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Sample records for reducing peginterferon alfa-2a

  1. Peginterferon Alfa-2a Injection

    MedlinePlus

    ... as a solution (liquid) in a vial, a prefilled syringe, and a disposable autoinjector to inject subcutaneously (into ... or switch between peginterferon alfa-2a in vials, prefilled syringes, and disposable autoinjectors without talking to your doctor. ...

  2. Peginterferon alfa-2a for AIDS-associated Kaposi sarcoma: experience with 10 patients.

    PubMed

    Rokx, Casper; van der Ende, Marchina E; Verbon, Annelies; Rijnders, Bart J A

    2013-11-01

    In this observational cohort study, 10 patients with extensive or treatment-refractory AIDS-associated Kaposi sarcoma were treated with peginterferon alfa-2a. Tumor responses were observed in 9 patients with a median progression-free survival of 645 days. Peginterferon alfa-2a could be an effective therapy for extensive or treatment-resistant Kaposi sarcoma.

  3. Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients(◆)

    PubMed Central

    Nelson, David R.; Zeuzem, Stefan; Andreone, Pietro; Ferenci, Peter; Herring, Robert; Jensen, Donald M.; Marcellin, Patrick; Pockros, Paul J.; Rodríguez-Torres, Maribel; Rossaro, Lorenzo; Rustgi, Vinod K.; Sepe, Thomas; Sulkowski, Mark; Thomason, Isaac R.; Yoshida, Eric M.; Chan, Anna; Hill, George

    2013-01-01

    Introduction Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin. Material and methods Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa-2a (40KD) 180 or 90 μg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns. Results The percentage of patients with undetectable HCV RNA was consistently higher in all balapiravir groups from week 2 to 12. However, high rates of dose modifications and discontinuations of one/all study drugs compromised the efficacy assessment and resulted in similar sustained virological response rates in the balapiravir groups (range 32-50%) and the peginterferon alfa-2a (40KD)/ribavirin group (43%). Balapiravir was discontinued for safety reasons in 28-36% of patients (most often for lymphopenia) and the percentage of patients with serious adverse events (especially hematological, infection, ocular events) was dose related. Serious hematological adverse events (particularly neutropenia, lymphopenia) were more common in balapiravir recipients. Two deaths in the balapiravir/peginterferon alfa-2a/ribavirin combination groups were considered possibly related to study medication. Conclusion Further development of balapiravir for the treatment of chronic hepatitis C has been halted because of the unacceptable benefit to risk ratio revealed in this study (www.ClinicalTrials.gov NCT 00517439). PMID:22166557

  4. Guillain-Barre syndrome associated with peginterferon alfa-2a for chronic hepatitis C: A case report

    PubMed Central

    Niazi, Mumtaz A; Azhar, Ashaur; Tufail, Kashif; Feyssa, Eyob L; Penny, Stephen F; McGregory, Marlene; Araya, Victor; Ortiz, Jorge A

    2010-01-01

    The recommended therapy for chronic hepatitis C (CHC) infection is the combination of a Pegylated interferon and Ribavirin. Almost all such patients on combination therapy experience one or more adverse events during the course of treatment. Significant neurological side effects are rare. A few cases of Bell’s Palsy, chronic inflammatory demyelinating polyneuropathy and even one case of acute demyelinating polyneuropathy with atypical features for Guillain-Barre syndrome (GBS) associated with Interferon therapy have been reported but no report of GBS with typical features has been published. We present a case report of typical GBS associated with Peginterferon alfa-2a and Ribavirin used for treatment of CHC infection. PMID:21160989

  5. Cost-effectiveness analysis of treatment with peginterferon-alfa-2a versus peginterferon-alfa-2b for patients with chronic hepatitis C under the public payer perspective in Brazil

    PubMed Central

    2013-01-01

    Background Chronic hepatitis C affects approximately 170 million people worldwide, and thus being one of the main causes of chronic liver disease. About 20% of patients with chronic hepatitis C will develop cirrhosis over 20 years, and present an increased risk of developing hepatic complications. Sustained virological response (SVR) is associated with a better prognosis compared to untreated patients and treatment failures. The objective of this analysis was to compare treatment costs and outcomes of pegylated interferon-alfa-2a versus pegylated interferon-alfa-2b, both associated with ribavirin, in the therapeutic scheme of 24 weeks and 48 week for hepatitis C genotypes 2/3 and genotype 1, respectively, under the Brazilian Public Health System (SUS) scenario. Methods To project disease progression, a Markov model was built based on clinical stages of chronic disease. A Delphi panel was conducted to evaluate medical resources related to each stage, followed by costing of related materials, services, procedures and pharmaceutical products. The evaluation was made from a public payer perspective. The source used for costing was government reimbursement procedures list (SAI/SIH–SUS). Drug acquisition costs were obtained from the Brazilian Official Gazette and “Banco de Preços em Saúde” (government official source). It was assumed a mean patient weight of 70 kg. Costs were reported in 2011 Brazilian Reais (US$1 ≈ $Brz1.80). A systematic review followed by a meta-analysis of the 7 identified randomized controlled trials (RCTs) which compared pegylated interferons, was conducted for obtaining relative efficacy of both drugs: for genotype 2/3, mean rate of SVR was 79.2% for peginterferon-alfa-2a and 73.8% for peginterferon-alfa-2b. For genotype 1, SVR mean rate was 42.09% versus 33.44% (peginterferon-alfa-2a and peginterferon-alfa-2b respectively). Time horizon considered was lifetime. Discount rate for costs and outcomes was 5%, according to Brazilian

  6. Cost-effectiveness analysis of adding low dose ribavirin to peginterferon alfa-2a for treatment of chronic hepatitis C infected thalassemia major patients in iran.

    PubMed

    Mehrazmay, Alireza; Alavian, Seyed Moayed; Moradi-Lakeh, Maziar; Mokhtari Payam, Mahdi; Hashemi-Meshkini, Amir; Behnava, Bita; Miri, Seyyed Mohammad; Karimi Elizee, Pegah; Tabatabaee, Seyed Vahid; Keshvari, Maryam; Bagheri Lankarani, Kamran

    2013-01-01

    The prevalence of hepatitis C in Iran is 1% and 18% in general population and thalassemia patients respectively. The cost effectiveness analysis of adding Ribavirin to Peginterferon alfa-2a (PEG IFN alfa-2a) as a combination treatment strategy of chronic hepatitis C in thalassemia patients in comparison with monotherapy could help clinicians and policy makers to provide the best treatment for the patients. In this study we aimed to assess whether adding Ribavirin to PEG IFN alfa-2a is a cost effective strategy in different genotypes and different subgroups of 280 patients with chronic hepatitis C infection from the perspective of society in Iranian setting. A cost effectiveness analysis including all costs and outcomes of treatments for chronic hepatitis C infected thalassemia major patients was conducted. We constructed a decision tree of treatment course in which a hypothetical cohort of 100 patients received "PEG IFN alfa-2a" or "Peg IFN alfa-2a plus Ribavirin." The cost analysis was based on cost data for 2008 and we used 9300 Iranian Rials (IR Rial) as exchange rate declared by the Iranian Central Bank on that time to calculating costs by US Dollar (USD). To evaluate whether a strategy is cost effective, one time and three times of GDP per capita were used as threshold based on recommendation of the World Health Organization. The Incremental Cost Effectiveness Ratio (ICER) for combination therapy in genotype-1 and genotypes non-1 subgroups was 2,673 and 19,211 US dollars (USD) per one Sustain Virological Response (SVR), respectively. In low viral load and high viral load subgroups, the ICER was 5,233 and 14,976 USD per SVR, respectively. The calculated ICER for combination therapy in subgroup of patients with previously resistant to monotherapy was 13,006 USD per SVR. Combination therapy in previously resistant patients to combination therapy was a dominant strategy. Adding low dose of Ribavirin to PEG IFN alfa-2a for treatment of chronic hepatitis C patients

  7. EFFECT OF HCV RNA SUPPRESSION DURING PEGINTERFERON ALFA-2A MAINTENANCE THERAPY ON CLINICAL OUTCOMES IN THE HALT-C TRIAL

    PubMed Central

    Shiffman, Mitchell L; Morishima, Chihiro; Dienstag, Jules L; Lindsay, Karen L; Hoefs, John C; Lee, William M; Wright, Elizabeth C.; Naishadham, Deepa; Everson, Gregory T; Lok, Anna S; Di Bisceglie, Adrian M; Bonkovsky, Herbert L; Ghany, Marc G

    2013-01-01

    Background and Aims The HALT-C trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine if suppressing HCV RNA during the trial was associated with a reduction in clinical outcomes. Methods 764 patients treated during the lead-in phase of HALT-C were randomized to either peginterferon alfa-2a (90 mcg/week) maintenance therapy or no treatment (control) for 3.5 years. Clinical outcomes included an increase in Child-Turcotte-Pugh score, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma and mortality. Results During the lead-in, ≥4 log10 decline in serum HCV RNA occurred in 178 patients; 82% of whom lost detectable HCV RNA and later broke through or relapsed. These patients had significantly (p=0.003) fewer clinical outcomes whether randomized to maintenance therapy or control. Following randomization serum HCV RNA increased significantly in all 90 control patients and 58/88 receiving maintenance therapy. Only 30 patients had persistent suppression of HCV RNA by ≥4 log10 during maintenance therapy. No significant reduction in clinical outcomes was observed in these patients. Conclusions Viral suppression by ≥4 log10 with full dose peginterferon/ribavirin is associated with a significant reduction in clinical outcomes. Continuing low dose peginterferon maintenance therapy, even in patients with persistent viral suppression, does not lead to a further decline in clinical outcomes. PMID:19747918

  8. Predicting sustained virological response and anaemia in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) plus ribavirin

    PubMed Central

    Snoeck, Eric; Wade, Janet R; Duff, Frank; Lamb, Matthew; Jorga, Karin

    2006-01-01

    Aim To assess the likelihood of a sustained virological response (SVR) vs. the likelihood of anaemia in patients with chronic hepatitis C. Methods Data from 1732 patients treated with peginterferon alfa-2a (40KD) plus ribavirin in two randomized, multinational studies were pooled. Probabilities of SVR and anaemia were modelled using the generalized additive logistic model, with numerous clinical variables considered for entry into the model. Baseline haemoglobin was only considered in the analysis for anaemia. Results The probability of anaemia increased from 6 to 16% as a function of the ribavirin dose kg−1 (12–16 mg kg−1), whereas the relationship between SVR and ribavirin dose kg−1 was influenced by hepatitis C virus (HCV) genotype. The probability of an SVR was not influenced by the ribavirin dose kg−1 in patients with HCV genotype 2 or 3 infection, but increased as a function of ribavirin dose kg−1 in patients with HCV genotype 1 infection (40–50% increase in probability of SVR for 12–16 mg kg−1 dose ribavirin increase). The probability of an SVR in patients included with HCV genotype 1 decreased with increasing HCV RNA level to about 3 million copies ml−1, but was relatively independent of increasing HCV RNA level thereafter. In addition, older age, a higher ribavirin apparent oral clearance and cirrhosis had a negative impact on achieving an SVR, but improved with increasing alanine aminotransferase (ALT) quotient. Sex and ribavirin dose kg−1 were the most important prognostic factors for anaemia, followed by baseline haemoglobin, age, baseline ALT quotient and cirrhosis. Conclusion This study supports individualizing ribavirin dosages by HCV genotype and body weight, and highlights several clinical variables that influence the likelihood of an SVR compared with anaemia in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) plus ribavirin. PMID:17118125

  9. [A case of Bell's palsy associated with peginterferon Alfa-2a and ribavirin therapy for chronic hepatitis C virus infection].

    PubMed

    Lee, Moo Yeol; Cho, Hoon; Kim, Yeong Muk; Lee, Joon Sang

    2006-09-01

    Pegylated interferon alfa-2a (PEG-IFN) and ribavirin combination therapy is the first line treatment for chronic HCV infection. There are four reports of Bell's palsy associated with interferon-alpha (IFN-alpha) and ribavirin therapy. We report here a case of Bell's palsy that occurred in a patient with chronic HCV infection during combination PEG-IFN and ribavirin therapy. The patient was 49-year-old man with chronic hepatitis C for 2 years. The liver biopsy showed grade 1 and stage 1. Therapy with PEG-IFN (Pegasys) 180 microgram/week and ribavirin 1200 mg/day was initiated. After 3 weeks of treatment, the patient showed a loss of muscular tone on the left side of his face. A diagnosis of Bell's palsy was made, and the PEG-IFN and ribavirin therapy was stopped. Prednisolone 45 mg/d was given and then tapered for 8 weeks. His palsy improved over 6 weeks.

  10. Efficacy and safety profile of boceprevir- or telaprevir-based triple therapy or dual peginterferon alfa-2a or alfa-2b plus ribavirin therapy in chronic hepatitis C: the real-world PegBase observational study

    PubMed Central

    Mangia, Alessandra; Foster, Graham R.; Berg, Christoph P.; Curescu, Manuela; Ledinghen, Victor De; Habersetzer, François; Manolakopoulos, Spilios; Negri, Elisa; Papatheodoridis, George; Ahlers, Silke; Castillo, Marco; Bakalos, Georgios; Mauss, Stefan

    2017-01-01

    Background The aim of the study was to determine the efficacy and safety of triple therapy with a first-generation protease inhibitor (PI; boceprevir, telaprevir) plus peginterferon alfa-2a or -2b plus ribavirin, and dual therapy (peginterferon alfa-2a or -2b plus ribavirin) in patients with chronic hepatitis C (CHC) in routine clinical practice. Methods PegBase was an international, prospective, observational study in which 4441 patients with CHC were enrolled in 27 countries. This analysis focuses on results in 4100 treatment-naïve and previously treated patients treated with PI-based triple therapy or dual therapy, according to the discretion of the investigator and local standards of practice. The primary efficacy outcome was sustained virological response after 12-week follow up (SVR12). Results SVR12 rates in treatment-naïve genotype (G) 1 patients were 56.6% and 62.9% for recipients of boceprevir plus peginterferon alfa-2a/ribavirin and boceprevir plus peginterferon alfa-2b/ribavirin, respectively, and 65.3% and 58.6% for recipients of telaprevir plus peginterferon alfa-2a/ribavirin and telaprevir plus peginterferon alfa-2b/ribavirin, respectively. In previously treated patients assigned to these four regimens, SVR12 rates were 43.6%, 48.3%, 60.3% and 56.1%, respectively. Among treatment-naïve patients assigned to peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin, respectively, SVR12 rates were 49.2% and 41.9% in G1 patients, 75.7% and 83.3% in G2 patients, 65.9% and 65.9% in G3 patients, and 49.7%, and 51.1% in G4 patients. The safety and tolerability of dual and triple therapy were consistent with previous reports. Conclusion The efficacy and safety of first-generation PI-based triple-therapy and dual-therapy regimens in this real-world cohort were broadly comparable to those of previous studies. PMID:28469364

  11. Efficacy and safety profile of boceprevir- or telaprevir-based triple therapy or dual peginterferon alfa-2a or alfa-2b plus ribavirin therapy in chronic hepatitis C: the real-world PegBase observational study.

    PubMed

    Mangia, Alessandra; Foster, Graham R; Berg, Christoph P; Curescu, Manuela; Ledinghen, Victor De; Habersetzer, François; Manolakopoulos, Spilios; Negri, Elisa; Papatheodoridis, George; Ahlers, Silke; Castillo, Marco; Bakalos, Georgios; Mauss, Stefan

    2017-01-01

    The aim of the study was to determine the efficacy and safety of triple therapy with a first-generation protease inhibitor (PI; boceprevir, telaprevir) plus peginterferon alfa-2a or -2b plus ribavirin, and dual therapy (peginterferon alfa-2a or -2b plus ribavirin) in patients with chronic hepatitis C (CHC) in routine clinical practice. PegBase was an international, prospective, observational study in which 4441 patients with CHC were enrolled in 27 countries. This analysis focuses on results in 4100 treatment-naïve and previously treated patients treated with PI-based triple therapy or dual therapy, according to the discretion of the investigator and local standards of practice. The primary efficacy outcome was sustained virological response after 12-week follow up (SVR12). SVR12 rates in treatment-naïve genotype (G) 1 patients were 56.6% and 62.9% for recipients of boceprevir plus peginterferon alfa-2a/ribavirin and boceprevir plus peginterferon alfa-2b/ribavirin, respectively, and 65.3% and 58.6% for recipients of telaprevir plus peginterferon alfa-2a/ribavirin and telaprevir plus peginterferon alfa-2b/ribavirin, respectively. In previously treated patients assigned to these four regimens, SVR12 rates were 43.6%, 48.3%, 60.3% and 56.1%, respectively. Among treatment-naïve patients assigned to peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin, respectively, SVR12 rates were 49.2% and 41.9% in G1 patients, 75.7% and 83.3% in G2 patients, 65.9% and 65.9% in G3 patients, and 49.7%, and 51.1% in G4 patients. The safety and tolerability of dual and triple therapy were consistent with previous reports. The efficacy and safety of first-generation PI-based triple-therapy and dual-therapy regimens in this real-world cohort were broadly comparable to those of previous studies.

  12. Sustained Virologic Response to a Dual Peginterferon alfa-2a and Ribavirin in Treating Chronic hepatitis C Infection

    PubMed Central

    Naing, Cho; Sitt, Than; Aung, Aye TD; Aung, Kyan

    2015-01-01

    Abstract In Myanmar, hepatitis C virus (HCV) infection prevalence is 2%. A combination therapy of pegylated interferon alfa-2a and ribavirin (PEG-IFNa/RBV) is a standard treatment, but the effect of this antiviral therapy needs evaluation as to determine the efficacy and safety of dual PEG-IFNa/RBV therapy in treating patients infected with HCV in Myanmar. This was a retrospective analysis of data from a single clinic exclusively for gastrointestinal diseases in Yangon, Myanmar. We assessed treatment responses at the defined time points and stratified by genotypes of HCV. We also determined incidences of adverse events (AEs). We investigated independent predictors of sustained virologic response (SVR) in the participants. A total of 362 HCV-infected cases were included in this study. The majority were females (51.7%) with mean age of 47.12 years (±11.6) and noncirrhosis patients (82%). Rapid virologic response (RVR), early virologic response (EVR), end of treatment response (ETR), and SVR 24 weeks after completion of the dual treatment were 50.3% (178/362), 88% (314/357), 80.1% (286/357), and 85.6% (167/195), respectively. The most frequently reported AEs were nausea/anorexia (72.8%) and flu-like symptoms (62.4%). In multivariate analysis, 4 factors were independently associated with SVR; SVR to genotype 3 (odds ratio [OR] 2.4, 95% CI: 1.24–4.62), EVR (OR 0.54, 95% CI: 0.3–0.95), and duration of treatment (OR 1.52, 95% CI: 1.18–1.98). Study limitations were acknowledged. The efficacy and safety of the dual therapy in treating HCV-infected patient in Myanmar was acceptable. We recommend a prospective randomized control trial looking at duration of therapy and rates of achieving SVR, which could significantly impact the care of HCV-infected patients in Myanmar and perhaps other countries as well. PMID:26222859

  13. Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negative patients treated with peginterferon alfa-2a.

    PubMed

    Rijckborst, Vincent; Hansen, Bettina E; Ferenci, Peter; Brunetto, Maurizia R; Tabak, Fehmi; Cakaloglu, Yilmaz; Lanza, A Galeota; Messina, Vincenzo; Iannacone, Claudio; Massetto, Benedetta; Regep, Loredana; Colombo, Massimo; Janssen, Harry L A; Lampertico, Pietro

    2012-05-01

    It was recently demonstrated that none of the hepatitis B e antigen (HBeAg)-negative patients without any serum hepatitis B surface antigen (HBsAg) decline and with <2log hepatitis B virus (HBV) DNA decline at week 12 of a 48-week peginterferon alfa-2a (PEG-IFN) treatment course achieved a sustained response (SR). We aimed at validating this stopping rule in two independent trials. HBeAg-negative patients receiving 48 or 96 weeks of PEG-IFN in the phase III registration trial (N=85) and PegBeLiver study (N=75) were stratified according to the presence of any HBsAg decline and/or 2log HBV DNA decline at week 12. SR was defined as HBV DNA <2000IU/ml and normal alanine aminotransferase 24 weeks after treatment. The original PARC trial included 102 patients (genotype A/D/other: 14/81/7), 25 (25%) had an SR. The validation dataset consisted of 160 patients (genotype A/B/C/D/other: 10/18/34/91/7), 57 (36%) achieved an SR. The stopping rule performed well across the two studies (p=0.001) and its negative predictive value [NPV] was 95% in the validation dataset harbouring genotypes A-D. Its performance was best for genotype D. Moreover, among the 34 patients treated for 96 weeks, none of the 7 (21%) without HBsAg decline and with <2log HBV DNA decline at week 12 achieved an SR (NPV 100%). We confirmed in two independent studies that the combination of HBsAg and HBV DNA levels at week 12 identifies HBeAg-negative patients with a very low chance of SR to either 48 or 96 weeks of PEG-IFN therapy. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  14. Induction dosing of peginterferon alfa-2a (40 KD) and/or high-dose ribavirin in genotype 1 CHC patients with difficult-to-treat characteristics: pharmacokinetic and viral kinetic (PK/VK) assessment from PROGRESS.

    PubMed

    Morcos, Peter N; Leong, Ruby; Thommes, James A; DePamphilis, Jean; Grippo, Joseph F; Brennan, Barbara J

    2015-01-01

    PROGRESS randomized chronic hepatitis C genotype 1 patients with a baseline viral load ≥400,000 IU/mL weighing ≥85 kg to regimens of 180 μg/week for 48 weeks or 360 μg/week for 12 weeks followed by 180 μg/week for 36 weeks peginterferon alfa-2a plus ribavirin. This analysis explored pharmacokinetics and early viral kinetics (VK) and evaluates differences between groups. Blood samples for pharmacokinetic and VK analyses were collected from 51 patients enrolled in the PROGRESS study. Mean peginterferon alfa-2a trough concentration at week 12 was 11.7±4.3 ng/mL for 180 μg and 23.4±11.3 ng/mL for 360 μg. Early VK profiles suggested a trend towards an enhanced viral decline in the 360 μg groups with a mean decrease in HCV RNA at 48 hours post first dose of 1.04 log10 (IU/mL) compared with 0.76 log10 (IU/mL) in the 180 μg groups. Mean beta slope increased with dose, ranging from 0.38±0.26 log10 IU/week at 180 μg to 0.52±0.32 log10 IU/week at 360 μg. Early viral de clines may be enhanced with the 360 μg dose. These data may suggest the utility of high-dose peginterfer on alfa-2a plus direct-acting antivirals (DAA) in select difficult-to-treat populations.

  15. Peginterferon alfa-2a plus Weight-Based or Flat-Dose Ribavirin for Treatment-Naïve Hepatitis C Virus Genotype 2 Rapid Responders: A Randomized Trial

    PubMed Central

    Liu, Chen-Hua; Huang, Chung-Feng; Liu, Chun-Jen; Dai, Chia-Yen; Huang, Jee-Fu; Lin, Jou-Wei; Liang, Cheng-Chao; Yang, Sheng-Shun; Lin, Chih-Lin; Su, Tung-Hung; Yang, Hung-Chih; Chen, Pei-Jer; Chen, Ding-Shinn; Chuang, Wan-Long; Kao, Jia-Horng; Yu, Ming-Lung

    2015-01-01

    The impact of ribavirin (RBV) dosage on sustained virologic response (SVR) rates remains elusive in hepatitis C virus genotype 2 (HCV-2) rapid responders receiving 16 weeks of peginterferon (Peg-IFN) plus RBV. Treatment-naïve HCV-2 patients with rapid virologic response (RVR) received Peg-IFN alfa-2a 180 μg/week plus weight-based RBV (1,000 or 1,200 mg/day; cut-off body weight: 75 kg) for 6 weeks, and then randomly received Peg-IFN alfa-2a 180 μg/week plus weight-based (1,000 or 1,200 mg/day; n = 247) or flat-dose (800 mg/day; n = 246) RBV for additional 10 weeks. The primary endpoint was SVR24. Patients receiving weight-based and flat-dose RBV therapies had comparable SVR24 rates (93.5% versus 91.9%, P = 0.49). The risk differences (RDs) of SVR24 receiving weight-based and flat-dose RBV arms were 7.1% [95% CI: 0.7% to 13.6%] in males, and −5.8% [95% CI: −12.1% to 0.5%] in females (interaction P = 0.01). The SVR24 rate was higher in males receiving ≥13 mg/kg/day than those receiving <13 mg/kg/day (96.3% versus 85.1%, P = 0.001). In conclusion, Peg-IFN alfa-2a plus weight-based or flat-dose RBV for 16 weeks provides comparable SVR24 rates in treatment-naïve HCV-2 rapid responders. However, males should receive weight-based RBV to achieve a high SVR24 rate. PMID:26469083

  16. Randomised clinical trial: escitalopram for the prevention of psychiatric adverse events during treatment with peginterferon-alfa-2a and ribavirin for chronic hepatitis C.

    PubMed

    de Knegt, R J; Bezemer, G; Van Gool, A R; Drenth, J P H; Hansen, B E; Droogleever Fortuyn, H A; Weegink, C J; Hengeveld, M W; Janssen, H L A

    2011-12-01

    BACKGROUND  Treatment of hepatitis C with peginterferon and ribavirin is associated with psychiatric side-effects, frequently necessitating dose reduction or therapy cessation. AIM  To assess the efficacy of prophylactic escitalopram to prevent psychiatric side-effects during peginterferon and ribavirin treatment in a randomised, double-blind, placebo-controlled trial. METHODS  Seventy-nine hepatitis C patients were treated with peginterferon and ribavirin. Patients received escitalopram (n = 40, 10 mg) or placebo (n = 39), which was initiated together with peginterferon and ribavirin. Primary outcomes were an increase of two points or more on the items reported sadness, inner tension and impaired concentration of the Montgomery-Asberg Depression Rating Scale, and hostile feelings of the Brief Anxiety Scale. Secondary outcome was the development of depression diagnosed by the Mini-International Neuropsychiatric Interview. Measurements were performed at baseline, week 4, 12 and 24 during anti-viral treatment, and 24 weeks thereafter. RESULTS  The incidence of psychiatric side-effects was significantly lower in patients treated with escitalopram compared with placebo for all primary and secondary outcomes, except for impaired concentration: reported sadness 27.5 vs. 48.7% (P = 0.052), inner tension 17.5 vs. 38.5% (P = 0.038), impaired concentration 55.0 vs. 66.7% (P = 0.288) and hostile feelings 22.5 vs. 43.6% (P = 0.046) (escitalopram vs. placebo, Chi-squared test). The sum scores of all four endpoints showed an overall beneficial effect of escitalopram (P = 0.009, Mann-Whitney U-test). Depression occurred in 12.5% of the patients in the escitalopram-group vs. 35.9% in the placebo-group (P = 0.015, Chi-squared test). CONCLUSIONS  Prophylactic treatment with escitalopram is effective in the prevention of psychiatric side-effects during interferon-based treatment of hepatitis C.

  17. Quantification of hepatitis C virus in patients treated with peginterferon-alfa 2a plus ribavirin treatment by COBAS TaqMan HCV test.

    PubMed

    Kanda, T; Imazeki, F; Yonemitsu, Y; Mikami, S; Takada, N; Nishino, T; Takashi, M; Tsubota, A; Kato, K; Sugiura, N; Tawada, A; Wu, S; Tanaka, T; Nakamoto, S; Mikata, R; Tada, M; Chiba, T; Kurihara, T; Arai, M; Fujiwara, K; Kanai, F; Yokosuka, O

    2011-07-01

    Extremely low levels of serum hepatitis C virus (HCV) RNA can be detected by COBAS TaqMan HCV test. To investigate whether the COBAS TaqMan HCV test is useful for measuring rapid virological response (RVR) and early virological response (EVR) to predict sustained virological response (SVR), we compared the virological response to PEG-IFN-alfa 2a plus RBV in 76 patients infected with HCV genotype 1 when undetectable HCV RNA by the COBAS TaqMan HCV test was used, with those when below 1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test was used, which corresponded to the use of traditional methods. Among the 76 patients, 28 (36.8%) had SVR, 13 (17.1%) relapsed, 19 (25.0%) did not respond, and 16 (21.0%) discontinued the treatment due to side effects. The positive predictive values for SVR based on undetectable HCV RNA by COBAS TaqMan HCV test at 24 weeks after the end of treatment [10/10 (100%) at week 4, 21/23 (91.3%) at week 8 and 26/33 (78.7%) at week 12] were superior to those based on <1.7 log IU/mL HCV RNA [17/19 (89.4%) at week 4, 27/38 (71.0%) at week 8, and 27/43 (62.7%) at week 12]. The negative predictive values for SVR based on <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test [46/57 (80.7%) at week 4, 37/38 (97.3%) at week 8, and 32/33 (96.9%) at week 12] were superior to those based on undetectable HCV RNA [48/66 (72.7%) at week 4, 46/53 (86.7%) at week 8, and 41/43 (95.3%) at week 12]. The utilization of both undetectable RNA and <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test is useful and could predict SVR and non-SVR patients with greater accuracy.

  18. Telaprevir alone or with peginterferon and ribavirin reduces HCV RNA in patients with chronic genotype 2 but not genotype 3 infections.

    PubMed

    Foster, Graham R; Hézode, Christophe; Bronowicki, Jean-Pierre; Carosi, Giampiero; Weiland, Ola; Verlinden, Lieselotte; van Heeswijk, Rolf; van Baelen, Ben; Picchio, Gaston; Beumont, Maria

    2011-09-01

    We evaluated antiviral activity of 2 weeks therapy with telaprevir alone, peginterferon alfa-2a and ribavirin (PR), or all 3 drugs (TPR) in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype 2 or 3 infections. We performed a randomized, multicenter, partially blinded study of patients (23 with HCV genotype 2, 26 with genotype 3) who received telaprevir (750 mg every 8 h), placebo plus PR (peginterferon, 180 μg, once weekly and ribavirin, 400 mg, twice daily), or TPR for 15 days, followed by PR for 22 or 24 weeks. Plasma levels of HCV RNA were quantified. Levels of HCV RNA decreased in all patients with HCV genotype 2, including those who received telaprevir monotherapy. The decrease was more rapid among patients who received telaprevir. By day 15, 0% (telaprevir), 40% (TPR), and 22% (PR) of patients with HCV genotype 2 had undetectable levels of HCV RNA; rates of sustained virologic response were 56%, 100%, and 89%, respectively. Overall, 6 of 9 HCV genotype 2 patients that received only telaprevir had viral breakthrough within 15 days after an initial response. HCV RNA levels decreased slightly among patients with HCV genotype 3 who received telaprevir and decreased rapidly among patients given PR or TPR (telaprevir had no synergistic effects with PR). Sustained virologic response rates were 50%, 67%, and 44% among patients given telaprevir, TPR, or PR respectively; 7 patients with HCV genotype 3 relapsed after therapy (2 given telaprevir, 3 given TPR, and 2 given PR) and 3 patients with HCV genotype 3 had viral breakthrough during telaprevir monotherapy. The incidence of adverse events was similar among groups. Telaprevir monotherapy for 2 weeks reduces levels of HCV RNA in patients with chronic HCV genotype 2 infections, but has limited activity in patients with HCV genotype 3. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  19. Peginterferon beta-1a reduces disability worsening in relapsing–remitting multiple sclerosis: 2-year results from ADVANCE

    PubMed Central

    Newsome, Scott D.; Kieseier, Bernd C.; Liu, Shifang; You, Xiaojun; Kinter, Elizabeth; Hung, Serena; Sperling, Bjoern

    2016-01-01

    Background: In the pivotal phase III 2-year ADVANCE study, subcutaneous peginterferon beta-1a 125 mcg every 2 weeks demonstrated significant improvements in clinical outcomes, including disability endpoints, in patients with relapsing–remitting multiple sclerosis (RRMS). Here, we aim to further evaluate disability data from ADVANCE, and explore associations between confirmed disability progression (CDP), functional status, and health-related quality of life (HRQoL). Methods: In total, 1512 patients were randomized to placebo or peginterferon beta-1a 125 mcg every 2 or 4 weeks. After 1 year, patients on placebo were re-randomized to peginterferon beta-1a every 2 or 4 weeks. CDP was defined as ⩾1.0 point increase from a baseline Expanded Disability Status Scale (EDSS) score ⩾ 1.0, or ⩾1.5-point increase from baseline 0, confirmed 12 or 24 weeks after onset. Results: Peginterferon beta-1a every 2 weeks significantly reduced risk of 12- and 24-week CDP at 1 year compared with placebo (12-week CDP: 6.8% versus 10.5%, p = 0.038; 24-week CDP: 4% versus 8.4%, p = 0.0069, peginterferon beta-1a every 2 weeks versus placebo, respectively). Benefits were maintained over 2 years (11.2% and 7.7%, peginterferon beta-1a every 2 weeks in 12- and 24-week CDP, respectively). Approximately 90% of patients with 24-week CDP had simultaneous worsening by ⩾1 point in at least one functional system score, most commonly pyramidal. Displaying a 24-week CDP was associated with worse scores on the Multiple Sclerosis Functional Composite (MSFC) scale and several HRQoL instruments; the impact of CDP was attenuated by treatment with peginterferon beta-1a every 2 weeks. Conclusions: Peginterferon beta-1a has the potential to prevent/delay worsening of disability in patients with relapsing–remitting multiple sclerosis. Furthermore, improved benefits in disability status with peginterferon beta-1a were also associated with improved functional status and HRQoL [Clinical

  20. Peginterferon beta-1a reduces disability worsening in relapsing-remitting multiple sclerosis: 2-year results from ADVANCE.

    PubMed

    Newsome, Scott D; Kieseier, Bernd C; Liu, Shifang; You, Xiaojun; Kinter, Elizabeth; Hung, Serena; Sperling, Bjoern

    2017-01-01

    In the pivotal phase III 2-year ADVANCE study, subcutaneous peginterferon beta-1a 125 mcg every 2 weeks demonstrated significant improvements in clinical outcomes, including disability endpoints, in patients with relapsing-remitting multiple sclerosis (RRMS). Here, we aim to further evaluate disability data from ADVANCE, and explore associations between confirmed disability progression (CDP), functional status, and health-related quality of life (HRQoL). In total, 1512 patients were randomized to placebo or peginterferon beta-1a 125 mcg every 2 or 4 weeks. After 1 year, patients on placebo were re-randomized to peginterferon beta-1a every 2 or 4 weeks. CDP was defined as ⩾1.0 point increase from a baseline Expanded Disability Status Scale (EDSS) score ⩾ 1.0, or ⩾1.5-point increase from baseline 0, confirmed 12 or 24 weeks after onset. Peginterferon beta-1a every 2 weeks significantly reduced risk of 12- and 24-week CDP at 1 year compared with placebo (12-week CDP: 6.8% versus 10.5%, p = 0.038; 24-week CDP: 4% versus 8.4%, p = 0.0069, peginterferon beta-1a every 2 weeks versus placebo, respectively). Benefits were maintained over 2 years (11.2% and 7.7%, peginterferon beta-1a every 2 weeks in 12- and 24-week CDP, respectively). Approximately 90% of patients with 24-week CDP had simultaneous worsening by ⩾1 point in at least one functional system score, most commonly pyramidal. Displaying a 24-week CDP was associated with worse scores on the Multiple Sclerosis Functional Composite (MSFC) scale and several HRQoL instruments; the impact of CDP was attenuated by treatment with peginterferon beta-1a every 2 weeks. Peginterferon beta-1a has the potential to prevent/delay worsening of disability in patients with relapsing-remitting multiple sclerosis. Furthermore, improved benefits in disability status with peginterferon beta-1a were also associated with improved functional status and HRQoL [ClinicalTrials.gov identifier: NCT00906399].

  1. Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial.

    PubMed

    Manns, Michael; Marcellin, Patrick; Poordad, Fred; de Araujo, Evaldo Stanislau Affonso; Buti, Maria; Horsmans, Yves; Janczewska, Ewa; Villamil, Federico; Scott, Jane; Peeters, Monika; Lenz, Oliver; Ouwerkerk-Mahadevan, Sivi; De La Rosa, Guy; Kalmeijer, Ronald; Sinha, Rekha; Beumont-Mauviel, Maria

    2014-08-02

    Pegylated interferon (peginterferon) alfa 2a or 2b plus ribavirin regimens were the standard of care in patients with hepatitis C virus (HCV) infection, but the sustained virological response can be suboptimum in patients with HCV genotype 1 infection. The efficacy, safety, and tolerability of the combination of simeprevir, a one-pill, once-daily, oral HCV NS3/4A protease inhibitor versus placebo, plus peginterferon alfa 2a or 2b plus ribavirin was assessed in treatment-naive patients with HCV genotype 1 infection. In the QUEST-2, phase 3 study, done at 76 sites in 14 countries (Europe, and North and South Americas), patients with confirmed chronic HCV genotype 1 infection and no history of HCV treatment were randomly assigned with a computer-generated allocation sequence in a ratio of 2:1 and stratified by HCV genotype 1 subtype and host IL28B genotype to receive simeprevir (150 mg once daily, orally), peginterferon alfa 2a (180 μg once weekly, subcutaneous injection) or 2b (according to bodyweight; 50 μg, 80 μg, 100 μg, 120 μg, or 150 μg once weekly, subcutaneous injection), plus ribavirin (1000-1200 mg/day or 800-1400 mg/day, orally; simeprevir group) or placebo (once daily, orally), peginterferon alfa 2a or 2b, plus ribavirin (placebo group) for 12 weeks, followed by just peginterferon alfa 2a or 2b plus ribavirin. Total treatment duration was 24 weeks or 48 weeks (simeprevir group) based on criteria for response-guided therapy (ie, HCV RNA <25 IU/mL undetectable or detectable at week 4 and undetectable week 12) or 48 weeks (placebo). Patients, study personnel, and the sponsor were masked to treatment assignment. The primary efficacy endpoint was sustained virological response at 12 weeks after the planned end of treatment (SVR12). Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01290679. Results from the primary (SVR12, week 60) analysis are presented. 209 (81%) of 257 patients in the simeprevir group and

  2. Pegylated interferon alfa-2a (40 kD) and ribavirin in haemodialysis patients with chronic hepatitis C.

    PubMed

    van Leusen, Robert; Adang, Rob P R; de Vries, Richard A; Cnossen, Trijntje T; Konings, Constantijn J A M; Schalm, Solko W; Tan, Adriaan C I T L

    2008-02-01

    Chronic hepatitis C virus (HCV) infection is associated with liver dysfunction and hepatocellular carcinoma. In patients with normal kidney function, treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV) frequently leads to eradication of HCV. Treatment in dialysis patients has long been controversial and until recently, the use of RBV was considered to be contra-indicated. We used plasma trough levels of RBV to promote tolerance, safety and efficacy. PEG-IFN alfa-2a (40 kD) was chosen because it is cleared predominantly via hepatic metabolism. Seven haemodialysis patients with chronic HCV infection were eligible and started with 135 microg PEG-IFN alfa-2a (40 kD) weekly and 200 mg RBV every other day. Dose adaptations were allowed following study guidelines. Genotypes 1 and 4 (five patients) were treated for 48 weeks and genotypes 2 and 3 (two patients) for 24 weeks. HCV-RNA was determined after 12, 24 and 48 weeks (and at 72 weeks for genotypes 1 and 4). RBV trough plasma levels were monitored regularly by HPLC-technique. All patients completed the treatment. In two patients, the PEG-IFN dose had to be reduced to 90 microg/week because of adverse events. To achieve the target range (1.5-2.5 microg/ml) of the plasma trough level, the mean RBV dose was increased to a dose between 133 and 200 mg each day in five patients. Despite an increase of the weekly erythropoietin (Epo) dose, two to a max of four red cell transfusions were given to four patients. A sustained viral response (SVR) was reached in five patients (3/5 with genotype 1/4 and 2/2 with genotype 2/3). In our series of seven patients, we were able to use RBV monitoring drug levels in combination with PEG-IFN alfa-2a (40 kD) and achieve high sustained response rates. However, Epo and transfusion requirements may increase. In two patients adverse events were observed, but manageable with dose reduction of PEG-IFN.

  3. Comparative study of systemic interferon alfa-2a plus isotretinoin versus isotretinoin in the treatment of recurrent condyloma acuminatum in men.

    PubMed

    Cardamakis, E; Kotoulas, I G; Relakis, K; Metalinos, K; Michopoulos, J; Stathopoulos, E; Mantouvalos, H

    1995-05-01

    Purpose of the present study was to evaluate the effectiveness of isotretinoin versus interferon alfa-2a plus isotretinoin in the treatment of recurrent condyloma acuminatum in 86 men. Men were randomly assigned to group A (n = 42) who received isotretinoin 1 mg/kg orally daily until remission was achieved, but not more than 3 months, or to group B (n = 44) who received interferon alfa-2a 3 x 10(5) IU subcutaneously three times weekly until remission was achieved, but not more than 8 weeks, plus isotretinoin in the same dosage as in group A. The reduced duration of treatment to achieve remission was statistically significant in group B (2.18 versus 2.5 months; P < 0.01) and the recurrence rate was less in group B (4 of 44 versus 16 of 42; P < 0.01). The results of this study are encouraging and demonstrated that the combination of isotretinoin plus interferon alfa-2a achieves higher remission rates and a shorter duration of treatment than isotretinoin alone.

  4. Peginterferon beta-1a reduces the evolution of MRI lesions to black holes in patients with RRMS: a post hoc analysis from the ADVANCE study.

    PubMed

    Arnold, Douglas L; You, Xiaojun; Castrillo-Viguera, Carmen

    2017-08-01

    The presence of chronic black holes, i.e., chronic lesions that are hypointense on T1-weighted images and are indicative of more severe tissue injury, has been increasingly utilized as a surrogate marker of therapeutic outcome in multiple sclerosis. The ADVANCE study was a 2-year, double-blind, pivotal trial evaluating the safety and efficacy of subcutaneous peginterferon beta-1a 125 mcg in 1512 patients with relapsing-remitting multiple sclerosis (RRMS). This report describes the correlation of clinical outcomes with the evolution of acute lesions into chronic black holes in ADVANCE, and the efficacy of peginterferon beta-1a in reducing this evolution. Treatment with peginterferon beta-1a significantly reduced the mean number of new/enlarging T2-weighted (NET2) lesions (0.76 vs. 1.03 from week 24, p = 0.0037; 0.44 vs. 0.99 from week 48, p < 0.0001) and new gadolinium-enhancing (Gd+) lesions (0.15 vs. 0.32 from week 24, p < 0.0001; 0.09 vs. 0.19 from week 48) that evolved into chronic black holes by 2 years. Patients with NET2 or Gd+ lesions at 24 weeks that evolved into chronic black holes showed significantly worse clinical outcomes, including a greater proportion with 12-week (14.9 vs. 8.4%; p = 0.0167) and 24-week (12.3 vs. 7.0%; p = 0.0333) confirmed disability worsening and higher mean annualized relapse rate (0.62 vs. 0.43; p = 0.0118), compared with patients with lesions that did not evolve into black holes. The correlation was independent of treatment. Reduced risk of evolution of new lesions into chronic black holes with peginterferon beta-1a treatment suggests potential to reduce long-term disability in RRMS by preventing irreversible tissue damage.

  5. Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial

    PubMed Central

    Gore, Martin E; Griffin, Clare L; Hancock, Barry; Patel, Poulam M; Pyle, Lynda; Aitchison, Michael; James, Nicholas; Oliver, Roderick TD; Mardiak, Jozef; Hussain, Tahera; Sylvester, Richard; Parmar, Mahesh KB; Royston, Patrick; Mulders, Peter FA

    2010-01-01

    Summary Background In metastatic renal cell carcinoma combinations of interferon alfa-2a, interleukin-2, and fluorouracil produce higher response rates and longer progression-free survival than do single agents. We aimed to compare overall survival in patients receiving combination treatment or interferon alfa-2a. Methods RE04/30012 was an open-label randomised trial undertaken in 50 centres across eight countries. 1006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were randomly allocated (1 to 1) by minimisation to receive interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. Treatment was not masked. The primary endpoint was overall survival. Treatment groups were compared with a non-stratified log-rank test. Analysis was by intention to treat. This study is registered, number ISRCTN 46518965. Findings 502 patients were randomly assigned to receive interferon alfa-2a and 504 to receive combined treatment. Median follow-up was 37·2 months (24·8–52·3). Median overall survival was 18·8 months (17·0–23·2) for patients receiving interferon alfa-2a versus 18·6 months (16·5–20·6) for those receiving combination therapy. Overall survival did not differ between the two groups (hazard ratio 1·05 [95% CI 0·90–1·21], p=0·55; absolute difference 0·3% (−5·1 to 5·6) at 1 year and 2·7% (−8·2 to 2·9) at 3 years). Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment. Interpretation Although combination therapy does not improve overall or progression-free survival compared with interferon alfa-2a alone, immunotherapy might still have a role because it can produce remissions that are of clinically relevant length in some patients. Identification of patients who will benefit from immunotherapy is crucial. Funding UK Medical Research Council. PMID:20153039

  6. A randomized phase 2b study of peginterferon lambda-1a for the treatment of chronic HCV infection.

    PubMed

    Muir, Andrew J; Arora, Sanjeev; Everson, Gregory; Flisiak, Robert; George, Jacob; Ghalib, Reem; Gordon, Stuart C; Gray, Todd; Greenbloom, Susan; Hassanein, Tarek; Hillson, Jan; Horga, Maria Arantxa; Jacobson, Ira M; Jeffers, Lennox; Kowdley, Kris V; Lawitz, Eric; Lueth, Stefan; Rodriguez-Torres, Maribel; Rustgi, Vinod; Shemanski, Lynn; Shiffman, Mitchell L; Srinivasan, Subasree; Vargas, Hugo E; Vierling, John M; Xu, Dong; Lopez-Talavera, Juan C; Zeuzem, Stefan

    2014-12-01

    Peginterferon lambda-1a (Lambda) is a type-III interferon with similar antiviral activity to alfa interferons but with a diminished extrahepatic receptor distribution, reducing the risk for extrahepatic adverse events. This was a randomized, blinded, actively-controlled, multicentre phase 2b dose-ranging study in patients chronically infected with HCV genotypes 1-4. Treatment-naive patients received Lambda (120/180/240 μg) or peginterferon alfa-2a (alfa; 180 μg) once-weekly with ribavirin for 24 (genotypes [GT] 2,3) or 48 (GT1,4) weeks. Rates of undetectable HCV-RNA at week 12 (complete early virologic response [cEVR]; primary end point) were significantly higher in GT1,4 patients receiving Lambda vs. alfa (170/304, 56% vs. 38/103, 37%); with similar cEVR rates for GT2,3 (80/88, 91% vs. 26/30, 87%). Rates of undetectable HCV-RNA at week 4 were significantly higher on 180 μg (15/102, 15% GT1,4; 22/29, 76% GT2,3) and 240 μg (17/104, 16% GT1,4; 20/30, 67% GT2,3) Lambda than alfa (6/103, 6% GT1,4; 9/30, 30% GT2,3). Sustained virologic responses (post-treatment week 24) were comparable between Lambda and alfa for GT1,4 (37-46% Lambda; 37% alfa) and GT2,3 (60-76% Lambda; 53% alfa). Aminotransferase and/or bilirubin elevations were the primary dose-limiting abnormalities for Lambda; a sponsor-mandated 240 to 180 μg dose reduction was therefore implemented. Serious adverse events were comparable (3-13% Lambda; 3-7% alfa). Grade 3-4 haemoglobin, neutrophil, and platelet reductions were lower on Lambda than alfa. Among alfa patients, 28/133 (21%) had peginterferon and 31/133 (23%) had ribavirin dose reductions for haematologic abnormalities vs. 0/392 and 8/392 (2%) on Lambda. Lambda demonstrated fewer musculoskeletal (16-28% vs. 47-63%) and influenza-like events (8-23% vs. 40-46%) than alfa. Lambda was associated with improved or similar rates of virologic response with fewer extrahepatic adverse events than alfa in chronic HCV infection. Copyright © 2014 European

  7. Coffee Consumption is Associated with Response to Peginterferon and Ribavirin Therapy in Patients with Chronic Hepatitis C

    PubMed Central

    Freedman, Neal D.; Curto, Teresa M.; Lindsay, Karen L.; Wright, Elizabeth C.; Sinha, Rashmi; Everhart, James E.

