultaneous presentation. In addition, simultaneous…

  12. An Evaluation of Three Methods of Saying "No" to Avoid an Escalating Response Class Hierarchy

    ERIC Educational Resources Information Center

    Mace, F. Charles; Pratt, Jamie L.; Prager, Kevin L.; Pritchard, Duncan

    2011-01-01

    We evaluated the effects of three different methods of denying access to requested high-preference activities on escalating problem behavior. Functional analysis and response class hierarchy (RCH) assessment results indicated that 4 topographies of problem behaviors displayed by a 13-year-old boy with high-functioning autism constituted an RCH…

  13. Development of Response Evaluation and Decision (Red) and Antisocial Behavior in Childhood and Adolescence

    ERIC Educational Resources Information Center

    Fontaine, Reid Griffith; Yang, Chongming; Dodge, Kenneth A.; Pettit, Gregory S.; Bates, John E.

    2009-01-01

    Using longitudinal data on 585 youths (48% female; 17% African American, 2% other ethnic minority), the authors examined the development of social response evaluation and decision (RED) across childhood (Study 1; kindergarten through Grade 3) and adolescence (Study 2; Grades 8 and 11). Participants completed hypothetical-vignette-based RED…

  14. 34 CFR 200.84 - Responsibilities of SEAs for evaluating the effectiveness of the MEP.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Responsibilities of SEAs for evaluating the effectiveness of the MEP. 200.84 Section 200.84 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING...

  15. 34 CFR 200.84 - Responsibilities of SEAs for evaluating the effectiveness of the MEP.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Responsibilities of SEAs for evaluating the effectiveness of the MEP. 200.84 Section 200.84 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING...

  16. 34 CFR 200.84 - Responsibilities of SEAs for evaluating the effectiveness of the MEP.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Responsibilities of SEAs for evaluating the effectiveness of the MEP. 200.84 Section 200.84 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING...

  17. Can a Multidimensional Test Be Evaluated with Unidimensional Item Response Theory?

    ERIC Educational Resources Information Center

    Wiberg, Marie

    2012-01-01

    The aim of this study was to evaluate possible consequences of using unidimensional item response theory (UIRT) on a multidimensional college admission test. The test consists of 5 subscales and can be divided into two sections, that is, it can be considered both as a unidimensional and a multidimensional test. The test was examined with both UIRT…

  18. Exact evaluation of the quadratic longitudinal response function for an unmagnetized Maxwellian plasma

    SciTech Connect

    Layden, B.; Cairns, Iver H.; Robinson, P. A.; Percival, D. J.

    2012-07-15

    The quadratic longitudinal response function describes the second-order nonlinear response of a plasma to electrostatic wave fields. An explicit expression for this function in the weak-turbulence regime requires the evaluation of velocity-space integrals involving the velocity distribution function and various resonant denominators. Previous calculations of the quadratic longitudinal response function were performed by approximating the resonant denominators to facilitate the integration. Here, we evaluate these integrals exactly for a non-relativistic collisionless unmagnetized isotropic Maxwellian plasma in terms of generalized plasma dispersion functions, and correct certain aspects of expressions previously derived for these functions. We show that in the appropriate limits the exact expression reduces to the approximate form used for interactions between two fast waves and one slow wave, such as the electrostatic decay of Langmuir waves into Langmuir waves and ion sound waves, and the scattering of Langmuir waves off thermal ions.

  19. Early detection of disease program: Evaluation of the cellular immune response

    NASA Technical Reports Server (NTRS)

    Criswell, B. S.; Knight, V.; Martin, R. R.; Kasel, J. A.

    1974-01-01

    The early cellular responses of specific components of the leukocyte and epithelial cell populations to foreign challenges of both an infectious and noninfectious character were evaluated. Procedures for screening potential flight crews were developed, documented, and tested on a control population. Methods for preparing suitable populations of lymphocytes, polymorphonuclear leukocytes, macrophages, and epithelial cells were first established and evaluated. Epithelial cells from viral infected individuals were screened with a number of anti-viral antisera. This procedure showed the earliest indication of disease as well as providing a specific diagnosis to the physicians. Both macrophages and polymorphonuclear leukocytes were studied from normal individuals, smokers, and patients with viral infections. Newer techniques enabling better definition of lymphocyte subpopulations were then developed, namely the E and EAC rosette procedures for recognition of T (thymus-derived) and B (bone-marrow-derived) lymphocyte subpopulations. Lymphocyte and lymphocyte subpopulation response to multiple mitogens have been evaluated.

  20. Features of Stroop and reverse-Stroop interference: analysis by response modality and evaluation.

    PubMed

    Ikeda, Yoshifumi; Hirata, Shogo; Okuzumi, Hideyuki; Kokubun, Mitsuru

    2010-04-01

    Stroop interference (the Stroop effect) is the phenomenon observed when naming the color of an incongruent stimulus, such as the word "red" printed in blue ink; typically, this color incongruence causes slower naming compared to a neutral stimulus, such as a blue square patch. Reverse-Stroop interference occurs when reading the stimulus takes longer than reading the neutral stimulus. Features of Stroop and reverse-Stroop interference were examined, focusing on the difference between the response modalities--oral response and manual response--and the difference between methods of evaluating performance (time or correct responses) and the interference score. Participants were 47 students (30 women, 17 men; M age=20.8 yr., range=19-29). The results were as follows: (1) the performance of the reverse-Stroop condition was higher than that of the Stroop condition for both oral and manual responses; (2) the Stroop interference score was significantly greater with the oral response than with the manual response; and (3) the reverse-Stroop interference score was constant regardless of the response modality. The results were discussed with respect to differences in processing speeds of verbal and sensory information.

  1. Evaluation of response from axitinib per Response Evaluation Criteria in Solid Tumors versus Choi criteria in previously treated patients with metastatic renal cell carcinoma

    PubMed Central

    Karakiewicz, Pierre I; Nott, Louise; Joshi, Abhishek; Kannourakis, George; Tarazi, Jamal; Alam, Mahmood

    2016-01-01

    Background Axitinib, a selective and potent tyrosine kinase inhibitor of vascular endothelial growth factor receptors, was available to patients from Canada and Australia, prior to regulatory approval of axitinib in these countries, for treatment of clear-cell metastatic renal cell carcinoma (mRCC) after failure of one prior systemic regimen. Methods This single-arm, open-label study of axitinib evaluated the efficacy, safety, and quality of life (QoL) in patients with mRCC whose disease progressed after one prior systemic first-line regimen. Primary objective was objective response rate evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) and Choi criteria. Progression-free survival, overall survival, safety, and QoL were secondary end points. Due to the small study size, analyses comprised of descriptive statistics. Results Fifteen patients were recruited, five from Canada and ten from Australia, over a limited recruitment period. Thirteen patients received sunitinib as prior therapy. All patients had clear-cell carcinoma, eleven had prior nephrectomy. Liver, lung, and lymph nodes were the most frequent sites of metastases; one patient had brain metastasis. Median time on axitinib was 118.0 days (range: 3.5–645.0 days); estimated survival probability at 12 months was 57.8%. Two (13.3%) patients had objective responses per RECIST versus nine (60.0%) per Choi criteria. Six patients had progressive disease based on RECIST versus three per Choi criteria. Nine (60.0%) events of progression or death occurred by the end of study, and three patients continued to receive the study drug. Fatigue (33%) and diarrhea (20%) were the most common grade ≥3 all-causality, treatment-emergent adverse events. The mean change in European Quality of Life – 5 Dimensions score from baseline to end of treatment was −0.0837. Conclusion The small number of patients and lack of a comparator arm limit the ability to draw definitive conclusions; however, safety and

  2. Antithrombotic activity of F 16618, a new PAR1 antagonist evaluated in extracorporeal arterio-venous shunt in the rat.

    PubMed

    Létienne, Robert; Leparq-Panissié, Anne; Calmettes, Yannick; Nadal-Wollbold, Florence; Perez, Michel; Le Grand, Bruno

    2010-06-01

    The purpose of the present work was the evaluation of the antithrombotic activity of a new PAR1 antagonist, F 16618 in arterio-venous shunt in the rat. Arterial thrombosis was induced by insertion of a silk thread (thrombogenic substrate) into an extracorporeal shunt. F 16618 was administered either by intravenous route (0.63-2.5mg/kg) or by oral route (20-80mg/kg). Oral activity of F 16618 was compared to that of aspirin (20-80mg/kg) and clopidogrel (0.63-10mg/kg). Finally, F 16618 was associated to aspirin and/or clopidogrel to test for possible antithrombotic activity and its effects on bleeding time. SFLLR-induced human platelet aggregation was evaluated in the presence of F 16618, demonstrating the anti-aggregant activity of this compound. F 16618 (1.25mg/kg) significantly delayed the time leading to occlusion by 52+/-17%, without affecting bleeding time and in absence of hemodynamic effects. F 16618 given orally dose-dependently increased the time to occlusion. The maximal effect was observed at 40mg/kg (984+/-95s versus 644+/-17s in vehicle group). Aspirin and clopidogrel also dose-dependently lengthened time to occlusion, but this effect was associated with an increase of bleeding time. F 16618 (20mg/kg) orally associated with either aspirin (40mg/kg) or with clopidogrel (1.25mg/kg) potentiated the antithrombotic effects of both compounds without further increasing of bleeding time. In conclusion, F 16618 exerted a potent antithrombotic activity by intravenous and oral routes, without affecting bleeding time. Furthermore, the antithrombotic activity was potentiated when combined with aspirin or clopidogrel.

  3. Development and evaluation of fully automated demand response in large facilities

    SciTech Connect

    Piette, Mary Ann; Sezgen, Osman; Watson, David S.; Motegi, Naoya; Shockman, Christine; ten Hope, Laurie

    2004-03-30

    This report describes the results of a research project to develop and evaluate the performance of new Automated Demand Response (Auto-DR) hardware and software technology in large facilities. Demand Response (DR) is a set of activities to reduce or shift electricity use to improve electric grid reliability, manage electricity costs, and ensure that customers receive signals that encourage load reduction during times when the electric grid is near its capacity. The two main drivers for widespread demand responsiveness are the prevention of future electricity crises and the reduction of electricity prices. Additional goals for price responsiveness include equity through cost of service pricing, and customer control of electricity usage and bills. The technology developed and evaluated in this report could be used to support numerous forms of DR programs and tariffs. For the purpose of this report, we have defined three levels of Demand Response automation. Manual Demand Response involves manually turning off lights or equipment; this can be a labor-intensive approach. Semi-Automated Response involves the use of building energy management control systems for load shedding, where a preprogrammed load shedding strategy is initiated by facilities staff. Fully-Automated Demand Response is initiated at a building or facility through receipt of an external communications signal--facility staff set up a pre-programmed load shedding strategy which is automatically initiated by the system without the need for human intervention. We have defined this approach to be Auto-DR. An important concept in Auto-DR is that a facility manager is able to ''opt out'' or ''override'' an individual DR event if it occurs at a time when the reduction in end-use services is not desirable. This project sought to improve the feasibility and nature of Auto-DR strategies in large facilities. The research focused on technology development, testing, characterization, and evaluation relating to Auto

  4. Evaluation of optimum profile modification curves of profile shifted spur gears based on vibration responses

    NASA Astrophysics Data System (ADS)

    Ma, Hui; Pang, Xu; Feng, Ranjiao; Wen, Bangchun

    2016-03-01

    In this paper, a mesh stiffness model is developed for profile shifted gears with addendum modifications and tooth profile modifications (TPMs). The time-varying mesh stiffness (TVMS), load sharing factor (LSF), loaded static transmission error (LSTE) and non-loaded static transmission error (NLSTE) of a profile shifted spur gear pair with TPMs are obtained by the analytical model. The optimum profile modification curve under different amounts of TPM is determined by analyzing the LSTE first. Then, considering the effect of NLSTE, finite element (FE) model of a geared rotor system is established. The system vibration responses under different TPM curves are analyzed and the optimum modification curve is further evaluated by amplitude frequency responses. The results show that the optimum modification curve is related to the amount of TPM and modification coefficients. The comparison of the optimum profile modification curves is evaluated by LSTE and vibration responses, which shows that the optimum modification curve should be determined by evaluating the vibration response of the geared rotor system in the low mesh frequency range.

  5. Evaluating quantitative formulas for dose-response assessment of chemical mixtures.

    PubMed Central

    Hertzberg, Richard C; Teuschler, Linda K

    2002-01-01

    Risk assessment formulas are often distinguished from dose-response models by being rough but necessary. The evaluation of these rough formulas is described here, using the example of mixture risk assessment. Two conditions make the dose-response part of mixture risk assessment difficult, lack of data on mixture dose-response relationships, and the need to address risk from combinations of chemicals because of public demands and statutory requirements. Consequently, the U.S. Environmental Protection Agency has developed methods for carrying out quantitative dose-response assessment for chemical mixtures that require information only on the toxicity of single chemicals and of chemical pair interactions. These formulas are based on plausible ideas and default parameters but minimal supporting data on whole mixtures. Because of this lack of mixture data, the usual evaluation of accuracy (predicted vs. observed) cannot be performed. Two approaches to the evaluation of such formulas are to consider fundamental biological concepts that support the quantitative formulas (e.g., toxicologic similarity) and to determine how well the proposed method performs under simplifying constraints (e.g., as the toxicologic interactions disappear). These ideas are illustrated using dose addition and two weight-of-evidence formulas for incorporating toxicologic interactions. PMID:12634126

  6. Dopamine Inactivation Efficacy Related to Functional DAT1 and COMT Variants Influences Motor Response Evaluation

    PubMed Central

    Bender, Stephan; Rellum, Thomas; Freitag, Christine; Resch, Franz; Rietschel, Marcella; Treutlein, Jens; Jennen-Steinmetz, Christine; Brandeis, Daniel; Banaschewski, Tobias; Laucht, Manfred

    2012-01-01

    Background Dopamine plays an important role in orienting, response anticipation and movement evaluation. Thus, we examined the influence of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of motor processing in a contingent negative variation (CNV) task. Methods 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as motor postimperative negative variation were assessed. Adolescents were genotyped for the COMT Val158Met and two DAT1 polymorphisms (variable number tandem repeats in the 3′-untranslated region and in intron 8). Results The results revealed a significant interaction between COMT and DAT1, indicating that COMT exerted stronger effects on lateralized motor post-processing (centro-parietal motor postimperative negative variation) in homozygous carriers of a DAT1 haplotype increasing DAT1 expression. Source analysis showed that the time interval 500–1000 ms after the motor response was specifically affected in contrast to preceding movement anticipation and programming stages, which were not altered. Conclusions Motor slow negative waves allow the genomic imaging of dopamine inactivation effects on cortical motor post-processing during response evaluation. This is the first report to point towards epistatic effects in the motor system during response evaluation, i.e. during the post-processing of an already executed movement rather than during movement programming. PMID:22649558

  7. 33 CFR 155.5052 - Response plan development and evaluation criteria for nontank vessels carrying group V petroleum...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... requirements of 33 CFR 155.1052. ... evaluation criteria for nontank vessels carrying group V petroleum oil. 155.5052 Section 155.5052 Navigation... Response plan development and evaluation criteria for nontank vessels carrying group V petroleum...

  8. Depersonalization Disorder: Disconnection of Cognitive Evaluation from Autonomic Responses to Emotional Stimuli

    PubMed Central

    Michal, Matthias; Koechel, Ansgar; Canterino, Marco; Adler, Julia; Reiner, Iris; Vossel, Gerhard; Beutel, Manfred E.; Gamer, Matthias

    2013-01-01

    Background Patients with depersonalization disorder (DPD) typically complain about emotional detachment. Previous studies found reduced autonomic responsiveness to emotional stimuli for DPD patients as compared to patients with anxiety disorders. We aimed to investigate autonomic responsiveness to emotional auditory stimuli of DPD patients as compared to patient controls. Furthermore, we examined the modulatory effect of mindful breathing on these responses as well as on depersonalization intensity. Methods 22 DPD patients and 15 patient controls balanced for severity of depression and anxiety, age, sex and education, were compared regarding 1) electrodermal and heart rate data during a resting period, and 2) autonomic responses and cognitive appraisal of standardized acoustic affective stimuli in two conditions (normal listening and mindful breathing). Results DPD patients rated the emotional sounds as significantly more neutral as compared to patient controls and standardized norm ratings. At the same time, however, they responded more strongly to acoustic emotional stimuli and their electrodermal response pattern was more modulated by valence and arousal as compared to patient controls. Mindful breathing reduced severity of depersonalization in DPD patients and increased the arousal modulation of electrodermal responses in the whole sample. Finally, DPD patients showed an increased electrodermal lability in the rest period as compared to patient controls. Conclusions These findings demonstrated that the cognitive evaluation of emotional sounds in DPD patients is disconnected from their autonomic responses to those emotional stimuli. The increased electrodermal lability in DPD may reflect increased introversion and cognitive control of emotional impulses. The findings have important psychotherapeutic implications. PMID:24058547

  9. Comprehensive evaluation of poly(I:C) induced inflammatory response in an airway epithelial model.

    PubMed

    Lever, Amanda R; Park, Hyoungshin; Mulhern, Thomas J; Jackson, George R; Comolli, James C; Borenstein, Jeffrey T; Hayden, Patrick J; Prantil-Baun, Rachelle

    2015-04-01

    Respiratory viruses invade the upper airway of the lung, triggering a potent immune response that often exacerbates preexisting conditions such as asthma and COPD. Poly(I:C) is a synthetic analog of viral dsRNA that induces the characteristic inflammatory response associated with viral infection, such as loss of epithelial integrity, and increased production of mucus and inflammatory cytokines. Here, we explore the mechanistic responses to poly(I:C) in a well-defined primary normal human bronchial epithelial (NHBE) model that recapitulates in vivo functions and responses. We developed functional and quantifiable methods to evaluate the physiology of our model in both healthy and inflamed states. Through gene and protein expression, we validated the differentiation state and population of essential cell subtypes (i.e., ciliated, goblet, club, and basal cells) as compared to the human lung. Assays for total mucus production, cytokine secretion, and barrier function were used to evaluate in vitro physiology and response to viral insult. Cells were treated apically with poly(I:C) and evaluated 48 h after induction. Results revealed a dose-dependent increase in goblet cell differentiation, as well as, an increase in mucus production relative to controls. There was also a dose-dependent increase in secretion of IL-6, IL-8, TNF-α, and RANTES. Epithelial barrier function, as measured by TEER, was maintained at 1501 ± 355 Ω*cm² postdifferentiation, but dropped significantly when challenged with poly(I:C). This study provides first steps toward a well-characterized model with defined functional methods for understanding dsRNA stimulated inflammatory responses in a physiologically relevant manner.

  10. Prasugrel compared to clopidogrel in patients with acute coronary syndrome undergoing percutenaous coronary intervention: a Spanish model-based cost effectiveness analysis.

    PubMed

    Davies, A; Sculpher, M; Barrett, A; Huete, T; Sacristán, J A; Dilla, T

    2013-01-01

    Objetivo: Evaluar a largo plazo el coste-efectividad de 12 meses de tratamiento con prasugrel frente a clopidogrel en pacientes con síndrome coronario agudo (SCA) sometidos a intervención coronaria percutánea (ICP) desde la perspectiva del sistema nacional de salud español. Métodos: Se desarrolló un modelo de Markov de transición entre estados para estimar los resultados en salud, los años de vida ajustados por calidad (AVACs), los años de vida (AV) y los costes a lo largo de la vida de los pacientes. Los datos clínicos fueron obtenidos de un análisis del ensayo clínico TRITON-TIMI 38. Los reingresos hospitalarios registrados durante el ensayo en un subestudio de pacientes provenientes de ocho países, (y las subsiguientes rehospitalizaciones fueron modeladas para acumularse más alla del horizonte temporal del ensayo) fueron asignados a grupos relacionados con el diagnóstico españoles para estimar los costes de hospitalización. Resultados: Los costes medios totales del tratamiento con prasugrel y clopidogrel fueron 11.427 ??y 10.910 ?, respectivamente. El coste medio del fármaco fue 538 ??superior para prasugrel frente a clopidogrel, pero los costes de rehospitalización a los 12 meses fueron 79 ??menores para prasugrel debido a la reducción en las tasas de revascularización. Los costes de hospitalización más allá de los 12 meses fueron 55 ??superiores con prasugrel, debido a la mayor esperanza de vida (+0,071 AV y +0,054 AVACs) asociada a la reducción de la tasa de infartos de miocardio no mortales en el grupo de prasugrel. El coste-efectividad incremental por año de vida y AVAC ganado con prasugrel fue 7.198 ??y 9.489 ?, respectivamente. Conclusión: Considerando el umbral de disponibilidad a pagar de 30.000 ?/ AVAC para España, prasugrel representa una opción coste-efectiva en comparación con clopidogrel en pacientes con SCA sometidos a ICP.

  11. Novel Oral P2Y12 Inhibitor Prasugrel vs. Clopidogrel in Patients with Acute Coronary Syndrome: Evidence Based on 6 Studies

    PubMed Central

    Jia, Min; Li, Zaibo; Chu, Hongtao; Li, Lin; Chen, Keyong

    2015-01-01

    Background Whether prasugrel can take the place of clopidogrel for patients with acute coronary syndrome (ACS) is not clear. The aim of this study was to perform a meta-analysis for systematically reviewing the evidence on prasugrel in comparison to clopidogrel in patients with ACS. Material/Methods Relevant prospective and retrospective studies were searched in databases. Six studies were finally included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to assess all causes of death, myocardial infarction (MI), stroke, major bleeding, major/minor bleeding, and stent thrombosis (for PCI performed). Results Compared with clopidogrel, prasugrel had similar risks of all cause of death (Pooled RR: 0.83; 95% CI: 0.64–1.06, p=0.14, I2=55%), MI (Pooled RR: 0.86; 95% CI: 0.71–1.04, p=0.12) and stroke (pooled RR: 0.88; 95% CI: 0.70–1.10, p=0.25). However, prasugrel was associated with significantly higher risk of both major bleeding (Pooled RR: 1.19; 95% CI: 0.99–1.44, p=0.06, I2=0%) and the risk of total major and minor bleeding (Pooled RR: 1.30; 95% CI: 1.15–1.48, p<0.0001, I2=0%). For the patients who underwent percutaneous coronary intervention (PCI), prasugrel was associated with significantly lower risk of stent thrombosis (Pooled RR: 0.47; 95% CI: 0.34–0.61, p<0.00001, I2=0%). Conclusions Prasugrel has similar effects as clopidogrel in terms of all causes of death, MI, and stroke in ACS patients. For the patients who underwent PCI, prasugrel contributes to lower risk of stent thrombosis. However, prasugrel is associated with significantly higher risk of bleeding. For the patients with active pathological bleeding or a history of stroke and/or TIA, prasugrel should not be recommended. PMID:25893318

  12. The Complexity of Practice: Participant Observation and Values Engagement in a Responsive Evaluation of a Professional Development School Partnership

    ERIC Educational Resources Information Center

    Freeman, Melissa; Hall, Jori N.

    2012-01-01

    All social and professional practices are historically situated, evolving forms of acting and interacting. Evaluation, as a practice, is shaped by and shapes the practice evaluated. This article contributes to responsive and values-engaged evaluation approaches by reflecting on the space where these two practices intersect. The evaluative task was…

  13. The effect of context on responses to racially ambiguous faces: changes in perception and evaluation.

    PubMed

    Willadsen-Jensen, Eve; Ito, Tiffany A

    2015-07-01

    Reactions to individuals who possess features associated with multiple racial groups may be particularly susceptible to external contextual influences, leading to meaningfully different racial perceptions and judgments in different situations. In the present study, we found that an extrinsic race-label cue not only changed evaluative associations activated by a racially ambiguous face, but also changed quickly occurring neural responses sensitive to racial perception. Behaviorally, prototypical Black faces and racially ambiguous faces labeled as Black activated more negative implicit associations than prototypical White faces and racially ambiguous faces labeled as White. Neurally, prototypical faces and racially ambiguous faces cued with the same race elicited similar responses. Specifically, prototypical Black and racially ambiguous faces labeled as Black elicited larger P200s but smaller N200s than prototypical White and racially ambiguous faces labeled as White. These results show that racial perception can be changed by an external cue and this, in turn, influences subsequent evaluative reactions. PMID:25344946

  14. Unidimensional Measurement May Evaluate Target Lymph Nodal Response After Induction Chemotherapy for Nasopharyngeal Carcinoma

    PubMed Central

    Chen, Chuanben; Zhang, Mingwei; Xu, Yuanji; Yue, Qiuyuan; Bai, Penggang; Zhou, Lin; Xiao, Youping; Zheng, Dechun; Lin, Kongqi; Qiu, Sufang; Chen, Yunbin; Pan, Jianji

    2016-01-01

    Abstract The aim of the study was to evaluate whether short axis and long axis on axial and coronal magnetic resonance imaging planes would reflect the tumor burden or alteration in size after induction chemotherapy in nasopharyngeal carcinoma. Patients with pathologically confirmed nasopharyngeal carcinoma (n = 37) with at least 1 positive cervical lymph node (axial short axis ≥15 mm) were consecutively enrolled in this prospective study. Lymph nodal measurements were performed along its short axis and long axis in both axial and coronal magnetic resonance imaging planes at diagnosis and after 2 cycles of induction chemotherapy. In addition, lymph nodal volumes were automatically calculated in 3D treatment-planning system, which were used as reference standard. Student's t test or nonparametric Mann–Whitney U test was used to compare the continuous quantitative variables. Meanwhile, the κ statistic and McNemar's test were used to evaluate the degree of agreement and discordance in response categorization among different measurements. Axial short axis was significantly associated with volumes at diagnosis (P < 0.001). A good agreement (κ=0.583) was found between axial short axis and volumetric criteria. However, the inconsistent lymph nodal shrinkage in 4 directions was observed. Axial short-axis shrinking was more rapid than the other 3 parameters. Interestingly, when utilizing the alternative planes for unidimensional measurements to assess tumor response, coronal short-axis showed the best concordance (κ=0.792) to the volumes. Axial short axis may effectively reflect tumor burden or change in tumor size in the assessment of target lymph nodal response after induction chemotherapy for nasopharyngeal carcinoma. However, it should be noted that axial short axis may amplify the therapeutic response. In addition, the role of coronal short axis in the assessment of tumor response needs further evaluation. PMID:26945354

  15. Digital Image Analysis for Morphometric Evaluation of Tissue Response after Implanting Alloplastic Vascular Prostheses

    NASA Astrophysics Data System (ADS)

    Zippel, Roland; Hoene, Andreas; Walschus, Uwe; Jarchow, Raymond; Ueberrueck, Torsten; Patrzyk, Maciej; Schlosser, Michael; Wilhelm, Lutz

    2006-07-01

    The aim of this study was to examine the suitability of digital image analysis, using the KS400 software system, for the morphometric evaluation of the tissue response after prosthesis implantation in an animal model. Twenty-four female pigs aged 10 weeks were implanted with infrarenal Dacron® prostheses for 14, 21, 28, and 116 days. Following the explantation and investigation of the neointima region, the expression of beta-1-integrin, the proliferation rate by means of Ki-67 positive cells, and the intima thickness were evaluated as exemplary parameters of the tissue response after implantation. Frozen tissue sections were immunohistochemically stained and subsequently examined using computer-aided image analysis. A maximum expression of 32.9% was observed for beta-1-integrin 14 days after implantation, gradually declining over time to 9.8% after 116 days. The proliferation rate was found to be 19% on day 14, increasing to 39% on day 21 with a subsequent gradual decline to 5% after 116 days. The intima thickness increased from 189.9 [mu]m on day 14 to 1228.0 [mu]m on day 116. In conclusion, digital image analysis was found to be an efficient and reproducible method for the morphometric evaluation of a peri-prosthetic tissue response.

  16. [Response of bone metastases to medical treatment: definition of evaluation criteria and classification trials].

    PubMed

    Belpomme, D; Droz, J P; Marie, F N; Namer, M; Tan, T N; Pecking, A; Rouesse, J; Vanel, D; Bock, P; Cappelaere, P

    1989-01-01

    Bone metastases are very frequent. Some are sensitive to the action of anticancer drugs. However, there is as yet an unsolved methodological problem in the evaluation of response to these drugs. The uniquely radiological UICC criteria are quite insufficient, in as much as they appear with a long delay and sometimes give erroneous results. In this work we give a brief review of biological and clinical knowledge about bone metastases, and we attempt to give an array of the possible evaluation criteria and their respective value. We propose as a working hypothesis a classification of responses taking into account the criteria: the urinary hydroxyproline to urinary creatinine ratio, the serum dosage of bone isoenzyme of alkaline phosphatase and propeptide of type III procollagen (P III NP), and as an essential element, an analysis of all available imaging techniques. A visual study of bone scintillation scans must precede that of radiographs and, when possible, it must be associated to computerized scintillation scanning. When metastasis are located to the pelvis, the vertebral column, or the sternum, a CT scan or better, a nuclear magnetic resonance study (IRM), is indispensable in order to have a direct measure of the tumor extension to soft tissues. Furthermore, in the case of isolated metastases, one of these imaging techniques allows a diagnostic biopsy. Finally an analysis of response at the bone level will always be associated with a measure of their duration and an evaluation of metastases to other sites.

  17. The effect of counterconditioning on evaluative responses and harm expectancy in a fear conditioning paradigm.

    PubMed

    Raes, An K; De Raedt, Rudi

    2012-12-01

    In fear conditioning, extinction targets harm expectancy as well as the fear response, but it often fails to eradicate the negative affective value that is associated with the conditioned stimulus. In the present study, we examined whether counterconditioning can serve to reduce evaluative responses within fear conditioning. The sample consisted of 70 nonselected students, 12 of whom were men. All participants received acquisition with human face stimuli as the conditioned stimuli and an unpleasant white noise as the unconditioned stimulus. After acquisition, one third of the sample was allocated to an extinction procedure. The other participants received counterconditioning with either a neutral stimulus (neutral tone) or a positive stimulus (baby laugh). Results showed that counterconditioning (with both neutral and positive stimuli), in contrast to extinction, successfully reduced evaluative responses. This effect was found on an indirect measure (affective priming task), but not on self-report. Counterconditioning with a positive stimulus also tended to enhance the reduction of conditioned skin conductance reactivity. The present data suggest that counterconditioning procedures might be a promising approach in diminishing evaluative learning and even expectancy learning in the context of fear conditioning.

  18. A new protein quality evaluation index based on growth responses of rats.

    PubMed

    Mercer, L P; Gustafson, J M

    1984-05-01

    The protein efficiency ratio (PER) is the official method for protein quality evaluation in the United States and Canada. Two other widely used indices of evaluation are the slope ratio and net protein ratio (NPR) methods. Each of these methods has problems associated with its calculation and interpretation. In this paper, a new index, actual protein utilization ( APU ) is discussed, and its relationship to the other indices is examined. Each of the indices is given a theoretical basis by relating it to the four parameter mathematical model for physiological responses. To compare the indices, growth bioassays were carried out using male rats (40, 60, 115 g) consuming three different proteins (casein, lactalbumin and soy) and an amino acid mixture (Rogers and Harper). Dose-response curves were generated for each diet, and the indices PER, NPR, Slope and APU were calculated. APU was shown to have certain characteristics that make it superior to the other methods of protein quality evaluation, i.e., it closely approximates the growth response curve and it incorporates a term for the protein intake required for maintenance.

  19. The 6 "ws" of rapid response systems: best practices for improving development, implementation, and evaluation.

    PubMed

    Lazzara, Elizabeth H; Benishek, Lauren E; Sonesh, Shirley C; Patzer, Brady; Robinson, Patricia; Wallace, Ruth; Salas, Eduardo

    2014-01-01

    Delays in care have been cited as one of the primary contributors of preventable mortality; thus, quality patient safety is often contingent upon the delivery of timely clinical care. Rapid response systems (RRSs) have been touted as one mechanism to improve the ability of suitable staff to respond to deteriorating patients quickly and appropriately. Rapid response systems are defined as highly skilled individual(s) who mobilize quickly to provide medical care in response to clinical deterioration. While there is mounting evidence that RRSs are a valid strategy for managing obstetric emergencies, reducing adverse events, and improving patient safety, there remains limited insight into the practices underlying the development and execution of these systems. Therefore, the purpose of this article was to synthesize the literature and answer the primary questions necessary for successfully developing, implementing, and evaluating RRSs within inpatient settings-the Who, What, When, Where, Why, and How of RRSs.

  20. The 6 "ws" of rapid response systems: best practices for improving development, implementation, and evaluation.

    PubMed

    Lazzara, Elizabeth H; Benishek, Lauren E; Sonesh, Shirley C; Patzer, Brady; Robinson, Patricia; Wallace, Ruth; Salas, Eduardo

    2014-01-01

    Delays in care have been cited as one of the primary contributors of preventable mortality; thus, quality patient safety is often contingent upon the delivery of timely clinical care. Rapid response systems (RRSs) have been touted as one mechanism to improve the ability of suitable staff to respond to deteriorating patients quickly and appropriately. Rapid response systems are defined as highly skilled individual(s) who mobilize quickly to provide medical care in response to clinical deterioration. While there is mounting evidence that RRSs are a valid strategy for managing obstetric emergencies, reducing adverse events, and improving patient safety, there remains limited insight into the practices underlying the development and execution of these systems. Therefore, the purpose of this article was to synthesize the literature and answer the primary questions necessary for successfully developing, implementing, and evaluating RRSs within inpatient settings-the Who, What, When, Where, Why, and How of RRSs. PMID:24595258

  1. Analytical ultrasonics for evaluation of composite materials response. Part 2: Generation and detection

    NASA Technical Reports Server (NTRS)

    Duke, J. C., Jr.; Henneke, E. G., II

    1986-01-01

    To evaluate the response of composite materials, it is imperative that the input excitation as well as the observed output be well characterized. This characterization ideally should be in terms of displacements as a function of time with high spatial resolution. Additionally, the ability to prescribe these features for the excitation is highly desirable. Various methods for generating and detecting ultrasound in advanced composite materials are examined. Characterization and tailoring of input excitation is considered for contact and noncontact, mechanical, and electromechanical devices. Type of response as well as temporal and spatial resolution of detection methods are discussed as well. Results of investigations at Virginia Tech in application of these techniques to characterizing the response of advanced composites are presented.

  2. Evaluation of response variables in computer-simulated virtual cataract surgery

    NASA Astrophysics Data System (ADS)

    Söderberg, Per G.; Laurell, Carl-Gustaf; Simawi, Wamidh; Nordqvist, Per; Skarman, Eva; Nordh, Leif

    2006-02-01

    We have developed a virtual reality (VR) simulator for phacoemulsification (phaco) surgery. The current work aimed at evaluating the precision in the estimation of response variables identified for measurement of the performance of VR phaco surgery. We identified 31 response variables measuring; the overall procedure, the foot pedal technique, the phacoemulsification technique, erroneous manipulation, and damage to ocular structures. Totally, 8 medical or optometry students with a good knowledge of ocular anatomy and physiology but naive to cataract surgery performed three sessions each of VR Phaco surgery. For measurement, the surgical procedure was divided into a sculpting phase and an evacuation phase. The 31 response variables were measured for each phase in all three sessions. The variance components for individuals and iterations of sessions within individuals were estimated with an analysis of variance assuming a hierarchal model. The consequences of estimated variabilities for sample size requirements were determined. It was found that generally there was more variability for iterated sessions within individuals for measurements of the sculpting phase than for measurements of the evacuation phase. This resulted in larger required sample sizes for detection of difference between independent groups or change within group, for the sculpting phase as compared to for the evacuation phase. It is concluded that several of the identified response variables can be measured with sufficient precision for evaluation of VR phaco surgery.

  3. Associations between maternal negative affect and adolescent's neural response to peer evaluation.

    PubMed

    Tan, Patricia Z; Lee, Kyung Hwa; Dahl, Ronald E; Nelson, Eric E; Stroud, Laura J; Siegle, Greg J; Morgan, Judith K; Silk, Jennifer S

    2014-04-01

    Parenting is often implicated as a potential source of individual differences in youths' emotional information processing. The present study examined whether parental affect is related to an important aspect of adolescent emotional development, response to peer evaluation. Specifically, we examined relations between maternal negative affect, observed during parent-adolescent discussion of an adolescent-nominated concern with which s/he wants parental support, and adolescent neural responses to peer evaluation in 40 emotionally healthy and depressed adolescents. We focused on a network of ventral brain regions involved in affective processing of social information: the amygdala, anterior insula, nucleus accumbens, and subgenual anterior cingulate, as well as the ventrolateral prefrontal cortex. Maternal negative affect was not associated with adolescent neural response to peer rejection. However, longer durations of maternal negative affect were associated with decreased responsivity to peer acceptance in the amygdala, left anterior insula, subgenual anterior cingulate, and left nucleus accumbens. These findings provide some of the first evidence that maternal negative affect is associated with adolescents' neural processing of social rewards. Findings also suggest that maternal negative affect could contribute to alterations in affective processing, specifically, dampening the saliency and/or reward of peer interactions during adolescence.

  4. Reliability and Validity of "Parents' Evaluation of Responsible Behaviors of 5-6 Year Old Children" Scale

    ERIC Educational Resources Information Center

    Polat, Ozgul; Dagal, Asude B.

    2013-01-01

    This study is aimed at developing a scale (Parents' Evaluation of Responsible Behaviors of 5-6 Year Old Children) for measuring parents' evaluation of their 5-6 year-old children's responsible behaviors. The construct validity of the scale was tested by Factor Analysis. Factor analysis determined that the scale can be clustered under 10 factors.…

  5. Adolescents' Increasing Stress Response to Social Evaluation: Pubertal Effects on Cortisol and Alpha-Amylase during Public Speaking

    ERIC Educational Resources Information Center

    van den Bos, Esther; de Rooij, Mark; Miers, Anne C.; Bokhorst, Caroline L.; Westenberg, P. Michiel

    2014-01-01

    Stress responses to social evaluation are thought to increase during adolescence, which may be due to pubertal maturation. However, empirical evidence is scarce. This study is the first to investigate the relation between pubertal development and biological responses to a social-evaluative stressor longitudinally. Participants performed the Leiden…

  6. Pitfalls and guidelines for the numerical evaluation of moderate-order system frequency response

    NASA Technical Reports Server (NTRS)

    Frisch, H. P.

    1981-01-01

    The design and evaluation of a feedback control system via frequency response methods relies heavily upon numerical methods. In application, one can usually develop low order simulation models which for the most part are devoid of numerical problems. However, when complex feedback interactions, for example, between instrument control systems and their flexible mounting structure, must be evaluated, simulation models become moderate to large order and numerical problems become common. A large body of relevant numerical error analysis literature is summarized in a large language understandable to nonspecialists. The intent is to provide engineers using simulation models with an engineering feel for potential numerical problems without getting intertwined in the complexities of the associated mathematical theory. Guidelines are also provided by suggesting alternate state of the art methods which have good numerical evaluation characteristics.

  7. Study on corporate social responsibility evaluation system based on stakeholder theory

    NASA Astrophysics Data System (ADS)

    Ma, J.; Deng, Liming

    2011-10-01

    The issue of Corporate Social Responsibility (CSR) has been attracting the attention from many disciplines such as economics, management, laws, sociality and philosophy since last century. The purpose of this study is to explore the impact of CSR on performance and develop a CSR evaluation system. Building on the definition of CSR and Stakeholder theory, this article built a path-relationship model of CSR and business operation performance. The paper also constructed CSR evaluation system based on KLD index, GRJ report, CSR accounting account, SA8000, ISO14000 etc. The research provides a basis for future studies about the relationship between CSR and business performance and shed some light on the evaluation of CSR practices.

  8. New Chemometrics Mode Based on Adjacent Data Points’ Differences for the Simultaneous Determination of Clopidogrel, Atorvastatin, and Aspirin in their Combined Ternary Drug Formulation

    PubMed Central

    Nejem, R’afat Mahmoud; Issa, Mahmoud Mohamed; Shanab, Alaa Abu; Stefan-Van Staden, Raluca-Ioana; Aboul-Enein, Hassan Y.

    2014-01-01

    Abstract A new method is proposed for the analysis of a ternary mixture composed of clopidogrel, atorvastatin, and aspirin without prior separation steps. The method combines the advantages of the mean centering of ratio spectra and derivative spectrophotometric methods. It is based on using the difference between adjacent data points in the absorbance spectra. The principal advantage of this method is the use of absorbance data, and not derivative data; hence the signal-to-noise ratio is not diminished. The mathematical explanation of the procedure is illustrated. Beer’s law was valid in the concentration range 0.3–35 μg.mL-1 for CLOP, 0.5–30 μg.mL-1 for ATOR, and 1–40 μg.mL-1 for ASP. Mean recoveries were obtained as 100.2, 100.1, and 100.2% for CLOP, ATOR, and ASP, respectively, in the prepared synthetic mixtures. The method has been successfully applied to the simultaneous determination of ternary mixtures of aspirin, clopidogrel bisulphate, and atorvastatin calcium. The analytical characteristics of the method were calculated. The results showed that the new method is simple, rapid, accurate, and precise. PMID:25853071

  9. The Usefulness of Serum CXCR3 Ligands for Evaluating the Early Treatment Response in Tuberculosis

    PubMed Central

    Chung, Wou Young; Yoon, Dukyong; Lee, Keu Sung; Jung, Yun Jung; Kim, Young Sun; Sheen, Seung Soo; Park, Kwang Joo

    2016-01-01

    Abstract Cell-mediated immunity plays an important role in the pathobiology of tuberculosis (TB). The ligands for CXC chemokine receptor 3 (CXCR3) activate the T-helper type 1 lymphocyte pathway. The CXCR3 ligands are reportedly useful clinical markers for the diagnosis and follow-up of TB. The objective of this study was to assess the utility of CXCR3 ligands for evaluating early treatment responses in TB. We recruited 88 patients who underwent antituberculous chemotherapy. The serum levels of interferon (IFN)-γ and the CXCR3 ligands CXCL9 (monokine induced by IFN-γ [MIG]), CXCL10 (IFN-γ-inducible 10-kDa protein [IP-10]), and CXCL11 (IFN-inducible T-cell α chemoattractant [I-TAC]) were measured before and 2 months after the start of treatment. Treatment responses were divided into “fast” and “slow” based on the clinical, radiological, and bacteriological improvement at 2 months. A change in level of 20% or more at 2 months was defined as “significant.” In patients with treatment success, 58 patients exhibited a fast response and 20 patients exhibited a slow response. Treatment failure occurred in 5 patients, and the diagnoses were changed to non-TB diseases in 5 patients. The levels of all CXCR3 ligands significantly decreased in the fast-response group (P < 0.01) but did not decrease in the other groups. IFN-γ levels showed no significant changes. The ability of significant decreases in marker levels to predict a fast response was evaluated. CXCL9 showed a sensitivity of 83%, and CXCL10 showed a specificity of 100%. Use of various combinations of CXCR3 ligands resulted in improvements in sensitivity (88%–93%), while specificity (92%–96%) was similar to that using single CXCR3 ligands. The decreases in CXCR3 ligand levels were less marked in the 2-month Mycobacterium tuberculosis culture-positive group than in the culture-negative group. There were significant differences in treatment outcomes in terms of 2-month culture positivity (P

  10. Multiple Response System: Evaluation of Policy Change in North Carolina’s Child Welfare System

    PubMed Central

    Lawrence, C. Nicole; Rosanbalm, Katie D.; Dodge, Kenneth A.

    2013-01-01

    Systemic challenges within child welfare have prompted many states to explore new strategies aimed at protecting children while meeting the needs of families, but doing so within the confines of shrinking budgets. Differential Response has emerged as a promising practice for low or moderate risk cases of child maltreatment. This mixed methods evaluation explored various aspects of North Carolina’s differential response system, known as the Multiple Response System (MRS), including: child safety, timeliness of response and case decision, frontloading of services, case distribution, implementation of Child and Family Teams, collaboration with community-based service providers and Shared Parenting. Utilizing Child Protective Services (CPS) administrative data, researchers found that compared to matched control counties, MRS: had a positive impact on child safety evidenced by a decline in the rates of substantiations and re-assessments; temporarily disrupted timeliness of response in pilot counties but had no effect on time to case decision; and increased the number of upfront services provided to families during assessment. Qualitative data collected through focus groups with providers and phone interviews with families provided important information on key MRS strategies, highlighting aspects that families and social workers like as well as identifying areas for improvement. This information is useful for continuous quality improvement efforts, particularly related to the development of training and technical assistance programs at the state and local level. PMID:24353361

  11. Trend tests for the evaluation of exposure-response relationships in epidemiological exposure studies

    PubMed Central

    Hothorn, Ludwig A; Vaeth, Michael; Hothorn, Torsten

    2009-01-01

    One possibility for the statistical evaluation of trends in epidemiological exposure studies is the use of a trend test for data organized in a 2 × k contingency table. Commonly, the exposure data are naturally grouped or continuous exposure data are appropriately categorized. The trend test should be sensitive to any shape of the exposure-response relationship. Commonly, a global trend test only determines whether there is a trend or not. Once a trend is seen it is important to identify the likely shape of the exposure-response relationship. This paper introduces a best contrast approach and an alternative approach based on order-restricted information criteria for the model selection of a particular exposure-response relationship. For the simple change point alternative H1 : π1 = ...= πq <πq+1 = ... = πk an appropriate approach for the identification of a global trend as well as for the most likely shape of that exposure-response relationship is characterized by simulation and demonstrated for real data examples. Power and simultaneous confidence intervals can be estimated as well. If the conditions are fulfilled to transform the exposure-response data into a 2 × k table, a simple approach for identification of a global trend and its elementary shape is available for epidemiologists. PMID:19265556

  12. Evaluation of the tip-bending response in clinically used endoscopes

    PubMed Central

    Rozeboom, Esther D.; Reilink, Rob; Schwartz, Matthijs P.; Fockens, Paul; Broeders, Ivo A. M. J.

    2016-01-01

    Background and study aims: Endoscopic interventions require accurate and precise control of the endoscope tip. The endoscope tip response depends on a cable pulling system, which is known to deliver a significantly nonlinear response that eventually reduces control. It is unknown whether the current technique of endoscope tip control is adequate for a future of high precision procedures, steerable accessories, and add-on robotics. The aim of this study was to determine the status of the tip response of endoscopes used in clinical practice. Materials and methods: We evaluated 20 flexible colonoscopes and five gastroscopes, used in the endoscopy departments of a Dutch university hospital and two Dutch teaching hospitals, in a bench top setup. First, maximal tip bending was determined manually. Next, the endoscope navigation wheels were rotated individually in a motor setup. Tip angulation was recorded with a USB camera. Cable slackness was derived from the resulting hysteresis plot. Results: Only two of the 20 colonoscopes (10 %) and none of the five gastroscopes reached the maximal tip angulation specified by the manufacturer. Four colonoscopes (20 %) and none of the gastroscopes demonstrated the recommended cable tension. Eight colonoscopes (40 %) had undergone a maintenance check 1 month before the measurements were made. The tip responses of these eight colonoscopies did not differ significantly from the tip responses of the other colonoscopes. Conclusion: This study suggests that the majority of clinically used endoscopes are not optimally tuned to reach maximal bending angles and demonstrate adequate tip responses. We suggest a brief check before procedures to predict difficulties with bending angles and tip responses. PMID:27092330

  13. Evaluating interhemispheric cortical responses to transcranial magnetic stimulation in chronic stroke: A TMS-EEG investigation.

    PubMed

    Borich, Michael R; Wheaton, Lewis A; Brodie, Sonia M; Lakhani, Bimal; Boyd, Lara A

    2016-04-01

    TMS-evoked cortical responses can be measured using simultaneous electroencephalography (TMS-EEG) to directly quantify cortical connectivity in the human brain. The purpose of this study was to evaluate interhemispheric cortical connectivity between the primary motor cortices (M1s) in participants with chronic stroke and controls using TMS-EEG. Ten participants with chronic stroke and four controls were tested. TMS-evoked responses were recorded at rest and during a typical TMS assessment of transcallosal inhibition (TCI). EEG recordings from peri-central gyral electrodes (C3 and C4) were evaluated using imaginary phase coherence (IPC) analyses to quantify levels of effective interhemispheric connectivity. Significantly increased TMS-evoked beta (15-30Hz frequency range) IPC was observed in the stroke group during ipsilesional M1 stimulation compared to controls during TCI assessment but not at rest. TMS-evoked beta IPC values were associated with TMS measures of transcallosal inhibition across groups. These results suggest TMS-evoked EEG responses can index abnormal effective interhemispheric connectivity in chronic stroke.

  14. Quantitative evaluation of photic driving response for computer-aided diagnosis

    NASA Astrophysics Data System (ADS)

    Fukami, Tadanori; Ishikawa, Fumito; Ishikawa, Bunnoshin; Saito, Yoichi

    2008-12-01

    The aim of our research is the quantification of the photic driving response, a routine electroencephalogram (EEG) examination, for computer-aided diagnosis. It is well known that the EEG responds not only to the fundamental frequency but also to all sub and higher harmonics of a stimulus. In this study, we propose a method for detecting and evaluating responses in screening data for individuals. This method consists of two comparisons based on statistical tests. One is an intraindividual comparison between the EEG at rest and the photic stimulation (PS) response reflecting enhancement and suppression by PS, and the other is a comparison between data from an individual and a distribution of normals reflecting the position of the individual's data in the distribution of normals in the normal database. These tests were evaluated using the Z-value based on the Mann-Whitney U-test. We measured EEGs from 130 normal subjects and 30 patients with any of schizophrenia, dementia and epilepsy. Normal data were divided into two groups, the first consisting of 100 data for database construction and the second of 30 data for test data. Using our method, a prominent statistical peak of the Z-value was recognized even if the harmonics and alpha band overlapped. Moreover, we found a statistical difference between patients and the normal database at diagnostically helpful frequencies such as subharmonics, the fundamental wave, higher harmonics and the alpha frequency band.

  15. Evaluation of spontaneous baroreflex response after 28 days head down tilt bedrest

    NASA Astrophysics Data System (ADS)

    Hughson, R. L.; Yamamoto, Y.; Butler, G. C.; Güell, A.; Gharib, C.

    The spontaneous baroreflex response was evaluated during supine rest and head up tilt (60°) before and immediately after a 28 day 6° HDT bedrest in 6 healthy adult men (age 30-42 years). Sequences of 3 or more beats where RR-interval and systolic blood pressure changed in the same direction were used to evaluate baroreflex response slope (BRS). Prior to bedrest, the mean BRS and RR-interval were 18.0 ± 3.9 ms/mm Hg and 926 ± 61 ms at rest and 10.5 ± 2.5 ms/mm Hg and 772 ± 63 ms during the first 10 min of 60° tilt. Following bedrest, these values changed to 15.6 ± 2.7 ms/mm Hg and 780 ± 53 ms at rest, and to 6.5 ± 1.2 ms/mm Hg and 636 ± 44 ms during tilt. Thus, (1) the spontaneous baroreflex can be evaluated in human subjects during experiments of orthostatic stress; (2) the baroreflex slope was reduced on going from supine to the head up tilt position; and (3) 28 days of bedrest reduced the spontaneous baroreflex slope.

  16. Toward diversity-responsive medical education: taking an intersectionality-based approach to a curriculum evaluation.

    PubMed

    Muntinga, M E; Krajenbrink, V Q E; Peerdeman, S M; Croiset, G; Verdonk, P

    2016-08-01

    Recent years have seen a rise in the efforts to implement diversity topics into medical education, using either a 'narrow' or a 'broad' definition of culture. These developments urge that outcomes of such efforts are systematically evaluated by mapping the curriculum for diversity-responsive content. This study was aimed at using an intersectionality-based approach to define diversity-related learning objectives and to evaluate how biomedical and sociocultural aspects of diversity were integrated into a medical curriculum in the Netherlands. We took a three-phase mixed methods approach. In phase one and two, we defined essential learning objectives based on qualitative interviews with school stakeholders and diversity literature. In phase three, we screened the written curriculum for diversity content (culture, sex/gender and class) and related the results to learning objectives defined in phase two. We identified learning objectives in three areas of education (medical knowledge and skills, patient-physician communication, and reflexivity). Most diversity content pertained to biomedical knowledge and skills. Limited attention was paid to sociocultural issues as determinants of health and healthcare use. Intersections of culture, sex/gender and class remained mostly unaddressed. The curriculum's diversity-responsiveness could be improved by an operationalization of diversity that goes beyond biomedical traits of assumed homogeneous social groups. Future efforts to take an intersectionality-based approach to curriculum evaluations should include categories of difference other than culture, sex/gender and class as separate, equally important patient identities or groups. PMID:26603884

  17. Evaluating the dynamic response of in-flight thrust calculation techniques during throttle transients

    NASA Technical Reports Server (NTRS)

    Ray, Ronald J.

    1994-01-01

    New flight test maneuvers and analysis techniques for evaluating the dynamic response of in-flight thrust models during throttle transients have been developed and validated. The approach is based on the aircraft and engine performance relationship between thrust and drag. Two flight test maneuvers, a throttle step and a throttle frequency sweep, were developed and used in the study. Graphical analysis techniques, including a frequency domain analysis method, were also developed and evaluated. They provide quantitative and qualitative results. Four thrust calculation methods were used to demonstrate and validate the test technique. Flight test applications on two high-performance aircraft confirmed the test methods as valid and accurate. These maneuvers and analysis techniques were easy to implement and use. Flight test results indicate the analysis techniques can identify the combined effects of model error and instrumentation response limitations on the calculated thrust value. The methods developed in this report provide an accurate approach for evaluating, validating, or comparing thrust calculation methods for dynamic flight applications.

  18. Impact induced response spectrum for the safety evaluation of the high flux isotope reactor

    SciTech Connect

    Chang, S.J.

    1997-05-01

    The dynamic impact to the nearby HFIR reactor vessel caused by heavy load drop is analyzed. The impact calculation is carried out by applying the ABAQUS computer code. An impact-induced response spectrum is constructed in order to evaluate whether the HFIR vessel and the shutdown mechanism may be disabled. For the frequency range less than 10 Hz, the maximum spectral velocity of impact is approximately equal to that of the HFIR seismic design-basis spectrum. For the frequency range greater than 10 Hz, the impact-induced response spectrum is shown to cause no effect to the control rod and the shutdown mechanism. An earlier seismic safety assessment for the HFIR control and shutdown mechanism was made by EQE. Based on EQE modal solution that is combined with the impact-induced spectrum, it is concluded that the impact will not cause any damage to the shutdown mechanism, even while the reactor is in operation. The present method suggests a general approach for evaluating the impact induced damage to the reactor by applying the existing finite element modal solution that has been carried out for the seismic evaluation of the reactor.

  19. Olive response to water availability: yield response functions, soil water content indicators and evaluation of adaptability to climate change

    NASA Astrophysics Data System (ADS)

    Riccardi, Maria; Alfieri, Silvia Maria; Basile, Angelo; Bonfante, Antonello; Menenti, Massimo; Monaco, Eugenia; De Lorenzi, Francesca

    2013-04-01

    Climate evolution, with the foreseen increase of temperature and frequency of drought events during the summer, could cause significant changes in the availability of water resources specially in the Mediterranean region. European countries need to encourage sustainable agriculture practices, reducing inputs, especially of water, and minimizing any negative impact on crop quantity and quality. Olive is an important crop in the Mediterranean region that has traditionally been cultivated with no irrigation and is known to attain acceptable production under dry farming. Therefore this crop will not compete for foreseen reduced water resources. However, a good quantitative knowledge must be available about effects of reduced precipitation and water availability on yield. Yield response functions, coupled with indicators of soil water availability, provide a quantitative description of the cultivar- specific behavior in relation to hydrological conditions. Yield response functions of 11 olive cultivars, typical of Mediterranean environment, were determined using experimental data (unpublished or reported in scientific literature). The yield was expressed as relative yield (Yr); the soil water availability was described by means of different indicators: relative soil water deficit (RSWD), relative evapotranspiration (RED) and transpiration deficit (RTD). Crops can respond nonlinearly to changes in their growing conditions and exhibit threshold responses, so for the yield functions of each olive cultivar both linear regression and threshold-slope models were considered to evaluate the best fit. The level of relative yield attained in rain-fed conditions was identified and defined as the acceptable yield level (Yrrainfed). The value of the indicator (RSWD, RED and RTD) corresponding to Yrrainfed was determined for each cultivar and indicated as the critical value of water availability. The error in the determination of the critical value was estimated. By means of a

  20. Evaluation of age-dependent response to NMDA receptor antagonism in zebrafish.

    PubMed

    Menezes, Fabiano Peres; Kist, Luiza Wilges; Bogo, Maurício Reis; Bonan, Carla Denise; Da Silva, Rosane Souza

    2015-04-01

    Imbalances in glutamatergic signaling have been proposed as the cause of several neurological disturbances. The use of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, to mimic features of these neurological disorders is effective both in mammals and in fish. However, the variability of the subunits comprising the NMDA receptor during development alters the pharmacokinetic properties of the receptor and leads to different responses to this drug. Here, we evaluated the locomotor response of zebrafish to MK-801 (1, 5, and 20 μM) through the development (30 days postfertilization [dpf] to 2 years postfertilization [ypf]). The NMDA receptor subunit gene expression was also analyzed through the development (7 dpf to 2 ypf). Zebrafish displayed an age-related response to MK-801 with a higher response at 60 and 120 dpf. The magnitude of hyperlocomotion promoted by MK-801 seems to be less powerful for zebrafish in relation to rodents. The verification of expression levels in zebrafish NMDA receptor subunits shows that NR1.1 had a slight reduction throughout the development, while the NR2 subunits, especially NR2A.2 and NR2C.1, vary their expression levels according to the stage of development. The time-specific locomotor response to MK-801 through the development could be a consequence of differential NMDA receptor subunit expression. This result of developmental response to MK-801 is a crucial component in the consolidation of zebrafish as a suitable model to study glutamatergic neurotransmission in early phases.