    2011-01-01

    Background & Aims High level coffee consumption has been associated with reduced progression of pre-existing liver diseases and lower risk of hepatocellular carcinoma. However, its relationship with therapy for Hepatitis C virus (HCV) infection has not been evaluated. Methods Patients (n=885) from the lead-in phase of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial recorded coffee intake before re-treatment with peginterferon alfa-2a (180 μg/wk) and ribavirin (1000–1200 mg/day). We assessed patients for early virologic response (EVR, 2 log10 reduction in level of HCV RNA at week 12; n=466) and undetectable HCV RNA at week 20 (W20VR; n=320), week 48 (end of treatment, EOT; n=284), and week 72 (sustained virologic response, SVR; n=157). Results The median log10 drop from baseline to week 20 was 2.0 (interquartile range: 0.6–3.9) among non-drinkers and 4.0 (2.1–4.7) among patients that drank ≥3 cup/day of coffee (P-trend <0.0001). In unadjusted models, the odds ratios (OR) and 95% confidence intervals (CI) for drinking ≥3 cups/day vs non-drinking were 3.2 (1.9–5.3) for EVR, 3.1 (1.8–5.1) for W20VR, 3.5 (2.0–5.9) for EOT, and 2.7 (1.4–5.3) for SVR (P-trend<0.0001 for all). After adjustment for age, race/ethnicity, sex, alcohol, cirrhosis, ratio of aspartate aminotransferase:alanine aminotransferase, the IL28B polymorphism rs12979860, dose reduction of peginterferon, and other covariates, the OR (95% CI) for EVR was 2.0 (1.1–3.6; P-trend = 0.004); for W20VR was 2.1 (1.1–3.9; p-trend=0.005); for EOT was 2.4 (1.3–4.6; P-trend=0.001), and for SVR was 1.8 (0.8–3.9; P-trend=0.034). Conclusion High-level consumption of coffee (more than 3 cups per day) is an independent predictor of improved virologic response to peginterferon plus ribavirin in patients with Hepatitis C. PMID:21376050

  8. The clinical effectiveness and cost-effectiveness of peginterferon alfa and ribavirin for the treatment of chronic hepatitis C in children and young people: a systematic review and economic evaluation.

    PubMed

    Hartwell, Debbie; Cooper, Keith; Frampton, Geoff K; Baxter, Louise; Loveman, Emma

    2014-10-01

    Optimal therapy for children with chronic hepatitis C is unclear. Two treatment regimens are currently licensed in children. To assess the clinical effectiveness and cost-effectiveness of peginterferon alfa-2a (Pegasys®, Roche) and peginterferon alfa-2b [ViraferonPeg®, Merck Sharp & Dohme (MSD)] in combination with ribavirin (RBV), within their licensed indications, for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3-17 years. Twelve electronic bibliographic databases, including The Cochrane Library, MEDLINE and EMBASE, were searched from inception to November 2012. Bibliographies of retrieved papers, key hepatitis C websites and symposia and manufacturers' submissions to the National Institute for Health and Care Excellence were also searched, and clinical experts were contacted. Systematic reviews of clinical effectiveness and cost-effectiveness were conducted, including studies of health-related quality of life (HRQoL), following standard guidelines to ensure methodological rigour. Clinical effectiveness studies were included if they were in children and young people aged 3-17 years with chronic compensated HCV of any severity, including those with human immunodeficiency virus co-infection and those who were treatment naive or had been previously treated. Eligible interventions were peginterferon alfa-2a or peginterferon alfa-2b, each in combination with RBV, compared against best supportive care (BSC) or against each other, and study designs were randomised controlled trials (RCTs) or non-RCTs, or uncontrolled cohort studies. Outcomes included sustained virological response (SVR) and adverse events. Previously published Markov state-transition economic models of chronic HCV in adults were adapted to estimate the cost-effectiveness of peginterferon alfa-2a and -2b (in combination with RBV), compared with BSC and with one another in children. The model extrapolated the impact of SVR on life expectancy, quality-adjusted life

  9. Extended duration versus standard duration of peginterferon alfa-2a in treatment of chronic hepatitis B: A systematic review and meta-analysis.

    PubMed

    Wang, Zhengyan; Sun, Ling; Wu, Yuwan; Xia, Qing

    2016-04-01

    In the last decade, PEG-IFNa-2a has been widely used in the treatment of chronic hepatitis B (CHB). The current standard duration is 48 weeks; however, several studies based on small sample sizes have indicated that treatment extended beyond 48 weeks improved clinical outcomes than standard 48 weeks of therapy. Therefore, we performed a meta-analysis to compare the efficacy and safety of extended duration versus standard duration treatment with PEG-IFNa-2a monotherapy for patients with CHB. Four studies comprising of 350 patients were included in our study. Our analysis showed that extended treatment resulted in a higher HBsAg clearance rate compared with the standard treatment at the end of treatment, 24 and 48 weeks post-treatment [odds ratio (OR)=2.45, 95% confidence intervals (CI) (1.17-5.11), P=0.02; OR=3.17, 95% CI (1.62-6.21), P<0.01; OR=5.02, 95% CI (1.63-15.45), P<0.01, respectively]. Higher HBeAg seroconversion rates were also obtained in the extended treatment group than the standard treatment group at the end of treatment and 48 weeks post-treatment [OR=2.09, 95% CI (1.10-3.98), P=0.02, and OR=2.67, 95% CI (1.39-5.13), P<0.01, respectively]. In addition, extended treatment was superior to standard treatment in HBV-DNA inhibition rate at 48 weeks post-treatment [OR=3.15, 95% CI (1.51-6.57), P<0.01]. Therefore, extended treatment with PEG-IFNa-2a beyond 48 weeks may be a promising strategy to achieve higher rates of sustained HBV-DNA inhibition, HBeAg seroconversion and HBsAg clearance off-therapy for patients with CHB.

  10. Extensive Psoriasis Induced by Pegylated Interferon Alfa-2a and Ribavirin in the Treatment of Chronic Hepatitis C

    PubMed Central

    Kim, Gun-Wook; Jwa, Seung-Wook; Song, Margaret; Kim, Hoon-Soo; Kim, Byung-Soo; Kim, Moon-Bum

    2013-01-01

    A 56-year-old man with chronic hepatitis C was treated with pegylated interferon alfa-2a in combination with ribavirin. However, psoriatic lesions appeared and worsened dramatically during therapy. Because of the extensive skin eruptions, he stopped therapy for chronic hepatitis C and subsequently started narrow-band ultraviolet B phototherapy and topical calcipotriol/betamethasone dipropionate ointment. After this, the psoriasis improved in a slow but comprehensive manner. Our case suggests that physicians should keep in mind the possibility of psoriasis as a side effect of interferon treatment for chronic hepatitis C. PMID:24371397

  11. Efficacy and safety of daclatasvir plus pegylated-interferon alfa 2a and ribavirin in previously untreated HCV subjects coinfected with HIV and HCV genotype-1: a Phase III, open-label study.

    PubMed

    Sulkowski, Mark S; Fessel, Walford J; Lazzarin, Adriano; Berenguer, Juan; Zakharova, Natalia; Cheinquer, Hugo; Côté, Pierre; Dieterich, Douglas; Gadano, Adrian; Matthews, Gail; Molina, Jean-Michel; Moreno, Christophe; Pineda, Juan Antonio; Pulido, Federico; Rivero, Antonio; Rockstroh, Jurgen; Hernandez, Dennis; McPhee, Fiona; Eley, Timothy; Liu, Zhaohui; Mendez, Patricia; Hughes, Eric; Noviello, Stephanie; Ackerman, Peter

    2017-03-01

    Daclatasvir (DCV) is a potent, pangenotypic, hepatitis C virus (HCV) non-structural protein 5A inhibitor with low potential for drug interactions with antiretroviral therapy (ART). We evaluated the safety and efficacy of DCV plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in HIV-1/HCV genotype-1-coinfected patients. AI444043 (NCT01471574), an open-label, Phase III, single-arm, response-guided treatment (RGT) study included 301 patients. They received DCV doses of 30, 60 or 90 mg once daily (depending on concomitant ART), plus weight-based RBV (<75 kg, 1000 mg/day; or ≥75 kg, 1200 mg/day), and once-weekly PegIFN 180 μg, for 24 weeks. If required by RGT, PegIFN/RBV without DCV was extended for an additional 24 weeks of therapy. The primary endpoint was the proportion of patients with sustained virologic response at post-treatment Week 12 (SVR12). Overall, 224 (74%) patients achieved SVR12 and the lower bound of the 95% confidence interval was higher than the historic SVR rate with PegIFN/RBV alone (70 vs. 29%). Most common adverse events (AEs) were fatigue, neutropenia, anemia, asthenia and headache. On-treatment serious AEs occurred in 24/301 (8%) patients; 18/301 (6%) discontinued treatment due to AE. DCV + PegIFN/RBV led to sustained HCV virologic response in the majority of HIV-1-HCV-coinfected patients, regardless of concomitant ART. HIV control was not compromised and no new safety signals were identified. This study supports DCV use in HIV-1-HCV-coinfected patients, while allowing the vast majority of patients to remain on their existing ART regimen.

  12. Clinical Experience of Interferon Alfa-2a Treatment for Refractory Uveitis in Behçet's Disease.

    PubMed

    Park, Ji-Youn; Chung, Yoo-Ri; Lee, Kihwang; Song, Ji Hun; Lee, Eun-So

    2015-07-01

    Behçet's disease (BD) involves multisystem vasculitis of unknown origin. Ocular manifestations of BD mostly include bilateral panuveitis and retinal vasculitis, which are very challenging to treat. Interferon alfa-2a (IFN) has been recently introduced for treating refractory Behçet uveitis, mainly in Germany and Turkey. Nonetheless, there is so far no consensus about the ideal treatment regimen of IFN for Behçet uveitis. We report our experience of IFN treatment in five Korean BD patients with refractory uveitis. All patients complained of oral ulcers; one patient had a positive pathergy test and 2 showed the presence of HLA-B51. Immunosuppressive agents used prior to IFN treatment included cyclosporine and methotrexate. The IFN treatment was commenced with a dose of 6-9 MIU/day for 7 days, adjusted according to individual ocular manifestations, tapered down to 3 MIU three times in a week, and then discontinued. All patients showed positive response to IFN treatment; 50% of them showed complete response without additional major ocular inflammation during the follow-up period. Other BD symptoms also improved after IFN treatment in most cases. After treatment, the relapse rate and the required dose of oral corticosteroid were decreased in most cases, showing a significant steroid-sparing effect. However, the visual acuity was not improved in most cases due to irreversible macular sequelae. Despite the small sample size of this study, we suggest that, in Korean patients, IFN is an effective treatment modality for BD uveitis as was observed in German and Turkish patients.

  13. The Combination of Ribavirin and Peginterferon Is Superior to Peginterferon and Placebo for Children and Adolescents Chronic Hepatitis C

    PubMed Central

    Schwarz, Kathleen B.; Gonzalez-Peralta, Regino P.; Murray, Karen F.; Molleston, Jean P.; Haber, Barbara A.; Jonas, Maureen M.; Rosenthal, Philip; Mohan, Parvathi; Balistreri, William F.; Narkewicz, Michael R.; Smith, Lesley; Lobritto, Steven J.; Rossi, Stephen; Valsamakis, Alexandra; Goodman, Zachary; Robuck, Patricia R.; Barton, Bruce A.

    2010-01-01

    Background & Aims Although randomized trials of adults infected with hepatitis C virus (HCV) have shown that ribavirin increases efficacy of pegylated interferon (PEG), such trials have not been performed in children. We conducted a randomized, controlled trial of PEG and ribavirin, compared with PEG and placebo, in children 5–17 years old with chronic hepatitis C. Methods HCV RNA-positive children from 11 university medical centers were randomly groups assigned to receive either the combination of peginterferon alfa-2a (PEG 2a; 180 μg/1.73 m2 body surface area, subcutaneously each week; n=59) and ribavirin (15 mg per kilogram orally in 2 doses daily) or PEG2a and placebo for 48 weeks (n=55). The primary endpoint was sustained virologic response (SVR, lack of detectable HCV RNA at least 24 weeks after stopping therapy). Results An SVR was achieved in 53% of children treated with PEG 2a and ribavirin, compared with 21% of children who received PEG 2a and placebo (P<0.001). Early virologic response (> 2 log10 IU reduction in HCV RNA at 12 weeks) had a negative predictive value of only 0.89 in children with genotype 1, indicating that these children might benefit from 24 weeks of therapy before stopping treatment. Side effects, especially neutropenia, led to dose modification in 40% of children. Eighty-two percent of the PEG/ribavirin and 86% of the PEG/placebo group were in compliance with the year-2 follow-up visit; the durability of virologic response was 100% in both groups. Conclusions The combination of PEG and ribavirin is superior to PEG and placebo as therapy for chronic hepatitis C in children and adolescents. PMID:21036173

  14. Pegylated Interferon Alfa-2a Monotherapy Results in Suppression of HIV Type 1 Replication and Decreased Cell-Associated HIV DNA Integration

    PubMed Central

    Azzoni, Livio; Foulkes, Andrea S.; Papasavvas, Emmanouil; Mexas, Angela M.; Lynn, Kenneth M.; Mounzer, Karam; Tebas, Pablo; Jacobson, Jeffrey M.; Frank, Ian; Busch, Michael P.; Deeks, Steven G.; Carrington, Mary; O'Doherty, Una; Kostman, Jay; Montaner, Luis J.

    2013-01-01

    Background. Antiretroviral therapy (ART)–mediated immune reconstitution fails to restore the capacity of the immune system to spontaneously control human immunodeficiency virus (HIV) replication. Methods. A total of 23 HIV type 1 (HIV-1)–infected, virologically suppressed subjects receiving ART (CD4+ T-cell count, >450 cells/μL) were randomly assigned to have 180 μg/week (for arm A) or 90 μg/week (for arm B) of pegylated (Peg) interferon alfa-2a added to their current ART regimen. After 5 weeks, ART was interrupted, and Peg–interferon alfa-2a was continued for up to 12 weeks (the primary end point), with an option to continue to 24 weeks. End points included virologic failure (viral load, ≥400 copies/mL) and adverse events. Residual viral load and HIV-1 DNA integration were also assessed. Results. At week 12 of Peg–interferon alfa-2a monotherapy, viral suppression was observed in 9 of 20 subjects (45%), a significantly greater proportion than expected (arm A, P = .0088; arm B, P = .0010; combined arms, P < .0001). Over 24 weeks, both arms had lower proportions of subjects who had viral load, compared with the proportion of subjects in a historical control group (arm A, P = .0046; arm B, P = .0011). Subjects who had a sustained viral load of <400 copies/mL had decreased levels of integrated HIV DNA (P = .0313) but increased residual viral loads (P = .0078), compared with subjects who experienced end-point failure. Conclusions. Peg–interferon alfa-2a immunotherapy resulted in control of HIV replication and decreased HIV-1 integration, supporting a role for immunomediated approaches in HIV suppression and/or eradication. Clinical Trials Registration. NCT00594880. PMID:23105144

  15. Changes in quality of life and sexual health are associated with low-dose peginterferon therapy and disease progression in patients with chronic hepatitis C

    PubMed Central

    Snow, Kristin K.; Bonkovsky, Herbert L.; Fontana, Robert J.; Kim, Hae-Young; Sterling, Richard K.; Di Bisceglie, Adrian M.; Morgan, Timothy R.; Dienstag, Jules L.; Ghany, Marc G.

    2010-01-01

    Background/Aim We assessed the effects of long-term peginterferon therapy and disease progression on health-related quality of life (HRQOL), symptoms, and sexual health in patients with chronic hepatitis C (CHC) and advanced fibrosis or cirrhosis. Methods 517 HALT-C Trial patients received peginterferon alfa-2a (90 μg/week); 532 received no additional treatment for 3.5 years. Patients were followed for outcomes of death, hepatocellular carcinoma and hepatic decompensation. Sexual health, SF-36 scores, and symptoms were serially assessed by repeated measures analyses of covariance. Results Patients with cirrhosis (n=427) reported lower general well-being and more fatigue (p<0.001) than patients with fibrosis (n=622). Physical scores declined significantly over time, independent of treatment, and patients with cirrhosis reported lower scores. Vitality scores were lower in those with cirrhosis, and treated patients experienced a greater decline over time than untreated patients; HRQOL rebounded after treatment ended. Patients with a clinical outcome had significantly greater declines in all SF-36 and symptom scores. Among men, sexual health scores were significantly worse in treated patients and in those with a clinical outcome. Conclusions Clinical progression of CHC and maintenance peginterferon therapy led to worsening of symptoms, HRQOL, and, in men, sexual health in a large patient cohort followed over 4 years. PMID:20070284

  16. Peginterferon Alfa-2b Injection (Sylatron)

    MedlinePlus

    ... injection is in a class of medications called interferons. It works by stopping the growth of cancer ... allergic to peginterferon alfa-2b injection (PegIntron, Sylatron), interferon alfa-2b (Intron), any other medications, or any ...

  17. Treatment outcomes and validation of the stopping rule for response to peginterferon in chronic hepatitis B: A Thai nationwide cohort study.

    PubMed

    Charatcharoenwitthaya, Phunchai; Sukeepaisarnjaroen, Wattana; Piratvisuth, Teerha; Thongsawat, Satawat; Sanpajit, Theeranun; Chonprasertsuk, Soonthorn; Jeamsripong, Woramon; Sripariwuth, Ekawee; Komolmit, Piyawat; Patcharatrakul, Tanisa; Boonsirichan, Rattana; Bunchorntavakul, Chalermrat; Tuntipanichteerakul, Supoj; Tanwandee, Tawesak

    2016-11-01

    Peginterferon has demonstrated effectiveness in clinical trials in patients with chronic hepatitis B (CHB). However, its efficacy in real-life settings remains unclear. We investigated the efficacy of peginterferon for CHB and validated the performance of previously identified response predictors in clinical practice. We analyzed prospectively collected data from a Thai nationwide cohort of CHB patients treated with peginterferon alfa-2a (180 µg/week, 48 weeks). Among a total of 233 patients, mostly with genotype B or C, sustained response was observed in 23% of 135 hepatitis B e antigen (HBeAg)-positive patients (HBeAg seroconversion with hepatitis B virus [HBV] DNA < 2000 IU/mL) and 42% of 98 HBeAg-negative patients (HBV DNA < 2000 IU/mL with aminotransferase normalization) at 24 weeks after treatment. Age, sex, presence of cirrhosis, genotype, and pretreatment levels of aminotransferase, HBV DNA, and hepatitis B surface antigen (HBsAg) were not identified as significant predictors of sustained response. In HBeAg-positive patients, HBsAg > 20 000 IU/mL at week 12 provided a good stopping rule, with a negative predictive value of 96%. In HBeAg-negative patients, the performance of 12-week stopping rules of no decline in HBsAg with a < 2log10 decline in HBV DNA and a < 10% log10 decline in HBsAg showed modest negative predictive values of 80% and 66%, respectively, for achieving sustained response. Outcomes in CHB patients treated with peginterferon in a clinical setting are similar to those demonstrated in clinical trials. Application of the early stopping rule based on HBsAg quantification may allow individualization of therapy, particularly in HBeAg-positive patients. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  18. Spotlight on peginterferon-alpha-2a (40KD) in chronic hepatitis C.

    PubMed

    Perry, Caroline M; Jarvis, Blair

    2002-01-01

    Peginterferon-alpha-2a (40KD) is a new 'pegylated' subcutaneous formulation of interferon-alpha-2a that has been developed to improve on the pharmacokinetic profile and therapeutic efficacy of interferon-alpha-2a. Peginterferon-alpha-2a (40KD) is produced by the covalent attachment of recombinant interferon-alpha-2a to a branched mobile 40KD polyethylene glycol moiety, which shields the interferon-alpha-2a molecule from enzymatic degradation, reduces systemic clearance and enables once-weekly administration. Peginterferon-alpha-2a (40KD) was significantly more effective than interferon-alpha-2a in interferon-alpha therapy-naive adults with chronic hepatitis C in three nonblind, randomised, multicentre trials. Virological responses (intention-to-treat results) were achieved in 44 to 69% of patients with or without cirrhosis after 48 weeks of treatment with peginterferon-alpha-2a (40KD) 180 microg/week; sustained virological responses 24 weeks after the end of treatment occurred in 30 to 39% of patients. Virological responses at the end of treatment and at long-term follow-up were significantly higher than those achieved with interferon-alpha-2a. Peginterferon-alpha-2a (40KD) was significantly more effective than interferon-alpha in patients with or without cirrhosis infected with HCV genotype 1. Sustained biochemical responses achieved with peginterferon-alpha-2a (40KD) 180 microg/week ranged from 34 to 45% and were significantly higher than with interferon-alpha-2a. Recipients of peginterferon-alpha-2a (40KD) also experienced histological improvements; 24 weeks after discontinuation of treatment with peginterferon-alpha-2a (40KD) 180 microg/week, 54% to 63% of patients had a >/=2-point improvement in histological activity index score. Peginterferon-alpha-2a (40KD) produced histological responses in patients (with or without cirrhosis) with or without a sustained virological response. Peginterferon-alpha-2a (40KD) produced better results than interferon-alpha-2a

  19. Peginterferon alfa and ribavirin for chronic hepatitis C in patients eligible for shortened treatment, re-treatment or in HCV/HIV co-infection: a systematic review and economic evaluation.

    PubMed

    Hartwell, D; Jones, J; Baxter, L; Shepherd, J

    2011-04-01

    -effectiveness of treatment strategies in subgroups of adults with chronic HCV who were eligible for shortened treatment and re-treatment and those with HCV/HIV co-infection. The model extrapolated the impact of SVR on life expectancy, quality-adjusted life expectancy and lifetime costs for each subgroup of patients with HCV. Categories of costs included in the model were drug acquisition, patient management, on-treatment monitoring, management of adverse events, and health-state costs for disease progression. In total, 2400 references were identified. Six RCTs were included in the review of clinical effectiveness, all reporting peginterferon alfa and ribavirin therapy in patients eligible for shortened treatment. In general, these RCTs were of good quality. No RCTs comparing peginterferon and ribavirin with BSC were identified for the re-treatment or co-infection populations. The results suggest that chronic HCV patients who have LVL at baseline and who achieve an RVR can be treated with shortened courses of therapy (24 weeks for genotype 1, 16 weeks for genotype 2/3) and achieve SVR rates that are comparable to those who receive the standard duration of treatment (ranges 84%-96% vs 83%-100%, respectively). However, patient numbers in the LVL/RVR subgroups were small and none of the trials was powered for this subgroup analysis, so results should be interpreted with caution. In the one trial reporting virological relapse rates in the subgroup of patients with LVL/RVR, rates were low and not statistically significantly different between those treated for 24 versus 48 weeks [3.6% vs 0%, respectively, difference 3.6%, 95% confidence interval (CI) -7.2% to 6.6%, p = 1.000]. In the cost-effectiveness analysis of shortened treatment with peginterferon alfa-2a, incremental cost-effectiveness ratios (ICERs) ranged from £35,000 to £65,000 for patients with genotype 1, whereas in patients with genotypes 2 and 3 shortened treatment dominated standard treatment. For patients with genotype 1

  20. Biological activity of EDQM CRS for Interferon alfa-2a and Interferon alfa-2b - assessment in two in vitro bioassays.

    PubMed

    Silva, M M C G; Gaines-Das, R E; Jones, C; Robinson, C J

    2007-12-01

    The European Directorate for the Quality of Medicines (EDQM) supplies Chemical Reference Substances (CRS) for Interferon (IFN) alfa-2a (CRS I0320300) and for IFN alfa-2b (CRS I0320301) for specified physicochemical tests. However, no information is provided as to their biological activity. In contrast, the World Health Organization (WHO) provides the 2nd International Standards (IS) for IFN alfa-2a (code 95/650) and for IFN alfa-2b (code 95/566), with activity defined in International Units (IU) for calibration of biological activity of preparations of IFN. We have compared the EDQM CRSs with the WHO ISs in two bioassay systems, one measuring the anti-proliferative activity in the Daudi cell line and the other measuring a reporter gene activation in an A549 cell line. In each of these assay systems, the CRSs gave dose - response relations, which were similar to those for the WHO ISs. Estimates of relative activity for each CRS, in terms of the respective IS, showed specific biological activity for the CRSs of the same order as the nominal specific activity for the ISs. However, the estimates of relative activity were not consistent between the two assays systems, emphasizing the need for calibration within each system, if the CRS were to be used as a working standard for bioassays. For structure-activity studies, both physicochemical and biological activity characterisation are required for the same biopharmaceutical preparation. CRS I0320300 and CRS I0320301 may prove useful as working standards for some bioassay systems.

  1. Cost effectiveness of peginterferon α-2b plus ribavirin versus interferon α-2b plus ribavirin for initial treatment of chronic hepatitis C

    PubMed Central

    Siebert, U; Sroczynski, G; Rossol, S; Wasem, J; Ravens-Sieberer, U; Kurth, B M; Manns, M P; McHutchison, J G; Wong, J B

    2003-01-01

    Background: Peginterferon α-2b plus ribavirin therapy in previously untreated patients with chronic hepatitis C yields the highest sustained virological response rates of any treatment strategy but is expensive. Aims: To estimate the cost effectiveness of treatment with peginterferon α-2b plus ribavirin compared with interferon α-2b plus ribavirin for initial treatment of patients with chronic hepatitis C. Methods: Individual patient level data from a randomised clinical trial with peginterferon plus ribavirin were applied to a previously published and validated Markov model to project lifelong clinical outcomes. Quality of life and economic estimates were based on German patient data. We used a societal perspective and applied a 3% annual discount rate. Results: Compared with no antiviral therapy, peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 4.2 and 4.7 years, respectively. Compared with standard interferon α-2b plus ribavirin, peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 0.5 and by 1.0 years with incremental cost effectiveness ratios of €11 800 and €6600 per quality adjusted life year (QALY), respectively. Subgroup analyses by genotype, viral load, sex, and histology showed that peginterferon plus weight based ribavirin remained cost effective compared with other well accepted medical treatments. Conclusions: Peginterferon α-2b plus ribavirin should reduce the incidence of liver complications, prolong life, improve quality of life, and be cost effective for the initial treatment of chronic hepatitis C. PMID:12584228

  2. Maintenance Peginterferon Therapy and Other Factors Associated with Hepatocellular Carcinoma in Patients with Advanced Hepatitis C

    PubMed Central

    Lok, Anna S.; Everhart, James E.; Wright, Elizabeth C.; Di Bisceglie, Adrian M.; Kim, Hae-Young; Sterling, Richard K.; Everson, Gregory T.; Lindsay, Karen L.; Lee, William M.; Bonkovsky, Herbert L.; Dienstag, Jules L.; Ghany, Marc G.; Morishima, Chihiro; Morgan, Timothy R.

    2010-01-01

    Background & Aims Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The Hepatitis C anti-viral long-term treatment against cirrhosis (HALT-C) trial showed that 4 years of maintenance therapy with peginterferon does not reduce liver disease progression. We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer post-treatment follow-up period. Methods The study included 1,048 patients with chronic Hepatitis C (Ishak fibrosis scores ≥3) who did not have a sustained virological response (SVR) to therapy. They were randomly assigned to groups given a half-dose of peginterferon or no treatment (controls) for 3.5 years and followed for a median 6.1 (maximum 8.7) years. Results Eighty-eight patients developed HCC (68 definite, 20 presumed): 37/515 that were given peginterferon (7.2%) and 51/533 controls (9.6%; P=0.24). There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis, but not fibrosis, based on analysis of baseline biopsy samples. After 7 years, the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio [HR]=0.45; 95% confidence interval [CI]: 0.24–0.83); in treated and control patients with fibrosis they were 8.3% and 6.8%, respectively (HR=1.44; 95% CI: 0.77–2.69). Treated patients with a ≥2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs. 9.4%; P=0.03). Conclusions Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs. Patients with cirrhosis who received peginterferon treatment had a lower risk for HCC than controls. PMID:21129375

  3. A randomized, controlled study of peginterferon lambda-1a/ribavirin ± daclatasvir for hepatitis C virus genotype 2 or 3.

    PubMed

    Foster, Graham R; Chayama, Kazuaki; Chuang, Wan-Long; Fainboim, Hugo; Farkkila, Martti; Gadano, Adrian; Gaeta, Giovanni B; Hézode, Christophe; Inada, Yukiko; Heo, Jeong; Kumada, Hiromitsu; Lu, Sheng-Nan; Marcellin, Patrick; Moreno, Christophe; Roberts, Stuart K; Strasser, Simone I; Thompson, Alexander J; Toyota, Joji; Paik, Seung Woon; Vierling, John M; Zignego, Anna L; Cohen, David; McPhee, Fiona; Wind-Rotolo, Megan; Srinivasan, Subasree; Hruska, Matthew; Myler, Heather; Portsmouth, Simon D

    2016-01-01

    Peginterferon Lambda was being developed as an alternative to alfa interferon for the treatment of chronic hepatitis C virus (HCV) infection. We compared peginterferon Lambda-1a plus ribavirin (Lambda/RBV) and Lambda/RBV plus daclatasvir (DCV; pangenotypic NS5A inhibitor) with peginterferon alfa-2a plus RBV (alfa/RBV) in treatment-naive patients with HCV genotype 2 or 3 infection. In this multicenter, double-blind, phase 3 randomized controlled trial, patients were assigned 2:2:1 to receive 24 weeks of Lambda/RBV, 12 weeks of Lambda/RBV + DCV, or 24 weeks of alfa/RBV. The primary outcome measure was sustained virologic response at post-treatment Week 12 (SVR12). Overall, 874 patients were treated: Lambda/RBV, n = 353; Lambda/RBV + DCV, n = 349; alfa/RBV, n = 172. Patients were 65 % white and 33 % Asian, 57 % male, with a mean age of 47 years; 52 % were infected with genotype 2 (6 % cirrhotic) and 48 % with genotype 3 (9 % cirrhotic). In the Lambda/RBV + DCV group, 83 % (95 % confidence interval [CI] 78.5, 86.5) achieved SVR12 (90 % genotype 2, 75 % genotype 3) whereas SVR12 was achieved by 68 % (95 % CI 63.1, 72.9) with Lambda/RBV (72 % genotype 2, 64 % genotype 3) and 73 % (95 % CI 66.6, 79.9) with peginterferon alfa/RBV (74 % genotype 2, 73 % genotype 3). Lambda/RBV + DCV was associated with lower incidences of flu-like symptoms, hematological abnormalities, and discontinuations due to adverse events compared with alfa/RBV. The 12-week regimen of Lambda/RBV + DCV was superior to peginterferon alfa/RBV in the combined population of treatment-naive patients with genotype 2 or 3 infection, with an improved tolerability and safety profile compared with alfa/RBV.

  4. Directly observed therapy of sofosbuvir/ribavirin +/- peginterferon with minimal monitoring for the treatment of chronic hepatitis C in people with a history of drug use in Chennai, India (C-DOT).

    PubMed

    Solomon, S S; Sulkowski, M S; Amrose, P; Srikrishnan, A K; McFall, A M; Ramasamy, B; Kumar, M S; Anand, S; Thomas, D L; Mehta, S H

    2017-07-18

    We assessed the feasibility of field-based directly observed therapy (DOT) with minimal monitoring to deliver HCV treatment to people with a history of drug use in Chennai, India. Fifty participants were randomized 1:1 to sofosbuvir+peginterferon alfa 2a+ribavirin (SOF+PR) for 12 weeks (Arm 1) vs sofosbuvir+ribavirin (SOF+R) for 24 weeks (Arm 2). SOF+R was delivered daily at participant chosen venues and weekly peginterferon injections at the study clinic. HCV RNA testing was performed to confirm active HCV infection and sustained virologic response 12 weeks after treatment completion (SVR12). No baseline genotyping or on-treatment viral loads were performed. Median age was 46 years. All were male and 20% had significant fibrosis/cirrhosis. All self-reported history of injection drug use, 18% recent noninjection drug use and 38% alcohol dependence. Six discontinued treatment (88% completed treatment in each arm). Of 22 who completed SOF+PR, all achieved SVR12 (22/25=88%); 15 of 22 who completed SOF+R achieved SVR12 (15/25=60%; P=.05). Among those completing SOF+R, SVR12 was significantly less common in participants reporting ongoing substance use (36% vs 100%) and missed doses. Active substance use and missed doses did not impact SVR with SOF+PR. Field-based DOT of HCV therapy without real-time HCV RNA monitoring was feasible; however, achieving 100% adherence was challenging. SOF+PR appeared superior to SOF+R in achieving SVR12, even when doses were missed with no discontinuations due to side effects. Further exploration of short duration treatment with peginterferon plus direct-acting antivirals is warranted. © 2017 John Wiley & Sons Ltd.

  5. Sustained virological response to peginterferon therapy in patients infected with HCV (genotypes 2 and 3), with or without HIV

    PubMed Central

    2014-01-01

    Background HIV infection leads to a faster progression of liver disease in subjects infected with HCV, as compared with HCV mono-infected patients. Previous reports suggest that sustained virological response (SVR) rates are lower in HIV/HCV coinfection than in HCV monoinfection. We aimed to compare SVR rates of these two populations. Methods We retrospectively analyzed clinical, biochemical and virological data of HCV and HIV/HCV infected patients with HCV genotypes 2 and 3 who started anti-HCV treatment between March 2004 and November 2012, at a single large center. Intention-to-treat (ITT) and per-protocol (PP) analysis were performed. Univariate and multivariate logistic regression analyses were performed to assess predictors of SVR. Results 461 patients were analyzed: 307 (66.6%) males, 76 (16.5%) infected with HIV. Several differences at baseline between HCV monoinfected and HIV/HCV coinfected patients were observed. HCV monoinfected group was characterized by higher prevalence of genotype 2 (53% vs 5.3%), higher baseline HCV viral load (50% vs 35%), shorter mean duration of treatment (19 vs 41 weeks), more frequent use of peginterferon alfa-2a (84.5% vs 69.7%), lower prevalence of cirrhosis (6% vs 31.6%). Globally, SVR was achieved by 353 (76.6%) patients and 321 (83.8%) in the PP analysis. No statistically relevant differences were found in SVR rates between the two groups, either in ITT [78.2% (n = 301/385) vs 68.4% (n = 52/76), p =0.066, respectively] than in PP analysis [83.6% (n = 276/330) vs 84.9% (n = 45/53), p = 0.8]. ITT analysis At univariate and multivariate analysis, baseline HCV-RNA >500.000 IU/ml [OR 0.4 (0.24-0.66), p = 0.0004], use of peginterferon alfa-2b [OR 0.5 (0.27-0.93) p = 0.033], platelets count <130.000/mm3 [OR 0.45 (0.2-0.99), p = 0.045], interruption of peginterferon therapy [OR 0.2 (0.1-0.4), p<0.0001], interruption of ribavirin treatment [OR 0.34 (0.17-0.69), p = 0.0026] were related with lower rate of SVR. PP analysis Only HCV

  6. Peginterferon-alpha-2a (40 kD): a review of its use in the management of chronic hepatitis C.

    PubMed

    Perry, C M; Jarvis, B

    2001-01-01

    Peginterferon-alpha-2a (40 kD) is a new 'pegylated' subcutaneous formulation of interferon-alpha-2a that has been developed to improve on the pharmacokinetic profile and therapeutic efficacy of interferon-alpha-2a. Peginterferon-alpha-2a (40 kD) is produced by the covalent attachment of recombinant interferon-alpha-2a to a branched mobile 40 kD polyethylene glycol moiety, which shields the interferon-alpha-2a molecule from enzymatic degradation, reduces systemic clearance and enables once-weekly administration. Peginterferon-alpha-2a (40 kD) was significantly more effective than interferon-alpha-2a in interferon-alpha therapy-naive adults with chronic hepatitis C in three nonblind, randomised, multicentre trials. Virological responses (intention-to-treat results) were achieved in 44 to 69% of patients with or without cirrhosis after 48 weeks of treatment with peginterferon-alpha-2a (40kD) 180 microg/week; sustained virological responses 24 weeks after the end of treatment occurred in 30 to 39% of patients. Virological responses at the end of treatment and at long-term follow-up were significantly higher than those achieved with interferon-alpha-2a. Peginterferon-alpha-2a (40 kD) was significantly more effective than interferon-alpha in patients with or without cirrhosis infected with HCV genotype 1. Sustained biochemical responses achieved with peginterferon-alpha-2a (40 kD) 180 microg/week ranged from 34 to 45% and were significantly higher than with interferon-alpha-2a. Recipients of peginterferon-alpha-2a (40 kD) also experienced histological improvements; 24 weeks after discontinuation of treatment with peginterferon-alpha-2a (40 kD) 180 microg/week, 54 to 63% of patients had a > or =2-point improvement in histological activity index score. Peginterferon-alpha-2a (40 kD) produced histological responses in patients (with or without cirrhosis) with or without a sustained virological response. Peginterferon-alpha-2a (40 kD) produced better results than interferon

  7. Efficacy and safety of peginterferon alpha-2a/ribavirin in treatment-naive Cameroonian patients with chronic hepatitis C.

    PubMed

    Njouom, Richard; Sartre, Michèle Tagni; Timba, Isabelle; Nerrienet, Eric; Tchendjou, Patrice; Pasquier, Christophe; Rousset, Dominique

    2008-12-01

    Data were examined from a day-to-day clinical practice in Yaounde, Cameroon to evaluate the efficacy and safety of peginterferon alfa-2a and ribavirin in treatment-naive Cameroonian patients with chronic hepatitis C. Ninety adults with chronic hepatitis C (mean age, 53 +/- 8 years; 79% males; 37.8% genotype 1; 23.3% genotype 2; and 38.9% genotype 4) were given at least 12 weeks of combination therapy between February 2003 and August 2007. Of these, 54 completed the treatment and the 24-week follow up. Subsequently, 18 continued treatment and 18 (20%) discontinued the treatment, 6 (6.7%) due to adverse effects. An intention-to-treat analysis showed that 38 (52.8%) had an end-of-treatment virologic response and 34 (47.2%) had a sustained virologic response. Sustained virologic response were significantly higher among patients with hepatitis C virus (HCV) genotype 2 (83.4%) than in those with genotype 1 (31%) or genotype 4 (42.3%) (P < 0.05). Non HCV-2 genotype, pretreatment fibrosis score >2, HCV RNA level >8.0 x 10(5) IU/ml and a non-virologic response at 12 weeks of treatment were associated with poor sustained virologic response (P < 0.05). Thus, HCV can be treated in a Sub-Saharan African country. It indicates that Cameroonian HCV-1 and -4 patients have a poorer sustained virologic response than the published results for Western and Middle-East countries. Virus subtype may influence the treatment outcome, since there is a great genetic diversity within Cameroonian HCV-1 and -4 genotypes.

  8. Incidence, characterization, and clinical impact analysis of peginterferon beta1a immunogenicity in patients with multiple sclerosis in the ADVANCE trial

    PubMed Central

    White, Joleen T.; Newsome, Scott D.; Kieseier, Bernd C.; Bermel, Robert A.; Cui, Yue; Seddighzadeh, Ali; Hung, Serena; Crossman, Mary; Subramanyam, Meena

    2016-01-01

    Background: Efficacy of interferon beta in multiple sclerosis (MS) can be dampened in patients who develop neutralizing antidrug antibodies (NAbs). Peginterferon beta1a is an interferon conjugated with a polyethylene glycol (PEG) moiety. Pegylation increases a drug’s half life and exposure, and may also reduce immunogenicity. Objective: The objective of this study was to characterize the incidence and impact of immunogenicity to peginterferon beta1a over 2 years in patients with MS. Methods: Patients with relapsing–remitting MS (N = 1512) were randomized to subcutaneous peginterferon beta1a 125 μg every 2 or 4 weeks, or placebo, for 1 year; patients in the placebo group were rerandomized to active treatment in year 2. The incidence and titers of binding antibodies (BAbs) and NAbs to interferon and antibodies to PEG (anti-PEG) were assessed in analytically validated assays. The clinical impact of immunogenicity on relapse and magnetic resonance imaging endpoints was evaluated. Results: Over 2 years, 6%, less than 1%, and 7% of patients developed anti-interferon BAbs, NAbs, and anti-PEG antibodies, respectively. There was no discernible clinically meaningful effect of antibody status on the pharmacodynamic, efficacy, or safety parameters evaluated, although these analyses were limited by the low incidence of treatment-emergent antibodies. Conclusion: The treatment effect of peginterferon beta1a in patients with relapsing–remitting MS is not expected to be attenuated by immunogenicity. PMID:27366230

  9. Sustained exacerbation of cryoglobulinaemia-related vasculitis following treatment of hepatitis C with peginterferon alfa.

    PubMed

    Batisse, Dominique; Karmochkine, Marina; Jacquot, Christian; Kazatchkine, Michel D; Weiss, Laurence

    2004-07-01

    Peginterferon is now the gold standard of therapy in patients with chronic hepatitis C virus infection. Extrahepatic manifestations of HCV are usually treated with interferon alfa. Here we report on a patient with HCV-related cirrhosis and cryoglobulinaemia who presented with an acute and long-lasting exacerbation of vasculitis during treatment with peginterferon. To our knowledge this is the first report of an acute exacerbation of cryoglobulinaemia-related vasculitis involving skin, peripheral nerve and kidney in a patient treated with peginterferon for HCV-related cirrhosis. The long half-life of peginterferon might explain the long-lasting symptoms of vasculitis. Clinicians should be aware of possible sustained flare of cryoglobulinaemia-associated vasculitis in patients receiving peginterferon.

  10. Protracted anaphylaxis developed after peginterferon α-2a administration for chronic hepatitis C

    PubMed Central

    Sakatani, Akihiko; Doi, Yoshinori; Matsuda, Takaaki; Sasai, Yasutaka; Nishida, Naohiro; Sakamoto, Megumi; Uenoyama, Naoto; Matsumoto, Yoshiya; Kinoshita, Kazuo

    2015-01-01

    Peginterferon is a key drug used to treat chronic viral hepatitis that is known for causing various side effects. Side effects occurring immediately after administration include headache, nausea, and influenza-like symptoms, such as fever and joint pain. However, reports of anaphylactic shock are extremely rare. Here we report a patient with protracted anaphylaxis who suffered shock symptoms after peginterferon α-2a administration for chronic hepatitis C. Although the patient improved temporarily with shock treatment, symptoms of anaphylaxis recurred. As peginterferon is often administered on an outpatient basis, it is important to recognize life-threatening side effects that may develop in a protracted manner. PMID:25759556

  11. Cost effectiveness of response-guided therapy with peginterferon in the treatment of chronic hepatitis B.

    PubMed

    Lo, Angeline Oi-Shan; Wong, Vincent Wai-Sun; Wong, Grace Lai-Hung; Chan, Henry Lik-Yuen; Dan, Yock-Young

    2015-02-01

    The high prevalence of chronic hepatitis B in Asian countries produces a substantial economic burden. Peginterferon has immunomodulatory effects and a finite course for treatment of hepatitis B, but also a high cost and side effects. The recent introduction of a 12-week stopping rule (stopping treatment after 12 weeks) has increased its appeal as a first-line treatment for hepatitis B. We aimed to determine the cost effectiveness of the 12-week stopping rule for peginterferon in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We used Markov modeling, with data from the Hong Kong population, to compare the cost effectiveness of peginterferon therapy with a 12-week stopping rule vs conventional therapy (48 weeks) and with other antiviral agents. For HBeAg-positive patients, stopping peginterferon therapy after 12 weeks had the lowest cost-effectiveness ratio (CER), of $9501/quality-adjusted life-year (QALY), compared with no treatment, making it the most cost-effective option. Conventional (48-week) peginterferon treatment had a CER of $9664/QALY. For HBeAg-negative patients, entecavir had the lowest CER ($34,310/QALY). Entecavir was more cost effective than either peginterferon strategies (CERs of $37,423/QALY for 12 weeks of peginterferon and $38,474/QALY for 48 weeks of treatment). The 12-week stopping rule increases the cost effectiveness of peginterferon therapy, and is the most cost-effective treatment for HBeAg-positive patients. The need for long-term antiviral therapy for HBeAg-negative patients makes entecavir the most cost-effective strategy. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  12. Consensus Interferon for Recurrent Hepatitis C Infection in Nonresponders to Peginterferon and Ribavirin After Liver Transplant.

    PubMed

    Nordstrom, Eric M; Biggins, Scott W; Gralla, Jane; Rosen, Hugo R; Everson, Gregory T; Burton, James R

    2015-12-01

    Hepatitis C virus infection universally recurs in liver transplant recipients. Peginterferon/ribavirin achieves a sustained virologic response rate of 30% in recipients infected with hepatitis C virus genotype 1. Consensus-interferon plus ribavirin yields sustained virologic response rates to 30% in patients failing to achieve sustained virologic response with peginterferon/ribavirin pretransplant, but it has not been studied posttransplant. We sought to evaluate the efficacy and tolerability of consensus-interferon and ribavirin in treating posttransplant hepatitis C virus. Clinical, laboratory, and virologic data were collected retrospectively from all patients who received at least 1 dose of consensus-interferon after transplant between January 2008 and December 2011. A standardized treatment protocol was used. The primary aim was sustained virologic response defined by undetectable hepatitis C virus RNA at 24 weeks after completing therapy. Twenty-three patients were treated with consensus-interferon/ribavirin; 15 with prior nonresponse (87%) or breakthrough (6.7%) during peginterferon/ribavirin, and 8 as initial therapy. The intention-to-treat sustained virologic response with consensus-interferon was 30%. Anemia, leukopenia, and growth factor requirement were similar between peginterferon and consensus-interferon cohorts. Consensus-interferon may rescue liver recipients who are nonresponders to peginterferon-based therapy. The efficacy of interferon-based treatment regimens may benefit from substitution of consensus-interferon for peginterferon.