  1. Evaluating the responses of a territorial solitary carnivore to potential mates and competitors.

    PubMed

    Allen, Maximilian L; Yovovich, Veronica; Wilmers, Christopher C

    2016-06-02

    Successful communication is critical to the fitness of individuals and maintenance of populations, but less is known regarding the social contexts and reactions to scent marking by other individuals in solitary carnivores, including pumas. We evaluated the responses of resident male pumas to visitation and scent marking by potential competitors (other male pumas) and potential mates (female pumas) by capturing and marking 46 pumas (Puma concolor), and documenting scent marking behaviours using motion-triggered video cameras. By comparing resident male puma visitation rates and communication behaviours in response to either male or female visitors, we found that their visitation and communication behaviours were best explained by the combination of visitation by both competitors and potential mates. Resident males returned to scent marking sites more quickly and increased their rate of flehmen response after visitation by a females, while they increased their rate of visitation and duration of visits in response to other males. Male pumas also visited less frequently in summer and autumn when female visitation rates were lower, but males created nearly twice as many scrapes during these visits. This study suggests that advertising for mates when scent marking may sometimes overshadow the importance of deterring competitors and claiming territory.

  2. Evaluating the responses of a territorial solitary carnivore to potential mates and competitors.

    PubMed

    Allen, Maximilian L; Yovovich, Veronica; Wilmers, Christopher C

    2016-01-01

    Successful communication is critical to the fitness of individuals and maintenance of populations, but less is known regarding the social contexts and reactions to scent marking by other individuals in solitary carnivores, including pumas. We evaluated the responses of resident male pumas to visitation and scent marking by potential competitors (other male pumas) and potential mates (female pumas) by capturing and marking 46 pumas (Puma concolor), and documenting scent marking behaviours using motion-triggered video cameras. By comparing resident male puma visitation rates and communication behaviours in response to either male or female visitors, we found that their visitation and communication behaviours were best explained by the combination of visitation by both competitors and potential mates. Resident males returned to scent marking sites more quickly and increased their rate of flehmen response after visitation by a females, while they increased their rate of visitation and duration of visits in response to other males. Male pumas also visited less frequently in summer and autumn when female visitation rates were lower, but males created nearly twice as many scrapes during these visits. This study suggests that advertising for mates when scent marking may sometimes overshadow the importance of deterring competitors and claiming territory. PMID:27251230

  3. Evaluating the responses of a territorial solitary carnivore to potential mates and competitors

    PubMed Central

    Allen, Maximilian L.; Yovovich, Veronica; Wilmers, Christopher C.

    2016-01-01

    Successful communication is critical to the fitness of individuals and maintenance of populations, but less is known regarding the social contexts and reactions to scent marking by other individuals in solitary carnivores, including pumas. We evaluated the responses of resident male pumas to visitation and scent marking by potential competitors (other male pumas) and potential mates (female pumas) by capturing and marking 46 pumas (Puma concolor), and documenting scent marking behaviours using motion-triggered video cameras. By comparing resident male puma visitation rates and communication behaviours in response to either male or female visitors, we found that their visitation and communication behaviours were best explained by the combination of visitation by both competitors and potential mates. Resident males returned to scent marking sites more quickly and increased their rate of flehmen response after visitation by a females, while they increased their rate of visitation and duration of visits in response to other males. Male pumas also visited less frequently in summer and autumn when female visitation rates were lower, but males created nearly twice as many scrapes during these visits. This study suggests that advertising for mates when scent marking may sometimes overshadow the importance of deterring competitors and claiming territory. PMID:27251230

  4. Early response evaluation and prediction in neoadjuvant-treated patients with esophageal cancer

    PubMed Central

    Theisen, Joerg; Krause, Bernd; Peschel, Christian; Schmid, Roland; Geinitz, Hans; Friess, Helmut

    2009-01-01

    Since the introduction of multimodal therapy regimens, the prognosis of esophageal cancer has improved. There is undoubtedly true for patients with surgically resected tumors in the case of a response to neoadjuvant chemotherapy or chemoradiation. Important conclusions can be drawn from this regarding the indication for perioperative therapies, the radicality of surgery, or the surgical indications. Thus, most of the current research in this field is aimed at the early identification of this subset of patients, at the beginning of, or even before, neoadjuvant treatment. Conventional staging tools have failed to predict responses to neoadjuvant therapy. However, molecular imaging methods, e.g. positron emission tomography (PET)-scans, have shown promising results in the early selection of responders and non-responders during the course of neoadjuvant therapy, allowing physicians to alter the treatment plan accordingly. Even more desirable is the identification of potential responders before the start of neoadjuvant therapy. Preliminary molecular data on biopsy specimens demonstrate the possibility of early response prediction in these patients. We present the current knowledge on response evaluation and prediction in esophageal cancer and draw conclusions for future clinical practice and studies in this review. PMID:21160793

  5. Detecting Functional Groups of Arabidopsis Mutants by Metabolic Profiling and Evaluation of Pleiotropic Responses

    PubMed Central

    Hofmann, Jörg; Börnke, Frederik; Schmiedl, Alfred; Kleine, Tatjana; Sonnewald, Uwe

    2011-01-01

    Metabolic profiles and fingerprints of Arabidopsis thaliana plants with various defects in plastidic sugar metabolism or photosynthesis were analyzed to elucidate if the genetic mutations can be traced by comparing their metabolic status. Using a platform of chromatographic and spectrometric tools data from untargeted full MS scans as well as from selected metabolites including major carbohydrates, phosphorylated intermediates, carboxylates, free amino acids, major antioxidants, and plastidic pigments were evaluated. Our key observations are that by multivariate statistical analysis each mutant can be separated by a unique metabolic signature. Closely related mutants come close. Thus metabolic profiles of sugar mutants are different but more similar than those of photosynthesis mutants. All mutants show pleiotropic responses mirrored in their metabolic status. These pleiotropic responses are typical and can be used for separating and grouping of the mutants. Our findings show that metabolite fingerprints can be taken to classify mutants and hence may be used to sort genes into functional groups. PMID:22639613

  6. Clinical evaluation of the vector algorithm for neonatal hearing screening using automated auditory brainstem response.

    PubMed

    Keohane, Bernie M; Mason, Steve M; Baguley, David M

    2004-02-01

    A novel auditory brainstem response (ABR) detection and scoring algorithm, entitled the Vector algorithm is described. An independent clinical evaluation of the algorithm using 464 tests (120 non-stimulated and 344 stimulated tests) on 60 infants, with a mean age of approximately 6.5 weeks, estimated test sensitivity greater than 0.99 and test specificity at 0.87 for one test. Specificity was estimated to be greater than 0.95 for a two stage screen. Test times were of the order of 1.5 minutes per ear for detection of an ABR and 4.5 minutes per ear in the absence of a clear response. The Vector algorithm is commercially available for both automated screening and threshold estimation in hearing screening devices.

  7. Physiological Response to Social Evaluative Threat in Adolescents with Autism Spectrum Disorder.

    PubMed

    Edmiston, E Kale; Jones, Robin M; Corbett, Blythe A

    2016-09-01

    The Trier Social Stress Test (TSST) was employed to study response to social evaluative threat in male adolescents with Autism Spectrum Disorder (ASD, n = 21) and typical development (n = 13). Participants wore a mobile electrocardiogram to collect heart rate data. There were significant group effects on respiratory sinus arrhythmia (RSA), a measure of parasympathetic nervous system function, with lower values in ASD (F = 4.97). Bivariate correlations also showed a significant relationship between parent reports of social problems and RSA response to the TSST (r = -0.586). These findings suggest that autonomic dysregulation may contribute to social deficits in adolescents with ASD. PMID:27318810

  8. Effects of glyphosate on hepatic tissue evaluating melanomacrophages and erythrocytes responses in neotropical anuran Leptodactylus latinasus.

    PubMed

    Pérez-Iglesias, Juan Manuel; Franco-Belussi, Lilian; Moreno, Liliana; Tripole, Susana; de Oliveira, Classius; Natale, Guillermo Sebastián

    2016-05-01

    Glyphosate (GLY) is the most used herbicide worldwide and its effects on anurans are well known. Pollutants can cause physiological and morphological effects. Therefore, this study evaluated the effects of GLY on hepatic melanomacrophages as a response to environmental stressors. Three treatments were exposed to different concentrations of pure GLY (100, 1000, and 10,000 μg g(-1), respectively), and there was also a control group. After the experimental time, liver and blood were analyzed. Melanomacrophages (MMCs) were located between the hepatocyte cordons, close to sinusoids. GLY increased the melanin area in MMCs of Leptodactylus latinasus exposed since lowest concentration until highest concentration. GLY also changed the occurrence of hepatic catabolism pigments into melanomacrophages and erythrocyte nuclear abnormalities; therefore, it can interfere with the hepatic metabolism. In conclusion, GLY promotes alterations in the hepatic tissue and erythrocyte nuclear abnormalities. Furthermore, MMCs may be useful as morphological responses of GLY effects. PMID:26856864

  9. Evaluating the effect of interactive audience response systems on the perceived learning experience of nursing students.

    PubMed

    Porter, Ava G; Tousman, Stuart

    2010-09-01

    Interactive Audience Response Systems (ARS) are widely used as tools to promote active learning in the classroom in many disciplines. Researchers have found that ARS technology with question-driven instruction (QDI) makes classroom instruction more student centered, while creating an environment for active learning. The purpose of this study was to evaluate the effect of ARS with QDI in one bachelors of science in nursing course on the perceived learning experience of the students. ARS technology with QDI was used in a beginning medical-surgical class of junior-level students throughout one semester. Descriptive statistical analyses indicated that nursing students positively evaluated the effect of ARS with QDI on their learning. Qualitative analyses indicated that students had better understanding of the material via post-question discussion of the rationales for answers, enhanced NCLEX-RN preparation, and increased interactivity, which led to paying more attention in class.

  10. Stress responses to repeated exposure to a combined physical and social evaluative laboratory stressor in young healthy males.

    PubMed

    Boyle, N B; Lawton, C; Arkbåge, K; West, S G; Thorell, L; Hofman, D; Weeks, A; Myrissa, K; Croden, F; Dye, L

    2016-01-01

    Repeated exposure to homotypic laboratory psychosocial stressors typically instigates rapid habituation in hypothalamic-pituitary-adrenal (HPA) axis-mediated stress responses in humans. However, emerging evidence suggests the combination of physical stress and social evaluative threat may be sufficient to attenuate this response habituation. Neuroendocrine, cardiovascular and subjective stress responses following repeated exposure to a combined physical and social evaluative stress protocol were assessed to examine the habituation response dynamic in this context. The speech task of the Trier social stress test (TSST; Kirschbaum et al., 1993) and the socially evaluated cold pressor task (SECPT; Schwabe et al., 2008) were administered in a combined stressor protocol. Salivary cortisol, cardiovascular and subjective stress responses to a non-stress control and repeat stressor exposure separated by six weeks were examined in males (N=24) in a crossover manner. Stressor exposure resulted in significant elevations in all stress parameters. In contrast to the commonly reported habituation in cortisol response, a comparable post-stress response was demonstrated. Cortisol, heart rate and subjective stress responses were also characterised by a heightened response in anticipation to repeated stress exposure. Blood pressure responses were comparatively uniform across repeated exposures. Findings suggest a combined physical and social evaluative stressor is a potentially useful method for study designs that require repeated presentation of a homotypic stressor. PMID:26441230

  11. Evaluation of diagnostic criteria for night eating syndrome using item response theory analysis.

    PubMed

    Allison, Kelly C; Engel, Scott G; Crosby, Ross D; de Zwaan, Martina; O'Reardon, John P; Wonderlich, Stephen A; Mitchell, James E; West, Delia Smith; Wadden, Thomas A; Stunkard, Albert J

    2008-12-01

    Uniform diagnostic criteria for the night eating syndrome (NES), a disorder characterized by a delay in the circadian pattern of eating, have not been established. Proposed criteria for NES were evaluated using item response theory (IRT) analysis. Six studies yielded 1,481 Night Eating Questionnaires which were coded to reflect the presence/absence of five night eating symptoms. Symptoms were evaluated based on the clinical usefulness of their diagnostic information and on the assumptions of IRT analysis (unidimensionality, monotonicity, local item independence, correct model specification), using a two parameter logistic (2PL) IRT model. Reports of (1) nocturnal eating and/or evening hyperphagia, (2) initial insomnia, and (3) night awakenings showed high precision in discriminating those with night eating problems, while morning anorexia and delayed morning meal provided little additional information. IRT is a useful tool for evaluating the diagnostic criteria of psychiatric disorders and can be used to evaluate potential diagnostic criteria of NES empirically. Behavioral factors were identified as useful discriminators of NES. Future work should also examine psychological factors in conjunction with those identified here.

  12. Evaluation of diagnostic criteria for night eating syndrome using item response theory analysis.

    PubMed

    Allison, Kelly C; Engel, Scott G; Crosby, Ross D; de Zwaan, Martina; O'Reardon, John P; Wonderlich, Stephen A; Mitchell, James E; West, Delia Smith; Wadden, Thomas A; Stunkard, Albert J

    2008-12-01

    Uniform diagnostic criteria for the night eating syndrome (NES), a disorder characterized by a delay in the circadian pattern of eating, have not been established. Proposed criteria for NES were evaluated using item response theory (IRT) analysis. Six studies yielded 1,481 Night Eating Questionnaires which were coded to reflect the presence/absence of five night eating symptoms. Symptoms were evaluated based on the clinical usefulness of their diagnostic information and on the assumptions of IRT analysis (unidimensionality, monotonicity, local item independence, correct model specification), using a two parameter logistic (2PL) IRT model. Reports of (1) nocturnal eating and/or evening hyperphagia, (2) initial insomnia, and (3) night awakenings showed high precision in discriminating those with night eating problems, while morning anorexia and delayed morning meal provided little additional information. IRT is a useful tool for evaluating the diagnostic criteria of psychiatric disorders and can be used to evaluate potential diagnostic criteria of NES empirically. Behavioral factors were identified as useful discriminators of NES. Future work should also examine psychological factors in conjunction with those identified here. PMID:18928902

  13. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the applicable response capability caps in Table 5 of this appendix shall identify sources of... contracting caps in Table 5 shall identify sources of additional equipment equal to twice the cap listed in... response equipment may be used to identify additional sources, a response plan must identify the...

  14. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the applicable response capability caps in Table 5 of this appendix shall identify sources of... contracting caps in Table 5 shall identify sources of additional equipment equal to twice the cap listed in... response equipment may be used to identify additional sources, a response plan must identify the...

  15. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the applicable response capability caps in Table 5 of this appendix shall identify sources of... contracting caps in Table 5 shall identify sources of additional equipment equal to twice the cap listed in... response equipment may be used to identify additional sources, a response plan must identify the...

  16. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the applicable response capability caps in Table 5 of this appendix shall identify sources of... contracting caps in Table 5 shall identify sources of additional equipment equal to twice the cap listed in... response equipment may be used to identify additional sources, a response plan must identify the...

  17. A systematic review and evaluation of response redirection as a treatment for challenging behavior in individuals with developmental disabilities.

    PubMed

    Lydon, Sinéad; Healy, Olive; O'Reilly, Mark; McCoy, Anna

    2013-10-01

    Response redirection is widely used in clinical practice as a treatment for repetitive behavior or stereotypy in persons with developmental disabilities. However, to date the procedure has received comparatively little empirical evaluation. The current review sought to examine the literature describing the efficacy of response redirection alone, response interruption and redirection (RIRD), and multi-element treatment packages incorporating response redirection, as interventions for challenging behavior in individuals with developmental disabilities. Additionally, the status of response redirection, and RIRD, as evidence-based practice was evaluated in accordance with Reichow's (2011) recently developed criteria. Results indicated that interventions involving response redirection or RIRD typically led to large decreases in challenging behavior but did not result in behavioral suppression. On the basis of the current literature and in accordance with Reichow's criteria, interventions incorporating response redirection do not yet constitute evidence-based practice. The implications of these findings, for both research and practice, are discussed.

  18. Evaluation of treatment response in depression studies using a Bayesian parametric cure rate model.

    PubMed

    Santen, Gijs; Danhof, Meindert; Della Pasqua, Oscar

    2008-10-01

    Efficacy trials with antidepressant drugs often fail to show significant treatment effect even though efficacious treatments are investigated. This failure can, amongst other factors, be attributed to the lack of sensitivity of the statistical method as well as of the endpoints to pharmacological activity. For regulatory purposes the most widely used efficacy endpoint is still the mean change in HAM-D score at the end of the study, despite evidence from literature showing that the HAM-D scale might not be a sensitive tool to assess drug effect and that changes from baseline at the end of treatment may not reflect the extent of response. In the current study, we evaluate the prospect of applying a Bayesian parametric cure rate model (CRM) to analyse antidepressant effect in efficacy trials with paroxetine. The model is based on a survival approach, which allows for a fraction of surviving patients indefinitely after completion of treatment. Data was extracted from GlaxoSmithKline's clinical databases. Response was defined as a 50% change from baseline HAM-D at any assessment time after start of therapy. Survival times were described by a log-normal distribution and drug effect was parameterised as a covariate on the fraction of non-responders. The model was able to fit the data from different studies accurately and results show that response to treatment does not lag for two weeks, as is mythically believed. In conclusion, we demonstrate how parameterisation of a survival model can be used to characterise treatment response in depression trials. The method contrasts with the long-established snapshot on changes from baseline, as it incorporates the time course of response throughout treatment.

  19. Development of a micro cell compression stimulator for evaluating real-time cellular responses

    NASA Astrophysics Data System (ADS)

    Nakashima, Y.; Yang, Y.; Minami, K.

    2012-05-01

    This paper presents a micro cell compression stimulator for evaluating real-time cellular responses to compression stimuli. The device was produced by a micro three-dimensional structure fabrication process using multiple exposures to the photoresist. The device consists of a pressure inlet port, cell inlet ports, a gasket, microchannels, cell culture chambers, and a diaphragm on the culture chamber for applying compressive pressure to cells. Compression stimuli applied to the cells can be controlled by regulating the expansion of the diaphragm via a pressure control. The device permits the observation of cellular responses to compressive pressure in real time because it is made of transparent materials and stimulates the cells without deforming the cell culture surface, when observed by optical microscopy. We demonstrated the validity of the fabrication process, evaluated the performance of the fabricated device, and compared the experimental results with the FEM structural analysis results. We found through operational testing that the diaphragm was deformed quickly by applying negative/positive pressure and that the diaphragm displacement became larger with increasing applied pressure. These results indicate that this device can be used to control the intensity and the cell stimulus profile by regulating the applied pressure. In all cases, the cellular deformation during compression stimulus was successfully observed in real time using an optical microscope. The device is expected to facilitate the control of stem cell differentiation and the clarification of cellular mechanoreceptor mechanisms and signal transduction pathways.

  20. Watershed Evaluation and Habitat Response to Recent Storms : Annual Report for 1999.

    SciTech Connect

    Rhodes, Jonathan J.; Huntington, Charles W.

    2000-02-01

    evaluated and the methods used to evaluate them. Watershed responses and attributes evaluated include mass failures, historic soil loss, the integration of roads with the drainage network, estimated flood recurrence intervals, and headwater channel morphology. Habitat attributes evaluated include large woody debris, pool frequency and depth, substrate conditions, and bank stability. Multiple analyses of habitat data in the Tucannon and Wenaha subbasins remain to be completed due to difficulties stemming from data characteristics that indicated that some of the pre-existing data may have be of questionable accuracy. Diagnostic attributes of the questionable data included a change in monitoring protocols during the pre- to post-flood analysis period, physically implausible temporal trends in some habitat attributes at some sites, and conflicting results for the same attribute at the same locations from different data sources. Since unreliable data can lead to spurious results, criteria were developed to screen the data for analysis, as described in this report. It is anticipated that while the data screening will prevent spurious results, it will also truncate some of the planned analysis in the Tucannon and Wenaha systems.

  1. Biocompatibility evaluation of pH and glutathione-responsive nanohydrogels after intravenous administration.

    PubMed

    Pérez, Elena; Olmo, Rosa; Teijón, César; Muñíz, Enriqueta; Montero, Nuria; Teijón, Jose M; Blanco, M Dolores

    2015-12-01

    Nanotoxicology has emerged as an important subdiscipline of nanotechnology due to the new healthy risks associated with the use of nanosystems for therapy and diagnostic. The biocompatibility of four stimuli-responsive nanohydrogel (NG) formulations based on different proportions of N-isopropylacrylamide (NIPA), N-hydroxyethyl acrylamide (HEAA) and 2-acrylamidoethyl carbamate (2AAECM), and cross-linked with N,N-cystaminebisacrylamide (CBA) or N-methylenebisacrylamide (NMBA) has been evaluated after intravenous injection in Wistar rats. All nanohydrogels were pH-sensitive, and those with CBA were also glutathione-responsive. Haematological and coagulation parameters revealed most nanogel formulations did not cause modification, only the NHA 80/15/5-CBA formulation induced a transitory light increase in platelets. Prothrombin time was in the reference normal range, there were no modifications of fibrinogen concentration and an increase in antithrombin III was observed on the last day of the study. Blood biochemical parameters such as AST, ALT, ALP, BUN, and creatinine were in the standard range for rats. The activity of enzyme antioxidant defences (SOD, CAT and GSSG-R) and total glutathione were evaluated in liver, kidney and spleen samples. Nanohydrogels cross-linked with the disulphide reducible CBA-cross-linker caused a decrease in GSSG/GSH content and an increase in GSSG-R activity in the spleen. The antioxidant response is also reflected by modifications of SOD activity in liver and kidney of NHA 80/15/5-CBA and NHA 80/10/10-NMBA groups. Histology showed no tissue damage, inflammation or morphological change in liver, kidney and spleen. Overall, the results demonstrated modifications of antioxidant defences; however, no acute or very significant changes in biomarkers of liver or kidney damage were observed.

  2. SU-E-J-148: Evaluating Tumor Response with a Commercially Available Deformable Registration System

    SciTech Connect

    Bowling, J; Ramsey, C

    2014-06-01

    Purpose: The purpose of this study is to present a method for evaluating the response to treatment using a commercially available deformable image registration software package (Velocity Medical Systems) and repeat PET/CT imaging. This technique can be used to identify volumes that are risk for tumor recurrence. Methods: Response to treatment was evaluated using PET/CT images acquired prior-to and post-treatment for radiation therapy patients treated with concurrent chemotherapy. Velocity (Version 3.0.1) was used to deform the initial PET/CT to the post treatment PET/CT. The post-treatment PET images were then subtracted from the pre-treatment PET images. The resulting re-sampled image is a three-dimensional SUV difference map that shows pixels with increasing SUV values. SUV values increases greater than 2.5 in the post treatment images were identified for additional follow-up. Results: A total of 5 Lung patients were analyzed as part of this study. One lung patient in the cohort had an SUV increase of +3.28 that was identified using the SUV difference map. This volume of increased uptake was located outside the treatment field and adjacent to the 35 Gy isodose line. The remaining four patients all had SUV decreases inside the planning target volume, and no unexpected areas of increase outside the irradiated volumes. All five patients were analyzed using standard tools inside the Velocity application. Conclusion: The response to treatment can easily be measured using serial PET/CT images and a commercially available deformable image registration. This provides both the radiation oncologists and medical oncologists with a quantitative assessment of their treatment to use in patient follow-up.

  3. Evaluating Spruce Peatland Responses Under Climatic and Environmental Change Using a Replicated In Situ Field Manipulation

    NASA Astrophysics Data System (ADS)

    Hanson, P. J.; Kolka, R. K.; Norby, R. J.; Palik, B.; Wullschleger, S. D.; Garten, C. T.; Sebestyen, S. D.; Thornton, P. E.; Bradford, J.; Mulholland, P. J.; Todd, D. E.; Iversen, C.; Warren, J.

    2010-12-01

    Identification of critical environmental response functions for terrestrial organisms, communities, and ecosystems to rapidly changing climate conditions are needed to evaluate ecological consequences and feedbacks. Such research has ‘real-world’ relevance when conclusions are drawn from controlled manipulations operating in natural field settings. We are in the process of developing an experimental platform to address climate change response mechanisms in a Picea/Larix/Sphagnum bog ecosystem located in northern Minnesota. This ecosystem located at the southern extent of the spatially expansive boreal peatland forests is considered to be especially vulnerable to climate change and to have important feedbacks on the atmosphere and climate. The replicated experiment will allow us to test mechanisms controlling vulnerability of organisms and ecosystem processes changes for multiple levels of warming (+0, 3, 6, and 9°C) combined with elevated CO2 exposures (800 to 900 ppm) at selected warming levels. New methods for whole-ecosystem warming at plot scales of 12 to 14 m diameter have been developed for this study and will be described. Through the execution of this experiment we plant to quantify thresholds for organism decline or mortality, limitations to regeneration, biogeochemical limitations to productivity, and changing greenhouse gas emissions to the atmosphere. The experiment will allow for the evaluation of responses across multiple spatial scales including: microbial communities, bryophyte populations, various higher plant types, and some faunal groups. Direct and indirect effects of these experimental perturbations will be tracked and analyzed over a decade for the development and refinement of models needed for full Earth system analyses.

  4. Failure Potential Evaluation in Engineering Experiments Using Load/Unload Response Ratio Method

    NASA Astrophysics Data System (ADS)

    Zhang, Lang-ping; Yu, Huai-zhong; Yin, Xiang-chu

    2013-01-01

    The Load/Unload Response Ratio (LURR) method is proposed for prediction of the failure of brittle heterogeneous materials. Application of the method typically involves evaluating the external load on materials or structures, differentiating between loading and unloading periods, determining the failure response during both periods from data input, and calculating the ratio between the two response rates. According to the method, the LURR time series usually climbs to an anomalously high peak prior to the macro-fracture. To show the validity of the approach in engineering practice, we applied it to the loading and unloading experimental data associated with a two-floor concrete-brick structure. Results show that the LURR time series of the two floors consists of the damage evolution of the structure: they are at low level for most of the time, and reach the maxima prior to the final fracture. We then attempt to combine the LURR values with damage variable ( D) to provide the health assessment of the structure. The relationship between LURR and D, defined as a function of Weibull stochastic distribution, is set up to provide more detailed underlying physical means to study damage evolution of the structure. The fact that the damage evolution of the structure correlates well with the variation of LURR time series may suggest that the LURR approach can be severed as a useful tool to provide the health assessment to big scale structures or ancient buildings.

  5. Endocytosis as a biological response in receptor pharmacology: evaluation by fluorescence microscopy.

    PubMed

    Campa, Víctor M; Capilla, Almudena; Varela, María J; de la Rocha, Arlet M Acanda; Fernandez-Troyano, Juan C; Barreiro, R Belén; Lopez-Gimenez, Juan F

    2015-01-01

    The activation of G-protein coupled receptors by agonist compounds results in diverse biological responses in cells, such as the endocytosis process consisting in the translocation of receptors from the plasma membrane to the cytoplasm within internalizing vesicles or endosomes. In order to functionally evaluate endocytosis events resulted from pharmacological responses, we have developed an image analysis method -the Q-Endosomes algorithm- that specifically discriminates the fluorescent signal originated at endosomes from that one observed at the plasma membrane in images obtained from living cells by fluorescence microscopy. Mu opioid (MOP) receptor tagged at the carboxy-terminus with yellow fluorescent protein (YFP) and permanently expressed in HEK293 cells was used as experimental model to validate this methodology. Time-course experiments performed with several agonists resulted in different sigmoid curves depending on the drug used to initiate MOP receptor endocytosis. Thus, endocytosis resulting from the simultaneous activation of co-expressed MOP and serotonin 5-HT2C receptors by morphine plus serotonin was significantly different, in kinetics as well as in maximal response parameters, from the one caused by DAMGO, sufentanyl or methadone. Therefore, this analytical tool permits the pharmacological characterization of receptor endocytosis in living cells with functional and temporal resolution.

  6. Genomic evaluation of oxalate-degrading transgenic soybean in response to Sclerotinia sclerotiorum infection.

    PubMed

    Calla, Bernarda; Blahut-Beatty, Laureen; Koziol, Lisa; Zhang, Yunfang; Neece, David J; Carbajulca, Doris; Garcia, Alexandre; Simmonds, Daina H; Clough, Steven J

    2014-08-01

    Oxalate oxidases (OxO) catalyse the degradation of oxalic acid (OA). Highly resistant transgenic soybean carrying an OxO gene and its susceptible parent soybean line, AC Colibri, were tested for genome-wide gene expression in response to the necrotrophic, OA-producing pathogen Sclerotinia sclerotiorum using soybean cDNA microarrays. The genes with changed expression at statistically significant levels (overall F-test P-value cut-off of 0.0001) were classified into functional categories and pathways, and were analysed to evaluate the differences in transcriptome profiles. Although many genes and pathways were found to be similarly activated or repressed in both genotypes after inoculation with S. sclerotiorum, the OxO genotype displayed a measurably faster induction of basal defence responses, as observed by the differential changes in defence-related and secondary metabolite genes compared with its susceptible parent AC Colibri. In addition, the experiment presented provides data on several other transcripts that support the hypothesis that S. sclerotiorum at least partially elicits the hypersensitive response, induces lignin synthesis (cinnamoyl CoA reductase) and elicits as yet unstudied signalling pathways (G-protein-coupled receptor and related). Of the nine genes showing the most extreme opposite directions of expression between genotypes, eight were related to photosynthesis and/or oxidation, highlighting the importance of redox in the control of this pathogen.

  7. Comparing Visible and Invisible Social Support: Non-evaluative Support Buffers Cardiovascular Responses to Stress.

    PubMed

    Kirsch, Julie A; Lehman, Barbara J

    2015-12-01

    Previous research suggests that in contrast to invisible social support, visible social support produces exaggerated negative emotional responses. Drawing on work by Bolger and colleagues, this study disentangled social support visibility from negative social evaluation in an examination of the effects of social support on negative emotions and cardiovascular responses. As part of an anticipatory speech task, 73 female participants were randomly assigned to receive no social support, invisible social support, non-confounded visible social support or visible social support as delivered in a 2007 study by Bolger and Amarel. Twelve readings, each for systolic blood pressure, diastolic blood pressure and heart rate were taken at 5-min intervals throughout the periods of baseline, reactivity and recovery. Cardiovascular outcomes were tested by incorporating a series of theoretically driven planned contrasts into tests of stress reactivity conducted through piecewise growth curve modelling. Linear and quadratic trends established cardiovascular reactivity to the task. Further, in comparison to the control and replication conditions, the non-confounded visible and invisible social support conditions attenuated cardiovascular reactivity over time. Pre- and post-speech negative emotional responses were not affected by the social support manipulations. These results suggest that appropriately delivered visible social support may be as beneficial as invisible social support.

  8. Evaluation of the accuracy of BOTDA systems based on the phase spectral response.

    PubMed

    Lopez-Gil, Alexia; Soto, Marcelo A; Angulo-Vinuesa, Xabier; Dominguez-Lopez, Alejandro; Martin-Lopez, Sonia; Thévenaz, Luc; Gonzalez-Herraez, Miguel

    2016-07-25

    We evaluate the Brillouin frequency shift (BFS) determination error when utilizing the Brillouin phase spectrum (BPS) instead of the Brillouin gain spectrum (BGS) in BOTDA systems. Systems based on the BPS perform the determination of the BFS through a linear fit around the zero de-phase frequency region. An analytical expression of the error obtained in the BFS determination as a function of the different experimental parameters is provided and experimentally validated. The experimental results show a good agreement with the theoretical predictions as a function of the number of sampling points, signal-to-noise ratio (SNR) and Brillouin spectral linewidth. For an equal SNR and linewidth, the phase response only provides a better BFS estimation than the gain response when the fit is performed over a restricted frequency range around the center of the spectral profile. This may reduce the measurement time of specific BOTDA systems requiring a narrow frequency scanning. When the frequency scan covers most of the Brillouin spectral profile, gain and phase responses give very similar estimations of the BFS and the BPS offers no crucial benefit.

  9. A process for evaluation and state approval of an emergency response atmospheric dispersion model for Rocky Flats, Colorado

    SciTech Connect

    Hodgin, C.R.

    1991-11-06

    This document contains copies of the vugraphs used by C. R. Hodgin for the November 6, 1991 presentation summarizing the process to be used for evaluation of the Emergency Response Dispersion Model. (MHB)

  10. An electro-responsive hydrogel for intravascular applications: an in vitro and in vivo evaluation.

    PubMed

    Verbrugghe, Peter; Verhoeven, Jelle; Coudyzer, Walter; Verbeken, Eric; Dubruel, Peter; Mendes, Eduardo; Stam, Frank; Meuris, Bart; Herijgers, Paul

    2015-11-01

    There is a growing interest in using hydrogels for biomedical applications, because of more favourable characteristics. Some of these hydrogels can be activated by using particular stimuli, for example electrical fields. These stimuli can change the hydrogel shape in a predefined way. It could make them capable of adaptation to patient-specific anatomy even post-implantation. This is the first paper aiming to describe in vivo studies of an electro-responsive, Pluronic F127 based hydrogel, for intravascular applications. Pluronic methacrylic acid hydrogel (PF127/MANa) was in vitro tested for its haemolytic and cytotoxic effects. Minimal invasive implantation in the carotid artery of sheep was used to evaluate its medium-term biological effects, through biochemical, macroscopic, radiographic, and microscopic evaluation. Indirect and direct testing of the material gave no indication of the haemolytic effects of the material. Determination of fibroblast viability after 24 h of incubation in an extract of the hydrogel showed no cytotoxic effects. Occlusion was obtained within 1 h following in vivo implantation. Evaluation at time of autopsy showed a persistent occlusion with no systemic effects, no signs of embolization and mild effects on the arterial wall. An important proof-of-concept was obtained showing biocompatibility and effectiveness of a pluronic based electro-responsive hydrogel for obtaining an arterial occlusion with limited biological impact. So the selected pluronic-methacrylic acid based hydrogel can be used as an endovascular occlusion device. More importantly it is the first step in further development of electro-active hydrogels for a broad range of intra-vascular applications (e.g. system to prevent endoleakage in aortic aneurysm treatment, intra-vascular drug delivery).

  11. An electro-responsive hydrogel for intravascular applications: an in vitro and in vivo evaluation.

    PubMed

    Verbrugghe, Peter; Verhoeven, Jelle; Coudyzer, Walter; Verbeken, Eric; Dubruel, Peter; Mendes, Eduardo; Stam, Frank; Meuris, Bart; Herijgers, Paul

    2015-11-01

    There is a growing interest in using hydrogels for biomedical applications, because of more favourable characteristics. Some of these hydrogels can be activated by using particular stimuli, for example electrical fields. These stimuli can change the hydrogel shape in a predefined way. It could make them capable of adaptation to patient-specific anatomy even post-implantation. This is the first paper aiming to describe in vivo studies of an electro-responsive, Pluronic F127 based hydrogel, for intravascular applications. Pluronic methacrylic acid hydrogel (PF127/MANa) was in vitro tested for its haemolytic and cytotoxic effects. Minimal invasive implantation in the carotid artery of sheep was used to evaluate its medium-term biological effects, through biochemical, macroscopic, radiographic, and microscopic evaluation. Indirect and direct testing of the material gave no indication of the haemolytic effects of the material. Determination of fibroblast viability after 24 h of incubation in an extract of the hydrogel showed no cytotoxic effects. Occlusion was obtained within 1 h following in vivo implantation. Evaluation at time of autopsy showed a persistent occlusion with no systemic effects, no signs of embolization and mild effects on the arterial wall. An important proof-of-concept was obtained showing biocompatibility and effectiveness of a pluronic based electro-responsive hydrogel for obtaining an arterial occlusion with limited biological impact. So the selected pluronic-methacrylic acid based hydrogel can be used as an endovascular occlusion device. More importantly it is the first step in further development of electro-active hydrogels for a broad range of intra-vascular applications (e.g. system to prevent endoleakage in aortic aneurysm treatment, intra-vascular drug delivery). PMID:26474577

  12. Laboratory study of the response of select insecticides to toxicity identification evaluation procedures

    USGS Publications Warehouse

    Kuivila, Kathryn M.; Crepeau, Kathryn L.

    1999-01-01

    A laboratory study was used to evaluate the response of select insecticides to toxicity identification evaluation procedures. Fourteen insecticides, one degradation product, and one synergist were spiked into organic-grade water and carried through toxicity identification evaluation procedures. Concentrations of each compound were analyzed by gas chromatography/mass spectrometry. During Phase I, the water sample was pumped through a C-8 solid-phase extraction cartridge and then eluted with methanol. Dimethoate was not removed by the extraction, but remained in the rinsate. In contrast, permethrin was removed by the extraction, but was not recovered by the methanol elution, and 80 percent of the permethrin remained on the cartridge, teflon tubing, and glassware. Chlorpyrifos also was not recovered completely with the methanol elution (only 62 percent was recovered). The other insecticides were extracted by C-8 solid-phase extraction cartridge and recovered by elution with methanol (80 percent or greater). During Phase II, a new spiked water sample was extracted by C-8 solid-phase extraction cartridge and then eluted with varying concentrations of methanol and water into different fractions. Each methanol:water fraction was analyzed for the added compounds. Most of the insecticides eluted in two fractions, with concentrations of 10 percent or greater. The largest number of insecticides eluted in the 75 percent methanol:water fraction.

  13. Liquid biopsy and therapeutic response: Circulating tumor cell cultures for evaluation of anticancer treatment

    PubMed Central

    Khoo, Bee Luan; Grenci, Gianluca; Jing, Tengyang; Lim, Ying Bena; Lee, Soo Chin; Thiery, Jean Paul; Han, Jongyoon; Lim, Chwee Teck

    2016-01-01

    The lack of a robust anticancer drug screening system to monitor patients during treatment delays realization of personalized treatment. We demonstrate an efficient approach to evaluate drug response using patient-derived circulating tumor cell (CTC) cultures obtained from liquid biopsy. Custom microfabricated tapered microwells were integrated with microfluidics to allow robust formation of CTC clusters without pre-enrichment and subsequent drug screening in situ. Rapid feedback after 2 weeks promotes immediate intervention upon detection of drug resistance or tolerance. The procedure was clinically validated with blood samples (n = 73) from 55 patients with early-stage, newly diagnosed, locally advanced, or refractory metastatic breast cancer. Twenty-four of these samples were used for drug evaluation. Cluster formation potential correlated inversely with increased drug concentration and therapeutic treatment. This new and robust liquid biopsy technique can potentially evaluate patient prognosis with CTC clusters during treatment and provide a noninvasive and inexpensive assessment that can guide drug discovery development or therapeutic choices for personalized treatment. PMID:27453941

  14. Human bedside evaluation versus automatic responsiveness testing in epilepsy (ARTiE).

    PubMed

    Touloumes, George; Morse, Elliot; Chen, William C; Gober, Leah; Dente, Jennifer; Lilenbaum, Rachel; Katzenstein, Emily; Pacelli, Ashley; Johnson, Emily; Si, Yang; Sivaraju, Adithya; Grover, Eric; Khozein, Rebecca; Cunningham, Courtney; Hirsch, Lawrence J; Blumenfeld, Hal

    2016-01-01

    Evaluation of behavioral impairment during epileptic seizures is critical for medical decision making, including accurate diagnosis, recommendations for driving, and presurgical evaluation. We investigated the quality of behavioral testing during inpatient video-electroencephalography (EEG) monitoring at an established epilepsy center, and introduce a technical innovation that may improve clinical care. We retrospectively reviewed video-EEG data from 152 seizures in 33 adult or pediatric patients admitted for video-EEG monitoring. Behavioral testing with questions or commands was performed in only 50% of seizures ictally, 73% of seizures postictally, and 80% with either ictal or postictal testing combined. Furthermore, the questions or commands were highly inconsistent and were performed by nonmedical personnel in about one fourth of cases. In an effort to improve this situation we developed and here introduce Automatic Responsiveness Testing in Epilepsy (ARTiE), a series of video-recorded behavioral tasks automatically triggered to play in the patient's room by computerized seizure detection. In initial technical testing using prerecorded or live video-EEG data we found that ARTiE is initiated reliably by automatic seizure detection. With additional clinical testing we hope that ARTiE will succeed in providing comprehensive and reliable behavioral evaluation during seizures for people with epilepsy to greatly improve their clinical care.

  15. Quantitative evaluation of slow traps near Ge MOS interfaces by using time response of MOS capacitance

    NASA Astrophysics Data System (ADS)

    Tanaka, Katsuhisa; Zhang, Rui; Takenaka, Mitsuru; Takagi, Shinichi

    2015-04-01

    Time-dependent changes in current and threshold voltage due to slow traps near Ge metal-oxide-semiconductor (MOS) interfaces is one of the most serious problems in Ge metal-oxide-semiconductor field-effect transistors (MOSFETs). In this study, we propose a new evaluation method of slow traps near MOS interfaces utilizing the time response of capacitance in MOS capacitors at a constant gate voltage, allowing us to evaluate the density and time constant of slow traps. We apply this method to Au/Al2O3/GeOx/Ge MOS capacitors and evaluate the density and average time constant of slow traps. The slow trap density of n-Ge MOS capacitors is found to be much larger than that of p-Ge MOS capacitors, indicating that a higher density of slow traps exists near the conduction band edge. We also examine the effects of post deposition annealing in a variety of ambient gases, including several hydrogen-based species, on the properties of slow traps.

  16. Evaluation of pleth variability index as a predictor of fluid responsiveness during orthotopic liver transplantation.

    PubMed

    Konur, Huseyin; Erdogan Kayhan, Gulay; Toprak, Huseyin Ilksen; Bucak, Nizamettin; Aydogan, Mustafa Said; Yologlu, Saim; Durmus, Mahmut; Yılmaz, Sezai

    2016-07-01

    Fluid management is challenging and still remains controversial in orthotopic liver transplantation (OLT). The pleth variability index (PVI) has been shown to be a reliable predictor of fluid responsiveness of perioperative and critically ill patients; however, it has not been evaluated in OLT. This study was designed to examine whether the PVI can reliably predict fluid responsiveness in OLT and to compare PVI with other hemodynamic indexes that are measured using the PiCCO2 monitoring system. Twenty-five patients were enrolled in this study. Each patient was monitored using the noninvasive Masimo and PiCCO2 monitoring system. PVI was obtained with a Masimo pulse oximeter. Cardiac index was obtained using a transpulmonary thermodilution technique (CITPTD). Stroke volume variation (SVV), pulse pressure variation, and systemic vascular resistance index were measured using the PiCCO2 system. Fluid loading (10 mL/kg colloid) was performed at two different phases during the operation, and fluid responsiveness was defined as an increase in CITPTD ≥ 15%. During the dissection phase and the anhepatic phase, respectively, 14 patients (56%) and 18 patients (75%) were classified as responders. There were no differences between the baseline values of the PVI of responders and nonresponders. Area under the curve for PVI was 0.56 (sensitivity 35%, specificity 90%, p = 0.58) at dissection phase, and was 0.55 (sensitivity 55%, specificity 66%, p = 0.58) at anhepatic phase. Of the parameters, a higher area under the curve value was found for SVV. We conclude that PVI was unable to predict fluid responsiveness with sufficient accuracy in patients undergoing OLT, but the SVV parameter was reliable. PMID:27450027

  17. Evaluation of the Phase-Dependent Rhythm Control of Human Walking Using Phase Response Curves

    PubMed Central

    Yamamoto, Yuki; Aoi, Shinya; Imai, Takashi; Aoyagi, Toshio; Tomita, Nozomi; Tsuchiya, Kazuo

    2016-01-01

    Humans and animals control their walking rhythms to maintain motion in a variable environment. The neural mechanism for controlling rhythm has been investigated in many studies using mechanical and electrical stimulation. However, quantitative evaluation of rhythm variation in response to perturbation at various timings has rarely been investigated. Such a characteristic of rhythm is described by the phase response curve (PRC). Dynamical simulations of human skeletal models with changing walking rhythms (phase reset) described a relation between the effective phase reset on stability and PRC, and phase reset around touch-down was shown to improve stability. A PRC of human walking was estimated by pulling the swing leg, but such perturbations hardly influenced the stance leg, so the relation between the PRC and walking events was difficult to discuss. This research thus examines human response to variations in floor velocity. Such perturbation yields another problem, in that the swing leg is indirectly (and weakly) perturbed, so the precision of PRC decreases. To solve this problem, this research adopts the weighted spike-triggered average (WSTA) method. In the WSTA method, a sequential pulsed perturbation is used for stimulation. This is in contrast with the conventional impulse method, which applies an intermittent impulsive perturbation. The WSTA method can be used to analyze responses to a large number of perturbations for each sequence. In the experiment, perturbations are applied to walking subjects by rapidly accelerating and decelerating a treadmill belt, and measured data are analyzed by the WSTA and impulse methods. The PRC obtained by the WSTA method had clear and stable waveforms with a higher temporal resolution than those obtained by the impulse method. By investigation of the rhythm transition for each phase of walking using the obtained PRC, a rhythm change that extends the touch-down and mid-single support phases is found to occur. PMID:27203839

  18. Evaluation of the Phase-Dependent Rhythm Control of Human Walking Using Phase Response Curves.

    PubMed

    Funato, Tetsuro; Yamamoto, Yuki; Aoi, Shinya; Imai, Takashi; Aoyagi, Toshio; Tomita, Nozomi; Tsuchiya, Kazuo

    2016-05-01

    Humans and animals control their walking rhythms to maintain motion in a variable environment. The neural mechanism for controlling rhythm has been investigated in many studies using mechanical and electrical stimulation. However, quantitative evaluation of rhythm variation in response to perturbation at various timings has rarely been investigated. Such a characteristic of rhythm is described by the phase response curve (PRC). Dynamical simulations of human skeletal models with changing walking rhythms (phase reset) described a relation between the effective phase reset on stability and PRC, and phase reset around touch-down was shown to improve stability. A PRC of human walking was estimated by pulling the swing leg, but such perturbations hardly influenced the stance leg, so the relation between the PRC and walking events was difficult to discuss. This research thus examines human response to variations in floor velocity. Such perturbation yields another problem, in that the swing leg is indirectly (and weakly) perturbed, so the precision of PRC decreases. To solve this problem, this research adopts the weighted spike-triggered average (WSTA) method. In the WSTA method, a sequential pulsed perturbation is used for stimulation. This is in contrast with the conventional impulse method, which applies an intermittent impulsive perturbation. The WSTA method can be used to analyze responses to a large number of perturbations for each sequence. In the experiment, perturbations are applied to walking subjects by rapidly accelerating and decelerating a treadmill belt, and measured data are analyzed by the WSTA and impulse methods. The PRC obtained by the WSTA method had clear and stable waveforms with a higher temporal resolution than those obtained by the impulse method. By investigation of the rhythm transition for each phase of walking using the obtained PRC, a rhythm change that extends the touch-down and mid-single support phases is found to occur.

  19. Evaluating the relationship between muscle and bone modeling response in older adults.

    PubMed

    Reider, Lisa; Beck, Thomas; Alley, Dawn; Miller, Ram; Shardell, Michelle; Schumacher, John; Magaziner, Jay; Cawthon, Peggy M; Barbour, Kamil E; Cauley, Jane A; Harris, Tamara

    2016-09-01

    Bone modeling, the process that continually adjusts bone strength in response to prevalent muscle-loading forces throughout an individual's lifespan, may play an important role in bone fragility with age. Femoral stress, an index of bone modeling response, can be estimated using measurements of DXA derived bone geometry and loading information incorporated into an engineering model. Assuming that individuals have adapted to habitual muscle loading forces, greater stresses indicate a diminished response and a weaker bone. The purpose of this paper was to evaluate the associations of lean mass and muscle strength with the femoral stress measure generated from the engineering model and to examine the extent to which lean mass and muscle strength account for variation in femoral stress among 2539 healthy older adults participating in the Health ABC study using linear regression. Mean femoral stress was higher in women (9.51, SD=1.85Mpa) than in men (8.02, SD=1.43Mpa). Percent lean mass explained more of the variation in femoral stress than did knee strength adjusted for body size (R(2)=0.187 vs. 0.055 in men; R(2)=0.237 vs. 0.095 in women). In models adjusted for potential confounders, for every percent increase in lean mass, mean femoral stress was 0.121Mpa lower (95% CI: -0.138, -0.104; p<0.001) in men and 0.139Mpa lower (95% CI: -0.158, -0.121; p<0.001) in women. The inverse association of femoral stress with lean mass and with knee strength did not differ by category of BMI. Results from this study provide insight into bone modeling differences as measured by femoral stress among older men and women and indicate that lean mass may capture elements of bone's response to load. PMID:27352990

  20. Evaluation of simulated photolysis rates and their response to solar irradiance variability

    NASA Astrophysics Data System (ADS)

    Sukhodolov, Timofei; Rozanov, Eugene; Ball, William T.; Bais, Alkiviadis; Tourpali, Kleareti; Shapiro, Alexander I.; Telford, Paul; Smyshlyaev, Sergey; Fomin, Boris; Sander, Rolf; Bossay, Sébastien; Bekki, Slimane; Marchand, Marion; Chipperfield, Martyn P.; Dhomse, Sandip; Haigh, Joanna D.; Peter, Thomas; Schmutz, Werner

    2016-05-01

    The state of the stratospheric ozone layer and the temperature structure of the atmosphere are largely controlled by the solar spectral irradiance (SSI) through its influence on heating and photolysis rates. This study focuses on the uncertainties in the photolysis rate response to solar irradiance variability related to the choice of SSI data set and to the performance of the photolysis codes used in global chemistry-climate models. To estimate the impact of SSI uncertainties, we compared several photolysis rates calculated with the radiative transfer model libRadtran, using SSI calculated with two models and observed during the Solar Radiation and Climate Experiment (SORCE) satellite mission. The importance of the calculated differences in the photolysis rate response for ozone and temperature changes has been estimated using 1-D a radiative-convective-photochemical model. We demonstrate that the main photolysis reactions, responsible for the solar signal in the stratosphere, are highly sensitive to the spectral distribution of SSI variations. Accordingly, the ozone changes and related ozone-temperature feedback are shown to depend substantially on the SSI data set being used, which highlights the necessity of obtaining accurate SSI variations. To evaluate the performance of photolysis codes, we compared the results of eight, widely used, photolysis codes against two reference schemes. We show that, in most cases, absolute values of the photolysis rates and their response to applied SSI changes agree within 30%. However, larger errors may appear in specific atmospheric regions because of differences, for instance, in the treatment of Rayleigh scattering, quantum yields, or absorption cross sections.

  1. Evaluating the relationship between muscle and bone modeling response in older adults.

    PubMed

    Reider, Lisa; Beck, Thomas; Alley, Dawn; Miller, Ram; Shardell, Michelle; Schumacher, John; Magaziner, Jay; Cawthon, Peggy M; Barbour, Kamil E; Cauley, Jane A; Harris, Tamara

    2016-09-01

    Bone modeling, the process that continually adjusts bone strength in response to prevalent muscle-loading forces throughout an individual's lifespan, may play an important role in bone fragility with age. Femoral stress, an index of bone modeling response, can be estimated using measurements of DXA derived bone geometry and loading information incorporated into an engineering model. Assuming that individuals have adapted to habitual muscle loading forces, greater stresses indicate a diminished response and a weaker bone. The purpose of this paper was to evaluate the associations of lean mass and muscle strength with the femoral stress measure generated from the engineering model and to examine the extent to which lean mass and muscle strength account for variation in femoral stress among 2539 healthy older adults participating in the Health ABC study using linear regression. Mean femoral stress was higher in women (9.51, SD=1.85Mpa) than in men (8.02, SD=1.43Mpa). Percent lean mass explained more of the variation in femoral stress than did knee strength adjusted for body size (R(2)=0.187 vs. 0.055 in men; R(2)=0.237 vs. 0.095 in women). In models adjusted for potential confounders, for every percent increase in lean mass, mean femoral stress was 0.121Mpa lower (95% CI: -0.138, -0.104; p<0.001) in men and 0.139Mpa lower (95% CI: -0.158, -0.121; p<0.001) in women. The inverse association of femoral stress with lean mass and with knee strength did not differ by category of BMI. Results from this study provide insight into bone modeling differences as measured by femoral stress among older men and women and indicate that lean mass may capture elements of bone's response to load.

  2. Evaluation of the Phase-Dependent Rhythm Control of Human Walking Using Phase Response Curves.

    PubMed

    Funato, Tetsuro; Yamamoto, Yuki; Aoi, Shinya; Imai, Takashi; Aoyagi, Toshio; Tomita, Nozomi; Tsuchiya, Kazuo

    2016-05-01

    Humans and animals control their walking rhythms to maintain motion in a variable environment. The neural mechanism for controlling rhythm has been investigated in many studies using mechanical and electrical stimulation. However, quantitative evaluation of rhythm variation in response to perturbation at various timings has rarely been investigated. Such a characteristic of rhythm is described by the phase response curve (PRC). Dynamical simulations of human skeletal models with changing walking rhythms (phase reset) described a relation between the effective phase reset on stability and PRC, and phase reset around touch-down was shown to improve stability. A PRC of human walking was estimated by pulling the swing leg, but such perturbations hardly influenced the stance leg, so the relation between the PRC and walking events was difficult to discuss. This research thus examines human response to variations in floor velocity. Such perturbation yields another problem, in that the swing leg is indirectly (and weakly) perturbed, so the precision of PRC decreases. To solve this problem, this research adopts the weighted spike-triggered average (WSTA) method. In the WSTA method, a sequential pulsed perturbation is used for stimulation. This is in contrast with the conventional impulse method, which applies an intermittent impulsive perturbation. The WSTA method can be used to analyze responses to a large number of perturbations for each sequence. In the experiment, perturbations are applied to walking subjects by rapidly accelerating and decelerating a treadmill belt, and measured data are analyzed by the WSTA and impulse methods. The PRC obtained by the WSTA method had clear and stable waveforms with a higher temporal resolution than those obtained by the impulse method. By investigation of the rhythm transition for each phase of walking using the obtained PRC, a rhythm change that extends the touch-down and mid-single support phases is found to occur. PMID:27203839

  3. Comparative evaluation of Space Transportation System (STS)-3 flight and acoustic test random vibration response of the OSS-1 payload

    NASA Technical Reports Server (NTRS)

    On, F. J.

    1983-01-01

    A comparative evaluation of the Space Transportation System (STS)-3 flight and acoustic test random vibration response of the Office of Space Science-1 (OSS-1) payload is presented. The results provide insight into the characteristics of vibroacoustic response of pallet payload components in the payload bay during STS flights.

  4. Using the Nominal Response Model to Evaluate Response Category Discrimination in the PROMIS Emotional Distress Item Pools

    ERIC Educational Resources Information Center

    Preston, Kathleen; Reise, Steven; Cai, Li; Hays, Ron D.

    2011-01-01

    The authors used a nominal response item response theory model to estimate category boundary discrimination (CBD) parameters for items drawn from the Emotional Distress item pools (Depression, Anxiety, and Anger) developed in the Patient-Reported Outcomes Measurement Information Systems (PROMIS) project. For polytomous items with ordered response…

  5. Evaluation of Hearing Aid Frequency Response Fittings in Pediatric and Young Adult Bimodal Recipients

    PubMed Central

    Davidson, Lisa S.; Firszt, Jill B.; Brenner, Chris; Cadieux, Jamie H.

    2015-01-01

    Background A coordinated fitting of a cochlear implant (CI) and contralateral hearing aid (HA) for bimodal device use should emphasize balanced audibility and loudness across devices. However, guidelines for allocating frequency information to the CI and HA are not well established for the growing population of bimodal recipients. Purpose The study aim was to compare the effects of three different HA frequency responses, when fitting a CI and an HA for bimodal use, on speech recognition and localization in children/young adults. Specifically, the three frequency responses were wideband, restricted high frequency, and nonlinear frequency compression (NLFC), which were compared with measures of word recognition in quiet, sentence recognition in noise, talker discrimination, and sound localization. Research Design The HA frequency responses were evaluated using an A B1 A B2 test design: wideband frequency response (baseline-A), restricted high-frequency response (experimental-B1), and NLFC-activated (experimental-B2). All participants were allowed 3–4 weeks between each test session for acclimatization to each new HA setting. Bimodal benefit was determined by comparing the bimodal score to the CI-alone score. Study Sample Participants were 14 children and young adults (ages 7–21 yr) who were experienced users of bimodal devices. All had been unilaterally implanted with a Nucleus CI24 internal system and used either a Freedom or CP810 speech processor. All received a Phonak Naida IX UP behind-the-ear HA at the beginning of the study. Data Collection and Analysis Group results for the three bimodal conditions (HA frequency response with wideband, restricted high frequency, and NLFC) on each outcome measure were analyzed using a repeated measures analysis of variance. Group results using the individual “best bimodal” score were analyzed and confirmed using a resampling procedure. Correlation analyses examined the effects of audibility (aided and unaided hearing

  6. New-onset atrial fibrillation after recent coronary stenting: Warfarin or non-vitamin K-antagonist oral anticoagulants to be added to aspirin and clopidogrel? A viewpoint.