  13. Safety and Efficacy of Adding Ribavirin to Interferon or Peginterferon in Treatment of Hepatitis C Infection in Patients With Thalassemia: A Systematic Review on Randomized Controlled Trials

    PubMed Central

    Aminizadeh, Ehsan; Alavian, Seyed Moayyed; Akbari Sari, Ali; Ebrahimi Daryani, Nasser; Behnava, Bita

    2016-01-01

    Context Hepatitis C virus (HCV) infection is a major cause of liver-morbidity and mortality among patients with thalassemia. Peginterferon plus ribavirin is currently the recommended therapy for hepatitis C infection in patients do not have thalassemia, but using ribavirin in patients with thalassemia is restricted due to its hemolytic effect. To evaluate the efficacy and safety of adding ribavirin to peginterferon or interferon, authors performed a systematic review on the available literatures. Evidence Acquisition Trials were identified through electronic database, manual searches of journals and bibliographies and approaching authors of trials. Randomized trials that enrolled patients with a diagnosis of thalassemia and chronic hepatitis C infection treated with interferon or peginterferon with or without ribavirin were included. Two investigators independently evaluated the trials for inclusion criteria, risk of bias and data extraction. The primary outcomes were sustained virological response (SVR), liver-related morbidity, mortality and adverse events. The odds ratios from each trial were calculated individually and in the subgroup analysis of trials. Data were analyzed with fixed-effect model. Results Three randomized clinical trials with 92 patients were included. All three trials had unclear risk of bias. Compared with peginterferon monotherapy, adding ribavirin to peginterferon had significant beneficial effect on sustained virological response (OR = 3.44, 95% CI: 1.18 - 10.06). There was no significant difference between combination therapy and monotherapy in the end of treatment achievement response. Other than about 30% increase in blood transfusion due to anemia that returned to normal level 2 - 3 months after treatment, there was no significant increase in side effects followed by adding ribavirin to pegylated interferon (Peg-IFN). Data were insufficient to determine the impact of genotype, viral load and age on the response to treatment

  14. The effectiveness of retreatment with peginterferon alfa and ribavirin in patients with chronic viral hepatitis C genotype 2 and 3: a prospective cohort study in Brazil

    PubMed Central

    2012-01-01

    Background More than 50% of patients infected with chronic hepatitis C virus (HCV) do not respond to treatment with conventional interferon (IFN) combined with ribavirin (RBV). The aim of our study was to evaluate the effectiveness of retreatment with peginterferon alfa-2a or 2b (PEG-IFN 2a or 2b) concomitantly with RBV in patients with HCV genotype 2 and 3, which were non-responders or relapsers to initial treatment with IFN / RBV and to identify possible predictors of sustained virological response (SVR). Methods From September 2003 to March 2009 a cohort of 216 patients who had previously failed therapy with a regimen of standard interferon and ribavirin, were followed in a specialized service implemented in the Brazilian Unified Health System, Rio Grande do Sul. All patients were retreated with PEG-IFN 2a or 2b per week, associated with RBV, through oral route, with doses determined according to weight (1,000 mg if weight ≤ 75 Kg and 1,250 mg if ≥ 75 Kg) per day for 48 weeks. The HCV-RNA was tested by Polymerase Chain Reaction (PCR). Virological Response (VR) within 48 weeks and SVR in the 72 weeks was considered for evaluation of treatment efficacy. Analyses were performed in patients who received at least one dose of PEG-IFN. Results The SVR rate for non-responders to previous treatment was 34.4% and for relapsers was 50% (p = 0.031). As predictive factors that contribute to improve SVR, were identified the age (p = 0.005), to be relapsers to previous treatment (p = 0.023) and present liver biopsy examination Metavir F0-F2 (p = 0.004). In assessing the safety profile, 51 patients (23.6%) discontinued treatment prematurely. Conclusions This alternative retreatment for patients who have failed prior therapies for anti-HCV, has demonstrated promising SVR rate, provided that it includes a careful selection of patients with predictors of response and adverse events monitored. PMID:23270376

  15. Daclatasvir vs telaprevir plus peginterferon alfa/ribavirin for hepatitis C virus genotype 1

    PubMed Central

    Jacobson, Ira; Zeuzem, Stefan; Flisiak, Robert; Knysz, Brygida; Lueth, Stefan; Zarebska-Michaluk, Dorota; Janczewska, Ewa; Ferenci, Peter; Diago, Moises; Zignego, Anna Linda; Safadi, Rifaat; Baruch, Yaacov; Abdurakhmanov, Dzhamal; Shafran, Stephen; Thabut, Dominique; Bruck, Rafael; Gadano, Adrian; Thompson, Alexander James; Kopit, Justin; McPhee, Fiona; Michener, Tracy; Hughes, Eric A; Yin, Philip D; Noviello, Stephanie

    2016-01-01

    AIM: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin (pegIFN/RBV), in treatment-naive hepatitis C virus (HCV) genotype (GT) 1-infected patients. METHODS: In this phase 3, randomized, open-label, noninferiority study, 602 patients were randomly assigned (2:1) to daclatasvir vs telaprevir, stratified by IL28B rs12979860 host genotype (CC vs non-CC), cirrhosis status (compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype (GT1a vs GT1b). Patients were selected by study inclusion criteria from a total of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or telaprevir 750 mg 3 times daily plus pegIFN/RBV. Daclatasvir recipients received 24 wk of daclatasvir plus pegIFN/RBV; those without an extended rapid virologic response (eRVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24 wk of pegIFN/RBV. Telaprevir-treated patients received 12 wk of telaprevir plus pegIFN/RBV followed by 12 (with eRVR) or 36 (no eRVR) wk of pegIFN/RBV. The primary objective was to compare for noninferiority of sustained virologic response rates at posttreatment week 12 (SVR12) in GT1b-infected patients. Key secondary objectives were to demonstrate that the rates of anemia (hemoglobin < 10 g/dL) and rash-related events, through week 12, were lower with daclatasvir + pegIFN/RBV than with telaprevir + pegIFN/RBV among GT1b-infected patients. Resistance testing was performed using population-based sequencing of the NS5A region for all patients at baseline, and for patients with virologic failure or relapse and HCV-RNA ≥ 1000 IU/mL, to investigate any link between NS5A polymorphisms associated with daclatasvir resistance and virologic outcome. RESULTS: Patient demographics and disease characteristics were generally balanced across treatment arms; however, there was a higher proportion of black/African Americans in the daclatasvir groups (6.0% and 8.2% in the GT1b and GT1a groups, respectively) than in the

  16. Cost-effectiveness analysis of peginterferon beta-1a compared with interferon beta-1a and glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis in the United States.

    PubMed

    Hernandez, Luis; Guo, Shien; Kinter, Elizabeth; Fay, Monica

    2016-07-01

    Objective Peginterferon beta-1a 125 mcg, administered subcutaneously (SC) every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved by the US Food and Drug Administration in 2014. This study assesses the cost-effectiveness of peginterferon beta-1a vs interferon beta-1a (44 mcg SC 3 times per week) and glatiramer acetate (20 mg SC once-daily) in the treatment of RRMS from the perspective of a US payer over 10 years. Methods A Markov cohort economic model was developed for this analysis. The model predicts disability progression, occurrence of relapses and other adverse events and translates them into quality-adjusted life years (QALYs) and costs. Natural history data were obtained from the placebo arm of the ADVANCE trial of peginterferon beta-1a, the London Ontario (Canada) database and a large population-based MS survey. Comparative efficacy of each DMT vs placebo was obtained from a network meta-analysis. Costs (in 2014 US dollars) were sourced from public databases and literature. Clinical and economic outcomes were discounted at 3% per year. Results Over 10 years, peginterferon beta-1a was dominant (i.e., more effective and less costly), with cost-savings of $22,070 and additional 0.06 QALYs when compared with interferon beta-1a 44 mcg and with cost-savings of $19,163 and 0.07 QALYs gained when compared with glatiramer acetate 20 mg. Results were most sensitive to variations in the treatment effect of each DMT, treatment acquisition costs of each DMT and the time horizon. Probabilistic sensitivity analyses indicated that peginterferon beta-1a remains dominant in >90% of 5,000 replications compared with either DMTs. Conclusion This analysis suggests that long-term treatment with peginterferon beta-1a improves clinical outcomes at reduced costs compared with interferon beta-1a 44 mcg and glatiramer acetate 20 mg and should be a valuable addition to managed care formularies for treating

  17. [Results of treatment with peginterferon plus ribavirin in patients with chronic hepatitis C].

    PubMed

    Pizarro, Carolina; Venegas, Mauricio; Hola, Karen; Smok, Gladys; Brahm, Javier

    2011-06-01

    The current treatment recommendation for chronic hepatitis C virus infection is the combination of peginterferon and ribavirin for 24 or 48 weeks, depending on the viral genotype. The aim of the therapy is to obtain a sustained virological response. To report our experience in the treatment of chronic hepatitis C. Analysis of 52 patients treated between September 2000 and June 2009. Patients with genotype 1 or 5 were treated with peginterferon alpha 2a (180 ug/week) and ribavirin (1000 mg/day for those weighing less than 75 kg and 1200 mg/day for those weighing more than 75 kg) during 48 weeks. Patients with genotypes 2 and 3 were treated for 24 weeks with the same dose of peginterferon and ribavirin 800 mg/day. Viral genotypes 1, 2, 3 and 5 were present in 81, 4, 11 and 4% of patients, respectively. Twenty four patients (46 %), 18 with genotype 1, achieved a sustained viral response. Age was the only variable that influenced the response to treatment. Approximately half of the patients with chronic hepatitis C, achieve a sustained viral response with peginterferon and ribavirin.

  18. Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3

    PubMed Central

    Marciano, Sebastián; Borzi, Silvia M; Dirchwolf, Melisa; Ridruejo, Ezequiel; Mendizabal, Manuel; Bessone, Fernando; Sirotinsky, María E; Giunta, Diego H; Trinks, Julieta; Olivera, Pablo A; Galdame, Omar A; Silva, Marcelo O; Fainboim, Hugo A; Gadano, Adrián C

    2015-01-01

    AIM: To evaluate pre-treatment factors associated with sustained virological response (SVR) in patients with hepatitis C virus (HCV) genotype 3 treated with peginterferon and ribavirin (RBV). METHODS: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index, steatosis, INFL3 polymorphism, pre-treatment HCV-RNA, type of peginterferon, RBV dose and adherence. RESULTS: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1 (± 1.8) wk. Overall, 58% (62/107) of the patients achieved an SVR and 42% (45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/mL (OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis (OR = 0.278, 95%CI: 0.113-0.684, P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥ 600000 UI/mL and advanced fibrosis, the probability of achieving an SVR was 29% (95%CI: 13.1-45.2). In patients with pre-treatment HCV-RNA < 600000 UI/mL and mild to moderate fibrosis, the probability of achieving an SVR was 81% (95%CI: 68.8-93.4). CONCLUSION: In patients with HCV genotype 3 infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agents-based regimes. PMID:25866607

  19. Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response.

    PubMed

    Feld, Jordan J; Nanda, Santosh; Huang, Ying; Chen, Weiping; Cam, Maggie; Pusek, Susan N; Schweigler, Lisa M; Theodore, Dickens; Zacks, Steven L; Liang, T Jake; Fried, Michael W

    2007-11-01

    The reasons for hepatitis C treatment failure remain unknown but may be related to different host responses to therapy. In this study, we compared hepatic gene expression in patients prior to and during peginterferon and ribavirin therapy. In the on-treatment group, patients received either ribavirin for 72 hours prior to peginterferon alpha-2a injection or peginterferon alpha-2a for 24 hours, prior to biopsy. The patients were grouped into rapid responders (RRs) with a greater than 2-log drop and slow responders (SRs) with a less than 2-log drop in hepatitis C virus RNA by week 4. Pretreatment biopsy specimens were obtained from a matched control group. The pretreatment patients were grouped as RRs or SRs on the basis of the subsequent treatment response. Gene expression profiling was performed with Affymetrix microarray technology. Known interferon-stimulated genes (ISGs) were induced in treated patients. In the pretreatment group, future SRs had higher pretreatment ISG expression than RRs. On treatment, RRs and SRs had similar absolute ISG expression, but when it was corrected for the baseline expression with the pretreatment group, RRs showed a greater fold change in ISGs, whereas SRs showed a greater change in interferon (IFN)-inhibitory pathways. The patients pretreated with ribavirin had heightened induction of IFN-related genes and down-regulation of genes involved in IFN inhibition and hepatic stellate cell activation. These data suggest that ISG inducibility is important for the treatment response and that ribavirin may improve outcomes by enhancing hepatic gene responses to peginterferon. Collectively, these mechanisms may provide a molecular basis for the improved efficacy of combination therapy.

  20. EXCESS MORTALITY IN PATIENTS WITH ADVANCED CHRONIC HEPATITIS C TREATED WITH LONG-TERM PEGINTERFERON

    PubMed Central

    Di Bisceglie, Adrian M.; Stoddard, Anne M.; Dienstag, Jules L.; Shiffman, Mitchell L.; Seeff, Leonard B.; Bonkovsky, Herbert L.; Morishima, Chihiro; Wright, Elizabeth C.; Snow, Kristin K.; Lee, William M.; Fontana, Robert J.; Morgan, Timothy R.; Ghany, Marc G.

    2011-01-01

    Background/Aims Chronic hepatitis C virus infection can cause chronic liver disease, cirrhosis and liver cancer. The HALT-C Trial was a prospective, randomized controlled study of long-term, low-dose peginterferon therapy in patients with advanced chronic hepatitis C who had failed to respond to a previous course of optimal antiviral therapy. The aim of this follow-up analysis was to describe the frequency and causes of death among this cohort of patients. Methods Deaths occurring during and after the HALT-C Trial were reviewed by a committee of investigators to determine the cause of death and to categorize each death as liver- or non-liver-related and as related or not to complications of peginterferon. Rates of liver transplantation were also assessed. Results Over a median of 5.7 years, 122 deaths occurred among 1,050 randomized patients (12%) of which 76 were considered liver-related (62%) and 46 non-liver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years, the cumulative mortality rate was higher in the treatment compared to the control group (20% versus 15%, p=0.049); the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum (14% versus 7%, p=0.01); comparable differences were observed when liver transplantation was included. Excess mortality, emerging after 3 years of treatment, was related largely to non-liver-related death; liver-related mortality was similar in the treatment and control groups. No specific cause of death accounted for the excess mortality, and only one death was suspected to be a direct complication of peginterferon. Conclusions Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to non-liver-related causes among patients with bridging fibrosis. PMID:21480316

  1. Peginterferon plus ribavirin versus interferon plus ribavirin for chronic hepatitis C.

    PubMed

    Hauser, Goran; Awad, Tahany; Brok, Jesper; Thorlund, Kristian; Štimac, Davor; Mabrouk, Mahasen; Gluud, Christian; Gluud, Lise Lotte

    2014-02-28

    Pegylated interferon (peginterferon) plus ribavirin is the recommended treatment for patients with chronic hepatitis C, but systematic assessment of the effect of this treatment compared with interferon plus ribavirin is needed. To systematically evaluate the benefits and harms of peginterferon plus ribavirin versus interferon plus ribavirin for patients with chronic hepatitis C. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index-Expanded, and LILACS. We also searched conference abstracts, journals, and grey literature. The last searches were conducted in September 2013. We included randomised clinical trials comparing peginterferon plus ribavirin versus interferon plus ribavirin with or without co-intervention(s) (e.g., other antiviral drugs) for chronic hepatitis C. Quasi-randomised and observational studies retrieved through the searches for randomised clinical trials were also considered for reports of harms. Our primary outcomes were liver-related morbidity, all-cause mortality, serious adverse events, adverse events leading to treatment discontinuation, other adverse events, and quality of life. Our secondary outcome was sustained virological response in serum, that is, undetectable hepatitis C virus RNA in serum by sensitive tests six months after the end of treatment. Two review authors independently used a standardised data collection form. We meta-analysed data with both fixed-effect and random-effects models. For each outcome, we calculated the odds ratio (OR) (for liver-related morbidity or all-cause mortality) or the risk ratio (RR) along with 95% confidence interval (CI) based on intention-to-treat analysis. We used domains of the trials to assess the risk of systematic errors (bias) and trial sequential analyses to assess the risk of random errors (play of chance).For each outcome, we calculated the RR with 95% CI based on

  2. Virology analyses of HCV genotype 4 isolates from patients treated with simeprevir and peginterferon/ribavirin in the Phase III RESTORE study.

    PubMed

    Fevery, B; Verbinnen, T; Peeters, M; Janssen, K; Witek, J; Jessner, W; De Meyer, S; Lenz, O

    2017-01-01

    Simeprevir is a hepatitis C virus NS3/4A protease inhibitor. Hepatitis C virus baseline NS3/4A polymorphisms and emerging mutations were characterized in treatment-naїve and treatment-experienced genotype 4-infected patients treated with simeprevir+peginterferon/ribavirin in the RESTORE study. Population sequencing of the NS3/4A region was performed and in vitro simeprevir activity against site-directed mutants or chimeric replicons with patient-derived NS3 protease sequences was assessed in a transient replicon assay. Simeprevir remained active against most (83/91 [91%]) baseline isolates tested in the chimeric replicon assay. Eight baseline isolates reduced simeprevir activity; these carried I132L or D168E substitutions reducing simeprevir median activity by 4.6- and 39-fold, respectively. Six of these eight isolates were from patients achieving sustained virologic response. Baseline NS3 Q80K polymorphism was not observed in the genotype 4-infected patients. Of the 107 simeprevir-treated patients, 37 did not achieve sustained virologic response for any reason. Of the 32 patients who failed treatment and had sequencing information, 28 (88%) had emerging mutations at NS3 positions 80, 122, 155, 156 and/or 168 at time of failure, similar to those in genotype 1. Emerging mutations were mainly D168V and D168E alone or combined with mutations at position 80. In general, isolates obtained at time of failure displayed high-level in vitro resistance to simeprevir (fold change ≥50) in a chimeric replicon assay with a median simeprevir fold change value of 440, consistent with observed mutations. In conclusion, emerging mutations in genotype 4 patients failing simeprevir+peginterferon/ribavirin treatment were similar to those in genotype 1 and conferred high-level resistance to simeprevir.

  3. Reversible bilateral ototoxicity in a patient with chronic hepatitis B during peginterferon alpha-2a treatment.

    PubMed

    Gozdas, Hasan Tahsin; Karabay, Oguz

    2015-01-01

    Peginterferon alpha-2a (PEG IFN α-2a) is frequently used in chronic hepatitis B (CHB)treatment. Numerous adverse events can be noted during this therapy such as flu-like disease, rash, weight loss and depression. However, PEG IFN α-2a related ototoxicity seems to be an uncommon entity. Ototoxicity can be detected objectively by audiometry. In this paper, we present a case of CHB who developed reversible bilateral ototoxicity during PEG IFN α-2a treatment. Due to ototoxicity detected objectively by audiogram, treatment was ceased at sixth month and ototoxicity completely recovered one month after stopping the drug.

  4. Bell's palsy and choreiform movements during peginterferon alpha and ribavirin therapy.

    PubMed

    Barut, Sener; Karaer, Hatice; Oksuz, Erol; Eken, Asli Gündoğdu; Basak, Ayse Nazli

    2009-08-07

    Neuropsychiatric side effects of long-term recombinant interferon-alpha therapy consist of a large spectrum of symptoms. In the literature, cranial neuropathy, especially Bell's palsy, and movement disorders, have been reported much less often than other neurotoxic effects. We report a case of Bell's palsy in a patient with chronic hepatitis C during peginterferon-alpha and ribavirin therapy. The patient subsequently developed clinically inapparent facial nerve involvement on the contralateral side and showed an increase in choreic movements related to Huntington's disease during treatment.

  5. Peginterferon alfa-2b and ribavirin in thalassaemia/chronic hepatitis C virus-co-infected non-responder to standard interferon-based.

    PubMed

    Hamidah, A; Thambidorai, C R; Jamal, R

    2005-10-01

    We describe a patient with HbE-beta thalassaemia and chronic hepatitis C virus infection (genotype 1a) who was treated successfully with peginterferon alfa-2b and ribavirin, following failure to respond to standard interferon and ribavirin therapy. She had sustained virological response for nearly 24 months after completing peginterferon alfa-2b and ribavirin therapy. Transfusion requirements were significantly increased during combination therapy due to ribavirin-induced haemolysis. The adverse effects of interferon were well tolerated. Combination therapy with peginterferon alfa-2b and ribavirin maybe a feasible treatment option for a subset of thalassaemia/HCV infected non-responders to standard interferon-based therapy.

  6. The pharmacokinetics of peginterferon lambda-1a following single dose administration to subjects with impaired renal function

    PubMed Central

    Hruska, Matthew W; Adamczyk, Robert; Colston, Elizabeth; Hesney, Michael; Stonier, Michele; Myler, Heather; Bertz, Richard

    2015-01-01

    Aims This open label study was conducted to assess the effect of renal impairment (RI) on the pharmacokinetics (PK) of peginterferon lambda-1a (Lambda). Methods Subjects (age 18–75 years, BMI 18–35 kg m–2) were enrolled into one of five renal function groups: normal (n = 12), mild RI (n = 8), moderate RI (n = 8), severe RI (n = 7), end-stage renal disease (ESRD, n = 8) based on estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) equation. Subjects received a single dose of Lambda (180 µg) subcutaneously on day 1 followed by PK serum sample collections through day 29. Safety, tolerability and immunogenicity data were collected through day 43. PK parameters were estimated and summarized by group. Geometric mean ratios (GMR) and 90% confidence intervals (CIs) were calculated between normal and RI groups. Results With decreasing eGFR, Lambda exposure (Cmax, AUC) increased while apparent clearance (CL/F) and apparent volume of distribution (V/F) decreased. Relative to subjects with normal renal function (geometric mean AUC = 99.5 ng ml–1 h), Lambda exposure estimates (AUC) were slightly increased in the mild RI group (geometric mean [90% CI]: 1.20 [0.82, 1.77]) and greater in the moderate (1.95 [1.35, 2.83]), severe RI (1.95 [1.30, 2.93]) and ESRD (1.88 [1.30, 2.73]) groups. Lambda was generally well tolerated. Conclusions The results demonstrated that RI reduces the clearance of Lambda and suggests that dose modifications may not be required in patients with mild RI but may be required in patients with moderate to severe RI or ESRD. PMID:25807956

  7. Randomized trial of combined triple therapy comprising two types of peginterferon with simeprevir in patients with hepatitis C virus genotype 1b.

    PubMed

    Tamori, Akihiro; Yoshida, Kanako; Kurai, Osamu; Kioka, Kiyohide; Hai, Hoang; Kozuka, Ritsuzo; Motoyama, Hiroyuki; Kawamura, Etsushi; Hagihara, Atsushi; Uchida-Kobayashi, Sawako; Morikawa, Hiroyasu; Enomoto, Masaru; Murakami, Yoshiki; Kawada, Norifumi

    2016-12-01

    Simeprevir (SMV) is a potent, macrocyclic hepatitis C virus (HCV) non-structural 3/4 A protease inhibitor. This prospective study compared the efficacy and safety of SMV in combination with peginterferon α2a + ribavirin (P2aR) and with peginterferon α2b + ribavirin (P2bR) in Japanese patients with HCV genotype 1b infection.

  8. Treatment discontinuation with peg-interferon: what to consider.

    PubMed

    Boccaccio, Vincenzo; Russo, Maria Luisa; Carbone, Marco; Bruno, Savino

    2015-01-01

    Eradication of chronic hepatitis C virus infection improves the outcome of both liver and extrahepatic-related diseases and interferon-based regimens represented, for years, the standard of care to achieve this goal. Several baseline and on-treatment predictors of response, associated with a lower chance to achieve sustained virological response after interferon-based treatment, were developed. In the past few years, the advent of direct acting antivirals has dramatically modified the landscape of antiviral therapy, leading to an evolution from interferon-based to interferon-free therapies. This review will focus on the usefulness of futility stopping rules that allow the discontinuation of therapy in patients with a reduced chance to obtain sustained virological response if treated with interferon-containing regimens.

  9. [Treatment of hepatitis C with peginterferon and ribavirin in Iceland from 2002-2012].

    PubMed

    Fridriksson, Benedikt; Bergmann, Ottar Mar; Olafsson, Sigurdur

    2017-01-01

    Hepatitis C is a major cause of chronic liver disease and cirrhosis in Western countries. Its treatment aims at eradicating the virus and patients are considered cured if the virus is undetectable by PCR in blood 12-24 weeks after end of treatment (sustained virological response, SVR). The aim of this study is to investigate the results of treating hepatitis C in Iceland during the period 2002-2012. Retrospective study including all patients with hepatitis C receiving treatment with peginterferone and ribavirin at Landspitali University hospital during the period 2002-2012. Patients who had been treated previously were excluded. Information was obtained from medical records and the hospital pharmacy. A total of 207 patients were included, 136 (66%) males and 71 (34%) females. Mean age was 38 years (range 17-66). Genotyping revealed that 71 (34%) patients had genotype 1, 135 (65%) genotype 3 and one genotype 2. A total of 147 (71%) patients achieved SVR. The rate of SVR was 77.8% for genotype 3 and 57.7% for genotype 1. 9 patients (4%) had cirrhosis and 3 of them had SVR. Of 161 patients who finished treatment per protocol, 87.5% and 77.1% with genotypes 3 and 1 respectively had SVR. The study demonstrates higher rates of SVR in clinical practice in Iceland compared to controlled clinical trials. The improved effectiveness may be explained by younger patient population, low rate of cirrhosis and close follow-up of patients. Key words: Hepatitis C, peg-interferon, sustained virological response. Correspondence: Sigurdur Olafsson, sigurdol@landspitali.is.

  10. Peginterferon alfa-2b and ribavirin: effective in patients with hepatitis C who failed interferon alfa/ribavirin therapy.

    PubMed

    Poynard, Thierry; Colombo, Massimo; Bruix, Jordi; Schiff, Eugene; Terg, Ruben; Flamm, Steven; Moreno-Otero, Ricardo; Carrilho, Flair; Schmidt, Warren; Berg, Thomas; McGarrity, Thomas; Heathcote, E Jenny; Gonçales, Fernando; Diago, Moises; Craxi, Antonio; Silva, Marcelo; Bedossa, Pierre; Mukhopadhyay, Pabak; Griffel, Louis; Burroughs, Margaret; Brass, Clifford; Albrecht, Janice

    2009-05-01

    Treatment with peginterferon alfa and ribavirin produces a sustained virologic response (SVR) in approximately 60% of hepatitis C virus (HCV)-infected patients. Alternate options are needed for patients who relapse or do not respond to therapy. This prospective, international, multicenter, open-label study evaluated efficacy and safety of peginterferon alfa-2b (1.5 microg/kg/wk) plus weight-based ribavirin (800-1400 mg/day) in 2333 chronic HCV-infected patients with significant fibrosis/cirrhosis whose previous interferon alfa/ribavirin therapy failed. Patients with undetectable HCV-RNA at treatment week (TW) 12 received 48 weeks of therapy; patients with detectable HCV-RNA at TW12 could enter maintenance studies at TW18; 188 patients with low/detectable HCV-RNA at TW12 continued therapy at the investigator's request. Overall, 22% of the patients attained SVR (56% with undetectable HCV-RNA and 12% with low/detectable HCV-RNA at TW12). SVR was better in relapsers (38%) than nonresponders (14%), regardless of previous treatment, and in patients previously treated with interferon-alfa/ribavirin (25%) than peginterferon alfa-ribavirin (17%). Predictors of response in patients with undetectable HCV-RNA at TW12 were genotype (2/3 vs 1, respectively; odds ratio [OR] 2.4; P < .0001), fibrosis score (F2 vs F4; OR, 2.2; F3 vs F4; OR, 1.7; P < .0001), and baseline viral load (< or =600,000 vs >600,000 IU/mL; OR, 1.4; P = .0223). These factors plus previous treatment and response were overall predictors of SVR. Safety was similar among fibrosis groups. Peginterferon alfa-2b plus weight-based ribavirin is effective and safe in patients who failed interferon alfa/ribavirin therapy. Genotype, baseline viral load, and fibrosis stage were predictors of response.

  11. Combination of Tenofovir Disoproxil Fumarate and Peginterferon α-2a Increases Loss of Hepatitis B Surface Antigen in Patients With Chronic Hepatitis B.

    PubMed

    Marcellin, Patrick; Ahn, Sang Hoon; Ma, Xiaoli; Caruntu, Florin A; Tak, Won Young; Elkashab, Magdy; Chuang, Wan-Long; Lim, Seng-Gee; Tabak, Fehmi; Mehta, Rajiv; Petersen, Joerg; Foster, Graham R; Lou, Lillian; Martins, Eduardo B; Dinh, Phillip; Lin, Lanjia; Corsa, Amoreena; Charuworn, Prista; Subramanian, G Mani; Reiser, Hans; Reesink, Hendrick W; Fung, Scott; Strasser, Simone I; Trinh, Huy; Buti, Maria; Gaeta, Giovanni B; Hui, Aric J; Papatheodoridis, George; Flisiak, Robert; Chan, Henry L Y

    2016-01-01

    Patients chronically infected with the hepatitis B virus rarely achieve loss of serum hepatitis B surface antigen (HBsAg) with the standard of care. We evaluated HBsAg loss in patients receiving the combination of tenofovir disoproxil fumarate (TDF) and peginterferon α-2a (peginterferon) for a finite duration in a randomized trial. In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus peginterferon for 48 weeks (group A), TDF plus peginterferon for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or peginterferon for 48 weeks (group D). The primary end point was the proportion of patients with serum HBsAg loss at week 72. At week seventy-two, 9.1% of subjects in group A had HBsAg loss compared with 2.8% of subjects in group B, none of the subjects in group C, and 2.8% of subjects in group D. A significantly higher proportion of subjects in group A had HBsAg loss than in group C (P < .001) or group D (P = .003). However, the proportions of subjects with HBsAg loss did not differ significantly between group B and group C (P = .466) or group D (P = .883). HBsAg loss in group A occurred in hepatitis B e antigen-positive and hepatitis B e antigen-negative patients with all major viral genotypes. The incidence of common adverse events (including headache, alopecia, and pyrexia) and treatment discontinuation due to adverse events was similar among groups. A significantly greater proportion of patients receiving TDF plus peginterferon for 48 weeks had HBsAg loss than those receiving TDF or peginterferon alone. ClinicalTrials.gov ID NCT01277601. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  12. Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial.

    PubMed

    Bourlière, Marc; Rabiega, Pascaline; Ganne-Carrie, Nathalie; Serfaty, Lawrence; Marcellin, Patrick; Barthe, Yoann; Thabut, Dominique; Guyader, Dominique; Hezode, Christophe; Picon, Magali; Causse, Xavier; Leroy, Vincent; Bronowicki, Jean Pierre; Carrieri, Patrizia; Riachi, Ghassan; Rosa, Isabelle; Attali, Pierre; Molina, Jean Michel; Bacq, Yannick; Tran, Albert; Grangé, Jean Didier; Zoulim, Fabien; Fontaine, Hélène; Alric, Laurent; Bertucci, Inga; Bouvier-Alias, Magali; Carrat, Fabrice

    2017-03-01

    Findings from uncontrolled studies suggest that addition of pegylated interferon in patients with HBe antigen (HBeAg)-negative chronic hepatitis B receiving nucleos(t)ide analogues with undetectable plasma hepatitis B virus (HBV) DNA might increase HBs antigen (HBsAg) clearance. We aimed to assess this strategy. In this randomised, controlled, open-label trial, we enrolled patients aged 18-75 years with HBeAg-negative chronic hepatitis B and documented negative HBV DNA while on stable nucleos(t)ide analogue regimens for at least 1 year from 30 hepatology tertiary care wards in France. Patients had to have an alanine aminotransferase concentration of less than or equal to five times the upper normal range, no hepatocellular carcinoma, and a serum α fetoprotein concentration of less than 50 ng/mL, normal dilated fundus oculi examination, and a negative pregnancy test in women. Patients with contraindications to pegylated interferon were not eligible. A centralised randomisation used computer-generated lists of random permuted blocks of four with stratification by HBsAg titres (< or ≥2·25 log10 IU/mL) to allocate patients (1:1) to receive a 48 week course of subcutaneous injections of 180 μg per week of pegylated interferon alfa-2a in addition to the nucleos(t)ide analogue regimen or to continue to receive nucleos(t)ide analogues only. The primary endpoint was HBsAg loss at week 96 by intention-to-treat analysis. This trial is closed and registered with ClinicalTrials.gov, number NCT01172392. Between Jan 20, 2011, and July 18, 2012, we randomly allocated 185 patients (92 [50%] to pegylated interferon and nucleos(t)ide analogues and 93 [50%] to nucleos(t)ide analogues alone). We excluded two patients from the pegylated interferon plus nucleos(t)ide analogues group from analyses because of withdrawal of consent (one patient) or violation of inclusion criteria (one patient). At week 96, loss of HBsAg was reported in seven (7·8%) of 90 patients in the pegylated

  13. Predicting response to peginterferon α‐2a, lamivudine and the two combined for HBeAg‐negative chronic hepatitis B

    PubMed Central

    Bonino, F; Marcellin, P; Lau, G K K; Hadziyannis, S; Jin, R; Piratvisuth, T; Germanidis, G; Yurdaydin, C; Diago, M; Gurel, S; Lai, M‐Y; Brunetto, M R; Farci, P; Popescu, M; McCloud, P

    2007-01-01

    Objective In a trial of patients with hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B, 24 week post‐treatment biochemical and virological response rates with peginterferon α‐2a with or without lamivudine were significantly higher than with lamivudine alone. The effect of pre‐treatment factors on post‐treatment responses was investigated. Methods Multivariate analyses were performed using available data from 518 patients treated with peginterferon α‐2a with or without lamivudine, or with lamivudine alone. A post‐treatment response was defined as alanine aminotransferase (ALT) normalisation and hepatitis B virus (HBV) DNA level of <20 000 copies/ml. Results In logistic regression analyses across all treatment arms, peginterferon α‐2a (with or without lamivudine) therapy, younger age, female gender, high baseline ALT, low baseline HBV DNA and HBV genotype were identified as significant predictors of combined response at 24 weeks post‐treatment. In the peginterferon α‐2a and lamivudine monotherapy arms, patients with genotypes B or C had a higher chance of response than genotype D infected patients (p<0.001), the latter responding better to the combination than to peginterferon α‐2a monotherapy (p = 0.015). At 1 year post‐treatment, response rates by intention‐to‐treat analysis were 19.2% for the peginterferon α‐2a, 19.0% for the combination, and 10.0% for the lamivudine groups, with genotypes B or C associated with a sustained combined response to peginterferon α‐2a with or without lamivudine therapy. Conclusions Baseline ALT and HBV DNA levels, patient age, gender, and infecting HBV genotype significantly influenced combined response at 24 weeks post‐treatment, in patients treated with peginterferon α‐2a and/or lamivudine. At 1 year post‐treatment HBV genotype was significantly predictive of efficacy for patients treated with peginterferon α‐2a with or without lamivudine. PMID:17127704

  14. Pre-existence and Persistence of Resistant Minority Hepatitis C Virus Variants in Genotype 1-Infected Patients Treated With Simeprevir/Peginterferon/Ribavirin.

    PubMed

    Fevery, Bart; Thys, Kim; Van Eygen, Veerle; Verbinnen, Thierry; Van Rossem, Elizabeth; Buelens, Annemie; Aerssens, Jeroen; Witek, James; Picchio, Gaston; De Meyer, Sandra; Lenz, Oliver

    2016-03-01

    Background.  The pre-existence of minority hepatitis C virus (HCV) variants and their impact on treatment outcome, as well as the persistence of emerging resistant variants posttreatment in patients failing treatment with simeprevir/peginterferon/ribavirin (SMV/PR), were assessed by deep sequencing (DS). Methods.  Population sequencing (PS) and Illumina DS were performed on HCV genotype 1 isolates from patients treated with SMV/PR in Phase 2b (PILLAR [NCT00882908] and ASPIRE [NCT00980330]) and Phase 3 (QUEST-1 [NCT01289782], QUEST-2 [NCT01290679], and PROMISE [NCT01281839]) trials. Results.  Minority polymorphisms (ie, detected pretreatment by DS only) reducing SMV activity in vitro were uncommon (3.6%, 19 of 534 patients). These SMV-resistant minority polymorphisms were detected in similar proportions of patients achieving (3.7%) and not achieving (3.3%) sustained virologic response with SMV/PR and generally did not emerge as major variants at time of failure. SMV-resistant variants emerging at time of failure were no longer detected at end of study in 69.3% and 52.0% of the patients by PS and DS, respectively. Conclusions.  Minority polymorphisms did not impact outcome of SMV/PR treatment. The majority of emerging variants that became undetectable at end of study by PS were also undetectable by DS. These results suggest no added value of DS for clinical usage of SMV.

  15. Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort

    PubMed Central

    Foster, Graham R.; Coppola, Carmine; Derbala, Moutaz; Ferenci, Peter; Orlandini, Alessandra; Reddy, K. Rajender; Tallarico, Ludovico; Shiffman, Mitchell L.; Ahlers, Silke; Bakalos, Georgios; Hassanein, Tarek

    2016-01-01

    Background Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0–9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with

  16. Overall safety profile of boceprevir plus peginterferon alfa-2b and ribavirin in patients with chronic hepatitis C genotype 1: a combined analysis of 3 phase 2/3 clinical trials.

    PubMed

    Manns, Michael P; McCone, Jonathan; Davis, Mitchell N; Rossaro, Lorenzo; Schiff, Eugene; Shiffman, Mitchel L; Bacon, Bruce; Bourliere, Marc; Sulkowski, Mark S; Bruno, Savino; Balart, Luis; Bronowicki, Jean-Pierre; Kwo, Paul; Poordad, Fred; Felizarta, Franco; Reddy, K Rajender; Helmond, Frans A; Sings, Heather L; Pedicone, Lisa D; Burroughs, Margaret; Brass, Clifford A; Albrecht, Janice K; Vierling, John M

    2014-05-01

    Triple therapy with peginterferon/ribavirin (PR) plus an NS3 protease inhibitor has emerged as the standard-of-care for patients with chronic hepatitis C genotype-1. We provide a detailed safety analysis comparing PR to boceprevir plus PR (BOC/PR) across three phase 2/3 studies. SPRINT-1 was an open-label phase 2 study in 595 treatment-naive patients. In the two phase 3 studies, 1500 patients (1097 treatment-naive, SPRINT-2; 403 treatment-failure, RESPOND-2) were randomized to receive PR alone, or one of two regimens where BOC was added to PR after a 4-wk PR lead-in. In this analysis, the respective BOC/PR and PR arms were combined for all three trials. The benefit of shortened duration of treatment using response-guided therapy (RGT) was also explored in the SPRINT-2 trial. Only two adverse events, anaemia and dysgeusia, occurred 20% more often with the BOC-containing regimens compared with PR. Nausea, diarrhoea and neutropenia were the only other common events with an incidence of at least 5% greater when BOC was added to the PR backbone. The proportions of patients reporting serious adverse events (AE), life-threatening AEs, and study drug discontinuation because of an AE were similar in the PR and BOC/PR arms. In treatment-naive patients, RGT generally did not result in a lower frequency of common AEs; however, RGT led to decreased exposure to all 3 study drugs and to a decrease in the mean duration of several clinically relevant AEs such as anaemia, neutropenia, fatigue and depression, as well as earlier normalization of haemoglobin and neutrophil counts. The safety profile of BOC combination therapy largely reflects the known profile of peginterferon and ribavirin, with incremental haematolgical effects and dysgeusia. Shorter treatment duration with RGT significantly reduced the duration of AEs. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Regional differences in hepatitis C treatment with peginterferon and ribavirin in Japan: a retrospective cohort study

    PubMed Central

    Ide, Kazuki; Kawasaki, Yohei; Yamada, Hiroshi; Masaki, Naohiko

    2016-01-01

    Purpose The aims of this study were to investigate regional differences in hepatitis C virus (HCV) infection treatment with peginterferon and ribavirin in Japan and to develop and validate statistical models for analysis of regional differences, using generalized linear mixed models. Methods Individuals with chronic HCV infection were identified from the Japanese Interferon Database (registered from December 2009 to April 2013). The total sustained virologic response rate and the rate in each prefecture were calculated. In the analysis using generalized linear mixed models, the following four models were constructed: 1) prefecture as a fixed effect, 2) prefecture and other confounding variables as fixed effects, 3) prefecture as a random effect, and 4) prefecture as a random effect and other confounding variables as fixed effects. The quality of the model fit was assessed using the Akaike information criterion and the Bayesian information criterion. All statistical analyses were performed using SAS Version 9.4 for Windows. Results From 36 prefectures, 16,349 cases were recorded in the study period. Of these, 4,677 were excluded according to certain criteria. The total sustained virologic response rate was 59.9% (range, 43.9%–71.6%). The statistical model including prefecture as a random effect and other confounding variables as fixed effects showed the best fit based on the Akaike information criterion (13,830.92) and Bayesian information criterion (13,845.17). Conclusion Regional differences may exist in HCV infection treatment in Japan. The model including prefecture as a random effect and other confounding variables as fixed effects was appropriate for analysis of such regional differences. Additional studies considering the medical situations of each patient would provide useful information that could contribute to improve and standardize HCV infection treatment. PMID:27042013

  18. Patterns of longitudinal change in hepatitis C virus neutralization titers correlate with the outcome of peginterferon and ribavirin combination therapy.

    PubMed

    Lin, Jianguo; Wang, Weihua; Xu, Yanjuan; Di Bisceglie, Adrian M; Fan, Xiaofeng

    2015-05-01

    In chronic hepatitis C virus (HCV) infection, combination therapy of peginterferon and ribavirin does not guarantee viral eradication. Among factors relevant to therapeutic efficacy, the role of humoral immunity has not been examined thoroughly. In the current study, HCV pseudoparticles (HCVpp) were first generated with 80 patient-derived full-length HCV envelope clones, followed by detailed characterization with regard to virus productivity, infectivity and neutralizing activity. Selective HCVpp were used to measure HCV neutralization titers in two independent patient cohorts consisting of 102 patients undergoing antiviral therapy. The HCV neutralization titers at the baseline fitted with a power-law distribution among patients. Pretreatment neutralization titers in both patient cohorts were not correlated with treatment outcomes. In the patient cohort 2 (n = 28) that had samples available at multiple time points, however, HCV neutralization titers displayed clearly distinct patterns over therapeutic course and follow-up. No virological responders (n = 10) had neutralization titers stabilized at low level while it was increased significantly in both sustained virological responders (n = 10) and relapsers (n = 8). High HCV neutralization titers were maintained only in sustained virological responders but not in relapsers after treatment cessation. Therefore, patterns of longitudinal change of HCV neutralization titers, but not pretreatment titers, correlate with the treatment outcome in patients undergoing peginterferon and ribavirin combination therapy.

  19. Twenty four-week peginterferon plus ribavirin after interferon-β induction for genotype 1b chronic hepatitis C

    PubMed Central

    Okushin, Hiroaki; Morii, Kazuhiko; Uesaka, Koichi; Yuasa, Shiro

    2010-01-01

    AIM: To investigate the possibility of shortening the duration of peginterferon (Peg-IFN) plus ribavirin (RBV) combination therapy by incorporating interferon-β (IFN-β) induction therapy. METHODS: A one treatment arm, cohort prospective study was conducted on seventy one patients. The patients were Japanese adults with genotype 1b chronic hepatitis C, HCV-RNA levels of ≥ 5.0 Log IU/mL or 100 KIU/mL, and platelet counts of ≥ 90 000/μL. The treatment regimen consisted of a 2 wk course of twice-daily administration of IFN-β followed by 24 wk Peg-IFN plus RBV combination therapy. We prolonged the duration of the Peg-IFN plus RBV therapy to 48 wk if the patient requested it. RESULTS: The patients, including 44% males, were characterized by an median age of 63 years (range: 32-78 years), an median platelet count of 13.9 (range: 9.1-30.6) × 104/μL, 62% IFN-naïve, and median HCV-RNA of 6.1 (range: 5.1-7.2) Log IU/mL. The sustained virologic response (SVR) rates were 34% (Peg-IFN: 1-24 wk, n = 61, 95% confidence interval (CI): 24%-47%) and 55% (Peg-IFN: 20-24 wk, n = 31, 95% CI: 38%-71%, P < 0.001; vs Peg-IFN: 1-19 wk). The SVR rate when the administration was discontinued early was 13% (Peg-IFN: 1-19 wk, n = 30, 95% CI: 5%-30%), and that when the administration was prolonged was 50% (Peg-IFN: 25-48 wk, n = 10, 95% CI: 24%-76%, P < 0.05; vs Peg-IFN: 1-19 wk). In the patients who received 20-24 wk of Peg-IFN plus RBV, only the higher platelet count (≥ 130 000/μL) was significantly correlated with the SVR (odds ratio: 11.680, 95% CI: 2.3064-79.474, P = 0.0024). In 45% (14/31) of the patients with a higher platelet count (≥ 130 000/μL) before therapy, the HCV-RNA level decreased to below 3.3 Log IU/mL at the completion of IFN-β, and their SVR rate was 93% (13/14) after 20-24 wk administration of Peg-IFN plus RBV. CONCLUSION: These results suggest the possibilities of shortening the duration of Peg-IFN plus RBV combination therapy by actively reducing HCV

  20. Cost-effectiveness analysis of simeprevir in combination with peginterferon and ribavirin for treatment-naïve chronic hepatitis C genotype 1 patients in Japan.

    PubMed

    Kuwabara, Hiroyo; Westerhout, Kirsten; Treur, Maarten; Cerri, Karin; Mahlich, Joerg; Yatsuhashi, Hiroshi

    2015-01-01

    Simeprevir (SMV), a protease inhibitor, recently became available for the treatment of chronic hepatitis C (HCV) genotype 1 patients in Japan. The introduction of triple therapy using SMV in combination with peginterferon and ribavirin (PR) significantly improves the cure rate. The aim was to assess the cost-effectiveness of SMV with PR (SMV/PR) compared to telaprevir with PR (TVR/PR), PR alone, or no treatment in treatment-naïve patients in Japan. A Markov model was developed to reflect the natural disease progression of HCV and to estimate the average life years and lifetime healthcare costs per patient. Sustained virologic response rates were obtained from a network meta-analysis including randomized clinical trials conducted in Japan. Patient baseline characteristics, HCV progression rates, mortality, medical resource utilization, and unit costs were obtained from Japanese sources. Outcomes were reported as incremental cost-effectiveness ratios as well as incremental cost and life years. Various sensitivity analyses were conducted to assess the uncertainty around model outcomes. SMV/PR was estimated to be a cost-effective treatment option as more life years were gained by 0.235 and 0.873 years at a reduced cost by ¥263,037 and ¥776,900 compared to TVR/PR and PR alone, respectively. The results were robust to sensitivity analyses, in particular in the comparison of SMV/PR with PR alone. The multivariate probabilistic sensitivity analyses showed that the probability of SMV/PR being cost-effective was relatively constant at ∼87% at any willingness to pay. SMV/PR is estimated to be the most cost-effective treatment strategy for treatment-naïve HCV genotype 1 patients in Japan.

  1. Peginterferon Beta-1a Shows Antitumor Activity as a Single Agent and Enhances Efficacy of Standard of Care Cancer Therapeutics in Human Melanoma, Breast, Renal, and Colon Xenograft Models.

    PubMed

    Boccia, Antonio; Virata, Cyrus; Lindner, Daniel; English, Nicki; Pathan, Nuzhat; Brickelmaier, Margot; Hu, Xiao; Gardner, Jennifer L; Peng, Liaomin; Wang, Xinzhong; Zhang, Xiamei; Yang, Lu; Perron, Keli; Yco, Grace; Kelly, Rebecca; Gamez, James; Scripps, Thomas; Bennett, Donald; Joseph, Ingrid B; Baker, Darren P

    2017-01-01

    Because of its tumor-suppressive effect, interferon-based therapy has been used for the treatment of melanoma. However, limited data are available regarding the antitumor effects of pegylated interferons, either alone or in combination with approved anticancer drugs. We report that treatment of human WM-266-4 melanoma cells with peginterferon beta-1a induced apoptotic markers. Additionally, peginterferon beta-1a significantly inhibited the growth of human SK-MEL-1, A-375, and WM-266-4 melanoma xenografts established in immunocompromised mice. Peginterferon beta-1a regressed large, established WM-266-4 xenografts in nude mice. Treatment of SK-MEL-1 tumor-bearing mice with a combination of peginterferon beta-1a and the MEK inhibitor PD325901 ((R)-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide) significantly improved tumor growth inhibition compared with either agent alone. Examination of the antitumor activity of peginterferon beta-1a in combination with approved anticancer drugs in breast and renal carcinomas revealed improved antitumor activity in these preclinical xenograft models, as did the combination of peginterferon beta-1a and bevacizumab in a colon carcinoma xenograft model.