    PubMed

    Rubboli, Andrea; Agewall, Stefan; Huber, Kurt; Lip, Gregory Y H

    2015-10-01

    The antithrombotic management of patients on oral anticoagulation (OAC), with either warfarin or non-vitamin K-antagonist oral anticoagulants (NOACs), undergoing percutaneous coronary intervention with stent (PCI-S) has been recently addressed in a joint European consensus document. In accordance, triple therapy (TT) of OAC, aspirin and clopidogrel should generally be given as the initial therapy. More uncertainty exists over whether warfarin or a NOAC should be added in patients already on dual antiplatelet therapy of aspirin and clopidogrel (DAPT) after recent PCI-S. Upon review of available data, it appears that the risk of major bleeding of TT as compared to DAPT is similar with either warfarin or a NOAC. In particular, TT consistently appears associated to an approximately 2.5 fold increase in the risk of major bleeding. Because of the higher convenience, NOACs might be considered the preferred OAC to be added to DAPT. Given the reported different safety profiles of the various NOACs on the incidence of major, and gastrointestinal, bleeding, the NOACs, and the dose, showing the greatest safety in this regard should be selected. In accordance, dabigatran 110 mg and apixaban 2.5mg twice daily appear as the most valuable options in patients who are not and who are respectively, at increased risk of bleeding. As an alternative, apixaban 5mg twice daily might be considered in patients at risk of bleeding not increased, whereas rivaroxaban 15 mg once daily may be considered in the presence of increased risk of bleeding (essentially when related to moderate renal impairment). PMID:26093527

  7. The risk of bleeding of triple therapy with vitamin K-antagonists, aspirin and clopidogrel after coronary stent implantation: Facts and questions

    PubMed Central

    Rubboli, Andrea

    2011-01-01

    Background Triple therapy (TT) with vitamin K-antagonists (VKA), aspirin and clopidogrel is the recommended antithrombotic treatment following percutaneous coronary intervention with stent implantation (PCI-S) in patients with an indication for oral anticoagulation. TT is associated with an increased risk of bleeding, but available evidence is flawed by important limitations, including the limited size and the retrospective design of most of the studies, as well as the rare reporting of the incidence of in-hospital bleeding and the treatment which was actually ongoing at the time of bleeding. Since the perceived high bleeding risk of TT may deny patients effective strategies, the determination of the true safety profile of TT is of paramount importance. Methods All the 27 published studies where the incidence of bleeding at various time points during follow-up has been reported separately for patients on TT were reviewed, and the weakness of the data was analyzed. Results The absolute incidence of major bleeding upon discharge at in-hospital, ≤ 1 month, 6 months, 12 months and ≥ 12 months was: 3.3% ± 1.9%, 5.1% ± 6.7%, 8.0% ± 5.2%, 9.0% ± 8.0, and 6.2% ± 7.8%, respectively, and not substantially different from that observed in previous studies with prolonged dual antiplatelet treatment with aspirin and clopidogrel. Conclusions While waiting for the ongoing, large-scale, registries and clinical trials to clarify the few facts and to answer the many questions regarding the risk of bleeding of TT, this treatment should not be denied to patients with an indication for VKA undergoing PCI-S provided that the proper measures and cautions are implemented. PMID:22783307

  8. 33 CFR 155.1052 - Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. 155.1052 Section 155.1052....1052 Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. (a) Owners and operators of vessels that carry group V petroleum oil as a primary...

  9. 33 CFR 155.1052 - Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. 155.1052 Section 155.1052....1052 Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. (a) Owners and operators of vessels that carry group V petroleum oil as a primary...

  10. 33 CFR 155.1052 - Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. 155.1052 Section 155.1052....1052 Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. (a) Owners and operators of vessels that carry group V petroleum oil as a primary...

  11. 33 CFR 155.1052 - Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. 155.1052 Section 155.1052....1052 Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. (a) Owners and operators of vessels that carry group V petroleum oil as a primary...

  12. 33 CFR 155.1052 - Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. 155.1052 Section 155.1052....1052 Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. (a) Owners and operators of vessels that carry group V petroleum oil as a primary...

  13. Laboratory test methods for evaluating the fire response of aerospace materials

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.

    1979-01-01

    The test methods which were developed or evaluated were intended to serve as means of comparing materials on the basis of specific responses under specific sets of test conditions, using apparatus, facilities, and personnel that would be within the capabilities of perhaps the majority of laboratories. Priority was given to test methods which showed promise of addressing the pre-ignition state of a potential fire. These test methods were intended to indicate which materials may present more hazard than others under specific test conditions. These test methods are discussed and arranged according to the stage of a fire to which they are most relevant. Some observations of material performance which resulted from this work are also discussed.

  14. Analysis of skin conductance response during evaluation of preferences for cosmetic products

    PubMed Central

    Ohira, Hideki; Hirao, Naoyasu

    2015-01-01

    We analyzed skin conductance response (SCR) as a psychophysiological index to evaluate affective aspects of consumer preferences for cosmetic products. To examine the test-retest reliability of association between preferences and SCR, we asked 33 female volunteers to complete two experimental sessions approximately 1 year apart. The participants indicated their preferences in a typical paired comparison task by choosing the better option from a combination of two products among four products. We measured anticipatory SCR prior to expressions of the preferences. We found that the mean amplitude of the SCR elicited by the preferred products was significantly larger than that elicited by the non-preferred products. The participants' preferences and corresponding SCR patterns were well preserved at the second session 1 year later. Our results supported cumulating findings that SCR is a useful index of consumer preferences that has future potential, both in laboratory and marketing settings. PMID:25709593

  15. Further evaluation of response interruption and redirection as treatment for stereotypy.

    PubMed

    Ahrens, Erin N; Lerman, Dorothea C; Kodak, Tiffany; Worsdell, April S; Keegan, Courtney

    2011-01-01

    The effects of 2 forms of response interruption and redirection (RIRD)-motor RIRD and vocal RIRD-were examined with 4 boys with autism to evaluate further the effects of this intervention and its potential underlying mechanisms. In Experiment 1, the effects of motor RIRD and vocal RIRD on vocal stereotypy and appropriate vocalizations were compared for 2 participants. In Experiment 2, the effects of both RIRD procedures on both vocal and motor stereotypy and appropriate vocalizations were compared with 2 additional participants. Results suggested that RIRD was effective regardless of the procedural variation or topography of stereotypy and that vocal RIRD functioned as a punisher. This mechanism was further explored with 1 participant by manipulating the schedule of RIRD in Experiment 3. Results were consistent with the punishment interpretation. PMID:21541130

  16. A Participatory Action Research Pilot Study of Urban Health Disparities Using Rapid Assessment Response and Evaluation

    PubMed Central

    Brown, David Richard; Hernández, Agueda; Saint-Jean, Gilbert; Evans, Siân; Tafari, Ida; Brewster, Luther G.; Celestin, Michel J.; Gómez-Estefan, Carlos; Regalado, Fernando; Akal, Siri; Nierenberg, Barry; Kauschinger, Elaine D.; Schwartz, Robert; Page, J. Bryan

    2008-01-01

    Healthy People 2010 made it a priority to eliminate health disparities. We used a rapid assessment response and evaluation (RARE) to launch a program of participatory action research focused on health disparities in an urban, disadvantaged Black community serviced by a major south Florida health center. We formed partnerships with community members, identified local health disparities, and guided interventions targeting health disparities. We describe the RARE structure used to triangulate data sources and guide intervention plans as well as findings and conclusions drawn from scientific literature and epidemiological, historic, planning, clinical, and ethnographic data. Disenfranchisement and socioeconomic deprivation emerged as the principal determinants of local health disparities and the most appropriate targets for intervention. PMID:18048802

  17. Validating bioindicators of PAH effects in fish: Evaluating responsiveness to creosote exposure in aquatic mesocosms

    SciTech Connect

    Munro, K.A.; Solomon, K.R.; Gensemer, R.W.; Van Der Kraak, G.J.; Day, K.E.; Servos, M.R.

    1994-12-31

    While studies involving controlled exposures to PAHs have typically studied the effects of exposure to individual compounds, PAHs are usually present in the environment in complex mixtures. Some of these (eg. creosote) have been widely used and present potential risks to aquatic ecosystems. The objective of the current research is to evaluate whether population effects visible in fish at high creosote concentrations would be reflected in biomarker responses at lower concentrations. Goldfish (Carassius auratus) were exposed to five levels of creosote contamination in microcosms containing a simple community structure (including macroinvertebrates and macrophytes). Preliminary results have shown that changes in P450 induction, bile fluorescence, and levels of reproductive hormones are visible at lower concentrations than population effects such as increased mortality, reduced secondary sexual characteristics, and reduced fecundity.

  18. Further evaluation of response interruption and redirection as treatment for stereotypy.

    PubMed

    Ahrens, Erin N; Lerman, Dorothea C; Kodak, Tiffany; Worsdell, April S; Keegan, Courtney

    2011-01-01

    The effects of 2 forms of response interruption and redirection (RIRD)-motor RIRD and vocal RIRD-were examined with 4 boys with autism to evaluate further the effects of this intervention and its potential underlying mechanisms. In Experiment 1, the effects of motor RIRD and vocal RIRD on vocal stereotypy and appropriate vocalizations were compared for 2 participants. In Experiment 2, the effects of both RIRD procedures on both vocal and motor stereotypy and appropriate vocalizations were compared with 2 additional participants. Results suggested that RIRD was effective regardless of the procedural variation or topography of stereotypy and that vocal RIRD functioned as a punisher. This mechanism was further explored with 1 participant by manipulating the schedule of RIRD in Experiment 3. Results were consistent with the punishment interpretation.

  19. Evaluation of a wind-tunnel gust response technique including correlations with analytical and flight test results

    NASA Technical Reports Server (NTRS)

    Redd, L. T.; Hanson, P. W.; Wynne, E. C.

    1979-01-01

    A wind tunnel technique for obtaining gust frequency response functions for use in predicting the response of flexible aircraft to atmospheric turbulence is evaluated. The tunnel test results for a dynamically scaled cable supported aeroelastic model are compared with analytical and flight data. The wind tunnel technique, which employs oscillating vanes in the tunnel throat section to generate a sinusoidally varying flow field around the model, was evaluated by use of a 1/30 scale model of the B-52E airplane. Correlation between the wind tunnel results, flight test results, and analytical predictions for response in the short period and wing first elastic modes of motion are presented.

  20. Evaluation of Vocational Education: Roles, Responsibilities, and Responses of State and Federal Agencies. Research and Development Series No. 173.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO.

    The central purpose of this paper is to describe the origins, assumptions, approaches, and problems of the major evaluation efforts relating to vocational education specified in the Educational Amendments of 1976. The first of five chapters provides background information on vocational education, evaluation, and the Education Amendments of 1976.…

  1. Hortonian runoff closure relations for geomorphologic response units: evaluation against field data

    NASA Astrophysics Data System (ADS)

    Vannametee, E.; Karssenberg, D.; Hendriks, M. R.; Bierkens, M. F. P.

    2013-07-01

    This paper presents an evaluation of the closure relation for Hortonian runoff, proposed in Vannametee et al. (2012), that incorporates a scaling component to explicitly account for the process heterogeneity and scale effects in runoff generation for the real-world case studies. We applied the closure relation, which was embedded in an event-based lumped rainfall-runoff model, to a 15 km2 catchment in the French Alps. The catchment was disaggregated into a number of landform units, referred to as Geomorphologic Response Units (GRUs), to each of which the closure relation was applied. The scaling component in the closure relation was identified using the empirical relations between rainstorm characteristics, geometry, and local-scale measurable properties of the GRUs. Evaluation of the closure relation performance against the observed discharge shows that the hydrograph and discharge volume were quite satisfactorily simulated even without calibration. Performance of the closure relation can be mainly attributed to the use of scaling component, as it is shown that our closure relation outperforms a benchmark closure relation that lacks this scaling component. The discharge prediction is significantly improved when the closure relation is calibrated against the observed discharge, resulting in local-scale GRU-properties optimal for the predictions. Calibration was done by changing one local-scale observable, i.e. hydraulic conductivity (Ks), using a single pre-factor for the entire catchment. It is shown that the calibrated Ks values are somewhat comparable to the observed Ks values at a local scale in the study catchment. These results suggest that, in the absence of discharge observations, reasonable estimates of catchment-scale runoff responses can possibly be achieved with the observations at the sub-GRU (i.e. plot) scale. Our study provides a platform for the future development of low-dimensional, semi-distributed, physically based discharge models in ungauged

  2. EVALUATION OF SMOKE AND GAS SENSOR RESPONSES FOR FIRES OF COMMON MINE COMBUSTIBLES

    PubMed Central

    Perera, Inoka Eranda; Litton, Charles D.

    2015-01-01

    Experiments were conducted to evaluate the response characteristics of commercially available gas, smoke, and flame sensors to fires of common combustible mine materials. The experiments were conducted in the large-scale Fire gallery located at the National Institute for Occupational Safety and Health (NIOSH) Lake Lynn Laboratory (LLL) in Fairchance, PA, using Ponderosa Pine, Red Oak, Douglas-fir, high and low volatile coals, PVC and SBR conveyor belt, No. 2 diesel fuel, and diesel exhaust. All the experiments (except those using No. 2 diesel fuel and the diesel exhaust tests) were conducted in a similar manner, with combustible materials heated rapidly by electrical strip heaters producing smoldering fires that quickly transitioned into flaming fires. The sensors included a diffusion-type carbon monoxide (CO) sensor, photoelectric- and ionization-type smoke sensors, a video smoke/flame detector, and an optical flame detector. Simultaneous measurements were obtained for average gas concentrations, smoke mass concentrations, and smoke optical densities in order to quantify the levels of combustion products at the alert and alarm times of the sensors. Because the required sensor alarm levels are 10 ppm and 0.044 m−1 optical density for CO and smoke sensors, respectively, the different sensor alarms are compared to the time at which the CO and smoke reached these alarm levels (1). In addition, the potential impact of using smoke sensors that have met the performance standards from accredited testing laboratories is also evaluated using the response of an Underwriters’ Laboratory (UL)-approved combination photoelectric/ionization smoke detector. The results are discussed relative to fire sensor needs that can have a positive impact on mine fire safety. PMID:26229418

  3. Evaluation of outbreak response immunization in the control of pertussis using agent-based modeling

    PubMed Central

    Qian, Weicheng; Osgood, Nathaniel D.

    2016-01-01

    10 years of a campaign, respectively. During the same time periods, 53, 96, and 163 cases were averted in the 10–14 age group, and 6, 11, 20 in infants under 1 (p < 0.001, all groups). Numbers needed to vaccinate ranged from 49 to 221, from 130 to 519 and from 1,031 to 4,903 for all ages, the 10–14 age group and for infants, respectively. Most sensitivity analyses resulted in minimal impact on a number of cases averted. Discussion Our model generated 30 years of longitudinal data to evaluate effects of outbreak response immunization in a controlled study. Immunization campaign implemented as an outbreak response measure among adolescents may confer benefits across all ages accruing over a 10-year period. Our inference is dependent on having an outbreak of significant magnitude affecting predominantly the selected age and achieving a comprehensive vaccine coverage during the campaign. Economic evaluations and comparisons with other control measures can add to conclusions generated by our work.

  4. Evaluation of outbreak response immunization in the control of pertussis using agent-based modeling

    PubMed Central

    Qian, Weicheng; Osgood, Nathaniel D.

    2016-01-01

    10 years of a campaign, respectively. During the same time periods, 53, 96, and 163 cases were averted in the 10–14 age group, and 6, 11, 20 in infants under 1 (p < 0.001, all groups). Numbers needed to vaccinate ranged from 49 to 221, from 130 to 519 and from 1,031 to 4,903 for all ages, the 10–14 age group and for infants, respectively. Most sensitivity analyses resulted in minimal impact on a number of cases averted. Discussion Our model generated 30 years of longitudinal data to evaluate effects of outbreak response immunization in a controlled study. Immunization campaign implemented as an outbreak response measure among adolescents may confer benefits across all ages accruing over a 10-year period. Our inference is dependent on having an outbreak of significant magnitude affecting predominantly the selected age and achieving a comprehensive vaccine coverage during the campaign. Economic evaluations and comparisons with other control measures can add to conclusions generated by our work. PMID:27602299

  5. Evaluating the impact of aquifer layer properties on geomechanical response during CO2 geological sequestration

    SciTech Connect

    Bao, Jie; Xu, Zhijie; Lin, Guang; Fang, Yilin

    2013-04-01

    Numerical models play an essential role in understanding the facts of carbon dioxide (CO2) geological sequestration in the life cycle of a storage reservoir. We present a series of test cases that reflect a broad and realistic range of aquifer reservoir properties to systematically evaluate and compare the impacts on the geomechanical response to CO2 injection. In this study, a coupled hydro-mechanical model was introduced to simulate the sequestration process, and a quasi-Monte Carlo sampling method was introduced to efficiently sample the value of aquifer properties and geometry parameters. Aquifer permeability was found to be of significant importance to the geomechanical response to the injection. To study the influence of uncertainty of the permeability distribution in the aquifer, an additional series of tests is presented, based on a default permeability distribution site sample with various distribution deviations generated by the Monte Carlo sampling method. The results of the test series show that different permeability distributions significantly affect the displacement and possible failure zone.

  6. [Evaluation of results of a program of Responsible Alcoholic Beverage Dispensing].

    PubMed

    Terradillos, J; López-Goñi, J J; Olleta, A Arteaga

    2011-01-01

    Selective prevention programs in the Responsible Dispensing of Beverages (DRA - Dispensación Responsable de Bebidas Alcohólicas) have provided varying evidence of their effectiveness in other countries. In Spain, however, data is only available for the implementation of DRA in Barcelona. This article has two aims: to assess the effectiveness of an intervention in DRA with waiters in Pamplona, and to evaluate individual and group results in order to identify areas for improvement. The sample consisted of 40 hostelry professionals who participated in one of the 4 courses of DRA. Questionnaires were used to measure pre-/post-knowledge, attitudes, perceived self-efficacy and expectations about the training. We present descriptive analyses of all the variables and individual and overall results of the evolution of each participant. The DRA program provides overall data of significant improvements in knowledge, attitudes and expectations. The results show the need to consider the analysis of the evolution of individual subjects in each item. PMID:22233842

  7. Dynamic response evaluation of tall noise barrier on high speed railway structures

    NASA Astrophysics Data System (ADS)

    Tokunaga, Munemasa; Sogabe, Masamichi; Santo, Tetsuo; Ono, Kiyoshi

    2016-03-01

    The aim of this paper is to obtain a fundamental understanding of the dynamic response of tall noise barriers during the passage of high speed train and to develop a practical method for evaluating this in anticipation of planned increases in running speed in the future. Tall noise barriers recently installed on Japanese high speed railway structures have a low natural frequency; therefore, they may resonate with the train draft pressure that up until now has not been a crucial condition for practical design. As a result of field measurements and numerical simulations, it was found that the dynamic response of noise barriers excited by passing trains can be explained by the resonance effect between pulse excitation of the train draft and the natural frequency of the noise barriers and by the tail-pulses overlap effect. Methods to generalize the resonance effect with the multi-body system and the tail-pulses overlap effect with the free vibration theory of the single-degree-of-freedom system were shown. Finally, two design methods were proposed: a precise method based on simulation and a simple method based on static design load. The simple method uses a design train draft pressure which is a function of noise barrier natural frequency when train speed is 260 m/h or 360 m/h.

  8. Evaluation of antibody response to vaccination against West Nile virus in thick billed parrots (Rhynchopsitta pachyrhyncha).

    PubMed

    Glavis, Jennifer; Larsen, R Scott; Lamberski, Nadine; Gaffney, Patricia; Gardner, Ian

    2011-09-01

    West Nile virus (WNV) was first documented in North America in New York City in 1999. Several deaths attributable to WNV have been reported in captive thick-billed parrots (Rhynchopsitta pachyrhyncha), an endangered psittacine native to North America. The serologic responses in 12 captive adult thick-billed parrots after a series of three initial WNV vaccine injections with annual boosters over 6 yr was evaluated. In addition, the serologic responses of 11 thick-billed parrot chicks following an initial vaccination series to determine if there were seroconversions were also reported. Most adults (67%) had seroconverted after 5 yr of annual vaccination, with a median titer of 1:80 (range 1:40-1:160) for those that seroconverted. After the first year, birds were likely naturally exposed to WNV, which limited interpretation of titers. None of the chicks seroconverted during the initial three-vaccine series; only two of four chicks (50%) had seroconverted when tested at the 1-yr yearly booster, and at 2 yr, three of four chicks had seroconverted. Although some birds had detectable antibody titers, it is unclear whether this vaccine can reliably provide protection against WNV in thick-billed parrots.

  9. Hepatocellular Carcinoma and Diffusion-Weighted MRI: Detection and Evaluation of Treatment Response

    PubMed Central

    Gluskin, Jill S; Chegai, Fabrizio; Monti, Serena; Squillaci, Ettore; Mannelli, Lorenzo

    2016-01-01

    Differentiating between cancerous tissue and healthy liver parenchyma could represent a challenge with the only conventional Magnetic Resonance (MR) imaging. Diffusion weighted imaging (DWI) exploits different tissue characteristics to conventional Magnetic Resonance Imaging (MRI) sequences that enhance hepatocellular carcinoma (HCC) detection, characterization, and post-treatment evaluation. Detection of HCC is improved by DWI, infact this technology increases conspicuity of lesions that might otherwise not be identified due to obscuration by adjacent vessels or due to low contrast between the lesion and background liver. It is important to remember that DWI combined with contrast-enhanced MRI has higher sensitivity than DWI alone, and that some patients are not eligible for use of contrast on CT and MRI; in these patients DWI has a prominent role. MRI has advanced beyond structural anatomic imaging to now showing pathophysiologic processes. DWI is a promising way to characterize lesions utilizing the inherent contrast within the liver and has the benefit of not requiring contrast injection. DWI improves detection and characterization of HCC. Proposed clinical uses for DWI include: assessing prognosis, predicting response, monitoring response to therapy, and distinguishing tumor recurrence from treatment effect. Ideally, DWI will help risk stratify patients and will participate in prognostic modeling. PMID:27471573

  10. Evaluation of mussel immune responses as indicators of contamination in San Francisco Bay.

    PubMed

    Luengen, Allison C; Friedman, Carolyn S; Raimondi, Peter T; Flegal, A Russell

    2004-04-01

    Several immune parameters were evaluated in two species of mussels (Mytilus californianus and M. galloprovincialis/M. trossulus) as bioindicators of contaminant effects. The mussels were deployed in San Francisco Bay Estuary and a control site at Bodega Marine Laboratory. Assays for phagocytosis and phagocytic index (average number of particles engulfed per hemocyte) were conducted with hemocytes in their own hemolymph-the "Serum" method. The responses were compared with contaminant concentrations in those mussels. For both species, the contaminated South Bay Dumbarton Bridge and Redwood Creek sites had elevated phagocytosis relative to the Bodega control site, indicating contaminant stress. The results also showed that M. californianus had higher percentages of phagocytosis (74%) and a higher phagocytic index (4.6 particles per cell) than those of M. galloprovincialis/M. trossulus (60% phagocytosis and 3.5 particles per cell). As there is a difference in immune response to contaminants, it is suggested that future San Francisco Estuary monitoring should be conducted with endemic M. galloprovincialis/M. trossulus rather than with the currently utilized M. californianus, which is not found in the estuary.

  11. Evaluation of sprayable fixatives on a sandy soil for potential use in a dirty bomb response.

    PubMed

    Fritz, Brad G; Whitaker, John D

    2008-06-01

    After the events of 11 September 2001, the possibility of a dirty bomb being detonated within the United States seems more realistic. Development of tools for use in response to a dirty bomb detonation has become a topic of both discussion and research. While it has been reported that the health risk to the public from such an event would likely be small, it is thought that the psychological impact could be considerable. One response option that has been considered is adapting sprayable solutions for the purpose of fixing contamination in place, thereby limiting the spread of contamination by wind and rain and facilitating subsequent cleanup. This work evaluated two commercially available particle fixatives (IsoFIX-HT and IsoFIX-RC) for their effectiveness in preventing dispersal of simulated contamination. Nonradioactive cesium chloride and cobalt oxide particles were selected as the simulated contamination and applied to the surface of three outdoor test plots. Two test plots were treated with fixatives; the third plot provided a control. Samples were collected over 95 days to observe changes in tracer concentration on the surface of the test plots. One fixative (IsoFIX-RC) effectively held the tracer in place with no net loss of tracer, while the other fixative (IsoFIX-HT) had no impact on the loss of tracer relative to the control. Under the conditions tested, IsoFIX-RC appears capable of fixing surface contamination in place for at least several months.

  12. Evaluating Climate Predictability Signals in Response to Forcing: Mount Pinatubo as a Case Study

    NASA Astrophysics Data System (ADS)

    Gaddis, A. L.; Drake, J.; Evans, K. J.

    2012-12-01

    Volcanic eruptions serve as a benchmark for assessing aspects of predictability because they provide a sudden global impulse to the Earth's climate system. In particular, the 1991 eruption of Mt. Pinatubo in the Philippines is of interest since it was the largest aerosol perturbation to the stratosphere in the twentieth century and the most intensely observed eruption on record. Using instrumental measurements during the eruption, the predictive capabilities of climate models may be evaluated and the predictability of climate variables under forcing may be inferred. In this study, the evolution of the climate response to volcanic forcing is simulated in the Community Earth System Model, CESM1.0, using ensembles of forced and unforced global climate model runs. The predictability signals of all atmospheric climate model variables are systematically calculated using a unitless signal to noise ratio. The signals are compared to determine the most sensitive variables. Additionally, this work examines spatial predictability patterns, important for regional predictability, by mapping the signals globally and using empirical orthogonal functions. Phase plots are employed to highlight the response of variables to forcing, and comparisons with observations of the eruption are made to provide validation of the results.

  13. UAV Deployment Exercise for Mapping Purposes: Evaluation of Emergency Response Applications.

    PubMed

    Boccardo, Piero; Chiabrando, Filiberto; Dutto, Furio; Tonolo, Fabio Giulio; Lingua, Andrea

    2015-07-02

    Exploiting the decrease of costs related to UAV technology, the humanitarian community started piloting the use of similar systems in humanitarian crises several years ago in different application fields, i.e., disaster mapping and information gathering, community capacity building, logistics and even transportation of goods. Part of the author's group, composed of researchers in the field of applied geomatics, has been piloting the use of UAVs since 2006, with a specific focus on disaster management application. In the framework of such activities, a UAV deployment exercise was jointly organized with the Regional Civil Protection authority, mainly aimed at assessing the operational procedures to deploy UAVs for mapping purposes and the usability of the acquired data in an emergency response context. In the paper the technical features of the UAV platforms will be described, comparing the main advantages/disadvantages of fixed-wing versus rotor platforms. The main phases of the adopted operational procedure will be discussed and assessed especially in terms of time required to carry out each step, highlighting potential bottlenecks and in view of the national regulation framework, which is rapidly evolving. Different methodologies for the processing of the acquired data will be described and discussed, evaluating the fitness for emergency response applications.

  14. UAV Deployment Exercise for Mapping Purposes: Evaluation of Emergency Response Applications

    PubMed Central

    Boccardo, Piero; Chiabrando, Filiberto; Dutto, Furio; Giulio Tonolo, Fabio; Lingua, Andrea

    2015-01-01

    Exploiting the decrease of costs related to UAV technology, the humanitarian community started piloting the use of similar systems in humanitarian crises several years ago in different application fields, i.e., disaster mapping and information gathering, community capacity building, logistics and even transportation of goods. Part of the author’s group, composed of researchers in the field of applied geomatics, has been piloting the use of UAVs since 2006, with a specific focus on disaster management application. In the framework of such activities, a UAV deployment exercise was jointly organized with the Regional Civil Protection authority, mainly aimed at assessing the operational procedures to deploy UAVs for mapping purposes and the usability of the acquired data in an emergency response context. In the paper the technical features of the UAV platforms will be described, comparing the main advantages/disadvantages of fixed-wing versus rotor platforms. The main phases of the adopted operational procedure will be discussed and assessed especially in terms of time required to carry out each step, highlighting potential bottlenecks and in view of the national regulation framework, which is rapidly evolving. Different methodologies for the processing of the acquired data will be described and discussed, evaluating the fitness for emergency response applications. PMID:26147728

  15. Rasch analysis for the evaluation of rank of student response time in multiple choice examinations.

    PubMed

    Thompson, James J; Yang, Tong; Chauvin, Sheila W

    2013-01-01

    The availability of computerized testing has broadened the scope of person assessment beyond the usual accuracy-ability domain to include response time analyses. Because there are contexts in which speed is important, e.g. medical practice, it is important to develop tools by which individuals can be evaluated for speed. In this paper, the ability of Rasch measurement to convert ordinal nonparametric rankings of speed to measures is examined and compared to similar measures derived from parametric analysis of response times (pace) and semi-parametric logarithmic time-scaling procedures. Assuming that similar spans of the measures were used, non-parametric methods of raw ranking or percentile-ranking of persons by questions gave statistically acceptable person estimates of speed virtually identical to the parametric or semi-parametric methods. Because no assumptions were made about the underlying time distributions with ranking, generality of conclusions was enhanced. The main drawbacks of the non-parametric ranking procedures were the lack of information on question duration and the overall assignment by the model of variance to the person by question interaction.

  16. Evaluation drought response of tropical dry forests using advanced wireless sensor networks

    NASA Astrophysics Data System (ADS)

    Sanchez-Azofeifa, G. A.

    2015-12-01

    Understanding of the effects of persistent drought in tropical dry forests has not been fully studied until today. In this presentation we will discuss one of the first results on the response of tropical dry forests to drought using advanced wireless sensor networks and canopy phenology towers, that provide hyper-temporal information on micro-meteorological variables such Temperature, relative humidity, and Vapor Pressure Deficit (VPD). In addition, we will evaluate drought response to as function of the Fraction of the Photosynthetic Active Radiation (FPAR), and the Normalized Difference Vegetation Index (NDVI). Our work is conducted at the Santa Rosa Environmental Monitoring Super Site (NR-EMSS) located at the Guancaste Province, Costa Rica, Central America. Our results indicate significant changes in terms of FPAR, VPD manifested via strong changes on NDVI. Our results pose questions about the resilience of these understudied tropical ecosystems and their long-term survival under severe and persistent drought conditions. This results provide a reference framework for the need of more integrated research on the Central American Dry Forest corridor where just between Costa Rica and Nicaragua over 100,000 families are facing strong drought conditions.

  17. Rasch analysis for the evaluation of rank of student response time in multiple choice examinations.

    PubMed

    Thompson, James J; Yang, Tong; Chauvin, Sheila W

    2013-01-01

    The availability of computerized testing has broadened the scope of person assessment beyond the usual accuracy-ability domain to include response time analyses. Because there are contexts in which speed is important, e.g. medical practice, it is important to develop tools by which individuals can be evaluated for speed. In this paper, the ability of Rasch measurement to convert ordinal nonparametric rankings of speed to measures is examined and compared to similar measures derived from parametric analysis of response times (pace) and semi-parametric logarithmic time-scaling procedures. Assuming that similar spans of the measures were used, non-parametric methods of raw ranking or percentile-ranking of persons by questions gave statistically acceptable person estimates of speed virtually identical to the parametric or semi-parametric methods. Because no assumptions were made about the underlying time distributions with ranking, generality of conclusions was enhanced. The main drawbacks of the non-parametric ranking procedures were the lack of information on question duration and the overall assignment by the model of variance to the person by question interaction. PMID:24064578

  18. An evaluation of higher-order modal methods for calculating transient structural response

    NASA Technical Reports Server (NTRS)

    Camarda, Charles J.; Haftka, Raphael T.; Riley, Michael F.

    1987-01-01

    The present study evaluates a higher-order modal method proposed by Leung for transient structural analysis entitled the force-derivative method. This method repeatedly integrates by parts with respect to time the convolution-integral form of the structural response to produce successively better approximations to the contribution of the higher modes which are neglected in the modal summation. Comparisons are made of the force-derivative, the mode-displacement, and the mode-acceleration methods for several numerical example problems for various times, levels of damping, and forcing functions. The example problems include a tip-loaded cantilevered beam and a simply-supported multispan beam. The force-derivative method is shown to converge to an accurate solution in fewer modes than either the mode-displacement or the mode-acceleration methods. In addition, for problems in which there are a large number of closely-spaced frequencies whose mode shapes have a negligible contribution to the response, the force derivative method is very effective in representing the effect of the important, but otherwise neglected, higher modes.

  19. An evaluation of higher-order model methods for calculating transient structural response

    NASA Technical Reports Server (NTRS)

    Camarda, Charles J.; Haftka, Raphael T.; Riley, Michael F.

    1987-01-01

    A higher-order modal method proposed by Leung for transient structural analysis entitled the force-derivative method is evaluated. This method repeatedly integrates by parts with respect to time the convolution-integral form of the structural response to produce successively better approximations to the contribution of the higher modes which are neglected in the modal summation. Comparisons are made of the force-derivative, the mode-displacement, and the mode-acceleration methods for several numerical example problems for various times, levels of damping, and forcing functions. The example problems include a tip-loaded cantilevered beam and a simply-supported multispan beam. The force-derivative method is shown to converge to an accurate solution in fewer modes than either the mode-displacement or the mode-acceleration methods. In addition, for problems in which there are a large number of closely-spaced frequencies whose mode shapes have a negligible contribution to the response, the force-derivative method is very effective in representing the effect of the important, but otherwise neglected, higher modes.

  20. Hepatocellular Carcinoma and Diffusion-Weighted MRI: Detection and Evaluation of Treatment Response.

    PubMed

    Gluskin, Jill S; Chegai, Fabrizio; Monti, Serena; Squillaci, Ettore; Mannelli, Lorenzo

    2016-01-01

    Differentiating between cancerous tissue and healthy liver parenchyma could represent a challenge with the only conventional Magnetic Resonance (MR) imaging. Diffusion weighted imaging (DWI) exploits different tissue characteristics to conventional Magnetic Resonance Imaging (MRI) sequences that enhance hepatocellular carcinoma (HCC) detection, characterization, and post-treatment evaluation. Detection of HCC is improved by DWI, infact this technology increases conspicuity of lesions that might otherwise not be identified due to obscuration by adjacent vessels or due to low contrast between the lesion and background liver. It is important to remember that DWI combined with contrast-enhanced MRI has higher sensitivity than DWI alone, and that some patients are not eligible for use of contrast on CT and MRI; in these patients DWI has a prominent role. MRI has advanced beyond structural anatomic imaging to now showing pathophysiologic processes. DWI is a promising way to characterize lesions utilizing the inherent contrast within the liver and has the benefit of not requiring contrast injection. DWI improves detection and characterization of HCC. Proposed clinical uses for DWI include: assessing prognosis, predicting response, monitoring response to therapy, and distinguishing tumor recurrence from treatment effect. Ideally, DWI will help risk stratify patients and will participate in prognostic modeling. PMID:27471573

  1. Early life stress dampens stress responsiveness in adolescence: Evaluation of neuroendocrine reactivity and coping behavior.

    PubMed

    Hsiao, Young-Ming; Tsai, Tsung-Chih; Lin, Yu-Ting; Chen, Chien-Chung; Huang, Chiung-Chun; Hsu, Kuei-Sen

    2016-05-01

    Stressful experiences during early life (ELS) can affect brain development, thereby exerting a profound and long-lasting influence on mental development and psychological health. The stress inoculation hypothesis presupposes that individuals who have early experienced an attenuated form of stressors may gain immunity to its more virulent forms later in life. Increasing evidence demonstrates that ELS may promote the development of subsequent stress resistance, but the mechanisms underlying such adaptive changes are not fully understood. The present study evaluated the impact of fragmented dam-pup interactions by limiting the bedding and nesting material in the cage during postnatal days 2-9, a naturalistic animal model of chronic ELS, on the physiological and behavioral responses to different stressors in adolescent mice and characterized the possible underlying mechanisms. We found that ELS mice showed less social interaction deficits after chronic social defeat stress and acute restraint-tailshock stress-induced impaired long-term potentiation (LTP) and enhanced long-term depression (LTD) in hippocampal CA1 region compared with control mice. The effects of ELS on LTP and LTD were rescued by adrenalectomy. While ELS did not cause alterations in basal emotional behaviors, it significantly enhanced stress coping behaviors in both the tail suspension and the forced swimming tests. ELS mice exhibited a significant decrease in corticosterone response and trafficking of glucocorticoid receptors to the nucleus in response to acute restraint stress. Altogether, our data support the hypothesis that stress inoculation training, via early exposure to manageable stress, may enhance resistance to other unrelated extreme stressors in adolescence. PMID:26881834

  2. Evaluation of chemotherapy response in ovarian cancer treatment using quantitative CT image biomarkers: a preliminary study

    NASA Astrophysics Data System (ADS)

    Qiu, Yuchen; Tan, Maxine; McMeekin, Scott; Thai, Theresa; Moore, Kathleen; Ding, Kai; Liu, Hong; Zheng, Bin

    2015-03-01

    The purpose of this study is to identify and apply quantitative image biomarkers for early prediction of the tumor response to the chemotherapy among the ovarian cancer patients participated in the clinical trials of testing new drugs. In the experiment, we retrospectively selected 30 cases from the patients who participated in Phase I clinical trials of new drug or drug agents for ovarian cancer treatment. Each case is composed of two sets of CT images acquired pre- and post-treatment (4-6 weeks after starting treatment). A computer-aided detection (CAD) scheme was developed to extract and analyze the quantitative image features of the metastatic tumors previously tracked by the radiologists using the standard Response Evaluation Criteria in Solid Tumors (RECIST) guideline. The CAD scheme first segmented 3-D tumor volumes from the background using a hybrid tumor segmentation scheme. Then, for each segmented tumor, CAD computed three quantitative image features including the change of tumor volume, tumor CT number (density) and density variance. The feature changes were calculated between the matched tumors tracked on the CT images acquired pre- and post-treatments. Finally, CAD predicted patient's 6-month progression-free survival (PFS) using a decision-tree based classifier. The performance of the CAD scheme was compared with the RECIST category. The result shows that the CAD scheme achieved a prediction accuracy of 76.7% (23/30 cases) with a Kappa coefficient of 0.493, which is significantly higher than the performance of RECIST prediction with a prediction accuracy and Kappa coefficient of 60% (17/30) and 0.062, respectively. This study demonstrated the feasibility of analyzing quantitative image features to improve the early predicting accuracy of the tumor response to the new testing drugs or therapeutic methods for the ovarian cancer patients.

  3. Evaluation of Sleeping Comfort of Bed Mattresses using Physiological and Psychological Response Measurements

    NASA Astrophysics Data System (ADS)

    Aoi, Masataka; Kamijo, Masayoshi; Yoshida, Hiroaki

    The purpose of this study is to create a method of evaluating the quality of sleep based on the elastic properties of bed mattresses through measurement of physiological and psychological responses while sleeping. We gathered Profile of Mood States (POMS) results before and after sleep, and investigated changes in subjects' moods according to sleep. A total of 4 bed mattresses with different degrees of elasticity were prepared. They were all pocket coil mattresses. We conducted polysomnography (PSG) testing on subjects with a bioamplifier while they slept in each bed mattress, so that sleeping depth indicating the quality of sleep could be estimated. PSG is a comprehensive recording of the biophysiological changes that occur during sleep. As a result, the sleep depth of bed mattress with a high degree of elasticity increased in the PSG evaluation. Because the hip sinks in deeply from the waist, it is not easy to turn over on mattresses with a low degree of elasticity. We have therefore considered that the sleep depth of the subjects became shallow as a result. We have concluded that it is possible to estimate the quality of sleep through analysis of PSG and POMS results.

  4. [Information capability of the test with radioadaptive response in functiional evaluation of pilots].

    PubMed

    Alchinova, I B; Khlebnikova, N N; Karganov, M Iu

    2012-01-01

    Information capability of the radioadaptive response test was assessed during functional evaluation of pilots in the course of adaptation to fight factors. Functional evaluation was made on the system level, i.e., by cardiorespiratory parameters (spirometry and arteriorcardiography), the cellular level by individual sensitivity to ionized radiatiin of metabolic shifts (laser correlation spectroscopy of biological liquids). Changes in molecular composition of blood serum and cardiorespiratory functions were compared with individual radiosensitivity of pilots with varying fight time. Incidence of and strength of lymphocytes' RAR decreased with increasing flight hours. In light scattering spectra the input of particles with small hydrodynamic radius (no more than 11 nm) reduced and that of large particles (more than 200 nm) increased. Total power of the cardiac rhythm variability (CRV) spectrum decreased whereas stress-index grew in value. Breathing test raised peripheral systolic and diastolic blood pressure in masked pilots w/o RAR. Besides, it reduced total spectrum of systolic pressure variability and input of very low frequencies. In the group of RAR pilots, relative input of low frequencies into CRV grew and of high frequencies decreased; blood pressure did not alter Decreased input of small particles and increased input of large particles in light scattering as compared with baseline values were found only in RAR pilots suggesting shifts in metabolism and humoral immunity. It can be hypothesized that level of individual radiosensitivity reflects general resistance of organism to negative factors of environment. PMID:23074953

  5. Evaluation of response to restraint stress by salivary corticosterone levels in adult male mice

    PubMed Central

    NOHARA, Masakatsu; TOHEI, Atsushi; SATO, Takumi; AMAO, Hiromi

    2016-01-01

    Saliva as a sampling method is a low invasive technique for the detection of physiologically active substances, as opposed to sampling the plasma or serum. In this study, we obtained glucocorticoids transferred from the blood to the saliva from mice treated with 2.0 mg/kg via an intraperitoneal injection of cortisol. Next, to evaluate the effect of restraint stress using mouse saliva—collected under anesthesia by mixed anesthetic agents—we measured plasma and salivary corticosterone levels at 60 min after restraint stress. Moreover, to evaluate salivary corticosterone response to stress in the same individual mouse, an adequate recovery period (1, 3 and 7 days) after anesthesia was examined. The results demonstrate that exogenous cortisol was detected in the saliva and the plasma, in mice treated with cortisol. Restraint stress significantly increased corticosterone levels in both the plasma and saliva (P<0.001). Monitoring the results of individual mice showed that restraint stress significantly increased salivary corticosterone levels in all three groups (1-, 3- and 7-day recovery). However, the statistical evidence of corticosterone increase is stronger in the 7-day recovery group (P<0.001) than in the others (P<0.05). These results suggest that the corticosterone levels in saliva reflect its levels in the plasma, and salivary corticosterone is a useful, less-invasive biomarker of physical stress in mice. The present study may contribute to concepts of Reduction and Refinement of the three Rs in small animal experiments. PMID:26852731

  6. Energy harvesting from the discrete gust response of a piezoaeroelastic wing: Modeling and performance evaluation

    NASA Astrophysics Data System (ADS)

    Xiang, Jinwu; Wu, Yining; Li, Daochun

    2015-05-01

    The objective of this paper is to investigate energy harvesting from the unfavorable gust response of a piezoelectric wing. An aeroelectroelastic model is built for the evaluation and improvement of the harvesting performance. The structural model is built based on the Euler-Bernoulli beam theory. The unsteady aerodynamics, combined with 1-cosine gust load, are obtained from Jones' approximation of the Wagner function. The state-space equation of the aeroelectroelastic model is derived and solved numerically. The energy conversion efficiency and output density are defined to evaluate the harvesting performance. The effects of the sizes and location of the piezoelectric transducers, the load resistance in the external circuit, and the locations of the elastic axis and gravity center axis of the wing are studied, respectively. The results show that, under a given width of the transducers in chordwise direction, there are one thickness of the transducers corresponding to highest conversion efficiency and one smaller optimal value for the output density. The conversion efficiency has an approximate linear relationship with the width. As the transducers are placed at the wing root, a maximum conversion efficiency is reached under a certain length in the spanwise direction, whereas a smaller length helps reaching a larger output density. One optimal resistance is found to maximize the conversion efficiency. The rearward shift of either the elastic axis or gravity center axis improves the energy output while reducing the conversion efficiency.

  7. The design of a contextualized responsive evaluation framework for fishery management in Benin.

    PubMed

    Kouévi, A T; Van Mierlo, B; Leeuwis, C; Vodouhê, S D

    2013-02-01

    The main question addressed by this article is how to adapt the responsive evaluation (RE) approach to an intervention context characterized by repetition of ineffective interventions, ambiguous intervention action theories among stakeholders, and high complexity. The context is Grand-Popo, a fishing municipality located on Benin's southwest Atlantic coast. The fishery management interventionists and the fishing communities in the municipality all espoused concern for the sustainable improvement of fishing actors' livelihood conditions, but differed about the reasons for this livelihood impairment, and about what should be done, when, where, and by whom. Given this ambiguity, we identified RE as a promising action research approach to facilitate dialogue and mutual learning, and consequently to improve stakeholders' ability to resolve problems. However, this approach seems to have some shortcomings in the Grand-Popo context, regarding the repetitive ineffectiveness of interventions, high complexity, and uncertainty. Therefore, based on our empirical study, we add three dimensions to the existing RE framework: historical analysis to deal with routine interventions, exploration and discussion of incongruities of action theories to trigger double-loop learning, and system analysis to deal with complexity and uncertainty. This article does not intend to address the implications or impact of this adapted RE framework. Instead, we suggest some criteria and indicators for evaluating whether the proposed amended RE approach has assisted in resolving the fishery problems in Grand-Popo after the approach has been applied.

  8. Evaluation of Dynamic Coastal Response to Sea-level Rise Modifies Inundation Likelihood

    NASA Technical Reports Server (NTRS)

    Lentz, Erika E.; Thieler, E. Robert; Plant, Nathaniel G.; Stippa, Sawyer R.; Horton, Radley M.; Gesch, Dean B.

    2016-01-01

    Sea-level rise (SLR) poses a range of threats to natural and built environments, making assessments of SLR-induced hazards essential for informed decision making. We develop a probabilistic model that evaluates the likelihood that an area will inundate (flood) or dynamically respond (adapt) to SLR. The broad-area applicability of the approach is demonstrated by producing 30x30m resolution predictions for more than 38,000 sq km of diverse coastal landscape in the northeastern United States. Probabilistic SLR projections, coastal elevation and vertical land movement are used to estimate likely future inundation levels. Then, conditioned on future inundation levels and the current land-cover type, we evaluate the likelihood of dynamic response versus inundation. We find that nearly 70% of this coastal landscape has some capacity to respond dynamically to SLR, and we show that inundation models over-predict land likely to submerge. This approach is well suited to guiding coastal resource management decisions that weigh future SLR impacts and uncertainty against ecological targets and economic constraints.

  9. Application of spatial frequency response as a criterion for evaluating thermal imaging camera performance

    NASA Astrophysics Data System (ADS)

    Lock, Andrew; Amon, Francine

    2008-04-01

    Police, firefighters, and emergency medical personnel are examples of first responders that are utilizing thermal imaging cameras in a very practical way every day. However, few performance metrics have been developed to assist first responders in evaluating the performance of thermal imaging technology. This paper describes one possible metric for evaluating spatial resolution using an application of Spatial Frequency Response (SFR) calculations for thermal imaging. According to ISO 12233, the SFR is defined as the integrated area below the Modulation Transfer Function (MTF) curve derived from the discrete Fourier transform of a camera image representing a knife-edge target. This concept is modified slightly for use as a quantitative analysis of the camera's performance by integrating the area between the MTF curve and the camera's characteristic nonuniformity, or noise floor, determined at room temperature. The resulting value, which is termed the Effective SFR, can then be compared with a spatial resolution value obtained from human perception testing of task specific situations to determine the acceptability of the performance of thermal imaging cameras. The testing procedures described herein are being developed as part of a suite of tests for possible inclusion into a performance standard on thermal imaging cameras for first responders.

  10. An evaluation of three methods of saying "no" to avoid an escalating response class hierarchy.

    PubMed

    Mace, F Charles; Pratt, Jamie L; Prager, Kevin L; Pritchard, Duncan

    2011-01-01

    We evaluated the effects of three different methods of denying access to requested high-preference activities on escalating problem behavior. Functional analysis and response class hierarchy (RCH) assessment results indicated that 4 topographies of problem behaviors displayed by a 13-year-old boy with high-functioning autism constituted an RCH maintained by positive (tangible) reinforcement. Identification of the RCH comprised the baseline phase, during which computer access was denied by saying "no" and providing an explanation for the restriction. Two alternative methods of saying "no" were then evaluated. These methods included (a) denying computer access while providing an opportunity to engage in an alternative preferred activity and (b) denying immediate computer access by arranging a contingency between completion of a low-preference task and subsequent computer access. Results indicated that a hierarchy of problem behavior may be identified in the context of denying access to a preferred activity and that it may be possible to prevent occurrences of escalating problem behavior by either presenting alternative options or arranging contingencies when saying "no" to a child's requests. PMID:21541139

  11. Evaluation of dynamic coastal response to sea-level rise modifies inundation likelihood

    USGS Publications Warehouse

    Lentz, Erika E.; Thieler, E. Robert; Plant, Nathaniel G.; Stippa, Sawyer R.; Horton, Radley M.; Gesch, Dean B.

    2016-01-01

    Sea-level rise (SLR) poses a range of threats to natural and built environments1, 2, making assessments of SLR-induced hazards essential for informed decision making3. We develop a probabilistic model that evaluates the likelihood that an area will inundate (flood) or dynamically respond (adapt) to SLR. The broad-area applicability of the approach is demonstrated by producing 30 × 30 m resolution predictions for more than 38,000 km2 of diverse coastal landscape in the northeastern United States. Probabilistic SLR projections, coastal elevation and vertical land movement are used to estimate likely future inundation levels. Then, conditioned on future inundation levels and the current land-cover type, we evaluate the likelihood of dynamic response versus inundation. We find that nearly 70% of this coastal landscape has some capacity to respond dynamically to SLR, and we show that inundation models over-predict land likely to submerge. This approach is well suited to guiding coastal resource management decisions that weigh future SLR impacts and uncertainty against ecological targets and economic constraints.

  12. Dendrimer mediated clustering of bacteria: improved aggregation and evaluation of bacterial response and viability.

    PubMed

    Leire, Emma; Amaral, Sandra P; Louzao, Iria; Winzer, Klaus; Alexander, Cameron; Fernandez-Megia, Eduardo; Fernandez-Trillo, Francisco

    2016-06-24

    Here, we evaluate how cationic gallic acid-triethylene glycol (GATG) dendrimers interact with bacteria and their potential to develop new antimicrobials. We demonstrate that GATG dendrimers functionalised with primary amines in their periphery can induce the formation of clusters in Vibrio harveyi, an opportunistic marine pathogen, in a generation dependent manner. Moreover, these cationic GATG dendrimers demonstrate an improved ability to induce cluster formation when compared to poly(N-[3-(dimethylamino)propyl]methacrylamide) [p(DMAPMAm)], a cationic linear polymer previously shown to cluster bacteria. Viability of the bacteria within the formed clusters and evaluation of quorum sensing controlled phenotypes (i.e. light production in V. harveyi) suggest that GATG dendrimers may be activating microbial responses by maintaining a high concentration of quorum sensing signals inside the clusters while increasing permeability of the microbial outer membranes. Thus, the reported GATG dendrimers constitute a valuable platform for the development of novel antimicrobial materials that can target microbial viability and/or virulence. PMID:27127812

  13. Comparative evaluation of test methods to simulate acoustic response of shroud-enclosed spacecraft structures

    NASA Technical Reports Server (NTRS)

    On, F. J.

    1975-01-01

    Test methods were evaluated to ascertain whether a spacecraft, properly tested within its shroud, could be vibroacoustic tested without the shroud, with adjustments made in the acoustic input spectra to simulate the acoustic response of the missing shroud. The evaluation was based on vibroacoustic test results obtained from a baseline model composed (1) of a spacecraft with adapter, lower support structure, and shroud; (2) of the spacecraft, adapter, and lower structure, but without the shroud; and (3) of the spacecraft and adapter only. Emphasis was placed on the magnitude of the acoustic input changes required to substitute for the shroud and the difficulty of making such input changes, and the degree of missimulation which can result from the performance of a particular, less-than optimum test. Conclusions are drawn on the advantages and disadvantages derived from the use of input spectra adjustment methods and lower support structure simulations. Test guidelines were also developed for planning and performing a launch acoustic-environmental test.

  14. Self-compassion training modulates alpha-amylase, heart rate variability, and subjective responses to social evaluative threat in women.

    PubMed

    Arch, Joanna J; Brown, Kirk Warren; Dean, Derek J; Landy, Lauren N; Brown, Kimberley D; Laudenslager, Mark L

    2014-04-01

    A growing body of research has revealed that social evaluative stressors trigger biological and psychological responses that in chronic forms have been linked to aging and disease. Recent research suggests that self-compassion may protect the self from typical defensive responses to evaluation. We investigated whether brief training in self-compassion moderated biopsychological responses to the Trier Social Stress Test (TSST) in women. Compared to attention (placebo) and no-training control conditions, brief self-compassion training diminished sympathetic (salivary alpha-amylase), cardiac parasympathetic, and subjective anxiety responses, though not HPA-axis (salivary cortisol) responses to the TSST. Self-compassion training also led to greater self-compassion under threat relative to the control groups. In that social stress pervades modern life, self-compassion represents a promising approach to diminishing its potentially negative psychological and biological effects.

  15. Providing Reliability Services through Demand Response: A Prelimnary Evaluation of the Demand Response Capabilities of Alcoa Inc.

    SciTech Connect

    Starke, Michael R; Kirby, Brendan J; Kueck, John D; Todd, Duane; Caulfield, Michael; Helms, Brian

    2009-02-01

    Demand response is the largest underutilized reliability resource in North America. Historic demand response programs have focused on reducing overall electricity consumption (increasing efficiency) and shaving peaks but have not typically been used for immediate reliability response. Many of these programs have been successful but demand response remains a limited resource. The Federal Energy Regulatory Commission (FERC) report, 'Assessment of Demand Response and Advanced Metering' (FERC 2006) found that only five percent of customers are on some form of demand response program. Collectively they represent an estimated 37,000 MW of response potential. These programs reduce overall energy consumption, lower green house gas emissions by allowing fossil fuel generators to operate at increased efficiency and reduce stress on the power system during periods of peak loading. As the country continues to restructure energy markets with sophisticated marginal cost models that attempt to minimize total energy costs, the ability of demand response to create meaningful shifts in the supply and demand equations is critical to creating a sustainable and balanced economic response to energy issues. Restructured energy market prices are set by the cost of the next incremental unit of energy, so that as additional generation is brought into the market, the cost for the entire market increases. The benefit of demand response is that it reduces overall demand and shifts the entire market to a lower pricing level. This can be very effective in mitigating price volatility or scarcity pricing as the power system responds to changing demand schedules, loss of large generators, or loss of transmission. As a global producer of alumina, primary aluminum, and fabricated aluminum products, Alcoa Inc., has the capability to provide demand response services through its manufacturing facilities and uniquely through its aluminum smelting facilities. For a typical aluminum smelter, electric power

  16. Investigating Assessment Bias for Constructed Response Explanation Tasks: Implications for Evaluating Performance Expectations for Scientific Practice

    NASA Astrophysics Data System (ADS)

    Federer, Meghan Rector

    Assessment is a key element in the process of science education teaching and research. Understanding sources of performance bias in science assessment is a major challenge for science education reforms. Prior research has documented several limitations of instrument types on the measurement of students' scientific knowledge (Liu et al., 2011; Messick, 1995; Popham, 2010). Furthermore, a large body of work has been devoted to reducing assessment biases that distort inferences about students' science understanding, particularly in multiple-choice [MC] instruments. Despite the above documented biases, much has yet to be determined for constructed response [CR] assessments in biology and their use for evaluating students' conceptual understanding of scientific practices (such as explanation). Understanding differences in science achievement provides important insights into whether science curricula and/or assessments are valid representations of student abilities. Using the integrative framework put forth by the National Research Council (2012), this dissertation aimed to explore whether assessment biases occur for assessment practices intended to measure students' conceptual understanding and proficiency in scientific practices. Using a large corpus of undergraduate biology students' explanations, three studies were conducted to examine whether known biases of MC instruments were also apparent in a CR instrument designed to assess students' explanatory practice and understanding of evolutionary change (ACORNS: Assessment of COntextual Reasoning about Natural Selection). The first study investigated the challenge of interpreting and scoring lexically ambiguous language in CR answers. The incorporation of 'multivalent' terms into scientific discourse practices often results in statements or explanations that are difficult to interpret and can produce faulty inferences about student knowledge. The results of this study indicate that many undergraduate biology majors

  17. Coordination of cortisol response to social evaluative threat with autonomic and inflammatory responses is moderated by stress appraisals and affect.

    PubMed

    Laurent, Heidemarie K; Lucas, Todd; Pierce, Jennifer; Goetz, Stefan; Granger, Douglas A

    2016-07-01

    Recent approaches to stress regulation have emphasized coordination among multiple biological systems. This study builds on evidence that hypothalamic-pituitary-adrenal (HPA) axis activity should be considered in coordination with other stress-sensitive biological systems to characterize healthy responses. Healthy African-Americans (n=115) completed the Trier Social Stress Test, and biological responses were assessed through salivary cortisol, dehydroepiandrosterone-sulfate (DHEA-S), alpha amylase (sAA), and C-reactive protein (sCRP). Multilevel modeling demonstrated that cortisol responses typically aligned with changes in DHEA-S, sAA, and sCRP across the session. At the same time, the degree of cortisol coordination with sAA and sCRP varied by participants' subjective stress following the task; participants with higher secondary stress appraisals showed greater cortisol-sAA alignment, whereas those experiencing more negative affect showed greater cortisol-sCRP alignment. Results highlight the importance of a multisystem approach to stress and suggest that positive HPA axis coordination with the autonomic response, but not with the immune/inflammatory response, may be adaptive.