  2. Cryoglobulinemia-related vasculitis during effective anti-HCV treatment with PEG-interferon alfa-2b.

    PubMed

    De Blasi, T; Aguilar Marucco, D; Cariti, G; Maiello, A; De Rosa, F G; Di Perri, G

    2008-06-01

    HCV infection may be related to many extrahepatic manifestations including mixed cryoglobulinemia (MC). Clinical manifestations commonly associated to MC include arthralgia, purpura, vasculitis, peripheral neuropathy and renal function abnormalities. Treatment with interferon often leads to remission, especially in virological responders, or to disappearance of MC-related clinical manifestations. We report on a patient with chronic hepatitis C, deficit of G6P-DH, type II MC, who developed a cryoglobulinemic vasculitis with purpura, renal impairment and arterial hypertension, during treatment with PEG-interferon a-2b plus amantadine. The occurrence of purpuric lesions and MC-related nephropathy with increased cryocrit despite negative viremia, in a patient previously asymptomatic, during interferon treatment, is unusual.

  3. Tongue hyperpigmentation resulting from peginterferon alfa-2b and ribavirin treatment in a patient with chronic hepatitis C.

    PubMed

    Ghosh, Souvik; Duseja, Ajay; Dhiman, Radha Krishan; Chawla, Yogesh Kumar

    2012-03-01

    Hepatitis C virus (HCV) infection has been associated with several cutaneous diseases such as lichen planus, porphyria cutanea tarda, chronic pruritus, and cutaneous necrotizing vasculitis (Doutre, Arch Dermatol 135:1401-1403, 1999). The antiviral treatment for chronic HCV with interferon alfa (INF) or peginterferon alfa (PEG-INF) combined with rivabirin also leads to many skin side effects including injection site reaction, generalized skin rashes, pruritus, dry skin, alopecia, and exacerbation of autoimmune processes, particularly psoriasis, lichen planus or vitiligo (Dalekos et al., Eur J Gastroenterol Hepatol 10:933-939, 1998; Sookoian et al., Arch Dermatol 135:1000-1000, 1999). There are case reports of tongue hyperpigmentation during combination therapy of PEG IFN and RBV in chronic hepatitis C both in dark-skined as well as Caucasian. We report the first case of tongue hyperpigmentation associated with PEG-INF-2b plus ribavirin administration in a non-Caucasian patient with genotype 4.

  4. Biochemical surrogate markers of liver fibrosis and activity in a randomized trial of peginterferon alfa-2b and ribavirin.

    PubMed

    Poynard, Thierry; McHutchison, John; Manns, Michael; Myers, Rob P; Albrecht, Janice

    2003-08-01

    Liver fibrosis and activity indexes were validated in patients infected by hepatitis C virus (HCV) nontreated and treated by interferon. The aim was to validate their usefulness as surrogate markers of histologic features using the data of a randomized trial of combination peginterferon alfa-2b and ribavirin. Three hundred fifty-two patients who had had 2 interpretable liver biopsies and stored serum sample before and after treatment were selected. Two hundred eight patients received peginterferon alfa-2b 1.5 mcg per kg and ribavirin and 144 patients interferon alfa-2b 3 MU three times a week and ribavirin for 48 weeks. A fibrosis and an activity index combining 5 and 6 biochemical markers were assessed at baseline and at end of follow-up (24 weeks after treatment). The biochemical markers have significant predictive values both for the diagnosis of fibrosis and for activity. For the diagnosis of bridging fibrosis and/or moderate necroinflammatory activity, the area under the receiver operating characteristics curve of the activity index was 0.76 +/- 0.03 at baseline and 0.82 +/- 0.02 at end of follow-up. A cutoff of activity index at 0.30 (range, 0.00-1.00) had 90% sensitivity and 88% positive predictive value for the diagnosis of bridging fibrosis or moderate necroinflammatory activity. Sensitivity analyses with biopsy specimens of size greater than 15 mm suggest that a part of discordances between biochemical markers and histology were due to biopsy specimen sampling error. In conclusion, these biochemical markers of fibrosis and activity could be used as surrogate markers for liver biopsy in patients with chronic hepatitis C, both for the initial evaluation and for follow-up.

  5. Dynamics of PBMC gene expression in hepatitis C virus genotype 1-infected patients during combined peginterferon/ribavirin therapy

    PubMed Central

    Lu, Ming-Ying; Huang, Ching-I; Hsieh, Ming-Yen; Hsieh, Tusty-Juan; Hsi, Edward; Tsai, Pei-Chien; Tsai, Yi-Shan; Lin, Ching-Chih; Hsieh, Meng-Hsuan; Liang, Po-Cheng; Lin, Yi-Hung; Hou, Nai-Jen; Yeh, Ming-Lun; Huang, Chung-Feng; Lin, Zu-Yau; Chen, Shinn-Cherng; Huang, Jee-Fu; Chuang, Wan-Long; Dai, Chia-Yen; Yu, Ming-Lung

    2016-01-01

    Hepatitis C virus (HCV) can replicate in peripheral blood mononuclear cells (PBMCs), which can produce interferon to defend against virus infection. We hypothesized that dynamic gene expression in PBMCs might impact the treatment efficacy of peginterferon/ribavirin in HCV patients. PBMCs were collected at baseline, 1st week and 4th week of treatment from 27 chronic HCV-1 patients with 48-week peginterferon/ribavirin therapy (screening dataset n = 7; validation dataset n = 20). A sustained virologic response (SVR) was defined as undetectable HCV RNA throughout the 24 weeks after end-of-treatment. A complete early virologic response (cEVR) was defined as negative HCV RNA at treatment week 12. Forty-three differentially expressed genes identified by Affymetrix microarray were validated by quantitative polymerase chain reaction. Thirteen genes at week 1 and 24 genes at week 4 were upregulated in the SVR group compared with the non-SVR group. We selected 8 target genes (RSAD2, LOC26010, HERC5, HERC6, IFI44, SERPING1, IFITM3, and DDX60) at week 1 as the major components of the predictive model. This predictive model reliably stratified the responders and non-responders at week 1 (AUC = 0.89, p = 0.007 for SVR; AUC = 0.95, p = 0.003 for cEVR), especially among patients carrying the IL28B rs8099917 TT genotype (AUC = 0.89, p = 0.02 for SVR; AUC = 1.0, p = 0.008 for cEVR). The performance of this predictive model was superior to traditional predictors, including the rapid virologic response, viral load and IL28B genotype. PMID:27542257

  6. Patient education improves adherence to peg-interferon and ribavirin in chronic genotype 2 or 3 hepatitis C virus infection: A prospective, real-life, observational study

    PubMed Central

    Cacoub, Patrice; Ouzan, Denis; Melin, Pascal; Lang, Jean-Philippe; Rotily, Michel; Fontanges, Thierry; Varastet, Marina; Chousterman, Michel; Marcellin, Patrick

    2008-01-01

    AIM: To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response (SVR) in a real-life setting in genotype 2/3 hepatitis C, as there are few adherence data in genotype 2/3 infection, even from randomized trials. METHODS: This prospective survey included genotype 2/3 patients who received peg-interferon alfa-2b and ribavirin. There was no intervention. Adherence was self-reported over the past 4 wk (peg-interferon) or 7 d (ribavirin). Adherence to bitherapy was defined as adherence to the two drugs for ≥ 20 wk. SVR was defined as undetectable RNA ≥ 12wk after the end of treatment. RESULTS: 370/674 patients received education during the first 3 mo of treatment. After 6 mo, adherence to bitherapy was higher in educated patients (61% vs 47%, P = 0.01). Adherence to peg-interferon was 78% vs 69% (P = 0.06). Adherence to ribavirin was 70% vs 56% (P = 0.006). The SVR (77% vs 70%, P = 0.05) and relapse (10% vs 16%, P = 0.09) rates tended to be improved. After adjustment for baseline differences, education improved adherence [Odds ratio (OR) 1.58, P = 0.04] but not the SVR (OR 1.54, P = 0.06). CONCLUSION: In genotype 2/3 patients, therapeutic education helped maintain real-life adherence to bitherapy. PMID:18985810

  7. Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

    PubMed Central

    García-Samaniego, Javier; Romero, Miriam; Granados, Rafael; Alemán, Remedios; Jorge Juan, Miguel; Suárez, Dolores; Pérez, Ramón; Castellano, Gregorio; González-Portela, Carlos

    2013-01-01

    AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to peginterferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d). RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventy-eight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41

  8. Changes in liver fibrosis in HIV/HCV-coinfected patients following different outcomes with peginterferon plus ribavirin therapy.

    PubMed

    Labarga, P; Fernandez-Montero, J V; Barreiro, P; Pinilla, J; Vispo, E; de Mendoza, C; Plaza, Z; Soriano, V

    2014-07-01

    There is scarce information about the impact of antiviral treatment on subsequent progression of liver fibrosis in HIV-infected patients with chronic hepatitis C who experience different outcomes following peginterferon-ribavirin therapy. We conducted a retrospective study of a cohort of HIV/HCV-coinfected patients with longitudinal assessment of liver fibrosis using elastometry. Patients were split out into four groups according to the prior peginterferon-ribavirin response: sustained virological response (SVR), relapse (R), partial response (PR) and null response (NR). A group of untreated, coinfected patients was taken as control. Significant liver fibrosis progression (sLFP) was defined as a shift from baseline Metavir estimates ≤ F2 to F3-F4, or by >30% increase in liver stiffness in patients with baseline F3-F4. Conversely, significant liver fibrosis regression (sLFR) was defined as a shift from baseline Metavir estimates F3-F4 to ≤ F2, or by >30% reduction in liver stiffness in patients that kept on F3-F4. A total of 498 HIV/HCV-coinfected patients were examined. They were classified as follows: 138 (27.7%) SVR, 40 (8%) R, 61 (12.2%) PR, 71 (14.3%) NR and 188 (37.8%) naive. After a mean follow-up of 53.3 months, sLFP occurred less frequently in patients with SVR (7.2%) compared with R (25%; P = 0.002), PR (23%; P = 0.002), NR (29.6%; P < 0.001) and naïve (19.7%; P = 0.002). Conversely, sLFR was 26.1% in SVR compared with 10% in R (P = 0.03), 14.8% in PR (P = 0.06), 16.9% in NR (P = 0.07) and 10.6% in naïve (P < 0.001). Sustained clearance of serum HCV-RNA following a course of antiviral treatment is the major determinant of liver fibrosis regression in HIV/HCV-coinfected patients.

  9. Aplastic anemia and severe pancytopenia during treatment with peg-interferon, ribavirin and telaprevir for chronic hepatitis C.

    PubMed

    Lens, Sabela; Calleja, Jose L; Campillo, Ana; Carrión, Jose A; Broquetas, Teresa; Perello, Christie; de la Revilla, Juan; Mariño, Zoe; Londoño, María-Carlota; Sánchez-Tapias, Jose M; Urbano-Ispizua, Álvaro; Forns, Xavier

    2015-05-07

    Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin. Pancytopenia due to myelotoxicity caused by these drugs may occur, but severe hematological abnormalities or aplastic anemia (AA) have not been described. We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011. Among 142 cirrhotic patients receiving treatment, 7 cases of severe pancytopenia (5%) were identified and three were consistent with the diagnosis of AA. Mean age was 59 years, five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation. Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy. Three patients had pre-treatment hematological abnormalities related to splenomegaly. In six patients, antiviral treatment was interrupted at the onset of hematological abnormalities. Two patients died due to septic complications and one patient due to acute alveolar hemorrhage. The remaining patients recovered. Severe pancytopenia and especially AA, are not rare during triple therapy with telaprevir in patients with advanced liver disease. Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.

  10. Aplastic anemia and severe pancytopenia during treatment with peg-interferon, ribavirin and telaprevir for chronic hepatitis C

    PubMed Central

    Lens, Sabela; Calleja, Jose L; Campillo, Ana; Carrión, Jose A; Broquetas, Teresa; Perello, Christie; de la Revilla, Juan; Mariño, Zoe; Londoño, María-Carlota; Sánchez-Tapias, Jose M; Urbano-Ispizua, Álvaro; Forns, Xavier

    2015-01-01

    Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin. Pancytopenia due to myelotoxicity caused by these drugs may occur, but severe hematological abnormalities or aplastic anemia (AA) have not been described. We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011. Among 142 cirrhotic patients receiving treatment, 7 cases of severe pancytopenia (5%) were identified and three were consistent with the diagnosis of AA. Mean age was 59 years, five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation. Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy. Three patients had pre-treatment hematological abnormalities related to splenomegaly. In six patients, antiviral treatment was interrupted at the onset of hematological abnormalities. Two patients died due to septic complications and one patient due to acute alveolar hemorrhage. The remaining patients recovered. Severe pancytopenia and especially AA, are not rare during triple therapy with telaprevir in patients with advanced liver disease. Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications. PMID:25954117

  11. Cost utility of telaprevir-PR (peginterferon-ribavirin) versus boceprevir-PR and versus PR alone in chronic hepatitis C in The Netherlands.

    PubMed

    Vellopoulou, Aikaterini; van Agthoven, Michel; van der Kolk, Annemarie; de Knegt, Robert J; Berdeaux, Gilles; Cure, Sandrine; Bianic, Florence; Lamotte, Mark

    2014-12-01

    The hepatitis C virus may lead to cirrhosis, liver cancer, liver transplant, and increased mortality. With standard treatment peginterferon-alpha and ribavirin (PR), sustained viral response (SVR) was less than 50 %. SVR rates improve greatly when PR is combined with telaprevir or boceprevir. The aim of this study was to assess the cost utility of telaprevir-peginterferon-ribavirin (TPR) versus PR and boceprevir-peginterferon-ribavirin (BPR) in treatment-naïve (TN) and treatment-experienced (TE) adults with chronic hepatitis C in the Netherlands. A Markov model with a lifelong time horizon and annual cycles was developed. Clinical data stemmed from phase III trials (TPR vs PR, BPR vs PR). A mixed treatment comparison (MTC) was developed to compare TPR and BPR indirectly. Unit costs and utilities based on EQ-5D were established in a Dutch cross-sectional study. Cost per quality-adjusted life-years (QALYs) was calculated according to the societal perspective. Treating TN patients with TPR generates 1.12 additional QALYs with €333 additional cost compared with PR, resulting in an incremental cost-utility ratio of €299/QALY. In TE patients, TPR dominates PR with cost savings (-€7,819) and 1.63 additional QALYs. TPR dominates BPR yielding additional QALYs (0.26 in TN; 0.71 in TE) and cost savings (-€7,296, -€18,144, respectively). TPR seems a cost-effective alternative to PR in TN patients and dominant in TE patients. TPR was a dominant, more effective and less costly alternative to BPR in both patient types. The cost effectiveness of both TPR and BPR is well below generally accepted willingness-to-pay thresholds and may be considered cost effective.

  12. Management Strategies for Flu-Like Symptoms and Injection-Site Reactions Associated with Peginterferon Beta-1a

    PubMed Central

    Centonze, Diego; Newsome, Scott D.; Huang, DeRen; Robertson, Christopher; You, Xiaojun; Sabatella, Guido; Evilevitch, Vladimir; Leahy, Leslie

    2016-01-01

    Background: Flu-like symptoms (FLSs) and injection-site reactions (ISRs) have been reported with interferon beta treatments for multiple sclerosis (MS). We sought to obtain consensus on the characteristics/management of FLSs/ISRs in patients with relapsing-remitting MS based on experiences from the randomized, placebo-controlled ADVANCE study of peginterferon beta-1a. Methods: ADVANCE investigators with a predefined number of enrolled patients were eligible to participate in a consensus-generating exercise using a modified Delphi method. An independent steering committee oversaw the development of two sequential Delphi questionnaires. An average rating (AR) of 2.7 or more was defined as consensus a priori. Results: Thirty and 29 investigators (ie, responders) completed questionnaires 1 and 2, respectively, representing 374 patients from ADVANCE. Responders reported that the incidence/duration of FLSs/ISRs in their typical patient generally declined after 3 months of treatment. Responders reached consensus that FLSs typically last up to 24 hours (AR = 3.17) and have mild/moderate effects on activities of daily living (AR = 3.34). Patients should initiate acetaminophen/nonsteroidal anti-inflammatory drug treatment on a scheduled basis (AR = 3.31) and change the timing of injection (AR = 3.28) to manage FLSs. Injection-site rotation/cooling and drug administration at room temperature (all AR ≥ 3.10) were recommended for managing ISRs. Patient education on FLSs/ISRs was advocated before treatment initiation. Conclusions: Delphi responders agreed on the management strategies for FLSs/ISRs and agreed that patient education is critical to set treatment expectations and promote adherence. PMID:27551246

  13. [Cutaneous adverse events of telaprevir/peginterferon/ribavirin therapy for chronic hepatitis C: A multicenter prospective cohort study].

    PubMed

    Lorcy, S; Gaudy-Marqueste, C; Botta, D; Portal, I; Quiles, N; Oulies, V; Mancini, J; Grob, J-J; Richard, M-A

    2016-05-01

    Telaprevir, sale of which was suspended, has been approved in combination with pegylated interferon and ribavirin (triple therapy) in the treatment of chronic hepatitis C virus (HCV). Skin eruptions and isolated cases of severe cutaneous adverse reactions (SCAR) have been reported. Our aim was to assess the incidence of skin eruption and the clinical characteristics of mucocutaneous adverse events (AE), and to identify potential risk factors for telaprevir-associated skin eruption. A prospective observational multicenter follow-up cohort study with monthly controls by a dermatologist and additional examinations in case of any undercurrent AE. Among the 48 enrolled patients, the incidence of skin eruption was 58.4%, consisting mainly of maculopapular and eczematous lesions and only one case of SCAR. Telaprevir was discontinued in 6% of patients due to severe rash, whereas peginterferon and ribavirin were continued. The median time to onset of rash following telaprevir initiation was 25 days (range: 3-79 days). The rash was preceded by skin dryness and associated with pruritus in 100% and 90% of patients, respectively. Of those presenting with skin eruption, 37.5% also complained of conjunctival or oral lesions, or of anorectal symptoms. Neither a past history of dermatological conditions nor sociodemographic or viral status was predictive factor for skin rash. Telaprevir-related dermatitis has a high incidence but is mostly of mild intensity. In most cases, tri-therapy was continued under close dermatological follow-up allowing rapid detection of rare instances of severe drug eruptions. Ribavirin and Interferon were thus continued even in the event of diffuse eruptions, enabling confirmation of the causative role of telaprevir in these eruptions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Hepatitis C virus therapy with peg-interferon and ribavirin in Myanmar: A resource-constrained country.

    PubMed

    Hlaing, Naomi Khaing Than; Banerjee, Debolina; Mitrani, Robert; Arker, Soe Htet; Win, Kyaw San; Tun, Nyan Lin; Thant, Zaw; Win, Khin Maung; Reddy, K Rajender

    2016-11-21

    To investigate peg-interferon (peg-IFN) and ribavirin (RBV) therapy in Myanmar and to predict sustained virologic response (SVR). This single-center, open-label, study was conducted in Myanmar between 2009 and 2014. A total of 288 patients infected with HCV genotypes 1, 2, 3 and 6 were treated with peg-IFN alpha-2a (180 μg/wk) or alpha-2b (50 to 100 μg as a weight-based dose) and RBV as a weight-based dose (15 mg/kg/d). Treatment duration was 48 wk for genotypes 1 and 6, 24 wk for genotype 2, and 24 or 48 wk for genotype 3 based on rapid virologic response (RVR). Those co-infected with hepatitis B received 48 wk of therapy. Overall, SVR was achieved for 82% of patients and the therapy was well tolerated. All patients achieved SVR at equivalent rates regardless of HCV genotype (P = 0.314). Low fibrosis scores (P < 0.001), high baseline albumin levels (P = 0.028) and low baseline viral loads (P = 0.029) all independently predicted SVR. On the other hand, IL-28B TT and CC genotypes were not found to significantly predict SVR (P = 0.634; P = 0.618). Among those who completed treatment, the occurrence of RVR showed a > 96% positive predictive value for achieving SVR. Treatment duration did not significantly impact the likelihood of achieving SVR for patients infected with genotype 3 HCV (P = 0.371). The most common adverse events were fatigue (71%) and poor appetite (60%). Among patients with genotype 3 HCV, more patients in the 48-wk treatment group required erythropoietin than in the 24-wk treatment group (61.1% vs 49.2%). SVR rates were high with peg-IFN and RBV therapy in Myanmar. Fibrosis scores, baseline albumin, HCV RNA levels and RVR independently predicted SVR.

  15. Hepatitis C virus therapy with peg-interferon and ribavirin in Myanmar: A resource-constrained country

    PubMed Central

    Hlaing, Naomi Khaing Than; Banerjee, Debolina; Mitrani, Robert; Arker, Soe Htet; Win, Kyaw San; Tun, Nyan Lin; Thant, Zaw; Win, Khin Maung; Reddy, K Rajender

    2016-01-01

    AIM To investigate peg-interferon (peg-IFN) and ribavirin (RBV) therapy in Myanmar and to predict sustained virologic response (SVR). METHODS This single-center, open-label, study was conducted in Myanmar between 2009 and 2014. A total of 288 patients infected with HCV genotypes 1, 2, 3 and 6 were treated with peg-IFN alpha-2a (180 μg/wk) or alpha-2b (50 to 100 μg as a weight-based dose) and RBV as a weight-based dose (15 mg/kg/d). Treatment duration was 48 wk for genotypes 1 and 6, 24 wk for genotype 2, and 24 or 48 wk for genotype 3 based on rapid virologic response (RVR). Those co-infected with hepatitis B received 48 wk of therapy. RESULTS Overall, SVR was achieved for 82% of patients and the therapy was well tolerated. All patients achieved SVR at equivalent rates regardless of HCV genotype (P = 0.314). Low fibrosis scores (P < 0.001), high baseline albumin levels (P = 0.028) and low baseline viral loads (P = 0.029) all independently predicted SVR. On the other hand, IL-28B TT and CC genotypes were not found to significantly predict SVR (P = 0.634; P = 0.618). Among those who completed treatment, the occurrence of RVR showed a > 96% positive predictive value for achieving SVR. Treatment duration did not significantly impact the likelihood of achieving SVR for patients infected with genotype 3 HCV (P = 0.371). The most common adverse events were fatigue (71%) and poor appetite (60%). Among patients with genotype 3 HCV, more patients in the 48-wk treatment group required erythropoietin than in the 24-wk treatment group (61.1% vs 49.2%). CONCLUSION SVR rates were high with peg-IFN and RBV therapy in Myanmar. Fibrosis scores, baseline albumin, HCV RNA levels and RVR independently predicted SVR. PMID:27920482

  16. Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa.

    PubMed

    Liu, Chen-Hua; Kao, Jia-Horng

    2014-01-01

    Asia is endemic for hepatitis C virus (HCV) infection, which is the leading cause of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplantation worldwide. HCV has six major genotypes and each HCV genotype has its specific geographic distribution. HCV genotypes 1, 2, 3, and 6 are common in Asia. The aim of HCV treatment is to eradicate the virus by effective therapeutic agents; viral clearance is durable after long-term post-treatment follow-up. In most Asian countries, peginterferon alfa (PEG-IFN α) in combination with ribavirin remains the standard of care, and the overall sustained viral response (SVR) rate in Asian HCV patients is higher than that in Western patients. The differences are most significant in patients with HCV genotype 1 (HCV-1) infection, which is attributed to the higher frequency of IFN-responsive or favorable interleukin-28B (IL-28B) genotype in Asian populations than in other ethnic populations. In addition, the introduction of response-guided therapy, where the optimized treatment duration is based on the early viral kinetics during the first 12 weeks of treatment, increases the SVR rate. Recently, telaprevir or boceprevir-based triple therapy was found to further improve the SVR rate in treated and untreated HCV-1 patients and has become the new standard of care in Western and some Asian countries. Many novel direct-acting antiviral agents, either in combination with PEG-IFN α plus ribavirin or used as IFN-free regimens are under active investigation. At the time of this writing, simeprevir and sofosbuvir have been approved in the US. Because the SVR rates in Asian HCV patients receiving PEG-IFN α plus ribavirin therapy are high, health care providers should judiciously determine the clinical usefulness of these novel agents on the basis of treatment duration, anticipated viral responses, patient tolerance, financial burdens, and drug accessibility.

  17. Does Epoetin Beta Still Have a Place in Peginterferon Alpha-2a Plus Ribavirin Treatment Strategies for Chronic Hepatitis C?

    PubMed

    Veillon, Pascal; Fouchard-Hubert, Isabelle; Larrey, Dominique; Dao, Manh Thông; D'alteroche, Louis; Boyer-Darrigand, Nathalie; Picard, Nicolas; Le Guillou-Guillemette, Hélène; Saulnier, Patrick; Ducancelle, Alexandra; Loustaud-Ratti, Véronique; Lunel-Fabiani, Françoise

    2016-03-01

    To investigate the impact of epoetin beta (EPO) on sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients treated with peginterferon-ribavirin (RBV). Controlled, randomized, pragmatic multicenter study to assess 2 strategies, ie, the use (EPO group) or nonuse (control group) of EPO in terms of achieving SVR in treatment-naive, genotype non-2/non-3 HCV-infected patients receiving a 48-week treatment regimen of pegylated interferon α-2a (peg-IFN) plus RBV (randomization 2:1). The single-nucleotide polymorphisms of interferon lambda 3 (IFNL3) (rs12979860 and rs8099917), interferon lambda 4 (IFNL4) (ss469415590), and inosine triphosphatase (ITPA) (rs1127354 and rs7270101) were determined retrospectively. Two hundred twenty-seven patients were included in the study. In the global population (n = 227), the overall SVR rate was 52% (118/227). Nonresponse and relapse occurred in respectively 46/227 (20.3%) and 42/227 (18.5%) patients. In the intention-to-treat analysis, 55.5% of patients with anemia (n = 164) had a SVR, specifically 57.4% in the EPO group versus 52.4% in the control group, but the difference was not statistically significant. In the anemic population, independent factors associated with SVR were IFNL3 and IFNL4 polymorphisms, pretreatment HCV RNA level, iron level, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio. EPO has little impact on SVR in patients treated with peg-IFN+RBV and should be recommended only for patients with severe anemia.

  18. Delayed Viral Clearance after 6-Week Treatment with Peginterferon Plus Ribavirin in a Patient with Chronic Hepatitis C Virus Genotype 1b

    PubMed Central

    Sato, Akira; Ishii, Toshiya; Adachi, Kayo; Takahashi, Hideaki; Sano, Fumiaki; Matsumoto, Nobuyuki

    2016-01-01

    Following interferon-based therapy for chronic hepatitis C, the negativity of hepatitis C virus RNA is essential to achieve viral clearance at the end of treatment. We report a case of clearance of chronic hepatitis C virus infection following early discontinuation (at 6 weeks) of peginterferon plus ribavirin therapy, without negativity for hepatitis C virus RNA during the treatment period. The patient was a 76-year-old Japanese male infected with hepatitis C virus genotype 1b and TT of IL28B rs8099917. Hepatitis C virus RNA remained positive at persistently low levels for more than 2 months after the cessation of therapy and became negative at 7 months after the discontinuation of therapy. Spontaneous clearance of hepatitis C virus RNA can occur following antiviral failure in patients with persistently low viral loads, and virological follow-up is therefore necessary in chronic hepatitis C virus infection, even after antiviral failure. PMID:27721727

  19. Drug induced hypersensitivity syndrome by triple therapy of peginterferon alpha2b, ribavirin and telaprevir in patient with double positive for HBV and HCV.

    PubMed

    Takagi, Hitoshi; Hoshino, Takashi; Naganuma, Atsushi; Koitabashi, Eri; Uehara, Sanae; Sakamoto, Naomi; Kudo, Tomohiro; Ryusaki, Keiichirou; Kakizaki, Satoru; Okamoto, Hiroaki

    2013-10-01

    Sixty year-old male positive for both HCV-RNA and HBsAg was treated by triple therapy of peginterferon alpha2b, ribavirin and telaprevir. Eight weeks after the beginning of the therapy, the patient developed drug induced hypersensitivity syndrome (DIHS) with general erythema multiforme and 64 times anti-HHV6 antibody elevation. Sixty milligram of prednisolone was administered with gradual dose reduction and the skin lesion was improved. HBV-DNA and transaminase elevated one week after the steroid induction and entecavir improved them. DIHS itself and the aggravation of hepatitis B by corticosteroid should be kept in mind in cases with dual infection of HBV and HCV treated by antivirals including telaprevir.

  20. Peginterferon alpha-2b: a new approach to improving response in hepatitis C patients.

    PubMed

    Patel, K; McHutchison, J

    2001-08-01

    Chronic hepatitis C infection affects approximately four million Americans. Over the last decade, Type 1 interferons (IFNs) have been the mainstay of therapy for suitable patients. Recently, the combination of IFN plus ribavirin, with enhanced response rates, has replaced IFN monotherapy for treatment of these patients. The addition of a polyethylene glycol (peg) moiety to IFN alpha-2b has provided a drug with reduced clearance whilst retaining biological and antiviral activity. This formulation allows once-weekly dosing and enhances sustained response rates, without significantly changing the safety and tolerability of IFN. Clinical trials indicate a doubling of sustained virological response rates for regimens utilising pegIFN alpha-2b, compared with standard IFN-alpha 2b. The combination of pegIFN alpha-2b and ribavirin further increases the sustained virological response rates to > 50% for suitable patients. Future pegIFN alpha-2b studies will need to examine drug profiles in patients with co-morbid conditions (e.g., renal impairment, liver transplantation), as well as safety and efficacy issues in different ethnic groups. Further clinical trials are also required to determine the benefits of pegIFN alpha-2b in previous non-responders or relapse patients and as maintenance therapy to prevent disease progression. Finally, careful cost effectiveness analyses will need to be performed.

  1. Effect of Hepatitis C Virus Genotype 1b Core and NS5A Mutations on Response to Peginterferon Plus Ribavirin Combination Therapy.

    PubMed

    Nakamoto, Shingo; Imazeki, Fumio; Arai, Makoto; Yasui, Shin; Nakamura, Masato; Haga, Yuki; Sasaki, Reina; Kanda, Tatsuo; Shirasawa, Hiroshi; Yokosuka, Osamu

    2015-09-07

    We examined whether hepatitis C virus (HCV) genotype 1b core- and NS5A-region mutations are associated with response to peginterferon α-2b plus ribavirin combination therapy. A total of 103 patients with high HCV genotype 1b viral loads (≥ 100 KIU/mL) were treated with the combination therapy. Pretreatment mutations in the core region and interferon sensitivity determining region (ISDR) in the NS5A region were analyzed. In univariate analysis, arginine and leucine at positions 70 and 91 in the core region, defined as double wild (DW)-type, were associated with early virologic response (p = 0.002), sustained virologic response (SVR) (p = 0.004), and non-response (p = 0.005). Non-threonine at position 110 was associated with SVR (p = 0.004). Multivariate analysis showed the following pretreatment predictors of SVR: hemoglobin level ≥ 14 g/dL (odds ratio (OR) 6.2, p = 0.04); platelet count ≥ 14 × 10⁴/mm³ (OR 5.2, p = 0.04); aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio < 0.9 (OR 6.17, p = 0.009); DW-type (OR 6.8, p = 0.02); non-threonine at position 110 (OR 14.5, p = 0.03); and ≥ 2 mutations in the ISDR (OR 12.3, p = 0.02). Patients with non-DW-type, non-threonine at position 110, and < 2 ISDR mutations showed significantly lower SVR rates than others (11/45 (24.4%) vs. 27/37 (73.0%), respectively; p < 0.001). SVR can be predicted through core and NS5A region mutations and host factors like hemoglobin, platelet count, and AST/ALT ratio in HCV genotype 1b-infected patients treated with peginterferon and ribavirin combination therapy.

  2. Sustained Virologic Response at 24 Weeks after the End of Treatment Is a Better Predictor for Treatment Outcome in Real-World HCV-Infected Patients Treated by HCV NS3/4A Protease Inhibitors with Peginterferon plus Ribavirin

    PubMed Central

    Kanda, Tatsuo; Nakamoto, Shingo; Sasaki, Reina; Nakamura, Masato; Yasui, Shin; Haga, Yuki; Ogasawara, Sadahisa; Tawada, Akinobu; Arai, Makoto; Mikami, Shigeru; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Background. Direct-acting antiviral agents against HCV with or without peginterferon plus ribavirin result in higher eradication rates of HCV and shorter treatment duration. We examined which is better for predicting persistent virologic response, the assessment of serum HCV RNA at 12 or 24 weeks after the end of treatment for predicting sustained virologic response (SVR12 or SVR24, respectively) in patients treated by HCV NS3/4A protease inhibitors with peginterferon plus ribavirin. Methods. In all, 149 Japanese patients infected with HCV genotype 1b treated by peginterferon plus ribavirin with telaprevir or simeprevir were retrospectively analyzed: 59 and 90 patients were treated with telaprevir- and simeprevir-including regimens, respectively. HCV RNA was measured by TaqMan HCV Test, version 2.0, real-time PCR assay. SVR12 or SVR24, respectively, was defined as HCV RNA negativity at 12 or 24 weeks after ending treatment. Results. Total SVR rates were 78.0% and 66.7% in the telaprevir and simeprevir groups, respectively. In the telaprevir group, all 46 patients with SVR12 finally achieved SVR24. In the simeprevir group, 60 (93.8%) of the total 64 patients with SVR12 achieved SVR24, with the other 4 patients all being previous-treatment relapsers. Conclusions. SVR12 was suitable for predicting persistent virologic response in almost all cases. In simeprevir-including regimens, SVR12 could not always predict persistent virologic response. Clinicians should use SVR24 for predicting treatment outcome in the use of HCV NS3/4A protease inhibitors with peginterferon plus ribavirin for any group of real-world patients chronically infected with HCV. PMID:27076789

  3. Sustained Virologic Response at 24 Weeks after the End of Treatment Is a Better Predictor for Treatment Outcome in Real-World HCV-Infected Patients Treated by HCV NS3/4A Protease Inhibitors with Peginterferon plus Ribavirin.

    PubMed

    Kanda, Tatsuo; Nakamoto, Shingo; Sasaki, Reina; Nakamura, Masato; Yasui, Shin; Haga, Yuki; Ogasawara, Sadahisa; Tawada, Akinobu; Arai, Makoto; Mikami, Shigeru; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Direct-acting antiviral agents against HCV with or without peginterferon plus ribavirin result in higher eradication rates of HCV and shorter treatment duration. We examined which is better for predicting persistent virologic response, the assessment of serum HCV RNA at 12 or 24 weeks after the end of treatment for predicting sustained virologic response (SVR12 or SVR24, respectively) in patients treated by HCV NS3/4A protease inhibitors with peginterferon plus ribavirin. In all, 149 Japanese patients infected with HCV genotype 1b treated by peginterferon plus ribavirin with telaprevir or simeprevir were retrospectively analyzed: 59 and 90 patients were treated with telaprevir- and simeprevir-including regimens, respectively. HCV RNA was measured by TaqMan HCV Test, version 2.0, real-time PCR assay. SVR12 or SVR24, respectively, was defined as HCV RNA negativity at 12 or 24 weeks after ending treatment. Total SVR rates were 78.0% and 66.7% in the telaprevir and simeprevir groups, respectively. In the telaprevir group, all 46 patients with SVR12 finally achieved SVR24. In the simeprevir group, 60 (93.8%) of the total 64 patients with SVR12 achieved SVR24, with the other 4 patients all being previous-treatment relapsers. SVR12 was suitable for predicting persistent virologic response in almost all cases. In simeprevir-including regimens, SVR12 could not always predict persistent virologic response. Clinicians should use SVR24 for predicting treatment outcome in the use of HCV NS3/4A protease inhibitors with peginterferon plus ribavirin for any group of real-world patients chronically infected with HCV.

  4. An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR) in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 1 (GT1)

    PubMed Central

    Asselah, Tarik; Moreno, Christophe; Sarrazin, Christoph; Gschwantler, Michael; Foster, Graham R.; Craxí, Antonio; Buggisch, Peter; Ryan, Robert; Lenz, Oliver; Scott, Jane; Van Dooren, Gino; Lonjon-Domanec, Isabelle; Schlag, Michael; Buti, Maria

    2016-01-01

    Background Shortening duration of peginterferon-based HCV treatment reduces associated burden for patients. Primary objectives of this study were to assess the efficacy against the minimally acceptable response rate 12 weeks post-treatment (SVR12) and safety of simeprevir plus PR in treatment-naïve HCV GT1 patients treated for 12 weeks. Additional objectives included the investigation of potential associations of rapid viral response and baseline factors with SVR12. Methods In this Phase III, open-label study in treatment-naïve HCV GT1 patients with F0–F2 fibrosis, patients with HCV-RNA <25 IU/mL (detectable/undetectable) at Week 2, and undetectable HCV-RNA at Weeks 4 and 8, stopped all treatment at Week 12. All other patients continued PR for a further 12 weeks. Baseline factors significantly associated with SVR12 were identified through logistic regression. Results Of 163 patients who participated in the study, 123 (75%) qualified for 12-week treatment; of these, 81 (66%) achieved SVR12. Baseline factors positively associated with SVR12 rates in patients receiving the 12-week regimen were: IL28B CC genotype: (94% SVR12); HCV RNA ≤800,000 IU/mL (82%); F0–F1 fibrosis (74%). Among all 163 patients, 94% experienced ≥1 adverse event (AE), 4% a serious AE, and 2.5% discontinued due to an AE. Reduced impairment in patient-reported outcomes was observed in the 12-week vs >12-week regimen. Conclusions Overall SVR12 rate (66%) was below the target of 80%, indicating that shortening of treatment with simeprevir plus PR to 12 weeks based on very early response is not effective. However, baseline factors associated with higher SVR12 rates were identified. Therefore, while Week 2 response alone is insufficient to predict efficacy, GT1 patients with favourable baseline factors may benefit from a shortened simeprevir plus PR regimen. Trial Registration ClinicalTrials.gov NCT01846832 PMID:27428331

  5. Impact of the peginterferon-α 2a and ribavirin plasma levels on viral kinetics and sustained virological response in genotype 1 HCV/HIV-co-infected patients with the unfavourable non-CC IL28B genotypes.

    PubMed

    Torres-Cornejo, A; Ruiz-Valderas, R; Jimenez-Jimenez, L; Abad-Molina, C; Gutierrez-Valencia, A; Viciana, P; Lopez-Cortes, L F

    2014-03-01

    Studies on the association between the peginterferon-α and ribavirin levels and sustained virological response (SVR) have shown yielded conflicting results, but most of them were performed before the influence of IL28B polymorphisms was known. Our aim was to assess the effects of peginterferon-α 2a and ribavirin plasma levels on viral kinetics and SVR in hepatitis C virus genotype 1 HCV-1/HIV-co-infected patients according to IL28B genotype. This was a cohort study of HCV-1/HIV-co-infected patients who were HCV-treatment naïve and for whom the efficacy of peginterferon-α 2a plus ribavirin was evaluated by per-protocol analysis. The peginterferon-α 2a and ribavirin levels were measured by ELISA and HPLC-UV, respectively. The relationships among host and viral factors, the trough drugs levels and virological responses were analysed by multivariate regression analyses. A total of 131 Caucasian patients were included (cirrhosis:38.9%). Overall, SVR rate was 39.6%. In patients with CC IL28B genotype, SVR was related neither to peginterferon-α 2a nor to ribavirin plasma levels, while higher levels of both drugs were the only variables independently associated with SVR in individuals with CT/TT IL28B genotypes (OR, 5.02; CI95 , 1.45-17.1; P = 0.001 and 4.0; CI95 , 1.08-14.7; P = 0.038, respectively). Moreover, faster viral declines were observed in CT/TT patients when pegIFN-α 2a and ribavirin plasma levels were greater than 3400 pg/mL and 1.6 μg/mL, respectively. In contrast to the results for CC patients, the results in patients carrying the unfavourable CT/TT IL28B genotypes showed that plasma levels of both drugs have significant effects on viral kinetics and SVR. © 2013 John Wiley & Sons Ltd.

  6. Efficiency and Safety of an Early Dose Adjustment of Ribavirin in Patients Infected With Hepatitis C Underexposed to the Drug and Treated With Peginterferon Ribavirin.

    PubMed

    Loustaud-Ratti, Véronique; Maynard, Marianne; Thevenon, Sylvie; Pradat, Pierre; Rousseau, Annick; Alain, Sophie; Deny, Paul; Gagnieu, Marie-Claude; Tran, Albert; Dao, Thông; Silvain, Christine; Lunel-Fabiani, Françoise; Picard, Nicolas; Zublena, Irène; Marquet, Pierre; Trepo, Christian

    2016-12-01

    Ribavirin exposure after the first dose (D0AUC0-4h) >1755 mcg·h·L is predictive of sustained virological response (SVR) in patients with hepatitis C treated with peginterferon and ribavirin. The aim of this study was to test the benefit of ribavirin early dose adjustment based on this target in naïve patients infected with genotype 1. A multicenter randomized controlled trial with two parallel groups; fixed-dose (FD) group: standard of care in 2010-2011, ie, peginterferon-α2a 180 mcg·wk and weight-based ribavirin 1000-1200 mg/d during 48 weeks; adapted-dose (AD) group: increase of ribavirin dose if D0AUC0-4h <1755 mcg·h·L. A total of 221 patients were included, 110 in the AD group and 111 in the FD group with similar baseline characteristics. In the perprotocol analysis, SVR was higher in the AD group (55.1% versus 40.4%; P = 0.042), especially in patients with D0AUC0-4h <1755 mcg·h·L (54.3% versus 31.9%; P = 0.029). In the intention-to-treat analysis, the difference was not significant (50% versus 41%; P = 0.197). Ribavirin trough concentrations (C0s) at week 4 of treatment (intention-to-treat analysis) were higher in patients achieving SVR (2.06 versus 1.72 mg/L, P = 0.003). In the subgroup of patients with AUC0-4h <1755 mcg·h·L, 46% of patients with AD achieved a C0 >2.0 mg/L versus 22% of patients with FD (P = 0.013). Grade 1 anemia (but not other grades) was more frequent in the AD group (70% versus 48%, P = 0.001). The number of dose reductions or discontinuation of ribavirin was similar in both groups. Early ribavirin dose adjustment increases SVR in patients underexposed to ribavirin without increasing grade II-IV anemia. Such a strategy could be useful in patients with no access to new antiviral drugs.

  7. Early prediction of major depression in chronic hepatitis C patients during peg-interferon α-2b treatment by assessment of vegetative-depressive symptoms after four weeks

    PubMed Central

    Robaeys, Geert; De Bie, Jozef; Wichers, Marieke C; Bruckers, Liesbeth; Nevens, Frederik; Michielsen, Peter; Van Ranst, Marc; Buntinx, Frank

    2007-01-01

    AIM: To study the predictive value of the vegetative-depressive symptoms of the Zung Depression Rating Scale for the occurrence of depression during treatment with peg-interferon α-2b of chronic hepatitis C (CHC) patients. METHODS: The predictive value of vegetative-depressive symptoms at 4 wk of treatment for the occurrence of a subsequent diagnosis of major depressive disorder (MDD) was studied in CHC patients infected after substance use in a prospective, multi-center treatment trial in Belgium. The presence of vegetative-depressive symptoms was assessed using the Zung Scale before and 4 wk after the start of antiviral treatment. RESULTS: Out of 49 eligible patients, 19 (39%) developed MDD. The area under the ROC curve of the vegetative Zung subscale was 0.73, P = 0.004. The sensitivity at a cut-point of > 15/35 was 95% (95% CI: 74-100). The positive predictive value equalled 44% (95% CI: 29-60). CONCLUSION: In this group of Belgian CHC patients infected after substance use, antiviral treatment caused a considerable risk of depression. Seven vegetative-depressive symptoms of the Zung scale at wk 4 of treatment predicted 95% of all emerging depressions, at a price of 56% false positive test results. PMID:17963300

  8. Clinical Characteristics and Treatment Outcome of Peginterferon Plus Ribavirin in Patients Infected with Genotype 6 Hepatitis C Virus in Korea: A Multicenter Study

    PubMed Central

    Shin, Su Rin; Kim, Young Seok; Lim, Young-Seok; Lee, June Sung; Lee, Jin Woo; Kim, Sun Myung; Jeong, Sook-Hyang; Sohn, Joo Hyun; Lee, Myung Seok; Park, Sang Hoon

    2017-01-01

    Background/Aims Because of the limited geographic distribution, there have been insufficient data regarding hepatitis C virus (HCV) genotype 6 in Korea. This study aimed to investigate the clinical characteristics and available treatment outcomes of patients with genotype 6 HCV in Korea. Methods From 2004 to 2014, data were collected from Korean patients infected with genotype 6 HCV in eight hospitals. Results Thirty-two patients had genotype 6 HCV. The median age was 44 years, and 6c was the most common subtype. The baseline median alanine transaminase level was 88 (21 to 1,019) IU/mL, and the HCV RNA level was 1,405,000 (96,500 to 28,844,529) IU/mL. Twenty-five patients were treated with peginterferon (PEG-IFN) and ribavirin. Three follow-up losses occurred. Additionally, 13 patients attained a sustained virologic response (SVR), seven patients relapsed, and two patients exhibited a null response. The SVR rates were 40% and 75% for the 24- and more than 48-week treatments, respectively, and five of the six patients who achieved a rapid virologic response (RVR) attained a SVR. Conclusions Korean patients infected with genotype 6 HCV are relatively young, and 6c is the most common subtype. When treated with PEG-IFN and ribavirin, the SVR rate was 52%. Similar to other genotypes, a longer duration of treatment and attainment of RVR are important for SVR. PMID:27728965

  9. High MIG (CXCL9) plasma levels favours response to peginterferon and ribavirin in HCV-infected patients regardless of DPP4 activity.