  18. Building Effectiveness in Teaching through Targeted Evaluation and Response: Connecting Evaluation to Teaching Improvement in Higher Education

    ERIC Educational Resources Information Center

    Smith, Calvin

    2008-01-01

    This paper describes the development of a model for integrating student evaluation of teaching results with academic development opportunities, in new ways that take into account theoretical and practical developments in both fields. The model is described in terms of five phases or components: (1) the basic student evaluation system; (2) an…

  19. Evaluation of Users' Responses to the Information Analysis Products of the ERIC Clearinghouse on Tests, Measurement, and Evaluation.

    ERIC Educational Resources Information Center

    Hensley, Susan

    To obtain user evaluations of the information analysis products (IAPs) produced by the Educational Resources Information Center Clearinghouse on Tests, Measurement, and Evaluation (ERIC/TM), subjects were randomly drawn from a 1976 list of the clearinghouse's IAP orders. The sample was stratified by the title requested and the following…

  20. Evaluating Cumulative Ecosystem Response to Restoration Projects in the Columbia River Estuary, Annual Report 2004

    SciTech Connect

    Diefenderfer, Heida L.; Roegner, Curtis; Thom, Ronald M.; Dawley, Earl M.; Whiting, Allan H.; Johnson, Gary E.; Sobocinski, Kathryn L.; Anderson, Michael G.; Ebberts, Blaine

    2005-12-15

    The restoration of wetland salmon habitat in the tidal portion of the Columbia River is occurring at an accelerating pace and is anticipated to improve habitat quality and effect hydrological reconnection between existing and restored habitats. Currently multiple groups are applying a variety of restoration strategies in an attempt to emulate historic estuarine processes. However, the region lacks both a standardized means of evaluating the effectiveness of individual projects as well as methods for determining the cumulative effects of all restoration projects on a regional scale. This project is working to establish a framework to evaluate individual and cumulative ecosystem responses to restoration activities in order to validate the effectiveness of habitat restoration activities designed to benefit salmon through improvements to habitat quality and habitat opportunity (i.e. access) in the Columbia River from Bonneville Dam to the ocean. The review and synthesis of approaches to measure the cumulative effects of multiple restoration projects focused on defining methods and metrics of relevance to the CRE, and, in particular, juvenile salmon use of this system. An extensive literature review found no previous study assessing the cumulative effects of multiple restoration projects on the fundamental processes and functions of a large estuarine system, although studies are underway in other large land-margin ecosystems including the Florida Everglades and the Louisiana coastal wetlands. Literature from a variety of scientific disciplines was consulted to identify the ways that effects can accumulate (e.g., delayed effects, cross-boundary effects, compounding effects, indirect effects, triggers and thresholds) as well as standard and innovative tools and methods utilized in cumulative effects analyses: conceptual models, matrices, checklists, modeling, trends analysis, geographic information systems, carrying capacity analysis, and ecosystem analysis. Potential

  1. SU-E-QI-20: A Review of Advanced PET and CT Image Features for the Evaluation of Tumor Response

    SciTech Connect

    Lu, W

    2014-06-15

    Purpose: To review the literature in using quantitative PET and CT image features for the evaluation of tumor response. Methods: We reviewed and summarized more than fifty papers that use advanced, quantitative PET/CT image features for the evaluation of tumor response. We also discussed future works on extracting disease-specific features, combining multiple and complementary features in response modeling, delineating tumor in multimodality images, and exploring biological explanations of these advanced features. Results: Advanced PET image features considering spatial information, such as tumor volume, tumor shape, total glycolytic volume, histogram distance, and texture features (characterizing spatial distribution of FDG uptake) have been found more informative than the traditional SUVmax for the prediction of tumor response. Advanced CT features, including volumetric, attenuation, morphologic, structure, and texture descriptors, have also been found advantage over the traditional RECIST and WHO criteria in certain tumor types. Conclusions: Advanced, quantitative FDG PET/CT image features have been shown promising for the evaluation of tumor response. With the emerging multi-modality imaging performed at multiple time points for each patient, it becomes more important to analyze the serial images quantitatively, select and combine both complementary and contradictory information from various sources, for accurate and personalized evaluation of tumor response to therapy.

  2. Effects of dabigatran on the cellular and protein phase of coagulation in patients with coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel. Results from a prospective, randomised, double-blind, placebo-controlled study.

    PubMed

    Franchi, Francesco; Rollini, Fabiana; Cho, Jung Rae; King, Rhodri; Phoenix, Fladia; Bhatti, Mona; DeGroat, Christopher; Tello-Montoliu, Antonio; Zenni, Martin M; Guzman, Luis A; Bass, Theodore A; Ajjan, Ramzi A; Angiolillo, Dominick J

    2016-03-01

    There is growing interest in understanding the effects of adding an oral anticoagulant in patients on dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and clopidogrel represent the most broadly utilised oral anticoagulant and P2Y12 receptor inhibitor, respectively. However, VKAs can interfere with clopidogrel metabolism via the cytochrome P450 (CYP) system which in turn may result in an increase in platelet reactivity. Dabigatran is a direct acting (anti-II) oral anticoagulant which does not interfere with CYP and has favourable safety and efficacy profiles compared with VKAs. The pharmacodynamic (PD) effects on platelet reactivity and clot kinetic of adjunctive dabigatran therapy in patients on DAPT are poorly explored. In this prospective, randomised, double-blind, placebo-controlled PD study, patients (n=30) on maintenance DAPT with aspirin and clopidogrel were randomised to either dabigatran 150 mg bid or placebo for seven days. PD testing was performed before and after treatment using four different assays exploring multiple pathways of platelet aggregation and fibrin clot kinetics: light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA), kaolin-activated thromboelastography (TEG) and turbidimetric assays. There were no differences in multiple measures of platelet reactivity investigating purinergic and non-purinergic signaling pathways assessed by LTA, MEA and TEG platelet mapping. Dabigatran significantly increased parameters related to thrombin activity and thrombus generation, and delayed fibrin clot formation, without affecting clot structure or fibrinolysis. In conclusion, in patients on DAPT with aspirin and clopidogrel, adjunctive dabigatran therapy is not associated with modulation of profiles of platelet reactivity as determined by several assays assessing multiple platelet signalling pathways. However, dabigatran significantly interferes with parameters related to thrombin activity and delays fibrin clot formation

  3. [Quantitative evaluation of response at acetazolamide test using 99mTc-ECD SPECT; a trial of production of the response map].

    PubMed

    Oyama, T; Sutoh, H; Kawamura, H; Teraoka, S; Midorikawa, H

    1997-06-01

    In the method by Matsuda and Takeuchi et al. for easy regional cerebral blood flow (rCBF) measurements at pre- and post-acetazolamide tests using 99mTc-ECD, a study was done for producing the increase rate of rCBF as a response map after acetazolamide administration. To prepare the response map calculated from the arithmetic operation of [(rCBF image at administration--rCBF image at rest)/rCBF image at rest x 100], the images were preprocessed by combination of matrix size conversion and smoothing techniques and then areas outside the brain were masked to remove amplified noises. The response map seemed helpful for visual evaluation of the response after acetazolamide administration, and also for understanding the disease conditions and clinical courses.

  4. Response

    ERIC Educational Resources Information Center

    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…

  5. Toxicological Evaluation of Realistic Emission Source Aerosols (TERESA)-power plant studies: assessment of cellular responses

    PubMed Central

    Godleski, John J.; Diaz, Edgar A.; Lemos, Miriam; Long, Mark; Ruiz, Pablo; Gupta, Tarun; Kang, Choong-Min; Coull, Brent

    2013-01-01

    The Toxicological Evaluation of Realistic Emission Source Aerosols (TERESA) project assessed primary and secondary particulate by simulating the chemical reactions that a plume from a source might undergo during atmospheric transport and added other atmospheric constituents that might interact with it. Three coal-fired power plants with different coal and different emission controls were used. Male Sprague-Dawley rats were exposed for 6 h to either filtered air or aged aerosol from the power plant. Four exposure scenarios were studied: primary particles (P); primary + secondary (oxidized) particles (PO); primary + secondary (oxidized) particles + SOA (POS); and primary + secondary (oxidized) particles neutralized + SOA (PONS). Exposure concentrations varied by scenario to a maximum concentration of 257.1 ± 10.0 µg/m3. Twenty-four hours after exposure, pulmonary cellular responses were assessed by bronchoalveolar lavage (BAL), complete blood count (CBC), and histopathology. Exposure to the PONS and POS scenarios produced significant increases in BAL total cells and macrophage numbers at two plants. The PONS and P scenarios were associated with significant increases in BAL neutrophils and the presence of occasional neutrophils and increased macrophages in the airways and alveoli of exposed animals. Univariate analyses and random forest analyses showed that increases in total cell count and macrophage cell count were significantly associated with neutralized sulfate and several correlated measurements. Increases in neutrophils in BAL were associated with zinc. There were no significant differences in CBC parameters or blood vessel wall thickness by histopathology. The association between neutrophils increases and zinc raises the possibility that metals play a role in this response. PMID:21466245

  6. Basic emotions evoked by odorants: comparison between autonomic responses and self-evaluation.

    PubMed

    Alaoui-Ismaïli, O; Robin, O; Rada, H; Dittmar, A; Vernet-Maury, E

    1997-10-01

    The present study was designed to analyze the relationship between self-report and physiological expression of basic emotions (happiness, surprise, fear, sadness, disgust and anger) in response to odorants. 44 subjects inhaled five odorants: vanillin, menthol, eugenol, methyl methacrylate, and propionic acid. Six autonomic nervous systems (ANS) parameters were simultaneously recorded in real time and without interference: Skin Potential (SP), Skin Resistance (SR), Skin Temperature (ST), Skin Blood Flow (SBF), Instantaneous Respiratory Frequency (IRF) and Instantaneous Heart Rate (IHR). At the end of the recording, subjects were instructed i) to identify the odorants roughly II) to situate them on an 11-point hedonic scale from highly pleasant (0) to highly unpleasant (10); and iii) to define what type of basic emotion was evoked by each odorant. In this study, the expected affects were aroused in the subjects. Vanillin and menthol were rated pleasant, while methyl methacrylate and propionic acid were judged unpleasant. Eugenol was median in hedonic estimation. ANS evaluation (each autonomic pattern induced by an odorant was transcripted into a basic emotion) shows that pleasantly connoted odorants evoked mainly happiness and surprise, but that unpleasant ones induced mainly disgust and anger. Eugenol was associated with positive and negative affects. Comparison between conscious (verbal) and unconscious (ANS) emotions, reveals that these two estimations 1) were not significantly different as far as the two pleasant odorants were concerned, 2) showed a tendency to be significantly different for eugenol odorant which was variably scored on the hedonic axis, and 3) exhibited a significant difference for the two unpleasant odorants, for which the corresponding "verbal emotion" was mainly "disgust", while the most frequent ANS emotion was "anger". In conclusion, these results show quite a good correlation between verbal and ANS estimated basic emotions. The main

  7. Evaluation of Rock Mass Responses Using High Resolution Water-level Tiltmeter Arrays

    NASA Astrophysics Data System (ADS)

    Roberts, J. S.; Wang, H. F.; Fratta, D.; Stetler, L. D.; Volk, J. T.; Geox^Tm

    2010-12-01

    External forces act on the surface of the earth and produce deformation across all spatial and temporal scales. This research study focuses on the deformation evaluation of the rock-mass subjected to tidal, earthquake and surface forces. The events are monitored over horizontal distances of over 100 meters with tilt measurement arrays with a resolution of 10-8 radians. These measurements are obtained from hydrostatic leveling system (HLS) arrays that have been installed in the LaFarge mine in North Aurora, IL by Fermilab. Each sensor in the array is equipped with a water-filled reservoir beneath a capacitor. The amount of water in the reservoir is calculated as a function of the measured capacitance. Individual sensors are connected in a closed system via a water and air line. As the host rock expands and contracts sensors are raised relative to another and water is displaced. The water level in each reservoir is sent to a computer in the mine and recorded. In order to measure the tilt of the rock between two points, the difference in water levels between adjacent sensors is computed. The difference between the end sensors is also calculated to determine the larger-scale tilt of the array. The tiltmeters in LaFarge mine are supported by concrete pedestals installed on the floor of the drift. In the Homestake mine the tiltmeters are placed on similar pedestals, as well as platforms made of artificial wood decking. These platforms are fixed to the wall of the drift with a rock bolt. Time and frequency domain analyses were performed on time series ranging from hours to six months to capture relevant time scales including the response to the 2010 Chile Earthquake (hour-long scale), the stages of the moon (month scale), Fox River floods (flooding week long scales and pressure dissipation month-long scales). By monitoring tiltmeter array responses to different forces, we aim at making predictions about the material properties of rock masses.

  8. Evaluation of cardiovascular protective effect of different apple varieties - Correlation of response with composition.

    PubMed

    Serra, Ana Teresa; Rocha, J; Sepodes, B; Matias, Ana A; Feliciano, Rodrigo P; de Carvalho, Agostinho; Bronze, Maria R; Duarte, Catarina M M; Figueira, M E

    2012-12-15

    Epidemiological evidence supports the concept that diets rich in fruits and vegetables promote health and attenuate or delay the onset of cardiovascular disease (CVD). In particular, a reduced risk of CVD has been associated with apple consumption, probably due to the cholesterol-lowering effect of the main bioactive compounds, namely fibre and polyphenols. In this work, the effect of diet supplementation with 20% of three Portuguese apple cultivars (Bravo de Esmolfe, Malápio Serra and Golden), containing distinct phenolic and fibre concentrations, on serum lipid profile and oxLDL of male Wistar rats fed a cholesterol-enriched diet (2%) was evaluated. After 30 days, only Bravo de Esmolfe apple was able to decrease significantly serum levels of triglycerides, total and LDL cholesterol concentrations (reductions of 27.2%, 21.0% and 20.4%, respectively, in relation to the cholesterol-enriched diet group, P<0.05). The levels of oxLDL were also significantly improved with the consumption of this apple variety (reductions of 20.0% and 11.9%, in relation to the cholesterol-enriched diet group and control group, respectively, P>0.05) as well as with Malapio da Serra apple (reductions of 9.8% in relation to the cholesterol-enriched diet group, P<0.05). Correlation of the bioactive response with chemical composition showed that catechin, epicatechin, procyanidin B1 and β-carotene are the major phytocompounds responsible for the cholesterol lowering ability of apples. The antioxidant potential may have also contributed to this beneficial effect.

  9. Linear Modeling and Evaluation of Controls on Flow Response in Western Post-Fire Watersheds

    NASA Astrophysics Data System (ADS)

    Saxe, S.; Hogue, T. S.; Hay, L.

    2015-12-01

    This research investigates the impact of wildfires on watershed flow regimes throughout the western United States, specifically focusing on evaluation of fire events within specified subregions and determination of the impact of climate and geophysical variables in post-fire flow response. Fire events were collected through federal and state-level databases and streamflow data were collected from U.S. Geological Survey stream gages. 263 watersheds were identified with at least 10 years of continuous pre-fire daily streamflow records and 5 years of continuous post-fire daily flow records. For each watershed, percent changes in runoff ratio (RO), annual seven day low-flows (7Q2) and annual seven day high-flows (7Q10) were calculated from pre- to post-fire. Numerous independent variables were identified for each watershed and fire event, including topographic, land cover, climate, burn severity, and soils data. The national watersheds were divided into five regions through K-clustering and a lasso linear regression model, applying the Leave-One-Out calibration method, was calculated for each region. Nash-Sutcliffe Efficiency (NSE) was used to determine the accuracy of the resulting models. The regions encompassing the United States along and west of the Rocky Mountains, excluding the coastal watersheds, produced the most accurate linear models. The Pacific coast region models produced poor and inconsistent results, indicating that the regions need to be further subdivided. Presently, RO and HF response variables appear to be more easily modeled than LF. Results of linear regression modeling showed varying importance of watershed and fire event variables, with conflicting correlation between land cover types and soil types by region. The addition of further independent variables and constriction of current variables based on correlation indicators is ongoing and should allow for more accurate linear regression modeling.

  10. Hydrochlorothiazide-induced hyperuricaemia in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study

    PubMed Central

    Vandell, Alexander G.; McDonough, Caitrin W.; Gong, Yan; Langaee, Taimour Y.; Lucas, Anne M.; Chapman, Arlene B.; Gums, John G.; Beitelshees, Amber L.; Bailey, Kent R.; Johnson, Richard J.; Boerwinkle, Eric; Turner, Stephen T.; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.

    2014-01-01

    Objective Elevations in uric acid (UA) and the associated hyperuricaemia are commonly observed secondary to treatment with thiazide diuretics. We sought to identify novel single-nucleotide polymorphisms (SNPs) associated with hydrochlorothiazide (HCTZ)-induced elevations in UA and hyperuricaemia. Methods A genome-wide association study of HCTZ-induced changes in UA was performed in Caucasian and African American participants from the Pharmacogenomic Evaluation of Antihypertensive Response (PEAR) study who were treated with HCTZ monotherapy. Suggestive SNPs were replicated in Caucasians and African Americans from the PEAR study who were treated with HCTZ add-on therapy. Replicated regions were followed up through expression and pathway analysis. Results Five unique gene regions were identified in African Americans (LUC7L2, ANKRD17/COX18, FTO, PADI4 and PARD3B) and one region was identified in Caucasians (GRIN3A). Increases in UA of up to 1.8 mg/dL were observed following HCTZ therapy in individuals homozygous for risk alleles, with heterozygotes displaying an intermediate phenotype. Several risk alleles were also associated with an increased risk of HCTZ-induced clinical hyperuricaemia. A composite risk score, constructed in African Americans using the ‘top’ SNP from each gene region, was strongly associated with HCTZ-induced UA elevations (P = 1.79×10−7) and explained 11% of the variability in UA response. Expression studies in RNA from whole blood revealed significant differences in expression of FTO by rs4784333 genotype. Pathway analysis showed putative connections between many of the genes identified through common microRNAs. Conclusion Several novel gene regions were associated with HCTZ-induced UA elevations in African Americans (LUC7L2, COX18/ANKRD17, FTO, PADI4 and PARD3B) and one region was associated with these elevations in Caucasians (GRIN3A). PMID:24612202

  11. Audience-response systems for evaluation of pediatric lectures – comparison with a classic end-of-term online-based evaluation

    PubMed Central

    Bode, Sebastian Felix Nepomuk; Straub, Christine; Giesler, Marianne; Biller, Silke; Forster, Johannes; Krüger, Marcus

    2015-01-01

    Aim: Course evaluations are often conducted and analyzed well after the course has taken place. By using a digital audience response system (ARS), it is possible to collect, view and discuss feedback during or directly following a course or lecture session. This paper analyzes a student evaluation of a lecture course with ARS to determine if significant differences exist between the results of the ARS lecture evaluation and those of the online evaluation at the end of the semester. In terms of the overall evaluation, consideration is given to the level of students’ prior knowledge, the presentation of the lecture material by the lecturers and the relevance of the lecture topic for students. Method: During the 2011-12 winter semester, the lecture on Pediatrics at the Freiburg Center for Pediatric and Adolescent Medicine (Zentrum für Kinder- und Jugendmedizin (ZKJ) Freiburg) was evaluated using ARS. Thirty-four lectures were evaluated by an average of 22 (range 8-44) students, who responded to four questions each time an evaluation took place. Results: On a 6-point Likert scale (1=very good to 6=deficient), the students rated their level of preparedness with a mean of 3.18, the presentation of the lecture with 2.44, and the relevance of the lecture topic with 2.19. The overall evaluation of the lecture course by means of ARS resulted in 2.31. The online evaluation conducted at the end of the semester yielded a score of 2.45. Highly significant correlations were seen between the results of the ARS for the overall evaluation, assessment of prior knowledge, lecture presentation, and the estimated relevance of the lecture topic. Conclusion: The use of ARS is suitable for immediate evaluation of lectures, in particular regarding timely feedback for the individual lecturerlecturers. In comparison with an end-of-term evaluation, ARS yielded a better assessment. PMID:26038683

  12. Evaluating multi-level models to test occupancy state responses of Plethodontid salamanders

    USGS Publications Warehouse

    Kroll, Andrew J.; Garcia, Tiffany S.; Jones, Jay E.; Dugger, Catherine; Murden, Blake; Johnson, Josh; Peerman, Summer; Brintz, Ben; Rochelle, Michael

    2015-01-01

    Plethodontid salamanders are diverse and widely distributed taxa and play critical roles in ecosystem processes. Due to salamander use of structurally complex habitats, and because only a portion of a population is available for sampling, evaluation of sampling designs and estimators is critical to provide strong inference about Plethodontid ecology and responses to conservation and management activities. We conducted a simulation study to evaluate the effectiveness of multi-scale and hierarchical single-scale occupancy models in the context of a Before-After Control-Impact (BACI) experimental design with multiple levels of sampling. Also, we fit the hierarchical single-scale model to empirical data collected for Oregon slender and Ensatina salamanders across two years on 66 forest stands in the Cascade Range, Oregon, USA. All models were fit within a Bayesian framework. Estimator precision in both models improved with increasing numbers of primary and secondary sampling units, underscoring the potential gains accrued when adding secondary sampling units. Both models showed evidence of estimator bias at low detection probabilities and low sample sizes; this problem was particularly acute for the multi-scale model. Our results suggested that sufficient sample sizes at both the primary and secondary sampling levels could ameliorate this issue. Empirical data indicated Oregon slender salamander occupancy was associated strongly with the amount of coarse woody debris (posterior mean = 0.74; SD = 0.24); Ensatina occupancy was not associated with amount of coarse woody debris (posterior mean = -0.01; SD = 0.29). Our simulation results indicate that either model is suitable for use in an experimental study of Plethodontid salamanders provided that sample sizes are sufficiently large. However, hierarchical single-scale and multi-scale models describe different processes and estimate different parameters. As a result, we recommend careful consideration of study questions

  13. Randomised field trial to evaluate serological response after foot-and-mouth disease vaccination in Turkey.

    PubMed

    Knight-Jones, T J D; Bulut, A N; Gubbins, S; Stärk, K D C; Pfeiffer, D U; Sumption, K J; Paton, D J

    2015-02-01

    Despite years of biannual mass vaccination of cattle, foot-and-mouth disease (FMD) remains uncontrolled in Anatolian Turkey. To evaluate protection after mass vaccination we measured post-vaccination antibodies in a cohort of cattle (serotypes O, A and Asia-1). To obtain results reflecting typical field protection, participants were randomly sampled from across Central and Western Turkey after routine vaccination. Giving two-doses one month apart is recommended when cattle are first vaccinated against FMD. However, due to cost and logistics, this is not routinely performed in Turkey, and elsewhere. Nested within the cohort, we conducted a randomised trial comparing post-vaccination antibodies after a single-dose versus a two-dose primary vaccination course. Four to five months after vaccination, only a third of single-vaccinated cattle had antibody levels above a threshold associated with protection. A third never reached this threshold, even at peak response one month after vaccination. It was not until animals had received three vaccine doses in their lifetime, vaccinating every six months, that most (64% to 86% depending on serotype) maintained antibody levels above this threshold. By this time cattle would be >20 months old with almost half the population below this age. Consequently, many vaccinated animals will be unprotected for much of the year. Compared to a single-dose, a primary vaccination course of two-doses greatly improved the level and duration of immunity. We concluded that the FMD vaccination programme in Anatolian Turkey did not produce the high levels of immunity required. Higher potency vaccines are now used throughout Turkey, with a two-dose primary course in certain areas. Monitoring post-vaccination serology is an important component of evaluation for FMD vaccination programmes. However, consideration must be given to which antigens are present in the test, the vaccine and the field virus. Differences between these antigens affect the

  14. The R-CRAS and insanity evaluations: a re-examination of construct validity. Rogers Criminal Responsibility Assessment Scales.

    PubMed

    Rogers, R; Sewell, K W

    1999-01-01

    Insanity evaluations are characterized by continued professional debate and the paucity of empirical research. To address the latter, the construct validity of the Rogers Criminal Responsibility Assessment Scales (R-CRAS; Rogers, 1984) was examined via an extensive re-analysis of 413 insanity cases. A series of six separate discriminant analyses was examined to address major components of insanity evaluations. These analyses yielded highly discriminating patterns (M hit rates of 94.3%) and accounted for substantial proportion of the variance (M=63.7%). In general, predicted relationships between individual variables and the discriminant functions were supported. We also addressed the usefulness of the R-CRAS additional variables for the assessment of insanity. We found that these variables contributed substantially to the determination of criminal responsibility. Finally, we pose important and polemical issues for forensic experts conducting evaluations of criminal responsibility.

  15. Medical Operations Console Procedure Evaluation: BME Response to Crew Call Down for an Emergency

    NASA Technical Reports Server (NTRS)

    Johnson-Troop; Pettys, Marianne; Hurst, Victor, IV; Smaka, Todd; Paul, Bonnie; Rosenquist, Kevin; Gast, Karin; Gillis, David; McCulley, Phyllis

    2006-01-01

    International Space Station (ISS) Mission Operations are managed by multiple flight control disciplines located at the lead Mission Control Center (MCC) at NASA-Johnson Space Center (JSC). ISS Medical Operations are supported by the complementary roles of Flight Surgeons (Surgeon) and Biomedical Engineer (BME) flight controllers. The Surgeon, a board certified physician, oversees all medical concerns of the crew and the BME provides operational and engineering support for Medical Operations Crew Health Care System. ISS Medical Operations is currently addressing the coordinated response to a crew call down for an emergent medical event, in particular when the BME is the only Medical Operations representative in MCC. In this case, the console procedure BME Response to Crew Call Down for an Emergency will be used. The procedure instructs the BME to contact a Surgeon as soon as possible, coordinate with other flight disciplines to establish a Private Medical Conference (PMC) for the crew and Surgeon, gather information from the crew if time permits, and provide Surgeon with pertinent console resources. It is paramount that this procedure is clearly written and easily navigated to assist the BME to respond consistently and efficiently. A total of five BME flight controllers participated in the study. Each BME participant sat in a simulated MCC environment at a console configured with resources specific to the BME MCC console and was presented with two scripted emergency call downs from an ISS crew member. Each participant used the procedure while interacting with analog MCC disciplines to respond to the crew call down. Audio and video recordings of the simulations were analyzed and each BME participant's actions were compared to the procedure. Structured debriefs were conducted at the conclusion of both simulations. The procedure was evaluated for its ability to elicit consistent responses from each BME participant. Trials were examined for deviations in procedure task

  16. A framework for the analysis and evaluation of optical imaging systems with arbitrary response functions

    NASA Astrophysics Data System (ADS)

    Wang, Zhipeng

    The scientific applications and engineering aspects of multispectral and hyperspectral imaging systems have been studied extensively. The traditional geometric spectral imaging system model is specifically developed aiming at spectral sensors with spectrally non-overlapping bands. Spectral imaging systems with overlapping bands also exist. For example, the quantum-dot infrared photodetectors (QDIPs) for midwave- and longwave-infrared (IR) imaging systems exhibit highly overlapping spectral responses tunable through the bias voltages applied. This makes it possible to build spectrally tunable imaging system in IR range based on single QDIP. Furthermore, the QDIP based system can be operated as being adaptive to scenes. Other optical imaging systems like the human eye and some polarimetric sensing systems also have overlapping bands. To analyze such sensors, a functional analysis-based framework is provided in this dissertation. The framework starts from the mathematical description of the interaction between sensor and the radiation from scene reaching it. A geometric model of the spectral imaging process is provided based on the framework. The spectral response functions and the scene spectra are considered as vectors inside an 1-dimensional spectral space. The spectral imaging process is abstracted to represent a projection of scene spectrum onto sensor. The projected spectrum, which is the least-square error reconstruction of the scene vectors, contains the useful information for image processing. Spectral sensors with arbitrary spectral response functions are can be analyzed with this model. The framework leads directly to an image pre-processing algorithm to remove the data correlation between bands. Further discussion shows that this model can also serve the purpose of sensor evaluation, and thus facilitates comparison between different sensors. The spectral shapes and the Signal-to-Noise Ratios (SNR) of different bands are seen to influence the sensor

  17. 33 CFR Appendix B to Part 155 - Determining and Evaluating Required Response Resources for Vessel Response Plans

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... × planning application ratio (1 gal dispersant/20 gals oil = 0.05). E.g., 700,000 gal oil × (0.05) = 35,000... D, E, F, and G of this part. These guidelines will be used by the vessel owner or operator in... conditions or ranges. 2.6The requirements of subparts D, E, F, and G of this part establish response...

  18. Validity and accuracy of electric response audiometry using the auditory steady-state response: evaluation in an empirical design.

    PubMed

    Kaf, Wafaa A; Durrant, John D; Sabo, Diane L; Robert Boston, J; Taubman, Lisa B; Kovacyk, Kristie

    2006-04-01

    The validity and accuracy of the application of the auditory steady-state response (ASSR) to electric response audiometry (ERA) was tested further in a study permitting subjects to be their own controls for hearing loss. Simulated sensorineural hearing loss (SSHL) of complex configuration and varying degrees was effected using filtered masking noise. Thresholds estimated via ASSR-ERA were compared to those measured via conventional pure-tone audiometry. Further, the slow vertex potential N1-P2 was recorded to permit a comparison with an evoked-response test of common content validity and known accuracy. Results in a homogeneous subject sample demonstrated strong interest correlation and agreement within 10 dB at 1000 to 4000 Hz (on average), but not at 500 Hz. The configurations determined by ASSR-ERA followed behavioral audiometric patterns well, except for the mildest degree of SSHL tested. Consequently, limitations of ERA remain, although ASSR-ERA appears to be quite valid overall and promises (justifiably) broad clinical applicability. PMID:16684702

  19. [Ecological security evaluation of Heilongjiang Province with pressure-state-response model].