    PubMed

    Johansson, Susanne; Talloen, Willem; Tuefferd, Marianne; Darling, Jama; Fanning, Gregory; Fried, Michael W; Aerssens, Jeroen

    2016-03-01

    Sustained virological response (SVR) following peginterferon (pegIFN) and ribavirin (RBV) treatment in hepatitis C virus (HCV)-infected patients has been linked with the IL28B genotype and lower peripheral levels of the CXCR3-binding chemokine IP-10 (CXCL10). To further improve the understanding of these biomarkers we investigated plasma levels of the other CXCR3-binding chemokines and activity of the dipeptidyl peptidase IV (DPP4, CD26) protease, which cleaves IP-10, in relation to treatment response. African-American and Caucasian HCV genotype 1-infected patients (n = 401) were treated with pegIFN/RBV for 48 weeks (ViraHep-C cohort). Pretreatment plasma levels of MIG (CXCL9), I-TAC (CXCL11) and the type III interferon IL29 were investigated by Luminex and DPP4 activity by using a luciferase assay. Patients achieving SVR had higher baseline MIG plasma levels and lower DPP4 activity than non-SVR patients. MIG was higher in Caucasians, IL28B CC (rs1297860) genotype carriers and patients with higher ALT levels. MIG correlated with IP-10 in SVR patients, but not in non-SVRs. A high DPP4 activity correlated with higher IP-10 levels, while DPP4 activity was not associated with MIG or I-TAC levels. The associations of MIG with SVR status and IL28B genotype imply that higher MIG plasma levels could reflect a beneficial immunological state for response to pegIFN/RBV treatment. The correlation between MIG and IP-10 observed only in SVR patients may contribute to a better treatment response, whereas this MIG/IP-10 balance might be disrupted in non-SVR patients because of the increased DPP4 cleavage of IP-10 into a dysfunctional form. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. High MIG (CXCL9) plasma levels favors response to peginterferon and ribavirin in HCV-infected patients regardless of DPP4 activity

    PubMed Central

    Johansson, Susanne; Talloen, Willem; Tuefferd, Marianne; Darling, Jama; Fanning, Gregory; Fried, Michael W.; Aerssens, Jeroen

    2015-01-01

    Background & Aims Sustained virological response (SVR) following peginterferon (pegIFN) and ribavirin (RBV) treatment in hepatitis C virus (HCV) infected patients has been linked with the IL28B genotype and lower peripheral levels of the CXCR3-binding chemokine IP-10 (CXCL10). To further improve the understanding of these biomarkers we investigated plasma levels of the other CXCR3-binding chemokines and activity of the dipeptidyl peptidase IV (DPP4, CD26) protease, which cleaves IP-10, in relation to treatment response. Methods African-American and Caucasian HCV genotype 1 infected patients (n=401) were treated with pegIFN/RBV for 48 weeks (ViraHep-C cohort). Pretreatment plasma levels of MIG (CXCL9), I-TAC (CXCL11) and the type III interferon IL29 were investigated by Luminex and DPP4 activity by using a luciferase assay. Results Patients achieving SVR had higher baseline MIG plasma levels and lower DPP4 activity than non-SVR patients. MIG was higher in Caucasians, IL28B CC (rs1297860) genotype carriers and patients with higher ALT levels. MIG correlated with IP-10 in SVR patients, but not in non-SVRs. A high DPP4 activity correlated with higher IP-10 levels, while DPP4 activity was not associated with MIG or I-TAC levels. Conclusions The associations of MIG with SVR status and IL28B genotype imply that higher MIG plasma levels could reflect a beneficial immunological state for response to pegIFN/RBV treatment. The correlation between MIG and IP-10 observed only in SVR patients may contribute to a better treatment response whereas this MIG/IP-10 balance might be disrupted in non-SVR patients due to increased DPP4 cleavage of IP-10 into a dysfunctional form. PMID:26344576

  11. ECOG Phase II trial of graded-dose peginterferon α-2b in patients with metastatic melanoma over-expressing basic fibroblast growth factor (E2602)

    PubMed Central

    Go, Ronald S.; Lee, Sandra J.; Shin, Donghoon; Callister, Steven M.; Jobe, Dean A.; Conry, Robert M.; Tarhini, Ahmad A.; Kirkwood, John M.

    2013-01-01

    Purpose We investigated use of graded-dose peginterferon α-2b (Peg-IFN) in patients with stage IV melanoma overexpressing basic fibroblast growth factor (FGF-2). The primary objective was suppression of plasma FGF-2 to within normal range (≤7.5 pg/mL). Experimental Design Plasma FGF-2 was measured at baseline (Step 1), and patients with concentrations ≥15 pg/mL were eligible for study treatment (Step 2). Peg-IFN was given weekly at starting dose of 0.5 μg/kg/wk with increment every 3 weeks based on serial FGF-2 concentrations. Results Two hundred seven patients entered Step 1; 45 (22%) overexpressed FGF-2 (median=22 pg/dL). Twenty-nine eligible patients entered Step 2 and received treatment. Patients’ median age was 64 years (range, 29–84 years). Most had >2 prior therapies. FGF-2 decreased in 28 (97%) patients, with suppression to normal range in 10 (35%). Median time to FGF-2 suppression was 30 days. The best clinical responses were partial response (7%) and stable disease (17%). Median progression-free survival (PFS) and overall survival (OS) were 2.0 and 9.7 months, respectively. Patients who achieved FGF-2 suppression were more likely than those who did not to have a response or stable disease (P = 0.03). Vascular endothelial growth factor (VEGF) concentrations decreased in 27 patients (93%) during treatment and paralleled those of FGF-2 over time. We found no compensatory rise in VEGF among those with FGF-2 suppression. Conclusions Graded-dose Peg-IFN suppresses FGF-2 in patients with metastatic melanoma who overexpress FGF-2. Over a third of patients had complete suppression of plasma FGF-2, which correlated with clinical response to this therapy. PMID:24122792

  12. Assessment of hepatocellular carcinoma risk based on peg-interferon plus ribavirin treatment experience in this new era of highly effective oral antiviral drugs

    PubMed Central

    Lee, Seung Ho; Jin, Young-Joo; Shin, Jun Young; Lee, Jin-Woo

    2017-01-01

    Abstract In this new era of highly effective oral antiviral drugs for chronic hepatitis C virus (HCV), indications for antiviral treatment may be extendable. This study undertaken to identify suitable candidates for peg-interferon plus ribavirin (PEG-IFN/RBV) treatment by evaluating hepatocellular carcinoma (HCC) risk in patients with chronic HCV treated or not with PEG-IFN/RBV. This large-scale retrospective study was conducted on 1176 patients with chronic HCV without a history of HCC (treatment group [n = 489] and no-treatment group [n = 687]). In the treatment group, patients treated with PEG-IFN/RBV were dichotomized based on the achievement of sustained virologic response (SVR) into SVR (+) and SVR (−) groups. Median follow-up for all study subjects was 31 months (range 6–144 months). Three-year cumulative HCC development rates in the SVR (+) (1.1%) and SVR (−) (8.6%) subgroups were significantly lower than in the no-treatment group (13.5%) (P < 0.01 and P < 0.01, respectively). In all study subjects, presence of cirrhosis (hazard ratio [HR], 9.92, P < 0.01), age (HR 1.03, P < 0.01), SVR (−) (HR 7.02, P < 0.01), and no-treatment (HR 6.76, P < 0.01) were found to be independent risk factors of HCC development. In the treatment group, age, the presence of cirrhosis, and SVR (−) were predictors of HCC development. In the no-treatment group, age, male, and the presence of cirrhosis were independent predictors for HCC development. HCC risk increased in patients with chronic HCV with older age, cirrhosis, SVR (−) after PEG-IFN/RBV treatment, and no PEG-IFN/RBV treatment. Active antiviral therapy based on highly effective oral drugs needs to be considered in these patients. PMID:28072684

  13. No association between the IL28B SNP and response to peginterferon plus ribavirin combination treatment in Korean chronic hepatitis C patients.

    PubMed

    Heo, Nae-Yun; Lim, Young-Suk; Lee, Woochang; Oh, Minkyung; An, Jiyun; Lee, Danbi; Shim, Ju Hyun; Kim, Kang Mo; Lee, Han Chu; Lee, Yung Sang; Suh, Dong Jin

    2014-06-01

    There are few available data regarding the association between the single nucleotide polymorphisms (SNPs) of the gene encoding interleukin 28B (IL28B) and a sustained virologic response (SVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy in Korean chronic hepatitis C patients. This was a retrospective cohort study of 156 patients with chronic hepatitis C virus (HCV) infection who received combination treatment of PEG-IFN plus RBV. Blood samples from these patients were analyzed to identify the IL28B SNPs at rs12979860, rs12980275, rs8099917, and rs8103142. Association analyses were performed to evaluate the relationships between each IL28B SNP and SVRs. Seventy six patients with HCV genotype 1 and 80 with genotype non-1 were enrolled. The frequencies of rs12979860 CC and CT genotypes were 90.4% and 9.6%, respectively; those of rs12980275 AA and AG genotypes were 87.2% and 12.8%, respectively; those of rs8099917 TT and TG genotypes were 92.3% and 7.7%, respectively; and those of rs8103142 TT and CT genotypes were 90.4% and 9.6%, respectively. Among the patients with HCV genotype 1, the SVR rates were 69.7% and 80.0% for rs12979860 CC and CT, respectively (P=0.71). Among the HCV genotype non-1 patients, SVR rates were 88.0% and 100% for rs12979860 CC and CT (P=1.00), respectively. Genotypes of the IL28B SNP that are known to be favorable were present in most of the Korean patients with chronic hepatitis C in this study. Moreover, the IL28B SNP did not influence the SVR rate in either the HCV genotype 1 or non-1 patients. Therefore, IL28B SNP analysis might be not useful for the initial assessment, prediction of treatment outcomes, or treatment decision-making of Korean chronic hepatitis C patients.

  14. Regional Differences in Hepatitis C Treatment with Peginterferon and Ribavirin in Japan in Both Genotype 1 and Genotype 2: A Retrospective Cohort Study.

    PubMed

    Ide, Kazuki; Kawasaki, Yohei; Akutagawa, Maiko; Yamada, Hiroshi; Masaki, Naohiko

    2016-09-01

    There has been no report on the genotype-dependent regional, especially prefectural, differences in hepatitis C treatment in Japan. We conducted a retrospective cohort study using the nationwide database. The registration period of the database was from December 2009 to April 2013. Individuals with chronic hepatitis C were identified from the database. The sustained virologic response (SVR) rates in each prefecture were calculated stratified by genotype. Confounding variables were identified using stepwise logistic regression analysis. The range of the point estimate of the adjusted odds ratio explained prefectural differences in treatment outcomes. During the registration period, 36 prefectures registered cases to the database. A total of 16349 cases were registered and 11653 cases were included in the analysis. The mean age was 57.9±10.5 years; 7950 (68.2%) had hepatitis C virus (HCV) genotype 1 and 3703 (31.8%) had HCV genotype 2. The range in SVR rates was 30.0 to 63.0% for genotype 1 and 55.0 to 100.0% for genotype 2. In the multivariate analysis, the ranges of the adjusted odds ratio of each prefecture were 0.658 to 2.125 for genotype 1 and 0.364 to 2.630 for genotype 2. Our results suggest that regional, particularly prefectural, differences in chronic hepatitis C treatment with peg-interferon (IFN) and ribavirin (RBV) exist in Japan and that these regional differences may similarly exist both in HCV genotypes 1 and 2. Additional studies using these methods, considering medical situations in each prefecture and new treatments regimens, could greatly contribute to improving and standardizing chronic hepatitis C treatment.

  15. The combination of MK-5172, peginterferon, and ribavirin is effective in treatment-naive patients with hepatitis C virus genotype 1 infection without cirrhosis.

    PubMed

    Manns, Michael P; Vierling, John M; Bacon, Bruce R; Bruno, Savino; Shibolet, Oren; Baruch, Yaacov; Marcellin, Patrick; Caro, Luzelena; Howe, Anita Y M; Fandozzi, Christine; Gress, Jacqueline; Gilbert, Christopher L; Shaw, Peter M; Cooreman, Michael P; Robertson, Michael N; Hwang, Peggy; Dutko, Frank J; Wahl, Janice; Mobashery, Niloufar

    2014-08-01

    MK-5172 is an inhibitor of the hepatitis C virus (HCV) nonstructural protein 3/4A protease; MK-5172 is taken once daily and has a higher potency and barrier to resistance than licensed protease inhibitors. We investigated the efficacy and tolerability of MK-5172 with peginterferon and ribavirin (PR) in treatment-naive patients with chronic HCV genotype 1 infection without cirrhosis. We performed a multicenter, double-blind, randomized, active-controlled, dose-ranging, response-guided therapy study. A total of 332 patients received MK-5172 (100, 200, 400, or 800 mg) once daily for 12 weeks in combination with PR. Patients in the MK-5172 groups received PR for an additional 12 or 36 weeks, based on response at week 4. Patients in the control group (n = 66) received a combination of boceprevir and PR, dosed in accordance with boceprevir's US product circular. At 24 weeks after the end of therapy, sustained virologic responses were achieved in 89%, 93%, 91%, and 86% of the patients in the groups given the combination of PR and MK-5172 (100, 200, 400, or 800 mg), respectively, vs 61% of controls. In the MK-5172 group receiving 100 mg, 91% of patients had undetectable levels of HCV RNA at week 4 and qualified for the short duration of therapy. The combination of MK-5172 and PR generally was well tolerated. Transient increases in transaminase levels were noted in the MK-5172 groups given 400 and 800 mg, at higher frequencies than in the MK-5172 groups given 100 or 200 mg, or control groups. Once-daily MK-5172 (100 mg) with PR for 24 or 48 weeks was highly effective and well tolerated among treatment-naive patients with HCV genotype 1 infection without cirrhosis. Studies are underway to evaluate interferon-free MK-5172-based regimens. ClinicalTrials.gov number: NCT01353911. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Assessment of hepatocellular carcinoma risk based on peg-interferon plus ribavirin treatment experience in this new era of highly effective oral antiviral drugs.

    PubMed

    Lee, Seung Ho; Jin, Young-Joo; Shin, Jun Young; Lee, Jin-Woo

    2017-01-01

    In this new era of highly effective oral antiviral drugs for chronic hepatitis C virus (HCV), indications for antiviral treatment may be extendable. This study undertaken to identify suitable candidates for peg-interferon plus ribavirin (PEG-IFN/RBV) treatment by evaluating hepatocellular carcinoma (HCC) risk in patients with chronic HCV treated or not with PEG-IFN/RBV.This large-scale retrospective study was conducted on 1176 patients with chronic HCV without a history of HCC (treatment group [n = 489] and no-treatment group [n = 687]). In the treatment group, patients treated with PEG-IFN/RBV were dichotomized based on the achievement of sustained virologic response (SVR) into SVR (+) and SVR (-) groups.Median follow-up for all study subjects was 31 months (range 6-144 months). Three-year cumulative HCC development rates in the SVR (+) (1.1%) and SVR (-) (8.6%) subgroups were significantly lower than in the no-treatment group (13.5%) (P < 0.01 and P < 0.01, respectively). In all study subjects, presence of cirrhosis (hazard ratio [HR], 9.92, P < 0.01), age (HR 1.03, P < 0.01), SVR (-) (HR 7.02, P < 0.01), and no-treatment (HR 6.76, P < 0.01) were found to be independent risk factors of HCC development. In the treatment group, age, the presence of cirrhosis, and SVR (-) were predictors of HCC development. In the no-treatment group, age, male, and the presence of cirrhosis were independent predictors for HCC development.HCC risk increased in patients with chronic HCV with older age, cirrhosis, SVR (-) after PEG-IFN/RBV treatment, and no PEG-IFN/RBV treatment. Active antiviral therapy based on highly effective oral drugs needs to be considered in these patients.

  17. Cost-Effectiveness of Peg-Interferon, Interferon and Oral Nucleoside Analogues in the Treatment of Chronic Hepatitis B and D Infections in China.

    PubMed

    Goyal, Ashish; Murray, John M

    2016-08-01

    The cost-effectiveness of highly effective, but costly, peg-interferon (peg-IFN) treatment for chronic hepatitis B (CHB) infections in China is unknown. Endemic hepatitis D virus (HDV) may also modify the effectiveness of any HBV treatment option. The objective of this study is to determine the best antiviral treatment from a societal perspective in the Chinese population, which contains a mix of HBV and HDV infections. A Markov model is developed to simulate the clinical course of CHB and chronic hepatitis D (CHD) individuals. For a hypothetical Chinese cohort of 10,000 individuals aged 30-60 years, cost-utility analysis is performed for therapies with: lamivudine, adefovir, telbivudine, entecavir, IFN and Peg-IFN. Costs and quality-adjusted life-years (QALYs) are discounted at 3 % annually. A one-way sensitivity analysis is also conducted. Lamivudine, adefovir, telbivudine, and entecavir are all cost-effective treatments compared to palliative care at an incremental cost-effectiveness ratio (ICER) of -$418, -$197, -$443 and -$317 per QALY, respectively (2015 US dollars). Peg-IFN yields a maximum 156,000 QALYs with an ICER of $1149 per QALY while IFN results in the highest cumulative mortality of 48 % along with the lowest QALY gained. Probabilistic sensitivity analyses confirm that only Peg-IFN and ETV are the only two cost-effective options at the current willingness-to-pay (WTP) of $12,000 in China. However, entecavir has a higher probability of being cost-effective than Peg-IFN at current WTP for all age groups. Peg-IFN generates maximum QALYs compared to lamivudine, adefovir, telbivudine and interferon, and presents itself as a cost-effective option at current WTP. Alternatively entecavir can be used in China, generating 10 % lower QALYs than Peg-IFN but costing less than palliative care.

  18. Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial

    PubMed Central

    Abbas, Zaigham; Memon, Mohammad Sadik; Umer, Muhammad Amir; Abbas, Minaam; Shazi, Lubna

    2016-01-01

    AIM: To investigate the efficacy of pegylated interferon alfa (PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D. METHODS: Forty hepatitis D virus (HDV) RNA positive patients were randomized to receive either PEG-IFNα-2a 180 μg weekly in combination with entecavir 0.5 mg daily (n = 21) or PEG-IFNα alone (n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed. RESULTS: The mean age of the patients was 26.7 ± 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9 (43%) patients receiving combination therapy and 12 (63%) patients receiving PEG-IFNα alone (P = 0.199). Decline in hepatitis B surface antigen (HBsAg) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients (38%) receiving combination therapy and 10 patients (53%) receiving PEG-IFNα-2a alone. Virological response persisted in 7 (33%) and 8 (42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBsAg and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance. CONCLUSION: Administration of PEG-IFNα-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response. PMID:27190579

  19. Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial.

    PubMed

    Abbas, Zaigham; Memon, Mohammad Sadik; Umer, Muhammad Amir; Abbas, Minaam; Shazi, Lubna

    2016-05-18

    To investigate the efficacy of pegylated interferon alfa (PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D. Forty hepatitis D virus (HDV) RNA positive patients were randomized to receive either PEG-IFNα-2a 180 μg weekly in combination with entecavir 0.5 mg daily (n = 21) or PEG-IFNα alone (n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed. The mean age of the patients was 26.7 ± 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9 (43%) patients receiving combination therapy and 12 (63%) patients receiving PEG-IFNα alone (P = 0.199). Decline in hepatitis B surface antigen (HBsAg) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients (38%) receiving combination therapy and 10 patients (53%) receiving PEG-IFNα-2a alone. Virological response persisted in 7 (33%) and 8 (42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBsAg and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance. Administration of PEG-IFNα-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response.

  20. [Study of the transplacental transfer of interferon alfa-2a on the model of isolated perfused cotyledon].

    PubMed

    Dumas, J C; Giroux, M; Teixeira, M G; Puel, J; Waysbort, A; Berrebi, A; Houin, G; Grandjean, H

    1993-01-01

    Interferon can be used for VIH+ pregnant women, to decrease materno-fetal contamination. Added to maternal circulation, its behaviour was studied by human placental cotyledon ex vivo perfusion. Human recombinant IFN 2a and reference substance 3H2O were injected in intervillous chamber and their behaviours in venous fetal and maternal circulations was followed. At steady state, in fetal circulation 3H2O concentration was 37% of injected rate whereas no IFN transfer rate was observed. In both venous circulations IFN amounts were lower than injected ones 56% versus of 82% for water (p < 0.05). IFN didn't cross placental filter and disappeared partially during placental contact.

  1. Comparison of high ribavirin induction versus standard ribavirin dosing, plus peginterferon-α for the treatment of chronic hepatitis C in HIV-infected patients: the PERICO trial.

    PubMed

    Labarga, Pablo; Barreiro, Pablo; da Silva, Alfredo; Guardiola, Josep María; Rubio, Rafael; Aguirrebengoa, Koldo; Miralles, Pilar; Portu, Joseba; Téllez, Maria Jesús; Morano, Luis; Castro, Angeles; Pineda, Juan Antonio; Terrón, Alberto; Hernández-Quero, José; Mariño, Ana; Ríos, Maria José; Echeverría, Santiago; Asensi, Víctor; Vispo, Eugenia; Soriano, Vincent

    2012-09-15

    Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180 μg/d) plus either RBV standard dosing (1000 or 1200 mg/d if <75 or ≥ 75 kg, respectively) or RBV induction (2000 mg/d) along with subcutaneous erythropoietin β (450 IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. A total of 357 patients received ≥ 1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14 μg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3 mg/dL; P < .005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P = .004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P = .007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P = .03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P < .001) as predictors of SVR. A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV

  2. Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues

    PubMed Central

    Fan, Rong; Sun, Jian; Yuan, Quan; Xie, Qing; Bai, Xuefan; Ning, Qin; Cheng, Jun; Yu, Yanyan; Niu, Junqi; Shi, Guangfeng; Wang, Hao; Tan, Deming; Wan, Mobin; Chen, Shijun; Xu, Min; Chen, Xinyue; Tang, Hong; Sheng, Jifang; Lu, Fengmin; Jia, Jidong; Zhuang, Hui; Xia, Ningshao; Hou, Jinlin

    2016-01-01

    Objective The investigation regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) during chronic hepatitis B (CHB) treatment is limited. The aim of this study was to determine the performance of anti-HBc as a predictor for hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive CHB patients treated with peginterferon (Peg-IFN) or nucleos(t)ide analogues (NUCs), respectively. Design This was a retrospective cohort study consisting of 231 and 560 patients enrolled in two phase IV, multicentre, randomised, controlled trials treated with Peg-IFN or NUC-based therapy for up to 2 years, respectively. Quantitative anti-HBc evaluation was conducted for all the available samples in the two trials by using a newly developed double-sandwich anti-HBc immunoassay. Results At the end of trials, 99 (42.9%) and 137 (24.5%) patients achieved HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. We defined 4.4 log10 IU/mL, with a maximum sum of sensitivity and specificity, as the optimal cut-off value of baseline anti-HBc level to predict HBeAg seroconversion for both Peg-IFN and NUC. Patients with baseline anti-HBc ≥4.4 log10 IU/mL and baseline HBV DNA <9 log10 copies/mL had 65.8% (50/76) and 37.1% (52/140) rates of HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. In pooled analysis, other than treatment strategy, the baseline anti-HBc level was the best independent predictor for HBeAg seroconversion (OR 2.178; 95% CI 1.577 to 3.009; p<0.001). Conclusions Baseline anti-HBc titre is a useful predictor of Peg-IFN and NUC therapy efficacy in HBeAg-positive CHB patients, which could be used for optimising the antiviral therapy of CHB. PMID:25586058

  3. Peginterferon add-on results in more HBsAg decline compared to monotherapy in HBeAg-positive chronic hepatitis B patients.

    PubMed

    Brouwer, W P; Sonneveld, M J; Xie, Q; Guo, S; Zhang, N; Zeuzem, S; Tabak, F; Zhang, Q; Simon, K; Akarca, U S; Streinu-Cercel, A; Hansen, B E; Janssen, H L A

    2016-06-01

    It is unknown whether peginterferon (PEG-IFN) add-on to entecavir (ETV) leads to more HBsAg decline compared to PEG-IFN monotherapy or combination therapy, and whether ETV therapy may prevent HBsAg increase after PEG-IFN cessation. We performed a post hoc analysis of 396 HBeAg-positive patients treated for 72 weeks with ETV + 24 weeks PEG-IFN add-on from week 24 to 48 (add-on, n = 85), 72 weeks with ETV monotherapy (n = 90), 52 weeks with PEG-IFN monotherapy (n = 111) and 52 weeks PEG-IFN + lamivudine (combination, n = 110) within 2 randomized trials. HBsAg decline was assessed at the end of PEG-IFN (EOP) and 6 months after PEG-IFN (EOF) discontinuation. Differences in baseline characteristics were accounted for using inversed probability of treatment weights. At EOP, a HBsAg reduction of ≥1log10 IU/mL was more frequently achieved for patients in the add-on or combination therapy arms (both 36%), compared to PEG-IFN mono (20%) or ETV (8%) (add-on vs PEG-IFN mono P = 0.050). At EOF, the HBsAg reduction ≥1log10 IU/mL was only sustained in patients treated with ETV consolidation (add-on vs combination and PEG-IFN mono: 40% vs 23% and 18%, P = 0.029 and P = 0.003, respectively). For add-on, combination, PEG-IFN mono and ETV, the mean HBsAg-level change at EOF was -0.84, -0.81, -0.68 and -0.33 log10 IU/mL, respectively (P > 0.05 for PEG-IFN arms). HBeAg loss at EOF was 36%, 31%, 33% and 20%, respectively (P > 0.05). PEG-IFN add-on for 24 weeks results in more on-treatment HBsAg decline than does 52 weeks of PEG-IFN monotherapy. ETV therapy may maintain the HBsAg reduction achieved with PEG-IFN.

  4. Peginterferon-α does not improve early peripheral blood HBV-specific T-cell responses in HBeAg-negative chronic hepatitis.

    PubMed

    Penna, Amalia; Laccabue, Diletta; Libri, Irene; Giuberti, Tiziana; Schivazappa, Simona; Alfieri, Arianna; Mori, Cristina; Canetti, Diana; Lampertico, Pietro; Viganò, Mauro; Colombo, Massimo; Loggi, Elisabetta; Missale, Gabriele; Ferrari, Carlo

    2012-06-01

    The effect of IFN-α therapy on HBV-specific T-cell responses in HBeAg-negative, genotype D, chronic hepatitis B is largely undefined. Understanding to what extent IFN-α can modulate HBV-specific T-cells is important to define strategies to optimize IFN efficacy and to identify immunological parameters to predict response to therapy. HBV-specific T-cell responses were analyzed longitudinally ex vivo and after expansion in vitro in 15 patients with genotype D, HBeAg-negative chronic hepatitis B treated with peginterferon-α-2a. HBV proteins and synthetic peptides were used to stimulate T-cell responses. Analysis of the CD4 and CD8 T-cell functions was performed by ELISPOT, intracellular cytokine and tetramer staining. The effect of anti-PD-L1 on T-cell functions was also analyzed. Ex vivo IFN-γ production by total HBV-specific T-cells was significantly greater before therapy in patients who showed HBV DNA <50 IU/ml at weeks 24 and/or 48 of therapy. No significant improvement of T-cell proliferation, Th1 cytokine production and cytotoxicity was observed during IFN therapy by both ex vivo and in vitro analysis. PD-1/PD-L1 blockade showed a modest improvement of cytokine production in a total of 15% of T-cell lines. IFN-α did not improve peripheral blood HBV-specific T-cell responses in the first 24 weeks of treatment, consistent either with a predominant antiviral/antiproliferative effect or with an immunomodulatory activity on other arms of the immune system which were not analyzed in our study. A better pre-treatment ex vivo IFN-γ production was associated with better chances to control HBV replication during therapy and represents a promising predictor of IFN efficacy. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  5. Identification of groups with poor cost-effectiveness of peginterferon plus ribavirin for naïve hepatitis C patients with a real-world cohort and database.

    PubMed

    Tsai, Pei-Chien; Liu, Ta-Wei; Tsai, Yi-Shan; Ko, Yu-Min; Chen, Kuan-Yu; Lin, Ching-Chih; Huang, Ching-I; Liang, Po-Cheng; Lin, Yi-Hung; Hsieh, Ming-Yen; Hou, Nai-Jen; Huang, Chung-Feng; Yeh, Ming-Lun; Lin, Zu-Yau; Chen, Shinn-Cherng; Dai, Chia-Yen; Chuang, Wan-Long; Huang, Jee-Fu; Yu, Ming-Lung

    2017-06-01

    For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P < .001). Treatment-naïve G1 patients of old ages, those with advanced fibrosis, high viral loads, or interleukin-28B unfavorable genotypes, or those without a rapid virological response (RVR: undetectable HCV RNA at week 4), or those with complete early virological response (cEVR: undetectable HCV RNA at week 12). Treatment-naïve G2 patients with high viral loads or without RVR or cEVR incurred significantly higher costs per SVR than their counterparts. The cost/SVR was extremely high among patients without RVR and in patients without cEVR. We investigated the real-world cost effectiveness data for different subgroups of treatment-naïve HCV patients with PegIFN/RBV therapies, which could provide useful, informative evidence for making decisions

  6. Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B.

    PubMed

    Lampertico, Pietro; Viganò, Mauro; Di Costanzo, Giovan Giuseppe; Sagnelli, Evangelista; Fasano, Massimo; Di Marco, Vito; Boninsegna, Sara; Farci, Patrizia; Fargion, Silvia; Giuberti, Tiziana; Iannacone, Claudio; Regep, Loredana; Massetto, Benedetta; Facchetti, Floriana; Colombo, Massimo

    2013-02-01

    Treatment with peginterferon α-2a (PegIFN) for 48 weeks is the standard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus (HBV), but with limited treatment efficacy. A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population. 128 HBeAg-negative patients (120 genotype D) were randomised to weekly 180 μg PegIFN for 48 weeks (group A, n=51), 180 μg PegIFN for 48 weeks followed by 135 μg weekly for an additional 48 weeks (group B, n=52) or 180 μg PegIFN plus lamivudine (100 mg/day) for 48 weeks then 135 μg PegIFN for 48 weeks (group C, n=25). Endpoints were alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (primary), HBV DNA <2000 IU/ml and HBsAg clearance at 48 weeks after treatment. Forty-eight weeks after treatment, six patients in group A and 13 in group B achieved alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (11.8% vs 25.0%, p=0.08), 6 vs 15 patients had HBV DNA <2000 IU/ml (11.8% vs 28.8%, p=0.03), 0 vs 3 achieved HBsAg clearance (0% vs 5.8%, p=0.24) and 0 vs 5 had HBsAg <10 IU/ml (0% vs 9.6%, p=0.06). While extended PegIFN treatment was the strongest independent predictor of response, the combination with lamivudine did not improve responses. Discontinuation rates were similar among the groups (19.6%, 23.1%, 32.0%, p=0.81) and were mostly due to PegIFN-related adverse events. In HBeAg-negative genotype D patients with chronic hepatitis B, PegIFN treatment for 96 weeks was well tolerated and the post-treatment virological response improved significantly compared with 48 weeks of treatment. http://ClinicalTrials.gov registration number: NCT01095835.

  7. Identification of groups with poor cost-effectiveness of peginterferon plus ribavirin for naïve hepatitis C patients with a real-world cohort and database

    PubMed Central

    Tsai, Pei-Chien; Liu, Ta-Wei; Tsai, Yi-Shan; Ko, Yu-Min; Chen, Kuan-Yu; Lin, Ching-Chih; Huang, Ching-I; Liang, Po-Cheng; Lin, Yi-Hung; Hsieh, Ming-Yen; Hou, Nai-Jen; Huang, Chung-Feng; Yeh, Ming-Lun; Lin, Zu-Yau; Chen, Shinn-Cherng; Dai, Chia-Yen; Chuang, Wan-Long; Huang, Jee-Fu; Yu, Ming-Lung

    2017-01-01

    Abstract Background: For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. Methods: A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. Results: The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P < .001). Treatment-naïve G1 patients of old ages, those with advanced fibrosis, high viral loads, or interleukin-28B unfavorable genotypes, or those without a rapid virological response (RVR: undetectable HCV RNA at week 4), or those with complete early virological response (cEVR: undetectable HCV RNA at week 12). Treatment-naïve G2 patients with high viral loads or without RVR or cEVR incurred significantly higher costs per SVR than their counterparts. The cost/SVR was extremely high among patients without RVR and in patients without cEVR. Conclusion: We investigated the real-world cost effectiveness data for different subgroups of treatment-naïve HCV patients with PegIFN/RBV therapies, which could provide useful

  8. Predictors of Virological Response in 3,235 Chronic HCV Egyptian Patients Treated with Peginterferon Alpha-2a Compared with Peginterferon Alpha-2b Using Statistical Methods and Data Mining Techniques.

    PubMed

    El Raziky, Maissa; Fathalah, Waleed Fouad; Zakaria, Zeinab; Eldeen, Hadeel Gamal; Abul-Fotouh, Amr; Salama, Ahmed; Awad, Abubakr; Esmat, Gamal; Mabrouk, Mahasen

    2016-05-01

    Despite the appearance of new oral antiviral drugs, pegylated interferon (PEG-IFN)/RBV may remain the standard of care therapy for some time, and several viral and host factors are reported to be correlated with therapeutic effects. This study aimed to reveal the independent variables associated with failure of sustained virological response (SVR) to PEG-IFN alpha-2a versus PEG-IFN alpha-2b in treatment of naive chronic hepatitis C virus (HCV) Egyptian patients using both statistical methods and data mining techniques. This retrospective cohort study included 3,235 chronic hepatitis C patients enrolled in a large Egyptian medical center: 1,728 patients had been treated with PEG-IFN alpha-2a plus ribavirin (RBV) and 1,507 patients with PEG-IFN alpha-2b plus RBV between 2007 and 2011. Both multivariate analysis and Reduced Error Pruning Tree (REPTree)-based model were used to reveal the independent variables associated with treatment response. In both treatment types, alpha-fetoprotein (AFP) >10 ng/mL and HCV viremia >600 × 10(3) IU/mL were the independent baseline variables associated with failure of SVR, while male gender, decreased hemoglobin, and thyroid-stimulating hormone were the independent variables associated with good response (P < 0.05). Using REPTree-based model showed that low AFP was the factor of initial split (best predictor) of response for either PEG-IFN alpha-2a or PEG-IFN alpha-2b (cutoff value 8.53, 4.89 ng/mL, AUROC = 0.68 and 0.61, P = 0.05). Serum AFP >10 ng/mL and viral load >600 × 10(3) IU/mL are variables associated with failure of response in both treatment types. REPTree-based model could be used to assess predictors of response.

  9. Pilot Study of Pioglitazone Prior to HCV Re-treatment in HIV/HCV Genotype 1-Infected Subjects with Insulin Resistance and Prior Nonresponse to Peginterferon and Ribavirin Therapy: A5239

    PubMed Central

    Marks, Kristen; Kitch, Douglas; Chung, Raymond T.; Hadigan, Colleen; Andersen, Janet; Tien, Phyllis; Luetkemeyer, Annie; Alston-Smith, Beverly; Glesby, Marshall J.

    2014-01-01

    Insulin resistance (IR) is associated with nonresponse to HCV treatment. In this multicenter, single-arm pilot study, adult, HIV/HCV genotype 1 coinfected prior nonresponders to peginterferon/ribavirin (PegIFN/RBV) with homeostatic model assessment-IR >2.5 were treated with pioglitazone(PIO) for 24 weeks followed by PegIFN/RBV/PIO. 3/19 subjects (15.8%) achieved undetectable HCV RNA at week 24 of PegIFN/RBV/PIO which was not significantly different than the historical null rate of 10% (p=0.29, lower limit of the exact 1-sided 90% confidence interval 5.9%). Over the 24 weeks of PIO monotherapy, ALT and AST declined significantly and correlated with improved metabolic parameters. PMID:24525470

  10. Clinical effectiveness and cost effectiveness of tailoring chronic hepatitis C treatment with peginterferon alpha-2b plus ribavirin to HCV genotype and early viral response: a decision analysis based on German guidelines.

    PubMed

    Siebert, Uwe; Sroczynski, Gaby; Aidelsburger, Pamela; Rossol, Siegbert; Wasem, Jürgen; Manns, Michael P; McHutchison, John G; Wong, John B

    2009-01-01

    Recently developed German guidelines for antiviral treatment in patients with chronic hepatitis C recommend basing drug dosage, intended treatment duration and early stopping rules on the genotype of the hepatitis C virus and early viral responses to treatment. To evaluate effectiveness and cost effectiveness of different antiviral treatment strategies including the German guidelines, for chronic hepatitis C. A validated lifetime Markov model was used to project life expectancy, QALYs and lifetime costs for the following strategies: (i) no antiviral therapy (NoAVT); (ii) interferon-alpha-2b plus ribavirin for 48 weeks (IFN + R); (iii) peginterferon-alpha-2b plus weight-based ribavirin for 48 weeks (PEG + R); (iv) peginterferon-alpha-2b plus ribavirin according to German guidelines with genotype-dependent treatment duration, dosage and 12-week viral response evaluation (GUIDE). Clinical and resource utilization data were derived from a clinical trial, the published literature and a survey of German hepatologists. Incremental cost-effectiveness ratios (ICERs) were calculated adopting the German societal perspective. Costs (in euro, year 2005 values) and health outcomes were discounted at 3% annually. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Compared with NoAVT, PEG + R increased undiscounted life expectancy by 5.0 life-years (5.2 QALYs) and GUIDE increased undiscounted life expectancy by 4.9 years (5.1 QALYs). Compared with PEG + R, GUIDE saved 13% of hepatitis C virus-related lifetime costs per patient. GUIDE dominated IFN + R. Compared with NoAVT, discounted ICERs were euro1500 per QALY for GUIDE and euro3200 per QALY for PEG + R. Administering GUIDE should allow tailoring treatment efficiently to genotype, bodyweight and early viral response in patients with chronic hepatitis C, and appears cost effective compared with other well accepted medical interventions.

  11. A preliminary study on the efficacy and influencing factors of interferon for the treatment of genotype 1 chronic hepatitis C with different dosage forms.

    PubMed

    Ma, Ping; Yang, Ji-Ming; Hou, Wei; Song, Shi-Duo; Wang, Lei; Lu, Wei

    2013-05-01

    Nowadays, interferon alfa-2b is still in widespread use for the treatment of chronic hepatitis C in China. In this study, peginterferon alfa-2a plus ribavirin was compared with interferon alfa-2b plus ribavirin for the initial treatment of genotype 1 chronic hepatitis C. Overall, 168 patients with genotype 1 chronic hepatitis C were assigned peginterferon alfa-2a (135-180 µg subcutaneously/week) plus ribavirin (800-1200 mg/day orally) or interferon alfa-2b (300-500 million units, once every other day) plus ribavirin (800-1200 mg/day). According to HCV RNA levels at weeks 4 and 12, patients were reallocated to receive different interferon dosage forms or different courses of treatment. The primary endpoint was a sustained virological response (SVR). A total of 160 patients completed the entire study and eight cases were lost to follow-up. The SVR rates in patients treated with peginterferon alfa-2a plus ribavirin for 24 and 48 weeks were 67.9% (53/78) and 73.6% (14/19), respectively, whereas in patients treated with interferon alfa-2b plus ribavirin for 24 and 48 weeks the SVR rates were 52.4% (43/82) and 40% (8/20), respectively. The SVR rates in the groups with a rapid virological response (RVR) and without RVR were 68.8 and 16.9%, respectively. The SVR rates in the groups with an early virological response (EVR) and in the groups without EVR were 88.1 and 10.5%, respectively. Peginterferon alfa-2a plus ribavirin was more effective than interferon alfa-2b plus ribavirin, with similar safety. RVR can predict a greater chance of SVR. The duration of treatment should be shortened for patients with RVR. Treatment for patients without EVR should be discontinued.

  12. Peginterferon Beta-1a Injection

    MedlinePlus

    ... a solution (liquid) in a dosing pen or prefilled syringe to inject subcutaneously (under the skin). It is ... how to inject the medication.Use a new prefilled syringe or dosing pen each time you inject your ...

  13. REDUCTION IN HEPATIC INFLAMMATION IS ASSOCIATED WITH LESS FIBROSIS PROGRESSION AND FEWER CLINICAL OUTCOMES IN ADVANCED HEPATITIS C

    PubMed Central

    Morishima, Chihiro; Shiffman, Mitchell L.; Dienstag, Jules L.; Lindsay, Karen L; Szabo, Gyongyi; Everson, Gregory T.; Lok, Anna S.; Di Bisceglie, Adrian M.; Ghany, Marc G.; Naishadham, Deepa; Morgan, Timothy R.; Wright, Elizabeth C.

    2013-01-01

    Objective During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 prior interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation. Methods Relationships between change in hepatic inflammation (Ishak HAI) and serum ALT, fibrosis progression and clinical outcomes after randomization, and HCV RNA decline before and after randomization were evaluated. Histologic change was defined as a ≥2-point difference in HAI or Ishak fibrosis score between biopsies. Results Among 657 patients who received full-dose peginterferon/ribavirin “lead-in” therapy before randomization, year-1.5 HAI improvement was associated with lead-in HCV RNA suppression in both randomized treated (P <0.0001) and control (P = 0.0001) groups, even in the presence of recurrent viremia. This relationship persisted at year 3.5 in both treated (P = 0.001) and control (P = 0.01) groups. Among 834 patients followed for a median of 6 years, fewer clinical outcomes occurred in patients with improved HAI at year 1.5 compared to those without such improvement in both treated (P = 0.03) and control (P = 0.05) groups. Among patients with Ishak 3–4 fibrosis at baseline, those with improved HAI at year 1.5 had less fibrosis progression at year 1.5 in both treated (P = 0.0003) and control (P = 0.02) groups. Conclusion Reduced hepatic inflammation (measured 1.5 and 3.5 years after randomization) was associated with profound virological suppression during lead-in treatment with full-dose peginterferon/ribavirin and with decreased fibrosis progression and clinical outcomes, independent of randomized treatment. PMID:22688849

  14. Alisporivir with peginterferon/ribavirin in patients with chronic hepatitis C genotype 1 infection who failed to respond to or relapsed after prior interferon-based therapy: FUNDAMENTAL, a Phase II trial.

    PubMed

    Buti, M; Flisiak, R; Kao, J-H; Chuang, W-L; Streinu-Cercel, A; Tabak, F; Calistru, P; Goeser, T; Rasenack, J; Horban, A; Davis, G L; Alberti, A; Mazzella, G; Pol, S; Orsenigo, R; Brass, C

    2015-07-01

    Alisporivir (ALV) is an oral, investigational host-targeting agent, with pangenotypic activity against hepatitis C virus (HCV). This randomized, double-blind, placebo-controlled, Phase II study explored the efficacy and safety of ALV with peginterferon-α2a/ribavirin (PR) in patients with chronic HCV genotype 1 infection in whom prior PR had failed (43% relapsers, 34% null responders and 23% partial responders). Four-hundred-and-fifty-nine patients were randomized (1:1:1:1) to ALV 600 mg once daily (QD), ALV 800 mg QD, ALV 400 twice daily (BID) or placebo plus PR for 48 weeks. When the global ALV trial programme was put on clinical hold, all patients in this study had received ≥31 weeks of randomized treatment; patients completed 48 weeks on PR alone. All ALV groups demonstrated superior rates of complete early virologic response (cEVR; primary endpoint) vs PR alone (P ≤ 0.0131), with highest cEVR rate seen with ALV 400 mg BID (74% vs 36% with PR alone; P < 0.0001). Respective SVR12 rates (key secondary endpoint) were 65% vs 26% in prior relapsers, 63% vs 5% in partial responders and 68% vs 3% in null responders. In patients who received >40 weeks of randomized treatment, the SVR12 rate was 89% for ALV 400 mg BID vs 30% for PR alone (P = 0.0053). Rates of viral breakthrough and relapse were lowest with ALV 400 mg BID. One case of pancreatitis (fully recovered) occurred with ALV/PR. Common AEs were headache, fatigue, anaemia, neutropenia and nausea. Hypertension was infrequent, but more common with ALV. ALV merits further investigation in interferon-free regimens in combination with direct-acting antiviral agents.

  15. Cost Effectiveness of Daclatasvir/Asunaprevir Versus Peginterferon/Ribavirin and Protease Inhibitors for the Treatment of Hepatitis c Genotype 1b Naïve Patients in Chile

    PubMed Central

    Giglio, Andrés; Soza, Alejandro

    2015-01-01

    Introduction Daclatasvir and Asunaprevir (DCV/ASV) have recently been approved for the treatment of chronic hepatitis C virus infection. In association, they are more effective and safer than previous available treatments, but more expensive. It is unclear if paying for the additional costs is an efficient strategy considering limited resources. Methods A Markov model was built to estimate the expected costs in Chilean pesos (CL$) and converted to US dollars (US$) and benefits in quality adjusted life years (QALYs) in a hypothetic cohort of naive patients receiving DCV/ASV compared to protease inhibitors (PIs) and Peginterferon plus Ribavirin (PR). Efficacy was obtained from a mixed-treatment comparison study and costs were estimated from local sources. Utilities were obtained applying the EQ-5D survey to local patients and then valued with the Chilean tariff. A time horizon of 46 years and a discount rate of 3% for costs and outcomes was considered. The ICERs were estimated for a range of DCV/ASV prices. Deterministic and probabilistic sensitivity analyses were performed. Results PIs were extendedly dominated by DCV/ASV. The ICER of DCV/ASV compared to PR was US$ 16,635/QALY at a total treatment price of US$ 77,419; US$11,581 /QALY at a price of US$ 58,065; US$ 6,375/QALY at a price of US$ 38,710; and US$ 1,364 /QALY at a price of US$ 19,355. The probability of cost-effectiveness at a price of US$ 38,710 was 91.6% while there is a 21.43% probability that DCV/ASV dominates PR if the total treatment price was US$ 19,355. Although the results are sensitive to certain parameters, the ICER did not increase above the suggested threshold of 1 GDP per capita. Conclusions DCV/ASV can be considered cost-effective at any price of the range studied. These results provide decision makers useful information about the value of incorporating these drugs into the public Chilean healthcare system. PMID:26544203

  16. Cost Effectiveness of Daclatasvir/Asunaprevir Versus Peginterferon/Ribavirin and Protease Inhibitors for the Treatment of Hepatitis c Genotype 1b Naïve Patients in Chile.

    PubMed

    Vargas, Constanza L; Espinoza, Manuel A; Giglio, Andrés; Soza, Alejandro

    2015-01-01

    Daclatasvir and Asunaprevir (DCV/ASV) have recently been approved for the treatment of chronic hepatitis C virus infection. In association, they are more effective and safer than previous available treatments, but more expensive. It is unclear if paying for the additional costs is an efficient strategy considering limited resources. A Markov model was built to estimate the expected costs in Chilean pesos (CL$) and converted to US dollars (US$) and benefits in quality adjusted life years (QALYs) in a hypothetic cohort of naive patients receiving DCV/ASV compared to protease inhibitors (PIs) and Peginterferon plus Ribavirin (PR). Efficacy was obtained from a mixed-treatment comparison study and costs were estimated from local sources. Utilities were obtained applying the EQ-5D survey to local patients and then valued with the Chilean tariff. A time horizon of 46 years and a discount rate of 3% for costs and outcomes was considered. The ICERs were estimated for a range of DCV/ASV prices. Deterministic and probabilistic sensitivity analyses were performed. PIs were extendedly dominated by DCV/ASV. The ICER of DCV/ASV compared to PR was US$ 16,635/QALY at a total treatment price of US$ 77,419; US$11,581 /QALY at a price of US$ 58,065; US$ 6,375/QALY at a price of US$ 38,710; and US$ 1,364 /QALY at a price of US$ 19,355. The probability of cost-effectiveness at a price of US$ 38,710 was 91.6% while there is a 21.43% probability that DCV/ASV dominates PR if the total treatment price was US$ 19,355. Although the results are sensitive to certain parameters, the ICER did not increase above the suggested threshold of 1 GDP per capita. DCV/ASV can be considered cost-effective at any price of the range studied. These results provide decision makers useful information about the value of incorporating these drugs into the public Chilean healthcare system.

  17. Telaprevir for previously untreated chronic hepatitis C virus infection.

    PubMed

    Jacobson, Ira M; McHutchison, John G; Dusheiko, Geoffrey; Di Bisceglie, Adrian M; Reddy, K Rajender; Bzowej, Natalie H; Marcellin, Patrick; Muir, Andrew J; Ferenci, Peter; Flisiak, Robert; George, Jacob; Rizzetto, Mario; Shouval, Daniel; Sola, Ricard; Terg, Ruben A; Yoshida, Eric M; Adda, Nathalie; Bengtsson, Leif; Sankoh, Abdul J; Kieffer, Tara L; George, Shelley; Kauffman, Robert S; Zeuzem, Stefan

    2011-06-23

    In phase 2 trials, telaprevir, a hepatitis C virus (HCV) genotype 1 protease inhibitor, in combination with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients. In this international, phase 3, randomized, double-blind, placebo-controlled trial, we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups: a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks (T12PR group), followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks (T8PR group), followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria; or a group receiving placebo with peginterferon-ribavirin for 12 weeks, followed by 36 weeks of peginterferon-ribavirin (PR group). The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment (sustained virologic response). Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response (75% and 69%, respectively, vs. 44%; P<0.001 for the comparison of the T12PR or T8PR group with the PR group). A total of 58% of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment. Anemia, gastrointestinal side effects, and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon-ribavirin alone. The overall rate of discontinuation of the treatment regimen owing to adverse events was 10% in the T12PR and T8PR groups and 7% in the PR group. Telaprevir

  18. Durability of the response to peginterferon-α2b and ribavirin in patients with chronic hepatitis C: a cohort study in the routine clinical setting.