    PubMed

    Qiu, Wei; Zhao, Qing-liang; Li, Song; Chang, Chein-chi

    2008-04-01

    The ecological security index (ESI) system including 27 indices for Heilongjiang Province was built up with the pressure-state-response (P-S-R) model. The weights of the indices were determined by analytical hierarchy process (AHP) and the ecological security status classification was evaluated by the ESI model for the years of 2000-2005. Then the development trend of ecological security from 2006 to 2010 was forecasted with the grey dynamic model. The results showed that the ecological security ranked the V grade in 2000 and the III grade in 2005, indicating the increase of ecological security. The forecasting results show that the ecological security will be the III grade for 2006, the II grade for 2007-2009, and the I grade for 2010 (ideal security). Thus it can be seen that the ecological security is ascending year by year, and the ecological environment quality is obviously improved with the implementation of eco-province construction since 2000. Through the effective facilitation of eco-province construction etc., the sustainable and healthy development of ecological security will be finally realized in Heilongjiang Province.

  20. IMAGE-GUIDED EVALUATION AND MONITORING OF TREATMENT RESPONSE IN PATIENTS WITH DRY EYE DISEASE

    PubMed Central

    Hamrah, Pedram

    2014-01-01

    Dry eye disease (DED) is one of the most common ocular disorders worldwide. The pathophysiological mechanisms involved in the development of DED are not well understood and thus treating DED has been a significant challenge for ophthalmologists. Most of the currently available diagnostic tests demonstrate low correlation to patient symptoms and have low reproducibility. Recently, sophisticated in vivo imaging modalities have become available for patient care, namely, in vivo confocal microscopy (IVCM) and optical coherence tomography (OCT). These emerging modalities are powerful and non-invasive, allowing real-time visualization of cellular and anatomical structures of the cornea and ocular surface. Here we discuss how, by providing both qualitative and quantitative assessment, these techniques can be used to demonstrate early subclinical disease, grade layer-by-layer severity, and allow monitoring of disease severity by cellular alterations. Imaging-guided stratification of patients may also be possible in conjunction with clinical examination methods. Visualization of subclinical changes and stratification of patients in vivo, allows objective image-guided evaluation of tailored treatment response based on cellular morphological alterations specific to each patient. This image-guided approach to DED may ultimately improve patient outcomes and allow studying the efficacy of novel therapies in clinical trials. PMID:24696045

  1. A tumor deconstruction platform identifies definitive end points in the evaluation of drug responses.

    PubMed

    Naik, R R; Singh, A K; Mali, A M; Khirade, M F; Bapat, S A

    2016-02-11

    Tumor heterogeneity and the presence of drug-sensitive and refractory populations within the same tumor are almost never assessed in the drug discovery pipeline. Such incomplete assessment of drugs arising from spatial and temporal tumor cell heterogeneity reflects on their failure in the clinic and considerable wasted costs in the drug discovery pipeline. Here we report the derivation of a flow cytometry-based tumor deconstruction platform for resolution of at least 18 discrete tumor cell fractions. This is achieved through concurrent identification, quantification and analysis of components of cancer stem cell hierarchies, genetically instable clones and differentially cycling populations within a tumor. We also demonstrate such resolution of the tumor cytotype to be a potential value addition in drug screening through definitive cell target identification. Additionally, this real-time definition of intra-tumor heterogeneity provides a convenient, incisive and analytical tool for predicting drug efficacies through profiling perturbations within discrete tumor cell subsets in response to different drugs and candidates. Consequently, possible applications in informed therapeutic monitoring and drug repositioning in personalized cancer therapy would complement rational design of new candidates besides achieving a re-evaluation of existing drugs to derive non-obvious combinations that hold better chances of achieving remission. PMID:25915841

  2. Evaluating a new rapid response team: NP-led versus intensivist-led comparisons.

    PubMed

    Scherr, Kimberly; Wilson, Donna M; Wagner, Joan; Haughian, Maureen

    2012-01-01

    Evidence is needed to validate rapid response teams (RRTs), including those led by nurse practitioners (NPs). A descriptive-comparative mixed-methods study was undertaken to evaluate a newly implemented NP-led RRT at 2 Canadian hospitals. On the basis of data gathered on 255 patients who received an RRT call compared with the patient data for the previous year, no significant differences in the number of cardiorespiratory arrests, unplanned intensive care unit admissions, and hospital mortality were found. In addition, no significant differences in patient outcomes were identified between the NP-led and intensivist physician-led RRT calls. A paper survey revealed that ward nurses had confidence in the knowledge and skills of the NP-led RRT and believed that patient outcomes were improved as a result of their RRT call. These findings indicate that NP-led RRTs are a safe and effective alternative to intensivist-led teams, but more research is needed to demonstrate that RRTs improve hospital care quality and patient outcomes.

  3. Evaluation of genotypic variation of broccoli (Brassica oleracea var. italic) in response to selenium treatment.

    PubMed

    Ramos, Silvio J; Yuan, Youxi; Faquin, Valdemar; Guilherme, Luiz Roberto G; Li, Li

    2011-04-27

    Broccoli (Brassica oleracea var. italic) fortified with selenium (Se) has been promoted as a functional food. Here, we evaluated 38 broccoli accessions for their capacity to accumulate Se and for their responses to selenate treatment in terms of nutritional qualities and sulfur gene expresion. We found that the total Se content varied with over 2-fold difference among the leaf tissues of broccoli accessions when the plants were treated with 20 μM Na(2)SeO(4). Approximately half of total Se accumulated in leaves was Se-methylselenocysteine and selenomethionine. Transcriptional regulation of adenosine 5'-phosphosulfate sulfurylase and selenocysteine Se-methyltransferase gene expression might contribute to the different levels of Se accumulation in broccoli. Total glucosinolate contents were not affected by the concentration of selenate application for the majority of broccoli accessions. Essential micronutrients (i.e., Fe, Zn, Cu, and Mn) remained unchanged among half of the germplasm. Moreover, the total antioxidant capacity was greatly stimulated by selenate in over half of the accessions. The diverse genotypic variation in Se, glucosinolate, and antioxidant contents among accessions provides the opportunity to breed broccoli cultivars that simultaneously accumulate Se and other health benefit compounds.

  4. Identification, Interpretation—Evaluation, Response: An alternative framework for analyzing teacher discourse in science

    NASA Astrophysics Data System (ADS)

    Louca, Loucas T.; Zacharia, Zacharias C.; Tzialli, Dora

    2012-08-01

    Although research has come to recognize the importance of studying classroom-based student-teacher discourse in science, the emphasis remains largely on teachers' abilities to ask questions and provide students with feedback, or on students' abilities to ask questions or engage in argumentative discourse. Consequently, little research has focused on the discourse elements relating to teacher-student discourse interactions. In this article, we argue for a shift of research attention toward describing what the teacher is responding to (Identification of student inquiry), the process of deciding how to respond (Interpretation-Evaluation of student inquiry), and how the teacher is responding (Response to student inquiry). We propose a new methodological approach for studying teacher discourse, which involves a framework we developed while analyzing 1,385 minutes of fifth grade, whole-class science conversations covering a 2-year period and facilitated by an experienced science teacher. Then, as a case in point, we applied our framework to the teacher discourse data of the study, aiming to show that the framework can be a useful tool for examining how a teacher supports students' inquiry.

  5. Development and process evaluation of a web-based responsible beverage service training program

    PubMed Central

    2012-01-01

    Background Responsible beverage service (RBS) training designed to improve the appropriate service of alcohol in commercial establishments is typically delivered in workshops. Recently, Web-based RBS training programs have emerged. This report describes the formative development and subsequent design of an innovative Web-delivered RBS program, and evaluation of the impact of the program on servers’ knowledge, attitudes, and self-efficacy. Methods Formative procedures using focus groups and usability testing were used to develop a Web-based RBS training program. Professional alcohol servers (N = 112) who worked as servers and/or mangers in alcohol service settings were recruited to participate. A pre-post assessment design was used to assess changes associated with using the program. Results Participants who used the program showed significant improvements in their RBS knowledge, attitudes, and self-efficacy. Conclusions Although the current study did not directly observe and determine impact of the intervention on server behaviors, it demonstrated that the development process incorporating input from a multidisciplinary team in conjunction with feedback from end-users resulted in creation of a Web-based RBS program that was well-received by servers and that changed relevant knowledge, attitudes, and self-efficacy. The results also help to establish a needed evidence base in support of the use of online RBS training, which has been afforded little research attention. PMID:22999419

  6. Optimization of Preparation Conditions for Lysozyme Nanoliposomes Using Response Surface Methodology and Evaluation of Their Stability.

    PubMed

    Wu, Zhipan; Guan, Rongfa; Lyu, Fei; Liu, Mingqi; Gao, Jianguo; Cao, Guozou

    2016-01-01

    The main purpose of this study was to optimize the preparation of lysozyme nanoliposomes using response surface methodology and measure their stability. The stabilities of lysozyme nanoliposomes in simulated gastrointestinal fluid (SGF), simulated intestinal fluid (SIF), as well as pH, temperature and sonication treatment time were evaluated. Reverse-phase evaporation method is an easy, speedy, and beneficial approach for nanoliposomes' preparation and optimization. The optimal preparative conditions were as follows: phosphatidylcholine-to-cholesterol ratio of 3.86, lysozyme concentration of 1.96 mg/mL, magnetic stirring time of 40.61 min, and ultrasound time of 14.15 min. At the optimal point, encapsulation efficiency and particle size were found to be 75.36% ± 3.20% and 245.6 nm ± 5.2 nm, respectively. The lysozyme nanoliposomes demonstrated certain stability in SGF and SIF at a temperature of 37 °C for 4 h, and short sonication handling times were required to attain nano-scaled liposomes. Under conditions of high temperature, acidity and alkalinity, lysozyme nanoliposomes are unstable. PMID:27338315

  7. Histological evaluation of bone response to pediatric endodontic pastes: an experimental study in guinea pig.

    PubMed

    Lacativa, Andréa Mara; Loyola, Adriano M; Sousa, Cassio José Alves

    2012-01-01

    This study aimed to evaluate by the intra-osseous implant technique the most commonly used materials for pulp therapy in pediatric dentistry: calcium hydroxide (CH), Guedes Pinto paste and CTZ paste, according to FDI (1980) and ANSI/ADA (1982) recommendations. Thirty guinea pigs, 10 for each material, divided into experimental periods of 4 and 12 weeks received one implant on each side of the lower jaw symphysis. The external lateral tube wall served as control for the technique. At the end of the observation periods, the animals were euthanized and specimens were prepared for routine histological examination. It was observed that CH and CTZ paste induced severe inflammation, a large amount of necrotic tissue, lymphocytes, foreign body cells and bone resorption, while Guedes Pinto Paste induced little or no inflammation in the 4-week observation period. After 12 weeks, the reactions to CH and Guedes Pinto paste were also absent/mild, presenting a general pattern of replacement by recently formed bone tissue while a moderate to severe inflammatory response was observed with CTZ paste. Guedes Pinto paste presented acceptable biocompatibility levels in both analyzed periods; CH only showed acceptable biocompatibility in the 12-week period while CTZ paste showed no biocompatibility in both periods. Among the tested materials, only Guedes Pinto paste presented an acceptable biocompatibility.

  8. Evaluating Daily Load Stimulus Formulas in Relating Bone Response to Exercise

    NASA Technical Reports Server (NTRS)

    Pennline, James A.; Mulugeta, Lealem

    2014-01-01

    Six formulas representing what is commonly referred to as "daily load stimulus" are identified, compared and tested in their ability to relate skeletal mechanical loading to bone maintenance and osteogenic response. Particular emphasis is placed on exercise- induced skeletal loading and whether or not the formulas can adequately capture the known experimental observations of saturation of continuous cyclic loading, rest insertion between repetitions (cycles), recovery of osteogenic potential following saturation, and multiple shorter bouts versus a single long bout of exercise. To evaluate the ability of the formulas to capture these characteristics, a set of exercise scenarios with type of exercise bout, specific duration, number of repetitions, and rest insertion between repetitions is defined. The daily load values obtained from the formulas for the loading conditions of the set of scenarios is illustrated. Not all of the formulas form estimates of daily load in units of stress or in terms of strain at a skeletal site due to the loading force from a specific exercise prescription. The comparative results show that none of the formulas are able to capture all of the experimentally observed characteristics of cyclic loading. However, the enhanced formula presented by Genc et al. does capture several characteristics of cyclic loading that the others do not, namely recovery of osteogenic potential and saturation. This could be a basis for further development of mathematical formulas that more adequately approximates the amount of daily stress at a skeletal site that contributes to bone adaptation.

  9. A response adaptive randomization platform trial for efficient evaluation of Ebola virus treatments: A model for pandemic response.

    PubMed

    Berry, Scott M; Petzold, Elizabeth A; Dull, Peter; Thielman, Nathan M; Cunningham, Coleen K; Corey, G Ralph; McClain, Micah T; Hoover, David L; Russell, James; Griffiss, J McLeod; Woods, Christopher W

    2016-02-01

    The outbreak of Ebola virus disease in West Africa is the largest ever recorded. Numerous treatment alternatives for Ebola have been considered, including widely available repurposed drugs, but initiation of enrollment into clinical trials has been limited. The proposed trial is an adaptive platform design. Multiple agents and combinations will be investigated simultaneously. Additionally, new agents may enter the trial as they become available, and failing agents may be removed. In order to accommodate the many possible agents and combinations, a critical feature of this design is the use of response adaptive randomization to assign treatment regimens. As the trial progresses, the randomization ratio evolves to favor the arms that are performing better, making the design also suitable for all-cause pandemic preparedness planning. The study was approved by US and Sierra Leone ethics committees, and reviewed by the US Food and Drug Administration. Additionally, data management, drug supply lines, and local sites were prepared. However, in response to the declining epidemic seen in February 2015, the trial was not initiated. Sierra Leone remains ready to rapidly activate the protocol as an emergency response trial in the event of a resurgence of Ebola. (ClinicalTrials.gov Identifier: NCT02380625.) In summary, we have designed a single controlled trial capable of efficiently identifying highly effective or failing regimens among a rapidly evolving list of proposed therapeutic alternatives for Ebola virus disease and to treat the patients within the trial effectively based on accruing data. Provision of these regimens, if found safe and effective, would have a major impact on future epidemics by providing effective treatment options. PMID:26768569

  10. A response adaptive randomization platform trial for efficient evaluation of Ebola virus treatments: A model for pandemic response.

    PubMed

    Berry, Scott M; Petzold, Elizabeth A; Dull, Peter; Thielman, Nathan M; Cunningham, Coleen K; Corey, G Ralph; McClain, Micah T; Hoover, David L; Russell, James; Griffiss, J McLeod; Woods, Christopher W

    2016-02-01

    The outbreak of Ebola virus disease in West Africa is the largest ever recorded. Numerous treatment alternatives for Ebola have been considered, including widely available repurposed drugs, but initiation of enrollment into clinical trials has been limited. The proposed trial is an adaptive platform design. Multiple agents and combinations will be investigated simultaneously. Additionally, new agents may enter the trial as they become available, and failing agents may be removed. In order to accommodate the many possible agents and combinations, a critical feature of this design is the use of response adaptive randomization to assign treatment regimens. As the trial progresses, the randomization ratio evolves to favor the arms that are performing better, making the design also suitable for all-cause pandemic preparedness planning. The study was approved by US and Sierra Leone ethics committees, and reviewed by the US Food and Drug Administration. Additionally, data management, drug supply lines, and local sites were prepared. However, in response to the declining epidemic seen in February 2015, the trial was not initiated. Sierra Leone remains ready to rapidly activate the protocol as an emergency response trial in the event of a resurgence of Ebola. (ClinicalTrials.gov Identifier: NCT02380625.) In summary, we have designed a single controlled trial capable of efficiently identifying highly effective or failing regimens among a rapidly evolving list of proposed therapeutic alternatives for Ebola virus disease and to treat the patients within the trial effectively based on accruing data. Provision of these regimens, if found safe and effective, would have a major impact on future epidemics by providing effective treatment options.

  11. Depression history as a moderator of relations between cortisol and shame responses to social-evaluative threat in young adults

    PubMed Central

    Hellman, Natalie; Morris, Matthew C.; Rao, Uma; Garber, Judy

    2015-01-01

    Changes in cortisol and shame are commonly elicited by psychosocial stressors involving social-evaluative threat. According to social self preservation theory, this coordinated psychobiological response is adaptive. Individuals with a history of depression, however, may exhibit diminished cortisol reactivity to acute stressors, which could interfere with coordinated cortisol and shame responses. The present study examined temporal relations between cortisol and shame responses to a psychosocial stress task in young adults who varied in their history of depression (56 remitted-depressed, 46 never-depressed). Lagged effects multilevel models revealed that depression history moderated relations between cortisol levels and shame ratings 25 to 55 minutes later. The pattern of these interactions was similar: whereas higher cortisol levels predicted increases in shame in never-depressed individuals, cortisol levels were unrelated to shame responses in remitted-depressed individuals. Findings suggest a dissociation between cortisol and shame responses to stress in individuals with a history of depression. PMID:26048679

  12. Development and evaluation of a new method for predicting aircraft buffet response

    NASA Technical Reports Server (NTRS)

    Cunningham, A. M., Jr.; Waner, P. G., Jr.; Watts, J. D.; Benepe, D. B.; Riddle, D. W.

    1975-01-01

    The buffet prediction method uses rigid wind tunnel model fluctuating pressure data to form a buffet forcing function. The response is then calculated with a mathematical dynamic model of the airplane developed for gust response analysis. By including the extremes of phasing and contribution of symmetric and antisymmetric airplane responses, the upper and lower bounds are established for buffet response. F-111A flight test data show good agreement with predicted bounds for a variety of flight conditions.

  13. Evaluating vegetation response to water stress using close-range and satellite remote sensing

    NASA Astrophysics Data System (ADS)

    Swain, Sharmistha

    Drought is a weather related natural disaster that occurs in virtually all climatic zones of the world. In the last century, almost all parts of the contiguous United States have experienced several prolonged drought events with considerable impacts on the agricultural economy and environment. With changing climates, the droughts are expected to be more severe, longer, and widespread in many parts of the world including sections of the United States. Understanding the response of vegetation to water stress using remote sensing technologies will enhance our ability to detect and monitor drought. This research evaluates the response of vegetation to drought-related water stress at the leaf, canopy, and landscape scales using remotely sensed reflectance and/or thermal data. At the leaf level, a crop water stress index model was developed using high spatial resolution thermal imagery to estimate Relative Water Content (RWC) in soybean leaves. The model showed a higher accuracy in RWC determination (85%) compared to the raw temperature based RWC determination (69%). At the canopy level, multi-year close-range reflectance based vegetation indices (VIs) were correlated with soil moisture measured at four depths of maize and soybean root zone. Results indicated that maize VIs were significantly related to soil moisture at deeper depths and kept the soil moisture memory up to previous 45-days. Soybeans VIs were significantly related to soil moisture at shallower depths and kept a relatively shorter (5-days) memory of soil moisture compared to maize. At the landscape scale, Terra-MODIS Land Surface Temperature (LST) and Normalized Difference Vegetation Index (NDVI) products were used to detect drought-induced stress in vegetation including corn, soybeans, and three grassland cover types across the state of Nebraska. Results indicate that the majority of the land cover pixels experienced significantly higher daytime and nighttime LSTs and lower NDVI during the drought

  14. Dorsal Anterior Cingulate Cortex Responses to Repeated Social Evaluative Feedback in Young Women with and without a History of Depression

    PubMed Central

    Dedovic, Katarina; Slavich, George M.; Muscatell, Keely A.; Irwin, Michael R.; Eisenberger, Naomi I.

    2016-01-01

    The dorsal anterior cingulate cortex (dACC) is recruited when a person is socially rejected or negatively evaluated. However, it remains to be fully understood how this region responds to repeated exposure to personally-relevant social evaluation, in both healthy populations and those vulnerable to Major Depressive Disorder (MDD), as well as how responding in these regions is associated with subsequent clinical functioning. To address this gap in the literature, we recruited 17 young women with past history of MDD (previously depressed) and 31 healthy controls and exposed them to a social evaluative session in a neuroimaging environment. In two bouts, participants received an equal amount of positive, negative, and neutral feedback from a confederate. All participants reported increases in feelings of social evaluation in response to the evaluative task. However, compared to healthy controls, previously depressed participants tended to show greater increases in depressed mood following the task. At the neural level, in response to negative (vs. positive) feedback, no main effect of group or evaluation periods was observed. However, a significant interaction between group and evaluation periods was found. Specifically, over the two bouts of evaluation, activity in the dACC decreased among healthy participants while it increased among previously depressed individuals. Interestingly and unexpectedly, in the previously depressed group specifically, this increased activity in dACC over time was associated with lower levels of depressive symptoms at baseline and at 6-months following the evaluation session (controlling for baseline levels). Thus, the subset of previously depressed participants who showed increases in the recruitment of the dACC over time in response to the negative evaluation seemed to fair better emotionally. These findings suggest that examining how the dACC responds to repeated bouts of negative evaluation reveals a new dimension to the role of the d

  15. The UNESCO Bioethics Declaration 'social responsibility' principle and cost-effectiveness price evaluations for essential medicines.

    PubMed

    Faunce, Thomas Alured

    2005-07-01

    The United Nations Scientific, Education and Cultural Organisation (UNESCO) has commenced drafting a Universal Bioethics Declaration. Some in the relevant UNESCO drafting committee have previously desired to restrict its content to general principles concerning the application (but not necessarily the goals) of science and technology. As potentially a crucial agenda-setting statement of global bioethics, however, it is arguable important the Universal Bioethics Declaration transparently address major bioethical dilemmas in the field of public health, such as universal access to affordable, essential medicines. Article 13 (Social Responsibility) of the Preliminary Draft Universal Bioethics Declaration states: 'Any decision or practice shall ensure that progress in science and technology contributes, wherever possible, to the common good, including the achievement of goals such as: (i) access to quality health care and essential medicines, including for reproductive health and health of children.' Cost effectiveness pricing systems, such as that most notably used in Australia's Pharmaceutical Benefits Scheme (PBS), arguably represent one of the most scientifically effective mechanisms whereby public monies may be utilised to assist in the provision of medicines for the common good. They contain two essential elements: first, a process of scientific evaluation of objectively demonstrated therapeutic significance, and then, a fiscal lever (the government reimbursement price) attached to that evaluation. It is now well established that the US Pharmaceutical Research and Manufacturers Association (Pharma), through the assistance of the US Trade Representative (USTR), saw the Australia United States Free Trade Agreement (AUSFTA) as an opportunity to fulfill a legislative mandate to 'eliminate' the cost-effectiveness pricing system in Australia's PBS. One of the most remarkable features of the arguments raised against the PBS in this context was the fact that they made

  16. The UNESCO Bioethics Declaration 'social responsibility' principle and cost-effectiveness price evaluations for essential medicines.

    PubMed

    Faunce, Thomas Alured

    2005-07-01

    The United Nations Scientific, Education and Cultural Organisation (UNESCO) has commenced drafting a Universal Bioethics Declaration. Some in the relevant UNESCO drafting committee have previously desired to restrict its content to general principles concerning the application (but not necessarily the goals) of science and technology. As potentially a crucial agenda-setting statement of global bioethics, however, it is arguable important the Universal Bioethics Declaration transparently address major bioethical dilemmas in the field of public health, such as universal access to affordable, essential medicines. Article 13 (Social Responsibility) of the Preliminary Draft Universal Bioethics Declaration states: 'Any decision or practice shall ensure that progress in science and technology contributes, wherever possible, to the common good, including the achievement of goals such as: (i) access to quality health care and essential medicines, including for reproductive health and health of children.' Cost effectiveness pricing systems, such as that most notably used in Australia's Pharmaceutical Benefits Scheme (PBS), arguably represent one of the most scientifically effective mechanisms whereby public monies may be utilised to assist in the provision of medicines for the common good. They contain two essential elements: first, a process of scientific evaluation of objectively demonstrated therapeutic significance, and then, a fiscal lever (the government reimbursement price) attached to that evaluation. It is now well established that the US Pharmaceutical Research and Manufacturers Association (Pharma), through the assistance of the US Trade Representative (USTR), saw the Australia United States Free Trade Agreement (AUSFTA) as an opportunity to fulfill a legislative mandate to 'eliminate' the cost-effectiveness pricing system in Australia's PBS. One of the most remarkable features of the arguments raised against the PBS in this context was the fact that they made

  17. Interpersonal relationship modulates brain responses to outcome evaluation when gambling for/against others: an electrophysiological analysis.

    PubMed

    Leng, Yue; Zhou, Xiaolin

    2014-10-01

    When individuals play a gambling task and their actions have consequences for observers, how are the brain responses of the performers modulated by their interpersonal relationship with the observers? To address this issue, we examined the event-related potentials responses in performers while they played two gambling games: one during which they tried to earn money for the observers instead of themselves (i.e., Experiment 1) and another gambling game during which they attempted to earn money from the observers (i.e., Experiment 2). In Experiment 1, ERP results showed that when gambling for either the friends or the strangers, the feedback-related negativity (FRN) responses were more negative-going to the losses than to the gains. The FRN effect (loss minus gain) was significantly larger when gambling for the friends than for the strangers. The general P300 response was more positive-going when gambling for the friends than for the strangers. These results suggested that gambling for others enables individuals to assess the outcome from the interests of the other people, consequently, the FRN response may be driven by the evaluative process related to interests of the others. Because one׳s own economic interests were not involved, the performers׳ brain responses during both the early, semi-automatic stage (i.e., the FRN) and the later, controlled stage (i.e., the P300) of outcome evaluation were modulated by the interpersonal relationship between the performers and the observers. In Experiment 2, ERP results revealed that when gambling against others, the FRN response was more negative-going to the losses than to the gains, as well. However, neither the FRN effect nor the general FRN response was modulated by interpersonal relationship. The general P300 response was more positive-going when gambling against the stranger than against the friend. These results suggested that when gambling against others, the performers׳ FRN response may be driven by two evaluative

  18. Interpersonal relationship modulates brain responses to outcome evaluation when gambling for/against others: an electrophysiological analysis.

    PubMed

    Leng, Yue; Zhou, Xiaolin

    2014-10-01

    When individuals play a gambling task and their actions have consequences for observers, how are the brain responses of the performers modulated by their interpersonal relationship with the observers? To address this issue, we examined the event-related potentials responses in performers while they played two gambling games: one during which they tried to earn money for the observers instead of themselves (i.e., Experiment 1) and another gambling game during which they attempted to earn money from the observers (i.e., Experiment 2). In Experiment 1, ERP results showed that when gambling for either the friends or the strangers, the feedback-related negativity (FRN) responses were more negative-going to the losses than to the gains. The FRN effect (loss minus gain) was significantly larger when gambling for the friends than for the strangers. The general P300 response was more positive-going when gambling for the friends than for the strangers. These results suggested that gambling for others enables individuals to assess the outcome from the interests of the other people, consequently, the FRN response may be driven by the evaluative process related to interests of the others. Because one׳s own economic interests were not involved, the performers׳ brain responses during both the early, semi-automatic stage (i.e., the FRN) and the later, controlled stage (i.e., the P300) of outcome evaluation were modulated by the interpersonal relationship between the performers and the observers. In Experiment 2, ERP results revealed that when gambling against others, the FRN response was more negative-going to the losses than to the gains, as well. However, neither the FRN effect nor the general FRN response was modulated by interpersonal relationship. The general P300 response was more positive-going when gambling against the stranger than against the friend. These results suggested that when gambling against others, the performers׳ FRN response may be driven by two evaluative

  19. Making the Invisible Visible: A Responsive Evaluation Study of ESL and Spanish Language Services for Immigrants in a Small Rural County in Indiana

    ERIC Educational Resources Information Center

    Pawan, Faridah; Thomalla, Therese Groff

    2005-01-01

    This article describes a responsive evaluation study of ESL services and Spanish language services for immigrants in a rural county in Indiana. An ESL specialist led the evaluation of language services in the county from the perspectives of language providers and recipients. The responsive evaluation--a form of action research that uses…

  20. 33 CFR 154.1047 - Response plan development and evaluation criteria for facilities that handle, store, or transport...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... evaluation criteria for facilities that handle, store, or transport Group V petroleum oils. 154.1047 Section... Group V petroleum oils. (a) An owner or operator of a facility that handles, stores, or transports Group V petroleum oils must provide information in his or her response plan that identifies—...