    PubMed

    Giordanino, Chiara; Sacco, Marco; Ceretto, Simone; Smedile, Antonina; Ciancio, Alessia; Cariti, Giuseppe; De Blasi, Tiziano; Picciotto, Antonio; Marenco, Simona; Grasso, Alessandro; Pirisi, Mario; Smirne, Carlo; Colletta, Cosimo; Traverso, Antonio; Mazzucco, Dario; Ciccone, Giovannino; Simondi, Daniele; Rizzetto, Mario; Saracco, Giorgio

    2014-01-01

    To evaluate whether, in chronic hepatitis C-positive naive patients recruited in the routine clinical setting and treated with pegylated-interferon-α2b (Peg-IFN) and ribavirin (RBV), the sustained virologic response (SVR) is durable over the long term and whether it is associated with a decrease in liver complications and incidence of glucose abnormalities. This was a prospective long-term follow-up study of 182 naive patients enrolled in 2001-2002 and treated with Peg-IFN and RBV and followed up to December 2010, with clinical, biochemical, and virological evaluations every 6-12 months. None of the 115 (63.2%) sustained responders showed late viremic relapse during the follow-up. SVR was better defined at 24 weeks (16/16 relapsers, 100%) than at 12 weeks after the end of therapy (14/16 relapsers, 87.5%). On multivariable analysis, viral genotype (odds ratio 0.16, 95% confidence interval 0.07-0.36, P=0.0001) and a greater than 20% RBV reduction (odds ratio 5.21, 95% confidence interval 1.54-17.67, P=0.008) predicted long-term response (LTR) independently. The incidence of cirrhosis was significantly higher among nonresponders (21.3%) compared with long-term responders (0.9%, P≤0.0001), but the risk of developing glucose abnormalities was not significantly reduced in long-term responders (hazard ratio 1.36, P=0.363). Hepatocellular carcinoma occurred only in three cases. SVR achieved in patients treated in the routine clinical setting with Peg-IFN and RBV is durable over the long term and LTR significantly reduces the risk of progression to cirrhosis; however, in a population with mild liver fibrosis, the clinical impact of LTR on the risk of glucose abnormalities seems negligible.

  19. International, multicenter, randomized, controlled study comparing dynamically individualized versus standard treatment in patients with chronic hepatitis C.

    PubMed

    Zeuzem, Stefan; Pawlotsky, Jean-Michel; Lukasiewicz, Esther; von Wagner, Michael; Goulis, Ioannis; Lurie, Yoav; Gianfranco, Elia; Vrolijk, Jan-Maarten; Esteban, Juan I; Hezode, Christophe; Lagging, Martin; Negro, Francesco; Soulier, Alexandre; Verheij-Hart, Elke; Hansen, Bettina; Tal, Ronen; Ferrari, Carlo; Schalm, Solko W; Neumann, Avidan U

    2005-08-01

    The aim of this study was to increase virologic response rates by individualized treatment according to the early virologic response. Serum HCV-RNA was frequently quantified in patients with chronic hepatitis C (n=270) treated with peginterferon alfa-2a (180 microg/week) and ribavirin (1000-1200 mg/day). After 6 weeks patients were classified as rapid (RVR), slow (SPR), flat (FPR), or null responders (NUR) and randomized within each viral kinetic class to continue therapy either with an individualized or standard regimen. Individualized therapy comprised peginterferon monotherapy (48 weeks) or shorter combination therapy (24 weeks) for RVR, triple therapy with histamine (1 mg/day) (48 weeks) or prolonged combination therapy (72 weeks) for SPR, triple therapy for FPR, and high-dose peginterferon (360 microg/week) plus ribavirin for NUR patients. Patients were categorized as RVR (n=171), SPR (n=65), FPR (n=10), or NUR (n=22). Overall end-of-treatment and sustained virologic response rates were 77 and 60% in the individualized and 77 and 66% in the standard treatment arm, respectively. Histamine in addition to peginterferon and ribavirin and high-dose peginterferon plus ribavirin did not improve virologic response rates in patients with FPR and NUR, respectively. An improvement in virologic efficacy was not achieved with the available individualized treatment options.

  20. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B.

    PubMed

    Wursthorn, Karsten; Lutgehetmann, Marc; Dandri, Maura; Volz, Tassilo; Buggisch, Peter; Zollner, Bernhard; Longerich, Thomas; Schirmacher, Peter; Metzler, Frauke; Zankel, Myrga; Fischer, Conrad; Currie, Graeme; Brosgart, Carol; Petersen, Joerg

    2006-09-01

    Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for persistent infection of hepatocytes. The aim of this study was to determine changes in intrahepatic cccDNA in patients with chronic hepatitis B (CH-B) during 48 weeks of antiviral therapy and its correlation to virological, biochemical, and histological parameters. Twenty-six HBsAg-positive CH-B patients received combination treatment with pegylated interferon alpha-2b (peg-IFN) and adefovir dipivoxil (ADV) for 48 weeks. Paired liver biopsies from before and at the end of treatment were analyzed for intrahepatic HBV-DNA. Median serum HBV-DNA had decreased by -4.9 log10 copies/mL at the end of treatment and was undetectable in 13 individuals (54%). Median intrahepatic total HBV-DNA and cccDNA had decreased by -2.2 and -2.4 log10, respectively. Changes in intracellular HBV-DNA positively correlated with HBsAg serum reduction and were accompanied by a high number of serological responders. Eight of 15 HBeAg-positive patients lost HBeAg, and five developed anti-HBe antibodies during treatment. These eight patients exhibited lower cccDNA levels before and at the end of therapy than did patients without HBeAg loss. Four patients developed anti-HBs antibodies. ALT normalized in 11 patients. The number of HBs-antigen- and HBc-antigen-positive hepatocytes was significantly lower after treatment, suggesting the involvement of cytolytic mechanisms. In conclusion, combination therapy with peg-IFN and ADV led to marked decreases in serum HBV-DNA and intrahepatic cccDNA, which was significantly correlated with reduced HBsAg.

  1. Extended treatment with pegylated interferon alfa/ribavirin in patients with genotype 2/3 chronic hepatitis C who do not achieve a rapid virological response: final analysis of the randomised N-CORE trial.

    PubMed

    Shiffman, Mitchell L; Cheinquer, Hugo; Berg, Christoph P; Berg, Thomas; de Figueiredo-Mendes, Cláudio; Dore, Gregory J; Ferraz, Maria Lúcia; Mendes-Corrêa, Maria Cássia; Lima, Maria Patelli; Parise, Edison R; Rios, Alma Minerva Perez; Reuter, Tania; Sanyal, Arun J; Shafran, Stephen D; Hohmann, Marc; Tatsch, Fernando; Bakalos, George; Zeuzem, Stefan

    2014-10-01

    The combination of pegylated interferon alfa/ribavirin will likely remain the treatment of choice for HCV genotype 2/3 patients in financially constrained countries for the foreseeable future. Patients with poor on-treatment response may benefit from treatment extension. This study examined the effect of 48 versus 24 weeks of peginterferon alfa-2a/ribavirin on the sustained virological response (SVR) in patients with HCV genotype 2/3 who did not achieve rapid virological response (RVR). N-CORE was a multicentre, randomised, phase III study. HCV genotype 2/3 patients receiving peginterferon alfa-2a/ribavirin without a rapid but with an early virological response were randomised at week 24 to stop treatment (Arm A) or continue to 48 weeks (Arm B). The primary efficacy endpoint was SVR. Two hundred thirty-five patients were enrolled. End of treatment response was similar in both treatment arms. SVR24 rates were not significantly greater in the extended treatment arm compared with the standard 24-week treatment in either the intention-to-treat or the per-protocol populations (61 vs. 52 %, p = 0.1934 and 63 vs. 52 %, p = 0.1461, respectively). Serious adverse events occurred more frequently in patients receiving extended treatment duration (12 %) versus 24-week therapy (4 %). It is unclear whether the extension of peginterferon alfa-2a/ribavirin treatment may benefit HCV genotype 2/3 patients who do not achieve RVR. The study was stopped early because recruitment was slower than anticipated, and this may have limited the statistical impact of these findings.

  2. Peginterferon Alfa-2b (PEG-Intron)

    MedlinePlus

    ... pen with an alcohol pad. Remove the protective paper tab from the injection needle. Keep the injection ... hands thoroughly with soap and water, rinse, and towel dry. Check the expiration date printed on the ...

  3. Reducing Dropouts.

    ERIC Educational Resources Information Center

    Timpane, Michael; And Others

    A group of three conference papers, all addressing the subject of effective programs to decrease the number of school dropouts, is presented in this document. The first paper, "Systemic Approaches to Reducing Dropouts" (Michael Timpane), asserts that dropping out is a symptom of failures in the social, economic, and educational systems.…

  4. Adjuvant interferon therapy for patients with uveal melanoma at high risk of metastasis.

    PubMed

    Lane, Anne Marie; Egan, Kathleen M; Harmon, David; Holbrook, Amy; Munzenrider, John E; Gragoudas, Evangelos S

    2009-11-01

    To examine whether interferon (IFN)-alfa-2a treatment after radiation or enucleation reduces death rates in patients with uveal melanoma. Interventional, comparative case series. Subjects were identified through the ocular oncology clinic of the Massachusetts Eye and Ear Infirmary. Patients eligible for the study were at increased risk of metastasis because of the presence of at least one of the following characteristics: age >or=65 years, largest tumor diameter (LTD) >or=15 mm, ciliary body involvement of the tumor, or extrascleral tumor extension. Between May 1995 and June 1999, 121 patients with choroidal or ciliary body melanoma began a 2-year course of therapy (3 MIU IFN-alfa-2a subcutaneously 3 times per week), initiated within 3 years of primary therapy. All patients underwent regular monitoring for drug toxicity. To evaluate IFN-alfa-2a efficacy, we selected a series of historical controls frequency-matched (2:1) to IFN-alfa-2a-treated patients on age (+/-5 years), LTD (+/-3 mm), gender, and survival time between primary therapy and initiation of IFN therapy. Survival status was ascertained for all patients through December 2006. Melanoma-related mortality, metastasis, IFN-related toxicities. Fifty-five patients (45%) completed therapy; the median dose for IFN-alfa-2a-treated patients was 792 MIU (85% of the theoretic dose). The median follow-up time in the IFN-alfa-2a-treated group was approximately 9 years. Treatment and control groups were similar with respect to age (P = 0.78), LTD (P = 0.38), and gender (P = 1.0). Of 363 patients, 108 developed metastasis under observation; 42 of these were IFN-alfa-2a-treated patients. Cumulative 5-year melanoma-related death rates were 17% in the radiation or enucleation-only group, 15% in those who completed the entire IFN-alfa-2a course, and 35% in those who discontinued IFN-alfa-2a therapy. In multivariate Cox regression, IFN-alfa-2a had no significant influence on melanoma-related mortality (rate ratio = 1.02, 95

  5. Real-World Experiences with the Combination Treatment of Ledipasvir plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon plus Ribavirin with HCV NS3/4A Inhibitors.

    PubMed

    Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Suzuki, Eiichiro; Arai, Makoto; Ooka, Yoshihiko; Ogasawara, Sadahisa; Chiba, Tetsuhiro; Saito, Tomoko; Haga, Yuki; Takahashi, Koji; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Tawada, Akinobu; Maruyama, Hitoshi; Imazeki, Fumio; Kato, Naoya; Yokosuka, Osamu

    2017-04-25

    The aim of this study was to characterize the treatment response and serious adverse events of ledipasvir plus sofosbuvir therapies in Japanese patients infected with hepatitis C virus (HCV) genotype 1 (GT1). This retrospective study analyzed 240 Japanese HCV GT1 patients treated for 12 weeks with 90 mg of ledipasvir plus 400 mg of sofosbuvir daily. Sustained virological response at 12 weeks post-treatment (SVR12) was achieved in 236 of 240 (98.3%) patients. Among treatment-naïve patients, SVR12 was achieved in 136 of 138 (98.6%) patients, and among treatment-experienced patients, SVR12 was achieved in 100 of 102 (98.0%) patients. In patients previously treated with peginterferon plus ribavirin with various HCV NS3/4A inhibitors, 100% SVR rates (25/25) were achieved. Two relapsers had HCV NS5A resistance-associated variants (RAVs), but no HCV NS5B-S282 was observed after they relapsed. We experienced two patients with cardiac events during treatment. In conclusion, combination of ledipasvir plus sofosbuvir for 12 weeks is a potential therapy for HCV GT1 patients. Caution is needed for HCV NS5A RAVs, which were selected by HCV NS5A inhibitors and cardiac adverse events.

  6. Real-World Experiences with the Combination Treatment of Ledipasvir plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon plus Ribavirin with HCV NS3/4A Inhibitors

    PubMed Central

    Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Suzuki, Eiichiro; Arai, Makoto; Ooka, Yoshihiko; Ogasawara, Sadahisa; Chiba, Tetsuhiro; Saito, Tomoko; Haga, Yuki; Takahashi, Koji; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Tawada, Akinobu; Maruyama, Hitoshi; Imazeki, Fumio; Kato, Naoya; Yokosuka, Osamu

    2017-01-01

    The aim of this study was to characterize the treatment response and serious adverse events of ledipasvir plus sofosbuvir therapies in Japanese patients infected with hepatitis C virus (HCV) genotype 1 (GT1). This retrospective study analyzed 240 Japanese HCV GT1 patients treated for 12 weeks with 90 mg of ledipasvir plus 400 mg of sofosbuvir daily. Sustained virological response at 12 weeks post-treatment (SVR12) was achieved in 236 of 240 (98.3%) patients. Among treatment-naïve patients, SVR12 was achieved in 136 of 138 (98.6%) patients, and among treatment-experienced patients, SVR12 was achieved in 100 of 102 (98.0%) patients. In patients previously treated with peginterferon plus ribavirin with various HCV NS3/4A inhibitors, 100% SVR rates (25/25) were achieved. Two relapsers had HCV NS5A resistance-associated variants (RAVs), but no HCV NS5B-S282 was observed after they relapsed. We experienced two patients with cardiac events during treatment. In conclusion, combination of ledipasvir plus sofosbuvir for 12 weeks is a potential therapy for HCV GT1 patients. Caution is needed for HCV NS5A RAVs, which were selected by HCV NS5A inhibitors and cardiac adverse events. PMID:28441362

  7. Work productivity among treatment-naïve patients with genotype 1 chronic hepatitis C infection receiving telaprevir combination treatment.

    PubMed

    Aggarwal, J; Vera-Llonch, M; Donepudi, M; Suthoff, E; Younossi, Z; Goss, T F

    2015-01-01

    Work productivity is impacted in hepatitis C virus (HCV)-infected patients and has been linked to treatment. In two Phase 3 trials, ADVANCE and ILLUMINATE, treatment-naïve genotype 1 chronic HCV-infected patients received 12-week telaprevir (T) with 24 (T12PR24)- or 48 (T12PR48)-week peginterferon alfa-2a/ribavirin. The objective of this analysis was to examine the impact of chronic HCV infection and its treatment with combination therapy on work productivity. The 5-item, self-reported work productivity questionnaire (WPQ) was administered in Phase 3 trials to assess unemployment status, days unable to work due to HCV/treatment, reduced hours worked and impact on productivity in prior 4 weeks. Descriptive statistics and multivariate regression analyses were employed in analyses of pooled trial data. About 1147 patients were included; 22% (n = 255) were unemployed at baseline, with 8% being unemployed due to health reasons. At week 12, there were no differences by treatment regimen in the number of days unable to work. At week 48, improvements were observed earlier among patients receiving the shorter duration of T combination treatment. Mean (95% CI) change from baseline in days unable to work was -0.48 (-0.85, -0.11) days for T12PR24, 1.43 (0.63, 2.24) days for T12PR48 and 1.24 (0.18, 2.30) days for PR48 with placebo. Predictors of days unable to work were identified and include demographic characteristics, pretreatment and on-treatment levels of fatigue, as well regional variation. In post hoc analyses of the ADVANCE and ILLUMINATE trials, work productivity decreased during the initial 12 weeks regardless of treatment group. © 2014 John Wiley & Sons Ltd.

  8. Baseline factors associated with treatment response in patients infected with hepatitis C virus 1b by stratification of IL28B polymorphisms.

    PubMed

    Ling, Qihua; Chen, Jianjie; Zhou, Hua; Zhong, Jun; Chen, Yiyun; Ye, Qingyan; Zhuo, Yunhui; Min, Niehong; Shang, Binyi

    2015-04-01

    Although the single-nucleotide polymorphism (SNP) rs12979860 in the IL28B gene is a better predictor of sustained virological response to treatment of chronic hepatitis C (CHC) than other baseline factors, some CHC patients with the favorable C allele cannot achieve a sustained virological response when treated with peginterferon plus ribavirin. The aim of this study was to examine baseline factors as predictors of rapid virological response (RVR) and complete early virological response (cEVR) to peginterferon alfa-2a plus ribavirin treatment in Chinese CHC patients with hepatitis C virus (HCV) genotype 1b, with emphasis on the difference between the rs129860 CC and CT/TT genotypes. A total of 337 treatment-naïve patients participated in this study. All patients were treated with peginterferon alfa-2a plus ribavirin at standard dosage. Serum samples from all patients were collected at baseline, week 4, and week 12 for testing of laboratory parameters, and IL28B genotypes were determined. Multivariate analysis showed that among rs12979860 CC genotype patients, glucose level and aspartate amino transferase (AST) activity were inversely associated with RVR, while abnormal platelet count and allergy inversely associated with cEVR. Among rs12979860 CT genotype patients, age below 40 years and short infection duration were associated with RVR, while age below 40 years, short infection duration, high body mass index (BMI), and no history of allergies were associated with cEVR. The baseline factors associated with the response to CHC treatment may depend on the IL28B genotype. Refinement of the baseline predictors based on IL28B genotypes may be useful for management of HCV infection.

  9. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-11-01

    1-Octanol, 9vPnC-MnCc; Abiraterone acetate, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, Aminolevulinic acid hexyl ester, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, Aripiprazole, ARRY-520, AS-1404, Asimadoline, Atazanavir sulfate, AVE-0277, Azelnidipine; Bevacizumab, Bimatoprost, Boceprevir, Bortezomib, Bosentan, Botulinum toxin type B; Certolizumab pegol, Cetuximab, Clevudine, Contusugene ladenovec, CP-751871, Crofelemer, Cypher, CYT006-AngQb; Darbepoetin alfa, Desmopressin, Dexlansoprazole, DG-041; E-5555, Ecogramostim, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Falecalcitriol, Fampridine, Fesoterodine fumarate, Fingolimod hydrochloride; Gefitinib, Ghrelin (human), GS-7904L, GV-1001; HT-1001; Insulin detemir, ISIS-112989, Istradefylline; Laquinimod sodium, Latanoprost/timolol maleate, Lenalidomide, Levobetaxolol hydrochloride, Liposomal doxorubicin, Liposomal morphine sulfate, Lubiprostone, Lumiracoxib, LY-518674; MEM-1003, Mesna disulfide, Mipomersen sodium, MM-093, Mycophenolic acid sodium salt; Naptumomab estafenatox, Natalizumab; Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paclitaxel nanoparticles, Paclitaxel poliglumex, Pasireotide, Pazufloxacin mesilate, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimagedine, Pimecrolimus, Pramlintide acetate, Prasterone, Pregabalin, Prulifloxacin; QAE-397; Rec-15/2615, RFB4(dsFv)-PE38, rhGAD65, Roflumilast, Romiplostim, Rosuvastatin calcium, Rotigotine, Rupatadine fumarate; Safinamide mesilate, SIR-Spheres, Sitagliptin phosphate, Sodium phenylacetate, Sodium phenylacetate/Sodium benzoate, Sorafenib, SSR-244738; Taribavirin hydrochloride, Taxus, Teduglutide, Tegaserod maleate, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tigecycline, Tiotropium bromide, Trabectedin, Travoprost

  10. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-10-01

    [Methoxy-11c]PD-153035; Afamelanotide, Agalsidase beta, Alemtuzumab, Alkaline phosphatase, Amlodipine, Anecortave acetate, Apixaban, Aripiprazole, Atomoxetine hydrochloride; Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brimonidine tartrate/timolol maleate, Brivudine; Canakinumab, Cetuximab, Chlorotoxin, Cinaciguat; Dapagliflozin, Decitabine, Duloxetine hydrochloride; Elagolix sodium, Eplerenone, Eritoran tetrasodium, Escitalopram oxalate, Etoricoxib, Ezetimibe; Fospropofol disodium; G-207, Gabapentin enacarbil, Gefitinib, Golimumab; Human plasmin; Inotuzumab ozogamicin, Insulin glargine, Insulin glulisine, Istaroxime, Ixabepilone; KLH; Levodopa/carbidopa/entacapone; Miglustat, Mitumprotimut-T, MP-470; Oblimersen sodium, Olmesartan medoxomil; P53-SLP, PAN-811, Patupilone, Pazopanib hydrochloride, PC-515, Peginterferon alfa-2a, Pegylated arginine deiminase 20000, Pemetrexed disodium, Plitidepsin, Pregabalin; Rasagiline mesilate, Rotigotine; SCH-697243, Sirolimus-eluting stent, Sumatriptan succinate/naproxen sodium, Sunitinib malate; Tadalafil, Tapentadol hydrochloride, TMC-207; V-211, Valganciclovir hydrochloride; Zolpidem tartrate. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

  11. Reduce HIV Risk

    MedlinePlus

    ... incidence could be reduced if people changed their sexual behaviors. Our research has demonstrated remarkable success in reducing HIV risk-associated sexual behaviors among African American adolescents and adults." Spring 2008 ...

  12. A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: 2015 Update.

    PubMed

    Martin, Paul; Lau, Daryl T-Y; Nguyen, Mindie H; Janssen, Harry L A; Dieterich, Douglas T; Peters, Marion G; Jacobson, Ira M

    2015-11-01

    Chronic hepatitis B (CHB) continues to be an important public health problem worldwide, including in the United States. An algorithm for managing CHB was developed by a panel of United States hepatologists in 2004 and subsequently updated in 2006 and 2008. Since 2008, additional data on long-term safety and efficacy of licensed therapies have become available and have better defined therapeutic options for CHB. The evidence indicates that potent antiviral therapy can lead to regression of extensive fibrosis or even cirrhosis, thus potentially altering the natural history of CHB. In addition, appropriate choice of antiviral agent can minimize the risk of resistance. This updated algorithm for managing CHB is based primarily on evidence from the scientific literature. Where data were lacking, the panel relied on clinical experience and consensus expert opinion. The primary aim of antiviral therapy for CHB is durable suppression of serum hepatitis B virus (HBV) DNA to low or undetectable levels. CHB patients who have HBV DNA >2000 IU/mL, elevated alanine aminotransferase level, and any degree of fibrosis should receive antiviral therapy regardless of their hepatitis B e antigen status. CHB patients with HBV DNA >2000 IU/mL and elevated alanine aminotransferase level but no evidence of fibrosis may also be considered for antiviral therapy. Approved antiviral therapies for CHB are interferon alfa-2b, peginterferon alfa-2a, lamivudine, adefovir, entecavir, telbivudine, and tenofovir, although the preferred first-line treatment choices are peginterferon alfa-2a, entecavir, and tenofovir. In determining choice of therapy, considerations include efficacy, safety, rate of resistance, method of administration, duration, and cost. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. Plating under reduced pressure

    SciTech Connect

    Dini, J.W.; Beat, T.G.; Cowden, W.C. ); Ryan, L.E.; Hewitt, W.B. )

    1992-06-01

    Plating under reduced pressure was evaluated for both electroless nickel and electrodeposited copper systems. The objective was to reduce pitting of these coatings thereby further enhancing their usage for diamond turning applications. Cursory experiments with electroless nickel showed reduced porosity when deposition was done at around 500 torr. Detailed experiments with electrodeposited copper at around 100 torr provided similar results. Scanning tunneling microscopy was effectively used to show the improvement in the copper deposits plated under reduced pressure. Benefits included reduced surface roughness and finer and denser grain structure.

  14. Reducing Teacher Incompetence.

    ERIC Educational Resources Information Center

    Rich, John Martin

    1988-01-01

    Suggests how administrators may reduce teacher incompetence. Teacher incompetence can be reduced if administrators fully understand and undertake appropriate preventive and remedial measures. Two sections comprise this article. First, a taxonomy of teacher incompetence reveals the magnitude of the problem. Second, preventive and remedial measures…

  15. Reducible oxide based catalysts

    DOEpatents

    Thompson, Levi T.; Kim, Chang Hwan; Bej, Shyamal K.

    2010-04-06

    A catalyst is disclosed herein. The catalyst includes a reducible oxide support and at least one noble metal fixed on the reducible oxide support. The noble metal(s) is loaded on the support at a substantially constant temperature and pH.

  16. Reducing Childhood Obesity

    MedlinePlus

    ... Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... Ga. were the first three We Can! cities. Obesity Research: A New Approach The percentage of children ...

  17. Reduced shear power spectrum

    SciTech Connect

    Dodelson, Scott; Shapiro, Charles; White, Martin J.; /UC, Berkeley, Astron. Dept. /UC, Berkeley

    2005-08-01

    Measurements of ellipticities of background galaxies are sensitive to the reduced shear, the cosmic shear divided by (1-{kappa}) where {kappa} is the projected density field. They compute the difference between shear and reduced shear both analytically and with simulations. The difference becomes more important an smaller scales, and will impact cosmological parameter estimation from upcoming experiments. A simple recipe is presented to carry out the required correction.

  18. Reduced Magmatic Volatiles

    NASA Astrophysics Data System (ADS)

    Hirschmann, M. M.; Withers, A. C.; Ardia, P.; Stanley, B. D.; Foley, N.

    2012-12-01

    Volatiles in Earth's upper mantle are dominated by H2O and CO2, but under more reduced conditions likely deeper in the mantle, other volatile species may be important or dominant. However, the speciation, solubilities, and effect on physical properties of reduced magmatic volatiles are poorly constrained. Here we summarize results from an experimental campaign to better understand reduced volatiles in magmas. Experiments emphasize spectroscopic and SIMS characterization of dissolved species in experiments for which fluid fugacities are known, thereby facilitating thermodynamic parameterization. Experimental determinations of molecular H2 solubility in basaltic and andesitic liquids show concentrations that are proportional to H2 fugacity. Because H2 increases with fH2 whereas dissolved H2O increases with fH2O1/2, the relative importance of H2 increases with pressure and for more hydrous magmas. At 1 GPa and IW-1, solubility in basalt reaches 0.3 wt.% (equivalent to 2.7 wt.% H2O). Solubilities at pressures of the deep upper mantle have not been explored experimentally (as is also true for H2O and CO2), but H2 could become the dominant hydrous species at 400 km and deeper, and so deep hydrous melts may have chiefly H2 rather than H2O or OH. Experiments suggest an extremely low partial specific density (0.18 kg/m3) for dissolved H2 at low pressure, and so appreciable dissolved H2 in melt atop the 410 km discontinuity or in the lower mantle may promote positive buoyancy. Solubilities of reduced C-species remain poorly known. In contrast to results in Na2O-SiO2 liquids (Mysen et al., 2009), experiments with a haplobasaltic liquid at controlled CH4 fugacities indicated very small (<0.05 wt.%) CH4 solubilities even at very reduced conditions (reduced conditions and in

  19. Reduce FCCU fouling

    SciTech Connect

    Barlow, R.C.

    1986-07-01

    Fouling of equipment in fluid catalytic cracking units can significantly affect unit operation by reducing the necessary transfer of heat in heat exchangers, by restricting unit thruput due to increased pressure drop and, in general, by reducing the overall operating efficiency of the production unit. A loss in heat transfer can result in increased fuel costs to operate the unit or may affect product separation when the lost heat cannot be replaced by other means. The physical restriction of flow can cause production limitations due to increased pressure drop in the system. Pumparound or recycle stream flows may have to be reduced, which will affect heat recovery and product separation. Pluggage in the separation towers can also restrict necessary separation efficiencies and subsequent product separation. The overall unit performance can be adversely affected, even when the flexibility of unit operations exists to compensate for the effects of fouling.

  20. Tank closure reducing grout

    SciTech Connect

    Caldwell, T.B.

    1997-04-18

    A reducing grout has been developed for closing high level waste tanks at the Savannah River Site in Aiken, South Carolina. The grout has a low redox potential, which minimizes the mobility of Sr{sup 90}, the radionuclide with the highest dose potential after closure. The grout also has a high pH which reduces the solubility of the plutonium isotopes. The grout has a high compressive strength and low permeability, which enhances its ability to limit the migration of contaminants after closure. The grout was designed and tested by Construction Technology Laboratories, Inc. Placement methods were developed by the Savannah River Site personnel.

  1. Reduced Vector Preisach Model

    NASA Technical Reports Server (NTRS)

    Patel, Umesh D.; Torre, Edward Della; Day, John H. (Technical Monitor)

    2002-01-01

    A new vector Preisach model, called the Reduced Vector Preisach model (RVPM), was developed for fast computations. This model, derived from the Simplified Vector Preisach model (SVPM), has individual components that like the SVPM are calculated independently using coupled selection rules for the state vector computation. However, the RVPM does not require the rotational correction. Therefore, it provides a practical alternative for computing the magnetic susceptibility using a differential approach. A vector version, using the framework of the DOK model, is implemented. Simulation results for the reduced vector Preisach model are also presented.

  2. Reduce olefin plant fouling

    SciTech Connect

    Martin, J.F. )

    1988-11-01

    Process-side fouling reduces the overall operating efficiency of an olefin plant. The fouling is commonly caused by the formation of organic polymers which also can contain small amounts of inorganic constituents. The fouling is measured reduced if a properly selected antifoulant is used. Specific equipment and areas of the plant affected by process fouling are listed. The fouling tendency in each area is related to the pyrolysis furnace charge and unit operating conditions. To a lesser extent, the design of the plant will dictate which process equipment will experience fouling.

  3. Please Reduce Cycle Time

    DTIC Science & Technology

    2014-12-01

    Defense AT&L: November–December 2014 4 Please Reduce Cycle Time Brian Schultz “Time is what we want most but what we use worst.” — William Penn ...Schultz is a professor of program management at the Defense Acquisition University’s Mid-Atlantic Region in California, Md. As William Penn noted

  4. Demonstrating Reduced Gravity

    NASA Technical Reports Server (NTRS)

    Pearlman, Howard; Stocker, Dennis; Gotti, Daniel; Urban, David; Ross, Howard; Sours, Thomas

    1996-01-01

    A miniature drop tower, Reduced-Gravity Demonstrator is developed to illustrate the effects of gravity on a variety of phenomena including the way fluids flow, flames burn, and mechanical systems (such as pendulum) behave. A schematic and description of the demonstrator and payloads are given, followed by suggestions for how one can build his (her) own.

  5. Reduced journal rates

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    The American Institute of Physics (AIP) offers reduced rates for subscriptions to its journals to individual members of affiliated societies, including AGU. The offer is limited to one subscription per person to each journal.Rates for 1985 for AGU members are listed below

  6. Reducing Behavior through Reinforcement.

    ERIC Educational Resources Information Center

    Deitz, Diane E. D.; Repp, Alan C.

    1983-01-01

    The use of reinforcement to reduce inappropriate behaviors of mentally retarded and emotionally disturbed students may involve the following procedures: differential reinforcement of low rates of responding (DRL), the differential reinforcement of response omission (DRO), and the differential reinforcement of incompatible (DRI) or alternative…

  7. Reduced Braginskii equations

    SciTech Connect

    Yagi, M.; Horton, W. )

    1994-07-01

    A set of reduced Braginskii equations is derived without assuming flute ordering and the Boussinesq approximation. These model equations conserve the physical energy. It is crucial at finite [beta] that the perpendicular component of Ohm's law be solved to ensure [del][center dot][bold j]=0 for energy conservation.

  8. Reuse, Reduce, Recycle.

    ERIC Educational Resources Information Center

    Briscoe, Georgia

    1991-01-01

    Discussion of recycling paper in law libraries is also applicable to other types of libraries. Results of surveys of law libraries that investigated recycling practices in 1987 and again in 1990 are reported, and suggestions for reducing the amount of paper used and reusing as much as possible are offered. (LRW)

  9. Reduced Braginskii equations

    SciTech Connect

    Yagi, M.; Horton, W.

    1993-11-01

    A set of reduced Braginskii equations is derived without assuming flute ordering and the Boussinesq approximation. These model equations conserve the physical energy. It is crucial at finite {beta} that we solve the perpendicular component of Ohm`s law to conserve the physical energy while ensuring the relation {del} {center_dot} j = 0.

  10. Reduce FCC corrosion

    SciTech Connect

    Walker, H.B.

    1984-01-01

    Efficiency of fluid catalytic cracking (FCC) vapor recovery units can be significantly reduced by corrosion and fouling. The fundamentals of FCC light ends corrosion, including diagnoses, control and monitoring of hydrogen blistering, general metal loss, pitting, erosion and under-deposit attack are discussed, relating actual unit problems to effective treatment program solutions.

  11. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-09-01

    Aclidinium bromide, AE-37, Alemtuzumab, AMA1-C1/ISA 720, Amlodipine besylate/atorvastatin calcium, Arachidonic acid, Arbaclofen placarbil, Aripiprazole, ARQ-621, Azelnidipine, Azilsartan medoxomil potassium; Bevacizumab, Biphasic insulin aspart, Bortezomib; Choriogonadotropin alfa, CTS-1027; Dapagliflozin, Dasatinib, Deforolimus, Degarelix acetate, Denufosol tetrasodium, Desvenlafaxine succinate, Dronedarone hydrochloride, Duloxetine hydrochloride, Dutasteride; Enfuvirtide, Entecavir, Etaracizumab, Everolimus, Exenatide, Ezetimibe; Ferric carboxymaltose, Fludarabine, Foretinib; Gefitinib, GFT-505, GSK-256066; HPV-6/11/16/18, HuM195/rGel, HyperAcute-Lung cancer vaccine; I5NP, Imatinib mesylate, Imexon, Insulin detemir, Insulin glargine, Ivabradine hydrochloride; L2G7, Lacosamide, Lapatinib ditosylate, Lenalidomide, Lidocaine/prilocaine, Liposomal vincristine, Liraglutide, Lixivaptan; Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine, Methoxy polyethylene glycol-epoetin-β, Mirabegron, Morphine/oxycodone, MR Vaccine, MSC-1936369B, Mycophenolic acid sodium salt; Narlaprevir, N-Desmethylclozapine; Ocriplasmin, Olaparib, Olmesartan medoxomil, Olmesartan medoxomil/azelnidipine, ONO-5334, ONO-8539; Palifermin, Panitumumab, Pardoprunox hydrochloride, PCV7, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pexelizumab, PF-337210, Pitavastatin calcium; Raltegravir potassium, Recombinant interleukin-7, Regadenoson, Reniale, Roflumilast, Rosuvastatin calcium; Safinamide mesilate, SB-1518, SCH-527123, Selumetinib, Sipuleucel-T, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talaporfin sodium, Tanespimycin, Technosphere/Insulin, Telaprevir, Telatinib, Telcagepant, Telmisartan/hydrochlorothiazide, Teriparatide, Testosterone transdermal gel, TH-302, Tiotropium bromide, Tocilizumab, Trabedersen, Tremelimumab; Valsartan/amlodipine besylate, Vernakalant hydrochloride, Visilizumab, Voreloxin, Vorinostat.

  12. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2003-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 2F5, 2G12, abetimus sodium, ABI-007, adalimumab, adefovir dipivoxil, AE-941, alefacept, altropane, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminopterin, anakinra, aprinocarsen sodium, atazanavir, atlizumab, atomoxetine hydrochloride; B7-1 vaccine, bevacizumab, biricodar dicitrate, BMS-188667, brasofensine sulfate, bryostatin 1; cantuzumab mertansine, CHS-828, cinacalcet hydrochloride, cipamfylline, creatine, CVT-3146; darbepoetin alfa, DITPA, drotrecogin alfa (activated), duloxetine hydrochloride; edatrexate, efalizumab, ENMD-0997, epoetin, erlosamide, esomeprazole magnesium, etiprednol dicloacetate, etoricoxib, everolimus, ezetimibe; fampridine, fenretinide, FTY-720; IGF-I/IGFBP-3, IL-1 cytokine trap, ilodecakin, interferon beta, ISIS-104838, ISIS-2503, ISIS-5132, ivabradine hydrochloride; lafutidine, lanthanum carbonate, l-Arginine hydrochloride, LEA29Y, lerdelimumab, levetiracetam, levobupivacaine hydrochloride, levosimendan, lopinavir; melagatran, mibefradil hydrochloride, miglustat, morphine-6-glucuronide; nesiritide; omalizumab, omapatrilat; p24-VLP, parecoxib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pitavastatin calcium, plevitrexed, prasterone, pregabalin, PRO-2000, prucalopride; rapacuronium bromide, rebimastat, RGA-0853, rubitecan, ruboxistaurin mesilate hydrate, RWJ-67657; S-16020-2, sarizotan, SLV-306, stiripentol; TA-CIN, tenecteplase, teriparatide, tezacitabine, tipifarnib, trabectedin, troglitazone; valdecoxib, vardenafil; Z-338, ziconotide.

  13. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate. Copyright 2005 Prous Science. All rights reserved.

  14. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-06-01

    (+)-Dapoxetine hydrochloride; Abatacept, Adalimumab, Agalsidase beta, Alemtuzumab, Alglucosidase alfa, Aliskiren fumarate, Ambrisentan, Amlodipine, Aripiprazole, Atrasentan, Azacitidine, Azelnidipine; Belotecan hydrochloride, Bevacizumab, Bilastine, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, CG-100649, Cinacalcet hydrochloride, Clindamycin phosphate/ benzoyl peroxide; Dasatinib, Denosumab, Duloxetine hydrochloride, Dutasteride, Dutasteride/tamsulosin; Ecogramostim, Eculizumab, Eltrombopag olamine, EndoTAG-1, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe; FAHF-2, Fondaparinux sodium; Gefitinib, Golimumab; HEV-239, HSV-TK; Imatinib mesylate, Indium 111 ((111)In) ibritumomab tiuxetan, Influenza vaccine(surface antigen, inactivated, prepared in cell culture), Insulin glargine; Kisspeptin-54; Lidocaine/prilocaine, Lomitapide; Maraviroc, Mirodenafil hydrochloride, MK-8141, MVA-Ag85A; Nilotinib hydrochloride monohydrate; Olmesartan medoxomil; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pitavastatin calcium, Prasugrel; Recombinant human relaxin H2, RHAMM R3 peptide, Rivaroxaban, Rosuvastatin calcium, RRz2; Sagopilone, Salinosporamide A, SB-509, Serlopitant, Sirolimus-eluting stent, Sorafenib, Sunitinib malate; Tadalafil, Temsirolimus, Teriparatide, TG-4010, Tositumomab/iodine (I131) tositumomab; Velusetrag Hydrochloride; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

  15. Reducing rotor weight

    SciTech Connect

    Cheney, M.C.

    1997-12-31

    The cost of energy for renewables has gained greater significance in recent years due to the drop in price in some competing energy sources, particularly natural gas. In pursuit of lower manufacturing costs for wind turbine systems, work was conducted to explore an innovative rotor designed to reduce weight and cost over conventional rotor systems. Trade-off studies were conducted to measure the influence of number of blades, stiffness, and manufacturing method on COE. The study showed that increasing number of blades at constant solidity significantly reduced rotor weight and that manufacturing the blades using pultrusion technology produced the lowest cost per pound. Under contracts with the National Renewable Energy Laboratory and the California Energy Commission, a 400 kW (33m diameter) turbine was designed employing this technology. The project included tests of an 80 kW (15.5m diameter) dynamically scaled rotor which demonstrated the viability of the design.

  16. Reducing float coal dust

    PubMed Central

    Patts, J.R.; Colinet, J.F.; Janisko, S.J.; Barone, T.L.; Patts, L.D.

    2016-01-01

    Controlling float coal dust in underground coal mines before dispersal into the general airstream can reduce the risk of mine explosions while potentially achieving a more effective and efficient use of rock dust. A prototype flooded-bed scrubber was evaluated for float coal dust control in the return of a continuous miner section. The scrubber was installed inline between the face ventilation tubing and an exhausting auxiliary fan. Airborne and deposited dust mass measurements were collected over three days at set distances from the fan exhaust to assess changes in float coal dust levels in the return due to operation of the scrubber. Mass-based measurements were collected on a per-cut basis and normalized on the basis of per ton mined by the continuous miner. The results show that average float coal dust levels measured under baseline conditions were reduced by more than 90 percent when operating the scrubber. PMID:28018004

  17. Reducing health inequalities.

    PubMed

    Mason, Christine

    2017-08-23

    What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The article outlined the health inequalities that people with serious mental illness (SMI) may experience. It acknowledged the barriers they often encounter in accessing healthcare services, and discussed how lifestyle behaviours, symptoms of mental illness and the side effects of medication can contribute to reduced life expectancy.

  18. Reducing Spreadsheet Errors

    DTIC Science & Technology

    2009-09-01

    Basic for Applications ( VBA ) to improve spreadsheets. Program- ming and coding portions of a spreadsheet in VBA (especially iteration) can reduce...effort as well as errors. Users unfamiliar with VBA may begin learning by “recording macros” in Excel. Microsoft’s online tutorials...www.office.microsoft.com/en-us/excel) provide overviews of this and other VBA capabilities. 5) Thorough documentation of spreadsheet development and application is

  19. Reducing teenage pregnancy.

    PubMed

    Fallon, Debbie

    2011-03-01

    The Teenage Pregnancy Independent Advisory Group (TPIAG) was established in 2000 to advise the government about reducing teenage pregnancy rates and supporting teenage parents to continue with their education. The group reached the end of its tenure in December 2010. This short article highlights some of the key issues from the final report and provides some insights into past achievements and future directions from an interview with Gill Frances, TPIAG's chair.

  20. Naval electrochemical corrosion reducer

    DOEpatents

    Clark, Howard L.

    1991-10-01

    A corrosion reducer for use with ships having a hull, a propeller mounted a propeller shaft and extending through the hull, bearings supporting the shaft, at least one thrust bearing and one seal. The improvement includes a current collector and a current reduction assembly for reducing the voltage between the hull and shaft in order to reduce corrosion due to electrolytic action. The current reduction assembly includes an electrical contact, the current collector, and the hull. The current reduction assembly further includes a device for sensing and measuring the voltage between the hull and the shaft and a device for applying a reverse voltage between the hull and the shaft so that the resulting voltage differential is from 0 to 0.05 volts. The current reduction assembly further includes a differential amplifier having a voltage differential between the hull and the shaft. The current reduction assembly further includes an amplifier and a power output circuit receiving signals from the differential amplifier and being supplied by at least one current supply. The current selector includes a brush assembly in contact with a slip ring over the shaft so that its potential may be applied to the differential amplifier.

  1. Reducing Iatrogenic Risks

    PubMed Central

    Ely, E. Wesley; Speroff, Theodore; Pun, Brenda T.; Boehm, Leanne; Dittus, Robert S.

    2010-01-01

    ICUs are experiencing an epidemic of patients with acute brain dysfunction (delirium) and weakness, both associated with increased mortality and long-term disability. These conditions are commonly acquired in the ICU and are often initiated or exacerbated by sedation and ventilation decisions and management. Despite > 10 years of evidence revealing the hazards of delirium, the quality chasm between current and ideal processes of care continues to exist. Monitoring of delirium and sedation levels remains inconsistent. In addition, sedation, ventilation, and physical therapy practices proven successful at reducing the frequency and severity of adverse outcomes are not routinely practiced. In this article, we advocate for the adoption and implementation of a standard bundle of ICU measures with great potential to reduce the burden of ICU-acquired delirium and weakness. Individual components of this bundle are evidence based and can help standardize communication, improve interdisciplinary care, reduce mortality, and improve cognitive and functional outcomes. We refer to this as the “ABCDE bundle,” for awakening and breathing coordination, delirium monitoring, and exercise/early mobility. This evidence-based bundle of practices will build a bridge across the current quality chasm from the “front end” to the “back end” of critical care and toward improved cognitive and functional outcomes for ICU survivors. PMID:21051398

  2. Reducing Radiation Damage

    SciTech Connect

    Blankenbecler, Richard

    2006-06-05

    This talk describes the use of a modified treatment sequence, i.e., radiation dose, geometry, dwell time, etc., to mitigate some of the deleterious effects of cancer radiotherapy by utilizing natural cell repair processes. If bad side effects can be reduced, a more aggressive therapy can be put into place. Cells contain many mechanisms that repair damage of various types. If the damage can not be repaired, cells will undergo apoptosis (cell death). Data will be reviewed that support the fact that a small dose of radiation will activate damage repair genes within a cell. Once the mechanisms are fully active, they will efficiently repair the severe damage from a much larger radiation dose. The data ranges from experiments on specific cell cultures using microarray (gene chip) techniques to experiments on complete organisms. The suggested effect and treatment is consistent with the assumption that all radiation is harmful, no matter how small the dose. Nevertheless, the harm can be reduced. These mechanisms need to be further studied and characterized. In particular, their time dependence needs to be understood before the proposed treatment can be optimized. Under certain situations it is also possible that the deleterious effects of chemotherapy can be mitigated and the damage to radiation workers can be reduced.

  3. Gradual extinction reduces reinstatement

    PubMed Central

    Shiban, Youssef; Wittmann, Jasmin; Weißinger, Mara; Mühlberger, Andreas

    2015-01-01

    The current study investigated whether gradually reducing the frequency of aversive stimuli during extinction can prevent the return of fear. Thirty-one participants of a three-stage procedure (acquisition, extinction and a reinstatement test on day 2) were randomly assigned to a standard extinction (SE) and gradual extinction (GE) procedure. The two groups differed only in the extinction procedure. While the SE group ran through a regular extinction process without any negative events, the frequency of the aversive stimuli during the extinction phase was gradually reduced for the GE group. The unconditioned stimulus (US) was an air blast (5 bar, 10 ms). A spider and a scorpion were used as conditioned stimuli (CS). The outcome variables were contingency ratings and physiological measures (skin conductance response, SCR and startle response). There were no differences found between the two groups for the acquisition and extinction phases concerning contingency ratings, SCR, or startle response. GE compared to SE significantly reduced the return of fear in the reinstatement test for the startle response but not for SCR or contingency ratings. This study was successful in translating the findings in rodent to humans. The results suggest that the GE process is suitable for increasing the efficacy of fear extinction. PMID:26441581

  4. Reducing risk in smokers.

    PubMed

    Westmaas, J Lee; Brandon, Thomas H

    2004-07-01

    Tobacco smoking is a leading cause of lung cancer and chronic obstructive pulmonary disease. For smokers who want to quit, nicotine replacement therapy and bupropion are frequently recommended. Currently, disagreement surrounds the extent of risk reduction from quitting, the consequences of the change of nicotine replacement therapy to over-the-counter status, and the safety and efficacy of new tobacco products being marketed by tobacco companies. This article reviews the current evidence relevant to these and other developments in smoking interventions and describes the most effective strategies that smokers can use to reduce their risk. Although it may take approximately 10 to 30 years of abstinence for former smokers' risk of lung cancer to reach that of never smokers, quitting at any time is substantially less risky than continuing to smoke. Quitting after diagnosis also prolongs survival. Bupropion and nicotine replacement therapy are effective pharmacotherapies, doubling quit rates compared with self-quitting. However, many users of over-the-counter nicotine replacement therapy are using it inappropriately. More research is needed to determine the long-term health effects of modified tobacco products and their efficacy in helping smokers quit. Switching to "low tar" filter cigarettes to reduce lung cancer risk, however, is clearly ineffective. The most effective interventions for quitting continue to be a combination of behavioral and pharmacologic approaches. Health care practitioners should encourage all smokers to attempt cessation and emphasize pharmacotherapy as an important aid to quitting. Professionals who educate patients on the appropriate use of pharmacotherapy and follow-up on smokers' attempts to quit will help reduce the societal burden and personal risks of smoking.

  5. Coating Reduces Ice Adhesion

    NASA Technical Reports Server (NTRS)

    Smith, Trent; Prince, Michael; DwWeese, Charles; Curtis, Leslie

    2008-01-01

    The Shuttle Ice Liberation Coating (SILC) has been developed to reduce the adhesion of ice to surfaces on the space shuttle. SILC, when coated on a surface (foam, metal, epoxy primer, polymer surfaces), will reduce the adhesion of ice by as much as 90 percent as compared to the corresponding uncoated surface. This innovation is a durable coating that can withstand several cycles of ice growth and removal without loss of anti-adhesion properties. SILC is made of a binder composed of varying weight percents of siloxane(s), ethyl alcohol, ethyl sulfate, isopropyl alcohol, and of fine-particle polytetrafluoroethylene (PTFE). The combination of these components produces a coating with significantly improved weathering characteristics over the siloxane system alone. In some cases, the coating will delay ice formation and can reduce the amount of ice formed. SILC is not an ice prevention coating, but the very high water contact angle (greater than 140 ) causes water to readily run off the surface. This coating was designed for use at temperatures near -170 F (-112 C). Ice adhesion tests performed at temperatures from -170 to 20 F (-112 to -7 C) show that SILC is a very effective ice release coating. SILC can be left as applied (opaque) or buffed off until the surface appears clear. Energy dispersive spectroscopy (EDS) and x-ray photoelectron spectroscopy (XPS) data show that the coating is still present after buffing to transparency. This means SILC can be used to prevent ice adhesion even when coating windows or other objects, or items that require transmission of optical light. Car windshields are kept cleaner and SILC effectively mitigates rain and snow under driving conditions.

  6. Modelling reduced sparse data

    NASA Astrophysics Data System (ADS)

    Kozera, Ryszard; Noakes, Lyle

    2016-09-01

    In this paper we discuss the problem of fitting to an ordered collection of points in arbitary Euclidean space called reduced data. We are not given here the corresponding interpolation knots. Instead, these are estimated by new knots upon minimizing a relevant highly nonlinear optimization scheme based on natural spline interpolation. The existence of a global minimizer (i.e. the collection of interpolation knots in ascending order) is also addressed in this paper. Finally, Leap-Frog optimization tool is used to compute these knots approximating the unknown interpolation knots. This numerical scheme is subsequently compared with the Secant Method. Two illustrative examples are given.

  7. Nonlinearity-reduced interferometer

    NASA Astrophysics Data System (ADS)

    Wu, Chien-ming

    2007-12-01

    Periodic nonlinearity is a systematic error limiting the accuracy of displacement measurements at the nanometer level. It results from many causes such as the frequency mixing, polarization mixing, polarization-frequency mixing, and the ghost reflections. An interferometer having accuracy in displacement measurement of less than one-nanometer is necessary in nanometrology. To meet the requirement, the periodic nonlinearity should be less than deep sub-nanometer. In this paper, a nonlinearity-reduced interferometry has been proposed. Both the linear- and straightness-interferometer were tested. The developed interferometer demonstrated of a residual nonlinearity less than 25 pm.

  8. Skin-reducing mastectomy.

    PubMed

    Nava, Maurizio B; Cortinovis, Umberto; Ottolenghi, Joseph; Riggio, Egidio; Pennati, Angela; Catanuto, Giuseppe; Greco, Marco; Rovere, Guidubaldo Querci Della

    2006-09-01

    The authors propose a combined flap technique to reconstruct large and medium-sized ptotic breasts in a single-stage operation by use of anatomical permanent implants. The authors enrolled 28 patients fulfilling criteria for skin-sparing mastectomy and presenting with ptotic breasts whose areola-to-inframammary fold distance was more than 8 cm. All reconstructions were performed as a single-stage procedure. After preoperative planning, a large area in the lower half of the breast was deepithelialized according to the conventional Wise pattern. Mastectomy was then carried out. To perform reconstructions, the inferomedial fibers of the pectoralis major muscle were dissected and sutured to the superior border of the inferior dermal flap. An anatomical implant was then inserted into the pouch, which was closed laterally with the previously harvested serratus anterior fascia. Skin flaps were finally closed down to the inframammary fold. The authors performed 30 procedures on 28 patients. The medium size anatomical implants was 433 cc. Twelve women achieved symmetrization in a single stage ending in a symmetric inverted-T scar. The overall complication rate was 20 percent, with four cases (13 percent) complicated by severe, extensive necrosis of the skin flaps requiring implant removal. Breast cancer treatment must nowadays optimize cosmetic results. This can be accomplished in selected cases by means of a single-stage operation that the authors call "skin-reducing mastectomy." The final scars imitate those of cosmetic surgery. Careful patient selection and improvement in the learning curve may reduce the complication rate.

  9. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b

  10. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort

  11. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-03-01

    ABT-869, Acadesine, Acetylsalicylic acid/omeprazole, Adefovir, Adefovir dipivoxil, AEG-35156, Agatolimod sodium, Albiglutide, Alemtuzumab, Alipogene tiparvovec, Alogliptin benzoate, AMG-386, Amrubicin hydrochloride, Apremilast, Aripiprazole, Asoprisnil, Atorvastatin/fenofibrate, AVN-944, Axitinib; Belinostat, Bevacizumab, BHT-3021, BI-2536, Biapenem, Bilastine, Biphasic insulin aspart, Blinatumomab, Bortezomib, Bosentan; Catumaxomab, CD-NP, Cediranib, Certolizumab pegol, Cetuximab, Choline fenofibrate, Ciclesonide, CK-1827452,Clevudine, Clofarabine, CSL-360, CYT-997; Dapagliflozin, Darinaparsin, Denosumab, Densiron 68, Desloratadine, Dulanermin; Edoxaban tosilate, Emtricitabine, Entecavir, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fidaxomicintiacumiv, Fulvestrant; G-207, GCR-8015, Gefitinib, Ghrelin (human), Glufosfamide; HPV16L1E7CVLP; Ibutamoren mesilate, Imatinib mesylate, Insulin detemir, Insulin glargine, Iodine (I131) tositumomab, Istaroxime, ITMN-191, Ixabepilone; JZP-4, Lenalidomide; Levetiracetam, Linaclotide acetate, Liposomal cytarabine/daunorubicin, Liposomal doxorubicin, Liraglutide, LY-518674; Milatuzumab, MMR-V, Motesanib diphosphate, Mycophenolic acid sodium salt; Niacin/simvastatin; Obatoclax mesylate, Odanacatib; Paclitaxel nanoparticles, Paclitaxel-eluting stent, Pazufloxacin, PBT-2, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pemetrexed disodium, Perampanel, PfCP2.9, Pitavastatin calcium, Poly I:CLC, Pomalidomide, Pralatrexate, Pramlintide acetate, Prucalopride; rhGAD65, Roflumilast; RTS,S/AS02D; SCH-530348, Semagacestat, Sirolimus-eluting coronary stent, Sirolimus-Eluting Stent, SIR-Spheres, Sivelestat sodium hydrate, Sorafenib, Sunitinib malate; Tadalafil, Tafluprost, Tanespimycin, Teduglutide, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tiotropium bromide, TMC-435350, Tositumomab/iodine (I131) tositumomab, Travoprost/timolol, Triciribine

  12. Pressure reducing regulator

    DOEpatents

    Whitehead, J.C.; Dilgard, L.W.

    1995-10-10

    A pressure reducing regulator that controls its downstream or outlet pressure to a fixed fraction of its upstream or inlet pressure is disclosed. The regulator includes a housing which may be of a titanium alloy, within which is located a seal or gasket at the outlet end which may be made of annealed copper, a rod, and piston, each of which may be made of high density graphite. The regulator is insensitive to temperature by virtue of being without a spring or gas sealed behind a diaphragm, and provides a reference for a system in which it is being used. The rod and piston of the regulator are constructed, for example, to have a 1/20 ratio such that when the downstream pressure is less than 1/20 of the upstream pressure the regulator opens and when the downstream pressure exceeds 1/20 of the upstream pressure the regulator closes. 10 figs.

  13. Pressure reducing regulator

    DOEpatents

    Whitehead, John C.; Dilgard, Lemoyne W.

    1995-01-01

    A pressure reducing regulator that controls its downstream or outlet pressure to a fixed fraction of its upstream or inlet pressure. The regulator includes a housing which may be of a titanium alloy, within which is located a seal or gasket at the outlet end which may be made of annealed copper, a rod, and piston, each of which may be made of high density graphite. The regulator is insensitive to temperature by virtue of being without a spring or gas sealed behind a diaphragm, and provides a reference for a system in which it is being used. The rod and piston of the regulator are constructed, for example, to have a 1/20 ratio such that when the downstream pressure is less than 1/20 of the upstream pressure the regulator opens and when the downstream pressure exceeds 1/20 of the upstream pressure the regulator closes.

  14. Embodied intervention reduce depression

    NASA Astrophysics Data System (ADS)

    Song, Dong-Qing; Bi, Xin; Fu, Ying

    2011-10-01

    To investigate the difference of the selected-rate of undergraduates' depression with respect to time, gender and scales and the intervention effect of embodied exercise, 201 Undergraduates were measured with Self-Rating Depression Scale and Beck Depression Inventory (BDI).The result shows there are significant difference of the selected-rates of undergraduates' depression resulted from long-time interval rather than from short-time interval and gender. After the intervention, the selected-rates are decreased and no significant difference has been found between the embodied groups and the controlled group. Only the embodied groups maintain the better effects of the intervention in the tracking. Also the result shows that only the participants of embodied groups obtain more positive emotional experience. We conclude that there is significant difference of selected-rate of undergraduates' depression on scales, and the embodied exercise can effectively reduce undergraduate's depression.

  15. Reduced Order Podolsky Model

    NASA Astrophysics Data System (ADS)

    Thibes, Ronaldo

    2017-02-01

    We perform the canonical and path integral quantizations of a lower-order derivatives model describing Podolsky's generalized electrodynamics. The physical content of the model shows an auxiliary massive vector field coupled to the usual electromagnetic field. The equivalence with Podolsky's original model is studied at classical and quantum levels. Concerning the dynamical time evolution, we obtain a theory with two first-class and two second-class constraints in phase space. We calculate explicitly the corresponding Dirac brackets involving both vector fields. We use the Senjanovic procedure to implement the second-class constraints and the Batalin-Fradkin-Vilkovisky path integral quantization scheme to deal with the symmetries generated by the first-class constraints. The physical interpretation of the results turns out to be simpler due to the reduced derivatives order permeating the equations of motion, Dirac brackets and effective action.

  16. Reducing GWAS Complexity

    PubMed Central

    Hazelett, Dennis J.; Conti, David V.; Han, Ying; Al Olama, Ali Amin; Easton, Doug; Eeles, Rosalind A.; Kote-Jarai, Zsofia; Haiman, Christopher A.; Coetzee, Gerhard A.

    2016-01-01

    ABSTRACT Genome-wide association studies (GWAS) have revealed numerous genomic 'hits' associated with complex phenotypes. In most cases these hits, along with surrogate genetic variation as measure by numerous single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium, are not in coding genes making assignment of functionality or causality intractable. Here we propose that fine-mapping along with the matching of risk SNPs at chromatin biofeatures lessen this complexity by reducing the number of candidate functional/causal SNPs. For example, we show here that only on average 2 SNPs per prostate cancer risk locus are likely candidates for functionality/causality; we further propose that this manageable number should be taken forward in mechanistic studies. The candidate SNPs can be looked up for each prostate cancer risk region in 2 recent publications in 20151,2 from our groups. PMID:26771711

  17. Reducing medical waste.

    PubMed

    Conrardy, Julie; Hillanbrand, Mary; Myers, Sandra; Nussbaum, George F

    2010-06-01

    Medical waste is a necessary by-product of any hospital environment; however, the majority of regulated medical waste is produced in the OR from the use of disposable surgical supplies (eg, drapes, gowns, basins, gloves, sponges). We conducted a concept comparison project in the ORs of two large medical centers in Bethesda, Maryland, and Washington, DC, to evaluate the effects of using reusable surgical basins, gowns, and table and Mayo stand covers in place of disposable products. Survey results indicated that surgeons and surgical technologists found the reusable products to be preferable to the disposable products currently in use. In addition, using reusable products provided a means to decrease regulated medical waste generated in the OR by an average of 65% as well as reduce the cost of waste disposal. AORN recommends evaluating the environmental effects of using reusable, reposable, and disposable products; our findings provide evidence that may be useful to surgical facilities that seek to adopt a "green" approach.

  18. Measuring the reduced shear

    NASA Astrophysics Data System (ADS)

    Zhang, Jun

    2011-11-01

    Neglecting the second order corrections in weak lensing measurements can lead to a few percent uncertainties on cosmic shears, and becomes more important for cluster lensing mass reconstructions. Existing methods which claim to measure the reduced shears are not necessarily accurate to the second order when a point spread function (PSF) is present. We show that the method of Zhang (2008) exactly measures the reduced shears at the second order level in the presence of PSF. A simple theorem is provided for further confirming our calculation, and for judging the accuracy of any shear measurement method at the second order based on its properties at the first order. The method of Zhang (2008) is well defined mathematically. It does not require assumptions on the morphologies of galaxies and the PSF. To reach a sub-percent level accuracy, the CCD pixel size is required to be not larger than 1/3 of the Full Width at Half Maximum (FWHM) of the PSF, regardless of whether the PSF has a power-law or exponential profile at large distances. Using a large ensemble (gtrsim107) of mock galaxies of unrestricted morphologies, we study the shear recovery accuracy under different noise conditions. We find that contaminations to the shear signals from the noise of background photons can be removed in a well defined way because they are not correlated with the source shapes. The residual shear measurement errors due to background noise are consistent with zero at the sub-percent level even when the amplitude of such noise reaches about 1/10 of the source flux within the half-light radius of the source. This limit can in principle be extended further with a larger galaxy ensemble in our simulations. On the other hand, the source Poisson noise remains to be a cause of systematic errors. For a sub-percent level accuracy, our method requires the amplitude of the source Poisson noise to be less than 1/80 ~ 1/100 of the source flux within the half-light radius of the source, corresponding to

  19. Measuring the reduced shear

    SciTech Connect

    Zhang, Jun

    2011-11-01

    Neglecting the second order corrections in weak lensing measurements can lead to a few percent uncertainties on cosmic shears, and becomes more important for cluster lensing mass reconstructions. Existing methods which claim to measure the reduced shears are not necessarily accurate to the second order when a point spread function (PSF) is present. We show that the method of Zhang (2008) exactly measures the reduced shears at the second order level in the presence of PSF. A simple theorem is provided for further confirming our calculation, and for judging the accuracy of any shear measurement method at the second order based on its properties at the first order. The method of Zhang (2008) is well defined mathematically. It does not require assumptions on the morphologies of galaxies and the PSF. To reach a sub-percent level accuracy, the CCD pixel size is required to be not larger than 1/3 of the Full Width at Half Maximum (FWHM) of the PSF, regardless of whether the PSF has a power-law or exponential profile at large distances. Using a large ensemble (∼>10{sup 7}) of mock galaxies of unrestricted morphologies, we study the shear recovery accuracy under different noise conditions. We find that contaminations to the shear signals from the noise of background photons can be removed in a well defined way because they are not correlated with the source shapes. The residual shear measurement errors due to background noise are consistent with zero at the sub-percent level even when the amplitude of such noise reaches about 1/10 of the source flux within the half-light radius of the source. This limit can in principle be extended further with a larger galaxy ensemble in our simulations. On the other hand, the source Poisson noise remains to be a cause of systematic errors. For a sub-percent level accuracy, our method requires the amplitude of the source Poisson noise to be less than 1/80 ∼ 1/100 of the source flux within the half-light radius of the source

  20. Reducing miner absenteeism

    SciTech Connect

    Peters, R.H.; Clingan, M.R.; Randolph, R.F.

    1989-01-01

    The U. S. Bureau of Mines has prepared this report on strategies for maintaining high job attendance among underground coal miners because high absenteeism is a threat to miners' safety and seriously hampers productivity. A substantial number of research studies on the effectiveness of various strategies for reducing absenteeism among the employees of nonmining industries have been reported in the literature. These strategies have aimed at improving job attendance through one or more of the following: (1) improving employment procedures, (2) overcoming problems that adversely affect one's ability to attend work, and (3) increasing miners' motivation to attend work. Many of these strategies appear applicable to the mining industry, and are reviewed in the first half of this report. The second half of this report describes how one could develop and implement a program for maintaining high attendance at underground coal mines. The steps include measuring and evaluating attendance levels, formulating attendance goals and an absenteeism policy, developing and implementing an attendance promotion program and periodically going through the preceding steps (known as recycling).

  1. Stewarding a Reduced Stockpile

    SciTech Connect

    Goodwin, B T; Mara, G

    2008-04-18

    The future of the US nuclear arsenal continues to be guided by two distinct drivers: the preservation of world peace and the prevention of further proliferation through our extended deterrent umbrella. Timely implementation of US nuclear policy decisions depends, in part, on the current state of stockpile weapons, their delivery systems, and the supporting infrastructure within the Department of Defense (DoD) and the Department of Energy's National Nuclear Security Administration (NNSA). In turn, the present is a product of past choices and world events. Now more than ever, the nuclear weapons program must respond to the changing global security environment and to increasing budget pressures with innovation and sound investments. As the nation transitions to a reduced stockpile, the successes of the Stockpile Stewardship Program (SSP) present options to transition to a sustainable complex better suited to stockpile size, national strategic goals and budgetary realities. Under any stockpile size, we must maintain essential human capital, forefront capabilities, and have a right-sized effective production capacity. We present new concepts for maintaining high confidence at low stockpile numbers and to effectively eliminate the reserve weapons within an optimized complex. We, as a nation, have choices to make on how we will achieve a credible 21st century deterrent.

  2. Pollution reducing aircraft propulsion

    SciTech Connect

    Tamura, R.

    1980-07-29

    An aircraft pollution reducing propulsion airfoil system comprising a wing having upper and lower surfaces comprising wing skin plates extending longitudinally on the wing and being spaced one from another in chordwise directions, spars extending into the wing between the surfaces, stringer ducts extending along internal sides of the wing surfaces, the stringers having relatively rigid surface-supporting structure and having outward directed openings extending across the wing surfaces, interrupting the wing surfaces between edges of the wing skin plates, the ducts thereby forming stringer structural elements supporting the wing skin plates, the outward directed openings of the stringer ducts being arranged perpendicularly to the wing surfaces in a leading portion of the wing and tangential to the wing surfaces in a trailing portion of the wing surfaces, suction means connected to the stringer ducts with perpendicular opening for drawing gas into the ducts through those openings and blowing means connected to the ducts with tangential openings for flowing gas out of the tangential openings, combustion means connected to the suction means and to the blowing meanas for accelerating gas through the means.

  3. Generalized reduced magnetohydrodynamic equations

    SciTech Connect

    Kruger, S.E.

    1999-02-01

    A new derivation of reduced magnetohydrodynamic (MHD) equations is presented. A multiple-time-scale expansion is employed. It has the advantage of clearly separating the three time scales of the problem associated with (1) MHD equilibrium, (2) fluctuations whose wave vector is aligned perpendicular to the magnetic field, and (3) those aligned parallel to the magnetic field. The derivation is carried out without relying on a large aspect ratio assumption; therefore this model can be applied to any general configuration. By accounting for the MHD equilibrium and constraints to eliminate the fast perpendicular waves, equations are derived to evolve scalar potential quantities on a time scale associated with the parallel wave vector (shear-Alfven wave time scale), which is the time scale of interest for MHD instability studies. Careful attention is given in the derivation to satisfy energy conservation and to have manifestly divergence-free magnetic fields to all orders in the expansion parameter. Additionally, neoclassical closures and equilibrium shear flow effects are easily accounted for in this model. Equations for the inner resistive layer are derived which reproduce the linear ideal and resistive stability criterion of Glasser, Greene, and Johnson. The equations have been programmed into a spectral initial value code and run with shear flow that is consistent with the equilibrium input into the code. Linear results of tearing modes with shear flow are presented which differentiate the effects of shear flow gradients in the layer with the effects of the shear flow decoupling multiple harmonics.

  4. Reducing the impact.

    PubMed

    Mahathir, M

    1997-01-01

    In Asia, attempts to control HIV/AIDS through education have not achieved the necessary behavior changes. This is especially true for young women who are unable to apply their knowledge to their sex behavior because of inequalities in gender relations. Thus, the impact of AIDS on women is significantly greater in settings where the status of women is low. Women in developing countries are at greatest risk because the epidemic is fueled by poverty, lack of information, and lack of autonomy. Prosperity in a developing country, such as Malaysia, entails its own risks because it creates new social norms and values that exist in tandem with debilitating old norms, such as the patriarchy that disempowers women and a resurgence in polygamy and wife abandonment. Subservient gender roles not only increase women's chances of infection, they also target women as the primary caregivers for infected individuals. Young girls may have to abandon school to care for infected parents, and female health care providers are assigned to the lowest ranks of the profession. While most women have been infected by their husbands, they must also bear the stigma of being considered immoral infectors of their husbands. The futures of AIDS widows and orphans is jeopardized by the discrimination that attends the disease, and if the mother dies, her young children face a higher death rate. In settings new to the epidemic, it is difficult to convince men of the importance of addressing women's needs and of seeking the input of women in policy and program development. Only by empowering both sexes to work together to protect society will there be a reasonable chance of reducing the impact of HIV/AIDS.

  5. Reduced Gravity Walking Simulator

    NASA Technical Reports Server (NTRS)

    1963-01-01

    A test subject being suited up for studies on the Reduced Gravity Walking Simulator located in the hanger at Langley Research Center. The initial version of this simulator was located inside the hanger. Later a larger version would be located at the Lunar Landing Facility. The purpose of this simulator was to study the subject while walking, jumping or running. Researchers conducted studies of various factors such as fatigue limit, energy expenditure, and speed of locomotion. Francis B. Smith wrote in his paper 'Simulators For Manned Space Research,' 'I would like to conclude this talk with a discussion of a device for simulating lunar gravity which is very effective and yet which is so simple that its cost is in the order of a few thousand dollars at most, rather than hundreds of thousands. With a little ingenuity, one could almost build this type simulator in his backyard for children to play on. The principle is ...if a test subject is suspended in a sling so that his body axis makes an angle of 9 1/2 degrees with the horizontal and if he then 'stands' on a platform perpendicular to his body axis, the component of the earth's gravity forcing him toward the platform is one times the sine of 9 1/2 degrees or approximately 1/6 of the earth's normal gravity field. That is, a 180 pound astronaut 'standing' on the platform would exert a force of only 30 pounds - the same as if he were standing upright on the lunar surface.' Published in James R. Hansen, Spaceflight Revolution: NASA Langley Research Center From Sputnik to Apollo, NASA SP-4308; Francis B. Smith, 'Simulators For Manned Space Research,' Paper for 1966 IEEE International Convention, New York, NY, March 21-25, 1966.

  6. Reducing China's one billion.

    PubMed

    Lee, W Y

    1985-01-01

    China's population growth process has gone through 4 stages since 1950: 1) the period 1950-57, when there was a net population increase of 100 million people in response to postwar economic recovery; 2) the period 1958-61, when the birth rate declined and the death rate increased as a result of the upheavals caused by the "great leap forward" movement; 3) the period 1962-75, during which family planning was introduced; and 4) the period 1976-80, during which time family planning has been rigorously practiced. As a result of conscious population reduction measures, the natural growth rate has been reduced to less than 1% in the urban areas and slightly over 1.2% in rural areas. If an annual growth rate of 1.4% is maintained, China's population will grow to a peak of 1380 million before beginning its decline early in the 21st century. The total population of China stood at 1,008,175,288 at the time of the 1982 census, with a male to female ratio of 106.3:100. Over 60% of the population was born after 1949. Those born during the population peak periods of 1954-57 and 1962-75 have already reached reproductive age. The illiteracy rate has declined to 23.5%. The number of people employed in the primary sector has remained consistently high (80% of the total work force), while employment in the secondary sector has increased and employment in the tertiary sector has declined slightly. In 1982, 20.9% of China's population was urban and 6.7% of the population was from an ethnic minority grouping. Finally, the 1982 Census indicated an average life expectancy of 67.88 years. Population reduction measures in China have included the 1-child family policy, incentives and penalties, and social welfare measures for the elderly. In addition, family planning units at every level of government conduct family planning promotion activities, provide free family planning services, and encourage delayed 1st marriage.

  7. Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With or Without Ribavirin in HCV-Infected Patients Taking Concomitant Acid-Reducing Agents

    PubMed Central

    Shiffman, Mitchell L; Rustgi, Vinod; Bennett, Michael; Forns, Xavier; Asselah, Tarik; Planas Vila, Ramon; Liu, Li; Pedrosa, Marcos; Moller, Jonathan; Reau, Nancy

    2016-01-01

    OBJECTIVES: Acid-reducing agents (ARAs) and proton-pump inhibitors (PPIs) that increase gastric pH can alter the bioavailability of antiviral drugs, particularly relevant in patients with advanced liver disease caused by chronic hepatitis C virus (HCV) infection seeking therapy. Using integrated data from six phase 3 studies, we report the safety and efficacy of the 3-direct-acting antiviral (DAA) regimen containing ombitasvir (OBV, an NS5A inhibitor), ritonavir-boosted paritaprevir (PTV/r, an NS3/4A protease inhibitor), and dasabuvir (DSV, an NS5B polymerase inhibitor) with or without ribavirin (RBV) for HCV genotype 1 patients taking concomitant ARAs and PPIs. METHODS: Treatment-naïve or peginterferon/RBV treatment-experienced patients with or without compensated cirrhosis received OBV/PTV/r and DSV with or without weight-based RBV. Rates of sustained virologic response (SVR), defined as HCV RNA below the lower limit of quantification, 12 weeks post-treatment (SVR12) and safety were evaluated in patients who were receiving concomitant ARAs. RESULTS: Among 2,053 patients enrolled and dosed with study drug, 410 (20%) were receiving concomitant ARAs; of these, 308 (15%) were taking concomitant PPIs. Rates of SVR12 were 95.9% (95% confidence interval (CI) 93.5–97.4%) among patients receiving an ARA, and 96.3% (95% CI 95.3–97.2%) in patients not receiving a concomitant ARA. Similarly, among patients receiving a PPI or not, SVR12 was achieved in 95.1% (95% CI 92.1–97.0%) and 96.4% (95% CI 95.5–97.2%), respectively. Response rates were high regardless of treatment regimen (with or without RBV), and among patients receiving a standard or high dose of PPIs. Regarding safety, adverse events and serious adverse events were more frequently reported in patients taking concomitant ARAs, though baseline population differences may have played a role. CONCLUSIONS: In phase 3 trials of OBV/PTV/r plus DSV and RBV in HCV genotype 1-infected patients, SVR12 rates were high

  8. Reducing gas generators and methods for generating a reducing gas

    DOEpatents

    Scotto, Mark Vincent; Perna, Mark Anthony

    2015-11-03

    One embodiment of the present invention is a unique reducing gas generator. Another embodiment is a unique method for generating a reducing gas. Other embodiments include apparatuses, systems, devices, hardware, methods, and combinations for generating reducing gas. Further embodiments, forms, features, aspects, benefits, and advantages of the present application will become apparent from the description and figures provided herewith.

  9. Solid state reduced voltage starters

    SciTech Connect

    Posma, B.W.

    1982-11-01

    This article predicts that as the relatively low cost, reliability and flexibility of solid state starters become recognized, they will replace conventional devices for starting ac motors under reduced voltage conditions. It explains that reduced voltage starters are used to reduce motor starting current, and to limit starting torque which thereby reduces excessive shock to driven machinery. For squirrel cage motors, there are 2 types of reduced voltage starters: electromechanical (part-winding, autotransformer, primary resistor, wye-delta, and reactor) and solid state (using SCRs). Solid state reduced voltage starters (SRVSs) provide smooth, stepless acceleration of ac squirrel cage and wound rotor motors from standstill to full speed. A rugged, low cost SRVS teamed with a standard squirrel cage motor can perform the starter functions normally accomplished by fluid couplings, eddy current drives, wound rotor drives and even some dc motor drives.

  10. Oxygen-reducing catalyst layer

    DOEpatents

    O'Brien, Dennis P [Maplewood, MN; Schmoeckel, Alison K [Stillwater, MN; Vernstrom, George D [Cottage Grove, MN; Atanasoski, Radoslav [Edina, MN; Wood, Thomas E [Stillwater, MN; Yang, Ruizhi [Halifax, CA; Easton, E Bradley [Halifax, CA; Dahn, Jeffrey R [Hubley, CA; O'Neill, David G [Lake Elmo, MN

    2011-03-22

    An oxygen-reducing catalyst layer, and a method of making the oxygen-reducing catalyst layer, where the oxygen-reducing catalyst layer includes a catalytic material film disposed on a substrate with the use of physical vapor deposition and thermal treatment. The catalytic material film includes a transition metal that is substantially free of platinum. At least one of the physical vapor deposition and the thermal treatment is performed in a processing environment comprising a nitrogen-containing gas.

  11. Reduced Gravity Zblan Optical Fiber

    NASA Technical Reports Server (NTRS)

    Tucker, Dennis S.; Workman, Gary L.; Smith, Guy A.

    2000-01-01

    Two optical fiber pullers have been designed for pulling ZBLAN optical fiber in reduced gravity. One fiber puller was designed, built and flown on board NASA's KC135 reduced gravity aircraft. A second fiber puller has been designed for use on board the International Space Station.

  12. Reducing Cancer Patients' Painful Treatment

    NASA Image and Video Library

    A NASA light technology originally developed to aid plant growth experiments in space has proved to reduce the painful side effects resulting from chemotherapy and radiation treatment in bone marro...

  13. Reduced rates for AIP journals

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    The American Institute of Physics (AIP) offers reduced rates for subscriptions of its journals to individual members of affiliated societies. AGU is an A IP-affiliated society. The offer is limited to one subscription per person to each journal.

  14. How to Reduce Solid Waste.

    ERIC Educational Resources Information Center

    Martins, George; Clapp, Leallyn B.

    1974-01-01

    Discusses the problem of solid waste disposal in the United States, suggests ways in which solid wastes might be reduced, and proposes a number of related topics for student debate in classes or in science clubs. (JR)

  15. Reducing Failures in Reference Service.

    ERIC Educational Resources Information Center

    Douglas, Ian

    1988-01-01

    Summarizes the results of 11 selected studies of the accuracy of reference services and identifies six modes of failure of reference services. Methods of detecting and reducing failure in each of these modes are then discussed. (17 references) (MES)

  16. How to Reduce Solid Waste.

    ERIC Educational Resources Information Center

    Martins, George; Clapp, Leallyn B.

    1974-01-01

    Discusses the problem of solid waste disposal in the United States, suggests ways in which solid wastes might be reduced, and proposes a number of related topics for student debate in classes or in science clubs. (JR)

  17. Reduced Gravity Education Flight Program

    NASA Image and Video Library

    NASA'€™s Reduced Gravity Education Flight Program gives students and educators the opportunity to design, build and fly an experiment in microgravity and get a look at what it takes to be a NASA en...

  18. Reducing crosstalk between stereoscopic views

    NASA Astrophysics Data System (ADS)

    Lipscomb, James S.; Wooten, Wayne L.

    1994-04-01

    Crosstalk between the left and right eyes consists of the one eye's image seen faintly by the other. Image processing can reduce this. The technique is effective, but there are costs of course, and some surprises.

  19. ISS Update: Reduced Gravity Education

    NASA Image and Video Library

    NASA Public Affairs Officer Dan Huot interviews Veronica Seyl, Acting Manager for Reduced Gravity Education. NASA works with students and educators to design experiments for flight testing aboard t...

  20. Conventional Reduced Risk Pesticide Program

    EPA Pesticide Factsheets

    Find out about the Conventional Reduced Risk Pesticide Program, which expedites the review and regulatory decision-making process of conventional pesticides that pose less risk to human health and the environment than existing conventional alternatives.

  1. Learning to REDUCE: A Reduced Electricity Consumption Prediction Ensemble

    SciTech Connect

    Aman, Saima; Chelmis, Charalampos; Prasanna, Viktor

    2016-02-12

    Utilities use Demand Response (DR) to balance supply and demand in the electric grid by involving customers in efforts to reduce electricity consumption during peak periods. To implement and adapt DR under dynamically changing conditions of the grid, reliable prediction of reduced consumption is critical. However, despite the wealth of research on electricity consumption prediction and DR being long in practice, the problem of reduced consumption prediction remains largely un-addressed. In this paper, we identify unique computational challenges associated with the prediction of reduced consumption and contrast this to that of normal consumption and DR baseline prediction.We propose a novel ensemble model that leverages different sequences of daily electricity consumption on DR event days as well as contextual attributes for reduced consumption prediction. We demonstrate the success of our model on a large, real-world, high resolution dataset from a university microgrid comprising of over 950 DR events across a diverse set of 32 buildings. Our model achieves an average error of 13.5%, an 8.8% improvement over the baseline. Our work is particularly relevant for buildings where electricity consumption is not tied to strict schedules. Our results and insights should prove useful to the researchers and practitioners working in the sustainable energy domain.

  2. Determining Reduced Order Models for Optimal Stochastic Reduced Order Models

    SciTech Connect

    Bonney, Matthew S.; Brake, Matthew R.W.

    2015-08-01

    The use of parameterized reduced order models(PROMs) within the stochastic reduced order model (SROM) framework is a logical progression for both methods. In this report, five different parameterized reduced order models are selected and critiqued against the other models along with truth model for the example of the Brake-Reuss beam. The models are: a Taylor series using finite difference, a proper orthogonal decomposition of the the output, a Craig-Bampton representation of the model, a method that uses Hyper-Dual numbers to determine the sensitivities, and a Meta-Model method that uses the Hyper-Dual results and constructs a polynomial curve to better represent the output data. The methods are compared against a parameter sweep and a distribution propagation where the first four statistical moments are used as a comparison. Each method produces very accurate results with the Craig-Bampton reduction having the least accurate results. The models are also compared based on time requirements for the evaluation of each model where the Meta- Model requires the least amount of time for computation by a significant amount. Each of the five models provided accurate results in a reasonable time frame. The determination of which model to use is dependent on the availability of the high-fidelity model and how many evaluations can be performed. Analysis of the output distribution is examined by using a large Monte-Carlo simulation along with a reduced simulation using Latin Hypercube and the stochastic reduced order model sampling technique. Both techniques produced accurate results. The stochastic reduced order modeling technique produced less error when compared to an exhaustive sampling for the majority of methods.

  3. Reduced waste generation, FY 1986

    SciTech Connect

    Not Available

    1986-02-01

    The United States Department of Energy is committed to the principles of minimizing the quantity and transuranic content of its transuranium (TRU) waste being generated at its nuclear facilities. The reasons are to reduce costs associated with waste handling and disposal, and also to reduce radiation exposure to workers and risk for radionuclide release to man and the environment. The purpose of this document is to provide the USDOE with a plan of research and development tasks for waste minimization, and is prepared so as to provide the maximum impact on volumes based on cost/benefit factors. The document is to be updated annually or as needed to reflect current and future tasks. The Reduced Waste Generation (RWG) tasks encompass a wide range of activities with the principal goals of (1) preventing the generation of waste and (2) converting TRU waste into low-level wastes (LLW) by sorting or decontamination. Concepts for reducing the volume such as in incineration and compaction are considered within the discipline of Reduced Waste Generation, but are considered as somewhat developed technology with only a need for implementation. 33 refs.

  4. Strategies to Reduce Indoor Tanning

    PubMed Central

    Holman, Dawn M.; Fox, Kathleen A.; Glenn, Jeffrey D.; Guy, Gery P.; Watson, Meg; Baker, Katie; Cokkinides, Vilma; Gottlieb, Mark; Lazovich, DeAnn; Perna, Frank M.; Sampson, Blake P.; Seidenberg, Andrew B.; Sinclair, Craig; Geller, Alan C.

    2015-01-01

    Exposure to ultraviolet radiation from indoor tanning device use is associated with an increased risk of skin cancer, including risk of malignant melanoma, and is an urgent public health problem. By reducing indoor tanning, future cases of skin cancer could be prevented, along with the associated morbidity, mortality, and healthcare costs. On August 20, 2012, the CDC hosted a meeting to discuss the current body of evidence on strategies to reduce indoor tanning as well as research gaps. Using the Action Model to Achieve Healthy People 2020 Overarching Goals as a framework, the current paper provides highlights on the topics that were discussed, including (1) the state of the evidence on strategies to reduce indoor tanning; (2) the tools necessary to effectively assess, monitor, and evaluate the short- and long-term impact of interventions designed to reduce indoor tanning; and (3) strategies to align efforts at the national, state, and local levels through transdisciplinary collaboration and coordination across multiple sectors. Although many challenges and barriers exist, a coordinated, multilevel, transdisciplinary approach has the potential to reduce indoor tanning and prevent future cases of skin cancer. PMID:23683986

  5. Sleep can reduce proactive interference.

    PubMed

    Abel, Magdalena; Bäuml, Karl-Heinz T

    2014-01-01

    Sleep has repeatedly been connected to processes of memory consolidation. While extensive research indeed documents beneficial effects of sleep on memory, little is yet known about the role of sleep for interference effects in episodic memory. Although two prior studies reported sleep to reduce retroactive interference, no sleep effect has previously been found for proactive interference. Here we applied a study format differing from that employed by the prior studies to induce a high degree of proactive interference, and asked participants to encode a single list or two interfering lists of paired associates via pure study cycles. Testing occurred after 12 hours of diurnal wakefulness or nocturnal sleep. Consistent with the prior work, we found sleep in comparison to wake did not affect memory for the single list, but reduced retroactive interference. In addition we found sleep reduced proactive interference, and reduced retroactive and proactive interference to the same extent. The finding is consistent with the view that arising benefits of sleep are caused by the reactivation of memory contents during sleep, which has been suggested to strengthen and stabilise memories. Such stabilisation may make memories less susceptible to competition from interfering memories at test and thus reduce interference effects.

  6. Reduce air, reduce compliance cost new patented spray booth technology

    SciTech Connect

    McGinnis, F.

    1997-12-31

    A New Paint Spray Booth System that dramatically reduces air volumes normally required for capturing and controlling paint overspray that contains either Volatile Organic Compounds (VOC) or Hazardous Air Pollutants (HAP), or both. In turn, a substantial reduction in capital equipment expenditures for air abatement systems and air make-up heaters as well as related annual operating expenses is realized.

  7. Microbial methods of reducing technetium

    DOEpatents

    Wildung, Raymond E [Richland, WA; Garland, Thomas R [Greybull, WY; Gorby, Yuri A [Richland, WA; Hess, Nancy J [Benton City, WA; Li, Shu-Mei W [Richland, WA; Plymale, Andrew E [Richland, WA

    2001-01-01

    The present invention is directed toward a method for microbial reduction of a technetium compound to form other compounds of value in medical imaging. The technetium compound is combined in a mixture with non-growing microbial cells which contain a technetium-reducing enzyme system, a stabilizing agent and an electron donor in a saline solution under anaerobic conditions. The mixture is substantially free of an inorganic technetium reducing agent and its reduction products. The resulting product is Tc of lower oxidation states, the form of which can be partially controlled by the stabilizing agent. It has been discovered that the microorganisms Shewanella alga, strain Bry and Shewanelia putrifacians, strain CN-32 contain the necessary enzyme systems for technetium reduction and can form both mono nuclear and polynuclear reduced Tc species depending on the stabilizing agent.

  8. Power and reduced temporal discounting.

    PubMed

    Joshi, Priyanka D; Fast, Nathanael J

    2013-04-01

    Decision makers generally feel disconnected from their future selves, an experience that leads them to prefer smaller immediate gains to larger future gains. This pervasive tendency is known as temporal discounting, and researchers across disciplines are interested in understanding how to overcome it. Following recent advances in the power literature, we suggest that the experience of power enhances one's connection with the future self, which in turn results in reduced temporal discounting. In Study 1, we found that participants assigned to high-power roles were less likely than participants assigned to low-power roles to display temporal discounting. In Studies 2 and 3, priming power reduced temporal discounting in monetary and nonmonetary tasks, and, further, connection with the future self mediated the relation between power and reduced discounting. In Study 4, experiencing a general sense of power in the workplace predicted actual lifetime savings. These results have important implications for future research.

  9. Contrasting reduced overshadowing and blocking.

    PubMed

    Wheeler, Daniel S; Miller, Ralph R

    2007-07-01

    Preexposure of a cue without an outcome (X-) prior to compound pairings with the outcome (XZ-->O) can reduce overshadowing of a target cue (Z). Moreover, pairing a cue with an outcome (X-->O) before compound training can enhance its ability to compete with another cue (i.e., blocking). Four experiments were conducted in a conditioned bar-press suppression preparation with rats to determine whether spacing of the X- or X-->O trials would differentially affect reduced overshadowing and blocking. Experiment 1a showed that reduced overshadowing was larger with massed trials than with spaced trials. Experiment 1b found that blocking was larger with spaced trials than with massed trials. Experiments 2a and 2b indicated that these effects of trial spacing were both mediated by the associative status of the context at test. The results are interpreted in the framework of contemporary learning theories.

  10. Flexure Bearing Reduces Startup Friction

    NASA Technical Reports Server (NTRS)

    Clingman, W. Dean

    1991-01-01

    Design concept for ball bearing incorporates small pieces of shim stock, wire spokes like those in bicycle wheels, or other flexing elements to reduce both stiction and friction slope. In flexure bearing, flexing elements placed between outer race of ball bearing and outer ring. Elements flex when ball bearings encounter small frictional-torque "bumps" or even larger ones when bearing balls encounter buildups of grease on inner or outer race. Flexure of elements reduce high friction slopes of "bumps", helping to keep torque between outer ring and inner race low and more nearly constant. Concept intended for bearings in gimbals on laser and/or antenna mirrors.

  11. Isogeometric analysis in reduced magnetohydrodynamics

    NASA Astrophysics Data System (ADS)

    Ratnani, A.; Sonnendrücker, E.

    2012-01-01

    Isogeometric analysis (IGA) consists of using computer-aided design (CAD) models defining the geometry of the computational domain using both B-splines and non-uniform rational B-splines (NURBS) to represent the unknowns that are the solution of a partial differential equation using a finite element principle. In this paper, we review the main ideas of IGA and apply it to a reduced magnetohydrodynamic (MHD) model that is used in tokamak simulations. This is a first step towards arbitrary high-order and smooth approximations of reduced MHD generalizing the Bézier splines approach of Czarny and Huysmans (2008 J. Comput. Phys. 227 7423-45).

  12. Six ways to reduce inventory.

    PubMed

    Lunn, T

    1996-05-01

    The purpose of this presentation is to help you reduce the inventory in your operation. We will accomplish that task by discussing six specific methods that companies have used successfully to reduce their inventory. One common attribute of these successes is that they also build teamwork among the people. Every business operation today is concerned with methods to improve customer service. The real trick is to accomplish that task without increasing inventory. We are all concerned with improving our skills at keeping inventory low.

  13. Reducing cement's CO2 footprint

    USGS Publications Warehouse

    van Oss, Hendrik G.

    2011-01-01

    The manufacturing process for Portland cement causes high levels of greenhouse gas emissions. However, environmental impacts can be reduced by using more energy-efficient kilns and replacing fossil energy with alternative fuels. Although carbon capture and new cements with less CO2 emission are still in the experimental phase, all these innovations can help develop a cleaner cement industry.

  14. Reference Works in Reduced Size

    ERIC Educational Resources Information Center

    Hennessey, David

    1977-01-01

    Lower cost and less shelf space requirements have made major reference works in miniaturized print editions attractive to small libraries. The major disadvantage is the necessity of a magnifying glass for reading entries. A bibliography of reduced-size editions is included. (JAB)

  15. Reducing Poverty through Preschool Interventions

    ERIC Educational Resources Information Center

    Duncan, Greg J.; Ludwig, Jens; Magnuson, Katherine A.

    2007-01-01

    Greg Duncan, Jens Ludwig, and Katherine Magnuson explain how providing high-quality care to disadvantaged preschool children can help reduce poverty. In early childhood, they note, children's cognitive and socioemotional skills develop rapidly and are sensitive to "inputs" from parents, home learning environments, child care settings, and the…

  16. Hindlimb suspension reduces muscle regeneration

    NASA Technical Reports Server (NTRS)

    Mozdziak, P. E.; Truong, Q.; Macius, A.; Schultz, E.

    1998-01-01

    Exposure of juvenile skeletal muscle to a weightless environment reduces growth and satellite cell mitotic activity. However, the effect of a weightless environment on the satellite cell population during muscle repair remains unknown. Muscle injury was induced in rat soleus muscles using the myotoxic snake venom, notexin. Rats were placed into hindlimb-suspended or weightbearing groups for 10 days following injury. Cellular proliferation during regeneration was evaluated using 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and image analysis. Hindlimb suspension reduced (P < 0.05) regenerated muscle mass, regenerated myofiber diameter, uninjured muscle mass, and uninjured myofiber diameter compared to weightbearing rats. Hindlimb suspension reduced (P < 0.05) BrdU labeling in uninjured soleus muscles compared to weight-bearing muscles. However, hindlimb suspension did not abolish muscle regeneration because myofibers formed in the injured soleus muscles of hindlimb-suspended rats, and BrdU labeling was equivalent (P > 0.10) on myofiber segments isolated from the soleus muscles of hindlimb-suspended and weightbearing rats following injury. Thus, hindlimb suspension (weightlessness) does not suppress satellite cell mitotic activity in regenerating muscles before myofiber formation, but reduces growth of the newly formed myofibers.

  17. Reducing Life-Cycle Costs.

    ERIC Educational Resources Information Center

    Roodvoets, David L.

    2003-01-01

    Presents factors to consider when determining roofing life-cycle costs, explaining that costs do not tell the whole story; discussing components that should go into the decision (cost, maintenance, energy use, and environmental costs); and concluding that important elements in reducing life-cycle costs include energy savings through increased…

  18. Reduced-vibration tube array

    DOEpatents

    Bruck, Gerald J.; Bartolomeo, Daniel R.

    2004-07-20

    A reduced-vibration tube array is disclosed. The array includes a plurality of tubes in a fixed arrangement and a plurality of damping members positioned within the tubes. The damping members include contoured interface regions characterized by bracing points that selectively contact the inner surface of an associated tube. Each interface region is sized and shaped in accordance with the associated tube, so that the damping member bracing points are spaced apart a vibration-reducing distance from the associated tube inner surfaces at equilibrium. During operation, mechanical interaction between the bracing points and the tube inner surfaces reduces vibration by a damage-reducing degree. In one embodiment, the interface regions are serpentine shaped. In another embodiment, the interface regions are helical in shape. The interface regions may be simultaneously helical and serpentine in shape. The damping members may be fixed within the associated tubes, and damping member may be customized several interference regions having attributes chosen in accordance with desired flow characteristics and associated tube properties.

  19. Reducing Crime by Eliminating Cash.

    ERIC Educational Resources Information Center

    Warwick, David R.

    Ending the use of cash in the United States can provide substantial social and economic gain while requiring only modest levels of investment. One primary benefit is the reduction of cash-related crimes. Because most street crime is committed to obtain cash or uses cash as a transaction medium, elimination of cash will dramatically reduce crime.…

  20. Reduce Waste for Greener Holidays

    EPA Pesticide Factsheets

    DALLAS - (Dec. 15, 2015) Friends, family, parties, and travel are what make the holiday season great. You can make it even better by reducing waste as often as possible during your celebrations. The U.S. Environmental Protection Agency (EPA) wants t

  1. Reducing narcissus with a GRIN

    NASA Astrophysics Data System (ADS)

    Vizgaitis, Jay; Hastings, Arthur

    2015-06-01

    Narcissus is caused by the reflection of the cold stop off a lens surface back to the image plane of a cooled infrared system and can be very difficult to remove from a lens design perspective. New infrared GRIN materials show the ability to reduce the amount of narcissus in an optical system without the reduction in performance or addition of optical elements.

  2. METHOD OF REDUCING PLUTONIUM COMPOUNDS

    DOEpatents

    Johns, I.B.

    1958-06-01

    A method is described for reducing plutonium compounds in aqueous solution from a higher to a lower valence state. This reduction of valence is achieved by treating the aqueous solution of higher valence plutonium compounds with hydrogen in contact with an activated platinum catalyst.

  3. Heat shield reduces water loss.

    PubMed Central

    Fitch, C W; Korones, S B

    1984-01-01

    A heat shield covered by polyvinyl chloride film greatly reduced insensible water loss and radiant energy requirements in 12 preterm infants on a radiant cradle. Measured transmittance of radiant energy emitted by the radiant heater was impeded minimally by various thin film plastics but was blocked significantly by Perspex. Images Figure PMID:6486866

  4. Reducing Life-Cycle Costs.

    ERIC Educational Resources Information Center

    Roodvoets, David L.

    2003-01-01

    Presents factors to consider when determining roofing life-cycle costs, explaining that costs do not tell the whole story; discussing components that should go into the decision (cost, maintenance, energy use, and environmental costs); and concluding that important elements in reducing life-cycle costs include energy savings through increased…

  5. Reduced False Memory after Sleep

    ERIC Educational Resources Information Center

    Fenn, Kimberly M.; Gallo, David A.; Margoliash, Daniel; Roediger, Henry L., III; Nusbaum, Howard C.

    2009-01-01

    Several studies have shown that sleep contributes to the successful maintenance of previously encoded information. This research has focused exclusively on memory for studied events, as opposed to false memories. Here we report three experiments showing that sleep reduces false memories in the Deese-Roediger-McDermott (DRM) memory illusion. False…

  6. Reduced False Memory after Sleep

    ERIC Educational Resources Information Center

    Fenn, Kimberly M.; Gallo, David A.; Margoliash, Daniel; Roediger, Henry L., III; Nusbaum, Howard C.

    2009-01-01

    Several studies have shown that sleep contributes to the successful maintenance of previously encoded information. This research has focused exclusively on memory for studied events, as opposed to false memories. Here we report three experiments showing that sleep reduces false memories in the Deese-Roediger-McDermott (DRM) memory illusion. False…

  7. Pressure Reducer for Coal Gasifiers

    NASA Technical Reports Server (NTRS)

    Kendall, James M., Sr.

    1983-01-01

    Quasi-porous-plug pressure reducer is designed for gases containing abrasive particles. Gas used to generate high pressure steam to drive electric power generators. In giving up heat to steam, gas drops in temperature. Device used for coal gasification plants.

  8. Do Rewards Reduce Student Motivation?

    ERIC Educational Resources Information Center

    Malouf, David

    1983-01-01

    The reduced continuing motivation effect is examined with regard to research, theory, and implications for practice. The description of research focuses primarily on studies conducted with preschool-aged or school-aged subjects. Explanations based on self-perception or attributional theory and learning theory are examined. (Author/PN)

  9. Hindlimb suspension reduces muscle regeneration

    NASA Technical Reports Server (NTRS)

    Mozdziak, P. E.; Truong, Q.; Macius, A.; Schultz, E.

    1998-01-01

    Exposure of juvenile skeletal muscle to a weightless environment reduces growth and satellite cell mitotic activity. However, the effect of a weightless environment on the satellite cell population during muscle repair remains unknown. Muscle injury was induced in rat soleus muscles using the myotoxic snake venom, notexin. Rats were placed into hindlimb-suspended or weightbearing groups for 10 days following injury. Cellular proliferation during regeneration was evaluated using 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and image analysis. Hindlimb suspension reduced (P < 0.05) regenerated muscle mass, regenerated myofiber diameter, uninjured muscle mass, and uninjured myofiber diameter compared to weightbearing rats. Hindlimb suspension reduced (P < 0.05) BrdU labeling in uninjured soleus muscles compared to weight-bearing muscles. However, hindlimb suspension did not abolish muscle regeneration because myofibers formed in the injured soleus muscles of hindlimb-suspended rats, and BrdU labeling was equivalent (P > 0.10) on myofiber segments isolated from the soleus muscles of hindlimb-suspended and weightbearing rats following injury. Thus, hindlimb suspension (weightlessness) does not suppress satellite cell mitotic activity in regenerating muscles before myofiber formation, but reduces growth of the newly formed myofibers.

  10. Distinguishing iron-reducing from sulfate-reducing conditions

    USGS Publications Warehouse

    Chapelle, F.H.; Bradley, P.M.; Thomas, M.A.; McMahon, P.B.

    2009-01-01

    Ground water systems dominated by iron- or sulfate-reducing conditions may be distinguished by observing concentrations of dissolved iron (Fe2+) and sulfide (sum of H2S, HS-, and S= species and denoted here as "H2S"). This approach is based on the observation that concentrations of Fe2+ and H2S in ground water systems tend to be inversely related according to a hyperbolic function. That is, when Fe2+ concentrations are high, H2S concentrations tend to be low and vice versa. This relation partly reflects the rapid reaction kinetics of Fe2+ with H2S to produce relatively insoluble ferrous sulfides (FeS). This relation also reflects competition for organic substrates between the iron- and the sulfate-reducing microorganisms that catalyze the production of Fe2+ and H 2S. These solubility and microbial constraints operate in tandem, resulting in the observed hyperbolic relation between Fe2+ and H 2S concentrations. Concentrations of redox indicators, including dissolved hydrogen (H2) measured in a shallow aquifer in Hanahan, South Carolina, suggest that if the Fe2+/H2S mass ratio (units of mg/L) exceeded 10, the screened interval being tapped was consistently iron reducing (H2 ???0.2 to 0.8 nM). Conversely, if the Fe 2+/H2S ratio was less than 0.30, consistent sulfate-reducing (H2 ???1 to 5 nM) conditions were observed over time. Concomitantly high Fe2+ and H2S concentrations were associated with H2 concentrations that varied between 0.2 and 5.0 nM over time, suggesting mixing of water from adjacent iron- and sulfate-reducing zones or concomitant iron and sulfate reduction under nonelectron donor-limited conditions. These observations suggest that Fe2+/H2S mass ratios may provide useful information concerning the occurrence and distribution of iron and sulfate reduction in ground water systems. ?? 2009 National Ground Water Association.

  11. BCJ numerators from reduced Pfaffian

    NASA Astrophysics Data System (ADS)

    Du, Yi-Jian; Teng, Fei

    2017-04-01

    By expanding the reduced Pfaffian in the tree level Cachazo-He-Yuan (CHY) integrands for Yang-Mills (YM) and nonlinear sigma model (NLSM), we can get the Bern-Carrasco-Johansson (BCJ) numerators in Del Duca-Dixon-Maltoni (DDM) form for arbitrary number of particles in any spacetime dimensions. In this work, we give a set of very straightforward graphic rules based on spanning trees for a direct evaluation of the BCJ numerators for YM and NLSM. Such rules can be derived from the Laplace expansion of the corresponding reduced Pfaffian. For YM, the each one of the ( n - 2)! DDM form BCJ numerators contains exactly ( n - 1)! terms, corresponding to the increasing trees with respect to the color order. For NLSM, the number of nonzero numerators is at most ( n - 2)! - ( n - 3)!, less than those of several previous constructions.

  12. Ferroelectric capacitor with reduced imprint

    DOEpatents

    Evans, Jr., Joseph T.; Warren, William L.; Tuttle, Bruce A.; Dimos, Duane B.; Pike, Gordon E.

    1997-01-01

    An improved ferroelectric capacitor exhibiting reduced imprint effects in comparison to prior art capacitors. A capacitor according to the present invention includes top and bottom electrodes and a ferroelectric layer sandwiched between the top and bottom electrodes, the ferroelectric layer comprising a perovskite structure of the chemical composition ABO.sub.3 wherein the B-site comprises first and second elements and a dopant element that has an oxidation state greater than +4. The concentration of the dopant is sufficient to reduce shifts in the coercive voltage of the capacitor with time. In the preferred embodiment of the present invention, the ferroelectric element comprises Pb in the A-site, and the first and second elements are Zr and Ti, respectively. The preferred dopant is chosen from the group consisting of Niobium, Tantalum, and Tungsten. In the preferred embodiment of the present invention, the dopant occupies between 1 and 8% of the B-sites.

  13. Reducing carbon dioxide to products

    SciTech Connect

    Cole, Emily Barton; Sivasankar, Narayanappa; Parajuli, Rishi; Keets, Kate A

    2014-09-30

    A method reducing carbon dioxide to one or more products may include steps (A) to (C). Step (A) may bubble said carbon dioxide into a solution of an electrolyte and a catalyst in a divided electrochemical cell. The divided electrochemical cell may include an anode in a first cell compartment and a cathode in a second cell compartment. The cathode may reduce said carbon dioxide into said products. Step (B) may adjust one or more of (a) a cathode material, (b) a surface morphology of said cathode, (c) said electrolyte, (d) a manner in which said carbon dioxide is bubbled, (e), a pH level of said solution, and (f) an electrical potential of said divided electrochemical cell, to vary at least one of (i) which of said products is produced and (ii) a faradaic yield of said products. Step (C) may separate said products from said solution.

  14. Correlated Electrons in Reduced Dimensions

    SciTech Connect

    Bonesteel, Nicholas E

    2015-01-31

    This report summarizes the work accomplished under the support of US DOE grant # DE-FG02-97ER45639, "Correlated Electrons in Reduced Dimensions." The underlying hypothesis of the research supported by this grant has been that studying the unique behavior of correlated electrons in reduced dimensions can lead to new ways of understanding how matter can order and how it can potentially be used. The systems under study have included i) fractional quantum Hall matter, which is realized when electrons are confined to two-dimensions and placed in a strong magnetic field at low temperature, ii) one-dimensional chains of spins and exotic quasiparticle excitations of topologically ordered matter, and iii) electrons confined in effectively ``zero-dimensional" semiconductor quantum dots.

  15. Reduced graphene oxide molecular sensors.

    PubMed

    Robinson, Jeremy T; Perkins, F Keith; Snow, Eric S; Wei, Zhongqing; Sheehan, Paul E

    2008-10-01

    We demonstrate reduced graphene oxide as the active material for high-performance molecular sensors. Sensors are fabricated from exfoliated graphene oxide platelets that are deposited to form an ultrathin continuous network. These graphene oxide networks are tunably reduced toward graphene by varying the exposure time to a hydrazine hydrate vapor. The conductance change of the networks upon exposure to trace levels of vapor is measured as a function of the chemical reduction. The level of reduction affects both the sensitivity and the level of 1/ f noise. The sensors are capable of detecting 10 s exposures to simulants of the three main classes of chemical-warfare agents and an explosive at parts-per-billion concentrations.

  16. Alcohol reduces aversion to ambiguity

    PubMed Central

    Tyszka, Tadeusz; Macko, Anna; Stańczak, Maciej

    2015-01-01

    Several years ago, Cohen et al. (1958) demonstrated that under the influence of alcohol drivers became more risk prone, although their risk perception remained unchanged. Research shows that ambiguity aversion is to some extent positively correlated with risk aversion, though not very highly (Camerer and Weber, 1992). The question addressed by the present research is whether alcohol reduces ambiguity aversion. Our research was conducted in a natural setting (a restaurant bar), where customers with differing levels of alcohol intoxication were offered a choice between a risky and an ambiguous lottery. We found that alcohol reduced ambiguity aversion and that the effect occurred in men but not women. We interpret these findings in terms of the risk-as-value hypothesis, according to which, people in Western culture tend to value risk, and suggest that alcohol consumption triggers adherence to socially and culturally valued patterns of conduct different for men and women. PMID:25642202

  17. Alcohol reduces aversion to ambiguity.

    PubMed

    Tyszka, Tadeusz; Macko, Anna; Stańczak, Maciej

    2014-01-01

    Several years ago, Cohen et al. (1958) demonstrated that under the influence of alcohol drivers became more risk prone, although their risk perception remained unchanged. Research shows that ambiguity aversion is to some extent positively correlated with risk aversion, though not very highly (Camerer and Weber, 1992). The question addressed by the present research is whether alcohol reduces ambiguity aversion. Our research was conducted in a natural setting (a restaurant bar), where customers with differing levels of alcohol intoxication were offered a choice between a risky and an ambiguous lottery. We found that alcohol reduced ambiguity aversion and that the effect occurred in men but not women. We interpret these findings in terms of the risk-as-value hypothesis, according to which, people in Western culture tend to value risk, and suggest that alcohol consumption triggers adherence to socially and culturally valued patterns of conduct different for men and women.

  18. Contrails reduce daily temperature range.

    PubMed

    Travis, David J; Carleton, Andrew M; Lauritsen, Ryan G

    2002-08-08

    The potential of condensation trails (contrails) from jet aircraft to affect regional-scale surface temperatures has been debated for years, but was difficult to verify until an opportunity arose as a result of the three-day grounding of all commercial aircraft in the United States in the aftermath of the terrorist attacks on 11 September 2001. Here we show that there was an anomalous increase in the average diurnal temperature range (that is, the difference between the daytime maximum and night-time minimum temperatures) for the period 11-14 September 2001. Because persisting contrails can reduce the transfer of both incoming solar and outgoing infrared radiation and so reduce the daily temperature range, we attribute at least a portion of this anomaly to the absence of contrails over this period.

  19. Structural reducibility of multilayer networks

    NASA Astrophysics Data System (ADS)

    de Domenico, Manlio; Nicosia, Vincenzo; Arenas, Alexandre; Latora, Vito

    2015-04-01

    Many complex systems can be represented as networks consisting of distinct types of interactions, which can be categorized as links belonging to different layers. For example, a good description of the full protein-protein interactome requires, for some organisms, up to seven distinct network layers, accounting for different genetic and physical interactions, each containing thousands of protein-protein relationships. A fundamental open question is then how many layers are indeed necessary to accurately represent the structure of a multilayered complex system. Here we introduce a method based on quantum theory to reduce the number of layers to a minimum while maximizing the distinguishability between the multilayer network and the corresponding aggregated graph. We validate our approach on synthetic benchmarks and we show that the number of informative layers in some real multilayer networks of protein-genetic interactions, social, economical and transportation systems can be reduced by up to 75%.

  20. Mindfulness reduces the correspondence bias.

    PubMed

    Hopthrow, Tim; Hooper, Nic; Mahmood, Lynsey; Meier, Brian P; Weger, Ulrich

    2017-03-01

    The correspondence bias (CB) refers to the idea that people sometimes give undue weight to dispositional rather than situational factors when explaining behaviours and attitudes. Three experiments examined whether mindfulness, a non-judgmental focus on the present moment, could reduce the CB. Participants engaged in a brief mindfulness exercise (the raisin task), a control task, or an attention to detail task before completing a typical CB measure involving an attitude-attribution paradigm. The results indicated that participants in the mindfulness condition experienced a significant reduction in the CB compared to participants in the control or attention to detail conditions. These results suggest that mindfulness training can play a unique role in reducing social biases related to person perception.

  1. Reduced coking of fuel nozzles

    SciTech Connect

    Mancini, A.A.; Sager, J.W.; Kobish, T.R.

    1989-01-17

    This patent describes a fuel nozzle useful for a gas turbine engine and having a nozzle face, the combination of fuel supply means on the nozzle, the fuel supply means including an annular fuel discharge body converging in a downstream direction toward a longitudinal central axis of the nozzle and terminating in a downstream fuel discharge orifice substantially on the central axis for discharging fuel from the orifice for mixing with air downstream of the nozzle face, air supply means on the nozzle for discharging air from the nozzle face, and means on the nozzle around the fuel discharge body cooperating with the air supply means for controllably discharging sufficient air flow with locally reduced swirl strength over the fuel discharge body to establish a recirculation zone spaced away from the nozzle face downstream thereof a sufficient distance to substantially reduce coking on the nozzle face.

  2. Tandem motors reduce well costs

    SciTech Connect

    Hooper, M.; Daigle, C.; Crowe, R.

    1995-10-01

    The new generation of tandem mud motors that recently appeared on the drilling scene is significantly affecting drilling efficiency worldwide. These motors provide drillers with increased horsepower at the bit, higher torque, and faster rates of penetration (ROP). With advanced engineering and more durable materials, motor life is being extended, thereby increasing the time between bit trips and reducing drilling costs. This article reviews the performance, design, and operation of these motors.

  3. Aspirin for Reducing Cancer Metastases?

    PubMed Central

    Henschke, Ulrich K.; Luande, G. Jeff; Choppala, Johnson D.

    1977-01-01

    Distant metastases are the principal cause of death from cancer. Many animal experiments in the last 25 years have shown consistently that distant metastases can be significantly reduced by anticoagulants and fibrinolytic agents. Since aspirin inhibits platelet function and increases fibrinolytic activity in humans, it may be effective in preventing metastases in cancer patients. It is suggested that aspirin be offered as an option to cancer patients who are at risk for distant metastases. PMID:904011

  4. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a, Abacavir sulfate/lamivudine, Adalimumab, Aliskiren fumarate, Ambrisentan, Aripiprazole, AT-7519, Atazanavir sulfate, Atomoxetine hydrochloride, Azacitidine, Azelnidipine; Besifloxacin hydrochloride, Bevacizumab, Bioabsorbable everolimus-eluting coronary stent, Bortezomib, Bosentan, Budesonide/formoterol fumarate; CAIV-T, Carisbamate, Casopitant mesylate, Certolizumab pegol, Cetuximab, Ciclesonide, Ciprofloxacin/dexamethasone, CTCE-9908; Dalcetrapib, Darunavir, Deferasirox, Desloratadine, Disitertide, Drotrecogin alfa (activated), DTA-H19, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Efalizumab, Emtricitabine, Eribulin mesilate, Escitalopram oxalate, Eszopiclone, EUR-1008, Everolimus-eluting coronary stent, Exenatide; Fampridine, Fluticasone furoate, Formoterol fumarate/fluticasone propionate, Fosamprenavir calcium, Fulvestrant; Gabapentin enacarbil, GS-7904L; HPV-6/11/16/18, Human Secretin, Hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, Imexon, Inalimarev/Falimarev, Indacaterol, Indacaterol maleate, Inhalable human insulin, Insulin detemir, Insulin glargine, Ixabepilone; L-Alanosine, Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Loratadine/montelukast sodium, Lutropin alfa; MeNZB, Mepolizumab, Micafungin sodium, Morphine hydrochloride; Nabiximols, Nikkomycin Z; Olmesartan medoxomil, Omalizumab; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Perifosine, PF-489791, Plitidepsin, Posaconazole, Pregabalin; QAX-576; Raltegravir potassium, Ramelteon, Rasagiline

  5. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide

  6. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Activated protein C concentrate, Ad-CD154, Adeno-Interferon gamma, alemtuzumab, APC-8024, 9-aminocamptothecin, aprepitant, l-arginine hydrochloride, aripiprazole, arsenic trioxide, asimadoline; O6-Benzylguanine, bevacizumab, Bi-20, binodenoson, biphasic insulin aspart, bivatuzumab, 186Re-bivatuzumab, BMS-181176, bosentan, botulinum toxin type B, BQ-123, bryostatin 1; Carboxy- amidotriazole, caspofungin acetate, CB-1954, CC-4047, CDP-860, cerivastatin sodium, clevidipine, CTL-102; 3,4-DAP, darbepoetin alfa, decitabine, desloratadine, DHA-paclitaxel, duloxetine hydrochloride; Efalizumab, EGF vaccine, eletriptan, eniluracil, ENMD-0997, eplerenone, eplivanserin, erlosamide, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, eszopiclone, everolimus, exatecan mesilate, exenatide, ezetimibe; Fondaparinux sodium, FR-901228, FTY-720; Gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride; Hexyl insulin M2, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, iodine (I131) tositumomab, ISV-205, ivabradine hydrochloride, ixabepilone; Levetiracetam, levocetirizine, linezolid, liposomal NDDP, lonafarnib, lopinavir, LY-156735; Mafosfamide cyclohexylamine salt, magnesium sulfate, maxacalcitol, meclinertant, melagatran, melatonin, MENT, mepolizumab, micafungin sodium, midostaurin, motexafin gadolinium; Nesiritide, NS-1209, NSC-601316, NSC-683864; Osanetant; Palonosetron hydrochloride, parecoxib sodium, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegylated OB protein, pemetrexed disodium, perillyl alcohol, picoplatin, pimecrolimus, pixantrone maleate, plevitrexed

  7. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-10-01

    Gateways to clinical trials is a guide to the most recent trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (+)-Dapoxetine hydrochloride, (S)-Tenatoprazole sodium salt monohydrate 19-28z, Acotiamide hydrochloride hydrate, ADV-TK, AE-37, Aflibercept, Albinterferon alfa-2b, Aliskiren fumarate, Asenapine maleate, Axitinib; Bavituximab, Becatecarin, beta-1,3/1,6-Glucan, Bevacizumab, Bremelanotide; Calcipotriol/betamethasone dipropionate, Casopitant mesylate, Catumaxomab, CDX-110, Cediranib, CMD-193, Cositecan; Darinaparsin, Denosumab, DP-b99, Duloxetine hydrochloride; E75, Ecogramostim, Elacytarabine, EMD-273063, EndoTAG-1, Enzastaurin hydrochloride, Eplerenone, Eribulin mesilate, Esomeprazole magnesium, Etravirine, Everolimus, Ezetimibe; Faropenem daloxate, Febuxostat, Fenretinide; Ghrelin (human); I-131 ch-TNT-1/B, I-131-3F8, Iclaprim, Iguratimod, Iloperidone, Imatinib mesylate, Inalimarev/Falimarev, Indacaterol, Ipilimumab, Iratumumab, Ispinesib mesylate, Ixabepilone; Lapatinib ditosylate, Laquinimod sodium, Larotaxel dehydrate, Linezolid, LOR-2040; Mapatumumab, MKC-1, Motesanib diphosphate, Mycophenolic acid sodium salt; NK-012; Olanzapine pamoate, Oncolytic HSV, Ortataxel; Paclitaxel nanoparticles, Paclitaxel poliglumex, Paliperidone palmitate, Panitumumab, Patupilone, PCV-9, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pertuzumab, Picoplatin, Pimavanserin tartrate, Pimecrolimus, Plerixafor hydrochloride, PM-02734, Poly I:CLC, PR1, Prasugrel, Pregabalin, Progesterone caproate, Prucalopride, Pumosetrag hydrochloride; RAV-12, RB-006, RB-007, Recombinant human erythropoietin alfa, Rimonabant, Romidepsin; SAR-109659, Satraplatin, Sodium butyrate; Tadalafil, Talampanel, Tanespimycin, Tarenflurbil, Tariquidar

  8. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine

  9. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab, BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B, BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride, CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa, desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA-paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated), duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569, elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI-2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab, ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184, semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin

  10. Treatment of chronic hepatitis C genotype 3 with Sofosbuvir-based therpy: a real-life study.

    PubMed

    Sidhu, Sandeep Singh; Malhi, Nirmaljeet Singh; Goyal, Omesh; Singh, Rupinder; Dutta, Usha; Grover, Rajiv; Sidhu, J S; Nanda, Vijay; Saluja, Harmeet; Bansal, Ajesh; Singh, Gursewak; Sehgal, Alok; Kishore, Harsh; Sidhu, Simran

    2017-05-01

    Recently, Sofosbuvir was launched in India at affordable cost. We conducted a real-life study to determine the efficacy and safety of Sofosbuvir plus Ribavirin, with and without peginterferon-alfa 2a, in patients with chronic hepatitis C (CHC) genotype 3, the commonest genotype in South Asia. This study included data of CHC patients from 11 sites in northern India between March 2015 and December 2015 (n = 1203). Patients with CHC genotype 3 (n = 931), who were treated with either Sofosbuvir 400 mg plus weight-based Ribavirin, daily ×24 weeks (n = 432) (dual therapy), or Peginterferon-α2a 180 mcg weekly, Sofosbuvir 400 mg plus weight-based Ribavirin, daily ×12 weeks (n = 499) (triple therapy) were included for analysis. Primary outcome was the proportion of patients achieving sustained viral response at 12 weeks post-therapy. The overall SVR rates were 91 and 92% in the dual and triple therapy arms, respectively. The SVR rates in treatment experienced were 67 and 74% versus 93 and 96% in naïve patients, on the dual and triple therapy arms, respectively. The SVR rates of cirrhotics were 73 and 75% on the dual and triple treatment arms, respectively. The SVR rates were low in the experienced cirrhotic patients: 44% (dual therapy) and 58% (triple therapy). Common adverse events were fatigue, headache, and myalgia. Both dual and triple therapy regimes resulted in SVR rates of >95% in CHC genotype 3 who were naive non-cirrhotics. However, the SVR rates were low in treatment-experienced cirrhotics.

  11. MapReduce SVM Game

    DOE PAGES

    Vineyard, Craig M.; Verzi, Stephen J.; James, Conrad D.; ...

    2015-08-10

    Despite technological advances making computing devices faster, smaller, and more prevalent in today's age, data generation and collection has outpaced data processing capabilities. Simply having more compute platforms does not provide a means of addressing challenging problems in the big data era. Rather, alternative processing approaches are needed and the application of machine learning to big data is hugely important. The MapReduce programming paradigm is an alternative to conventional supercomputing approaches, and requires less stringent data passing constrained problem decompositions. Rather, MapReduce relies upon defining a means of partitioning the desired problem so that subsets may be computed independently andmore » recom- bined to yield the net desired result. However, not all machine learning algorithms are amenable to such an approach. Game-theoretic algorithms are often innately distributed, consisting of local interactions between players without requiring a central authority and are iterative by nature rather than requiring extensive retraining. Effectively, a game-theoretic approach to machine learning is well suited for the MapReduce paradigm and provides a novel, alternative new perspective to addressing the big data problem. In this paper we present a variant of our Support Vector Machine (SVM) Game classifier which may be used in a distributed manner, and show an illustrative example of applying this algorithm.« less

  12. MapReduce SVM Game

    SciTech Connect

    Vineyard, Craig M.; Verzi, Stephen J.; James, Conrad D.; Aimone, James B.; Heileman, Gregory L.

    2015-08-10

    Despite technological advances making computing devices faster, smaller, and more prevalent in today's age, data generation and collection has outpaced data processing capabilities. Simply having more compute platforms does not provide a means of addressing challenging problems in the big data era. Rather, alternative processing approaches are needed and the application of machine learning to big data is hugely important. The MapReduce programming paradigm is an alternative to conventional supercomputing approaches, and requires less stringent data passing constrained problem decompositions. Rather, MapReduce relies upon defining a means of partitioning the desired problem so that subsets may be computed independently and recom- bined to yield the net desired result. However, not all machine learning algorithms are amenable to such an approach. Game-theoretic algorithms are often innately distributed, consisting of local interactions between players without requiring a central authority and are iterative by nature rather than requiring extensive retraining. Effectively, a game-theoretic approach to machine learning is well suited for the MapReduce paradigm and provides a novel, alternative new perspective to addressing the big data problem. In this paper we present a variant of our Support Vector Machine (SVM) Game classifier which may be used in a distributed manner, and show an illustrative example of applying this algorithm.

  13. Interventions to Reduce Sedentary Behavior

    PubMed Central

    Manini, Todd M.; Carr, Lucas J.; King, Abby C.; Marshall, Simon; Robinson, Thomas N.; Rejeski, W. Jack

    2014-01-01

    Purpose This paper reports on presentations and discussion from the working group on “Influences on Sedentary Behavior & Interventions” as part of the Sedentary Behavior: Identifying Research Priorities Workshop. Methods Interventions were discussed in the context of targeting sedentary behavior (SB) as a concept distinct from physical activity (PA). It was recommended that interventions targeting SB should consider a life course perspective, a position predicated on the assumption that SB is age and life stage dependent. Additionally, targeting environments where individuals have high exposure to SB— such as workplace sitting— could benefit from new technology (e.g., computer-based prompting to stand or move), environmental changes (e.g., active workstations), policies targeting reduced sedentary time (e.g., allowing employees regular desk breaks), or by changing norms surrounding prolonged sitting (e.g., standing meetings). Results & Conclusions There are limited data about the minimal amount of SB change required to produce meaningful health benefits. In addition to developing relevant scientific and public health definitions of SB, it is important to further delineate the scope of health and quality of life outcomes associated with reduced SB across the life course, and clarify what behavioral alternatives to SB can be used to optimize health gains. SB interventions will benefit from having more clarity about the potential physiological and behavioral synergies with current PA recommendations, developing multi-level interventions aimed at reducing SB across all life phases and contexts, harnessing relevant and effective strategies to extend the reach of interventions to all sectors of society, as well as applying state-of-the-science adaptive designs and methods to accelerate advances in the science of sedentary behavior interventions. PMID:25222818

  14. Teleconsultations reduce greenhouse gas emissions.

    PubMed

    Oliveira, Tiago Cravo; Barlow, James; Gonçalves, Luís; Bayer, Steffen

    2013-10-01

    Health services contribute significantly to greenhouse gas emissions. New models of delivering care closer to patients have the potential to reduce travelling and associated emissions. We aimed to compare the emissions of patients attending a teleconsultation - an outpatient appointment using video-conferencing equipment - with those of patients attending a face-to-face appointment. We estimated the total distances travelled and the direct and indirect greenhouse gas emissions for 20,824 teleconsultations performed between 2004 and 2011 in Alentejo, a Portuguese region. These were compared to the distances and emissions that would have resulted if teleconsultations were not available and patients had to attend face-to-face outpatient appointments. Estimates were calculated using survey data on mode of transport, and national aggregate data for car engine size and fuel. A sensitivity analysis using the lower and upper quartiles for survey distances was performed. Teleconsultations led to reductions in distances and emissions of 95%. 2,313,819 km of travelling and 455 tonnes of greenhouse gas emissions were avoided (22 kg of carbon dioxide equivalent per patient). The incorporation of modes of transport and car engine size and fuel in the analysis led to emission estimates which were 12% smaller than those assuming all patients used an average car. The availability of remote care services can significantly reduce road travel and associated emissions. At a time when many countries are committed to reducing their carbon footprint, it is desirable to explore how these reductions could be incorporated into technology assessments and economic evaluations.

  15. [Methods of reducing peroperative bleeding].

    PubMed

    Brinquin, L; Ozcariz, D; Le Manach, Y; Sourd, J C; Bonsignour, J P

    1992-01-01

    The reduction of bleeding during surgery can be aimed at for two reasons: to facilitate the operation by providing a bloodless field and/or to avoid blood loss requiring compensation by transfusion. These aims can be reached by reducing blood pressure or by acting on blood-clotting. For inducing hypotension sodium nitroprussiate and isoflurane are mainly used. Complex and precise monitoring is required for patient safety. Two drugs have been used to diminish bleeding: desmopressin and aprotinin. With the latter an important reduction (40 to 50%) of the blood loss has been achieved.

  16. Reduced Vlasov-Maxwell simulations

    NASA Astrophysics Data System (ADS)

    Helluy, Philippe; Navoret, Laurent; Pham, Nhung; Crestetto, Anaïs

    2014-10-01

    In this paper we review two different numerical methods for Vlasov-Maxwell simulations. The first method is based on a coupling between a Discontinuous Galerkin (DG) Maxwell solver and a Particle-In-Cell (PIC) Vlasov solver. The second method only uses a DG approach for the Vlasov and Maxwell equations. The Vlasov equation is first reduced to a space-only hyperbolic system thanks to the finite-element method. The two numerical methods are implemented using OpenCL in order to achieve high performance on recent Graphic Processing Units (GPU).

  17. Combustion at reduced gravitational conditions

    NASA Technical Reports Server (NTRS)

    Berlad, A. L.; Wang, L. S.; Joshi, N.; Pai, C. I.

    1980-01-01

    The theoretical structures needed for the predictive analyses and interpretations for flame propagation and extinction for clouds of porous particulates are presented. Related combustion theories of significance to reduced gravitational studies of combustible media are presented. Nonadiabatic boundaries are required for both autoignition theory and for extinction theory. Processes that were considered include, pyrolysis and vaporization of particulates, heterogeneous and homogeneous chemical kinetics, molecular transport of heat and mass, radiative coupling of the medium to its environment, and radiative coupling among particles and volume elements of the combustible medium.

  18. Empowerment to reduce health disparities.

    PubMed

    Wallerstein, Nina

    2002-01-01

    This article articulates the theoretical construct of empowerment and its importance for health-enhancing strategies to reduce health disparities. Powerlessness is explored as a risk factor in the context of social determinants, such as poverty, discrimination, workplace hazards, and income inequities. Empowerment is presented and compared with social capital and community capacity as strategies to strengthen social protective factors. A case study of a youth empowerment and policy project in New Mexico illustrates the usefulness of empowerment strategies in both targeting social determinants, such as public policies which are detrimental to youth, and improving community capacities of youth to be advocates for social change. Challenges for future practice and research are articulated.

  19. Reducing violence in healthcare facilities.

    PubMed

    Vellani, Karim H

    2014-01-01

    Looking behind the statistics on increases in healthcare violence incidents, the author finds that these incidents directly impact a small percentage of employees. However he sees an opportunity for administrators and security professionals to use this heightened awareness to collaborate on comprehensive plans to manage workplace violence, not only to reduce the direct impact of workplace violence incidents, but also to mitigate the indirect impacts such as employee morale degradation, fear of workplace violence, and costs of workplace violence. In this article he provides the elements of an effective workplace violence management plan.

  20. Reducing rattlesnake-human conflicts

    USGS Publications Warehouse

    Nowak, Erika M.

    2006-01-01

    Arizona is home to 11 species of rattlesnakes. As rapidly growing Arizona communities move into formerly undeveloped landscapes, encounters between people and rattlesnakes increase. As a result, the management of nuisance snakes, or snakes found in areas where people do not want them, is increasingly important. Since 1994, the U.S. Geological Survey (USGS) has conducted research on the behavior and ecology of nuisance rattlesnake in Arizona national park units. A decade of research provides important insights into rattlesnake behavior that can be used by national parks and communities to reduce rattlesnake-human conflicts.

  1. Modified Process Reduces Porosity when Soldering in Reduced Gravity Environments

    NASA Technical Reports Server (NTRS)

    Watson, Kevin; Struk, Peter; Pettegrew, Richard; Downs, Robert; Haylett, Daniel

    2012-01-01

    A modified process yields lower levels of internal porosity for solder joints produced in reduced-gravity environments. The process incorporates both alternative materials and a modified procedure. The process provides the necessary cleaning action to enable effective bonding of the applied solder alloy with the materials to be joined. The modified process incorporates a commercially available liquid flux that is applied to the solder joint before heating with the soldering iron. It is subsequently heated with the soldering iron to activate the cleaning action of the flux and to evaporate most of the flux, followed by application of solder alloy in the form of commercially available solid solder wire (containing no flux). Continued heating ensures adequate flow of the solder alloy around and onto the materials to be joined. The final step is withdrawal of the soldering iron to allow alloy solidification and cooling of the solder joint.

  2. Reducing Misanthropic Memory Through Self-Awareness: Reducing Bias.

    PubMed

    Davis, Mark D

    2015-01-01

    Two experiments investigated the influence of self-awareness on misanthropic recall. Misanthropic recall is the tendency to recall more negative behaviors dispositionally attributed and positive behaviors situationally attributed than negative behaviors situationally attributed and positive behaviors dispositionally attributed. It was hypothesized that when one is self-aware, more systematic information processing would occur, thereby reducing misanthropic memory and influencing attitudinal judgments. The first experiment used a mirror and the second experiment used a live video to induce self-awareness. Participants were asked to form an impression of a group. The results of both experiments replicated the previously found pattern of misanthropic memory for non-self-aware participants (Ybarra & Stephan, 1996), and revealed less misanthropic recall bias in self-aware participants.

  3. Thiosulfate Reduces Calcium Phosphate Nephrolithiasis

    PubMed Central

    Asplin, John R.; Donahue, Susan E.; Lindeman, Christina; Michalenka, Anne; Strutz, Kelly Laplante; Bushinsky, David A.

    2009-01-01

    An uncontrolled trial reported that sodium thiosulfate reduces formation of calcium kidney stones in humans, but this has not been established in a controlled human study or animal model. Using the genetic hypercalciuric rat, an animal model of calcium phosphate stone formation, we studied the effect of sodium thiosulfate on urine chemistries and stone formation. We fed genetic hypercalciuric rats normal food with or without sodium thiosulfate for 18 wk and measured urine chemistries, supersaturation, and the upper limit of metastability of urine. Eleven of 12 untreated rats formed stones compared with only three of 12 thiosulfate-treated rats (P < 0.002). Urine calcium and phosphorus were higher and urine citrate and volume were lower in the thiosulfate-treated rats, changes that would increase calcium phosphate supersaturation. Thiosulfate treatment lowered urine pH, which would lower calcium phosphate supersaturation. Overall, there were no statistically significant differences in calcium phosphate supersaturation or upper limit of metastability between thiosulfate-treated and control rats. In vitro, thiosulfate only minimally affected ionized calcium, suggesting a mechanism of action other than calcium chelation. In summary, sodium thiosulfate reduces calcium phosphate stone formation in the genetic hypercalciuric rat. Controlled trials testing the efficacy and safety of sodium thiosulfate for recurrent kidney stones in humans are needed. PMID:19369406

  4. FIREhose: Reducing Data from FIRE

    NASA Astrophysics Data System (ADS)

    Fica, Haley Diane; Lambrides, Erini; Faherty, Jackie; Cruz, Kelle L.; BDNYC

    2016-01-01

    Brown dwarfs are stellar objects that do not have enough mass to ignite hydrogen fusion in their core. Their mass is between 0.08 solar masses and the mass of our sun. Brown dwarfs are very bright in the near-infrared wavelength band (0.8- 2.5 microns). We reduced data from the Folded-port InfraRed Echellette (FIRE) instrument on the Magellan Telescope at the Las Campanas Observatory. FIRE is a medium-resolution echelle spectrometer, whose data reduction results in a spectrum of a star. When reducing FIRE data, it is important to account for inconsistencies in the data, such as bad pixels, cosmic rays, and the effects of our atmosphere. Using the FIREhose pipeline, these inconsistencies can be accounted for and corrected using a A0 telluric with a known spectrum. After telluric correcting, the data reduction results in a primed spectrum for an object, which can then be used to determine an object's physical properties, such as atmospheric composition, radial velocity, effective temperature and surface gravity.

  5. Reduced discretization error in HZETRN

    SciTech Connect

    Slaba, Tony C.; Blattnig, Steve R.; Tweed, John

    2013-02-01

    The deterministic particle transport code HZETRN is an efficient analysis tool for studying the effects of space radiation on humans, electronics, and shielding materials. In a previous work, numerical methods in the code were reviewed, and new methods were developed that further improved efficiency and reduced overall discretization error. It was also shown that the remaining discretization error could be attributed to low energy light ions (A < 4) with residual ranges smaller than the physical step-size taken by the code. Accurately resolving the spectrum of low energy light particles is important in assessing risk associated with astronaut radiation exposure. In this work, modifications to the light particle transport formalism are presented that accurately resolve the spectrum of low energy light ion target fragments. The modified formalism is shown to significantly reduce overall discretization error and allows a physical approximation to be removed. For typical step-sizes and energy grids used in HZETRN, discretization errors for the revised light particle transport algorithms are shown to be less than 4% for aluminum and water shielding thicknesses as large as 100 g/cm{sup 2} exposed to both solar particle event and galactic cosmic ray environments.

  6. Reducing In-Stent Restenosis

    PubMed Central

    McDonald, Robert A.; Halliday, Crawford A.; Miller, Ashley M.; Diver, Louise A.; Dakin, Rachel S.; Montgomery, Jennifer; McBride, Martin W.; Kennedy, Simon; McClure, John D.; Robertson, Keith E.; Douglas, Gillian; Channon, Keith M.; Oldroyd, Keith G.; Baker, Andrew H.

    2015-01-01

    Background Drug-eluting stents reduce the incidence of in-stent restenosis, but they result in delayed arterial healing and are associated with a chronic inflammatory response and hypersensitivity reactions. Identifying novel interventions to enhance wound healing and reduce the inflammatory response may improve long-term clinical outcomes. Micro–ribonucleic acids (miRNAs) are noncoding small ribonucleic acids that play a prominent role in the initiation and resolution of inflammation after vascular injury. Objectives This study sought to identify miRNA regulation and function after implantation of bare-metal and drug-eluting stents. Methods Pig, mouse, and in vitro models were used to investigate the role of miRNA in in-stent restenosis. Results We documented a subset of inflammatory miRNAs activated after stenting in pigs, including the miR-21 stem loop miRNAs. Genetic ablation of the miR-21 stem loop attenuated neointimal formation in mice post-stenting. This occurred via enhanced levels of anti-inflammatory M2 macrophages coupled with an impaired sensitivity of smooth muscle cells to respond to vascular activation. Conclusions MiR-21 plays a prominent role in promoting vascular inflammation and remodeling after stent injury. MiRNA-mediated modulation of the inflammatory response post-stenting may have therapeutic potential to accelerate wound healing and enhance the clinical efficacy of stenting. PMID:26022821

  7. Reduced Mastication Impairs Memory Function.

    PubMed

    Fukushima-Nakayama, Y; Ono, Takehito; Hayashi, M; Inoue, M; Wake, H; Ono, Takashi; Nakashima, T

    2017-08-01

    Mastication is an indispensable oral function related to physical, mental, and social health throughout life. The elderly tend to have a masticatory dysfunction due to tooth loss and fragility in the masticatory muscles with aging, potentially resulting in impaired cognitive function. Masticatory stimulation has influence on the development of the central nervous system (CNS) as well as the growth of maxillofacial tissue in children. Although the relationship between mastication and cognitive function is potentially important in the growth period, the cellular and molecular mechanisms have not been sufficiently elucidated. Here, we show that the reduced mastication resulted in impaired spatial memory and learning function owing to the morphological change and decreased activity in the hippocampus. We used an in vivo model for reduced masticatory stimuli, in which juvenile mice were fed with powder diet and found that masticatory stimulation during the growth period positively regulated long-term spatial memory to promote cognitive function. The functional linkage between mastication and brain was validated by the decrease in neurons, neurogenesis, neuronal activity, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. These findings taken together provide in vivo evidence for a functional linkage between mastication and cognitive function in the growth period, suggesting a need for novel therapeutic strategies in masticatory function-related cognitive dysfunction.

  8. Reduced prefrontal connectivity in psychopathy.

    PubMed

    Motzkin, Julian C; Newman, Joseph P; Kiehl, Kent A; Koenigs, Michael

    2011-11-30

    Linking psychopathy to a specific brain abnormality could have significant clinical, legal, and scientific implications. Theories on the neurobiological basis of the disorder typically propose dysfunction in a circuit involving ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain imaging data to directly test whether psychopathy may indeed be associated with any structural or functional abnormality within this brain area. In this study, we employ two complementary imaging techniques to assess the structural and functional connectivity of vmPFC in psychopathic and non-psychopathic criminals. Using diffusion tensor imaging, we show that psychopathy is associated with reduced structural integrity in the right uncinate fasciculus, the primary white matter connection between vmPFC and anterior temporal lobe. Using functional magnetic resonance imaging, we show that psychopathy is associated with reduced functional connectivity between vmPFC and amygdala as well as between vmPFC and medial parietal cortex. Together, these data converge to implicate diminished vmPFC connectivity as a characteristic neurobiological feature of psychopathy.

  9. Reduced discretization error in HZETRN

    NASA Astrophysics Data System (ADS)

    Slaba, Tony C.; Blattnig, Steve R.; Tweed, John

    2013-02-01

    The deterministic particle transport code HZETRN is an efficient analysis tool for studying the effects of space radiation on humans, electronics, and shielding materials. In a previous work, numerical methods in the code were reviewed, and new methods were developed that further improved efficiency and reduced overall discretization error. It was also shown that the remaining discretization error could be attributed to low energy light ions (A < 4) with residual ranges smaller than the physical step-size taken by the code. Accurately resolving the spectrum of low energy light particles is important in assessing risk associated with astronaut radiation exposure. In this work, modifications to the light particle transport formalism are presented that accurately resolve the spectrum of low energy light ion target fragments. The modified formalism is shown to significantly reduce overall discretization error and allows a physical approximation to be removed. For typical step-sizes and energy grids used in HZETRN, discretization errors for the revised light particle transport algorithms are shown to be less than 4% for aluminum and water shielding thicknesses as large as 100 g/cm2 exposed to both solar particle event and galactic cosmic ray environments.

  10. Reduced vibration motor winding arrangement

    DOEpatents

    Slavik, C.J.; Rhudy, R.G.; Bushman, R.E.

    1997-11-11

    An individual phase winding arrangement having a sixty electrical degree phase belt width for use with a three phase motor armature includes a delta connected phase winding portion and a wye connected phase winding portion. Both the delta and wye connected phase winding portions have a thirty electrical degree phase belt width. The delta and wye connected phase winding portions are each formed from a preselected number of individual coils each formed, in turn, from an unequal number of electrical conductor turns in the approximate ratio of {radical}3. The individual coils of the delta and wye connected phase winding portions may either be connected in series or parallel. This arrangement provides an armature winding for a three phase motor which retains the benefits of the widely known and utilized thirty degree phase belt concept, including improved mmf waveform and fundamental distribution factor, with consequent reduced vibrations and improved efficiency. 4 figs.

  11. Reduced vibration motor winding arrangement

    DOEpatents

    Slavik, Charles J.; Rhudy, Ralph G.; Bushman, Ralph E.

    1997-01-01

    An individual phase winding arrangement having a sixty electrical degree phase belt width for use with a three phase motor armature includes a delta connected phase winding portion and a wye connected phase winding portion. Both the delta and wye connected phase winding portions have a thirty electrical degree phase belt width. The delta and wye connected phase winding portions are each formed from a preselected number of individual coils each formed, in turn, from an unequal number of electrical conductor turns in the approximate ratio of .sqroot.3. The individual coils of the delta and wye connected phase winding portions may either be connected in series or parallel. This arrangement provides an armature winding for a three phase motor which retains the benefits of the widely known and utilized thirty degree phase belt concept, including improved mmf waveform and fundamental distribution factor, with consequent reduced vibrations and improved efficiency.

  12. Moral Violations Reduce Oral Consumption

    PubMed Central

    Chan, Cindy; Van Boven, Leaf; Andrade, Eduardo B.; Ariely, Dan

    2014-01-01

    Consumers frequently encounter moral violations in everyday life. They watch movies and television shows about crime and deception, hear news reports of corporate fraud and tax evasion, and hear gossip about cheaters and thieves. How does exposure to moral violations influence consumption? Because moral violations arouse disgust and because disgust is an evolutionarily important signal of contamination that should provoke a multi-modal response, we hypothesize that moral violations affect a key behavioral response to disgust: reduced oral consumption. In three experiments, compared with those in control conditions, people drank less water and chocolate milk while (a) watching a film portraying the moral violations of incest, (b) writing about moral violations of cheating or theft, and (c) listening to a report about fraud and manipulation. These findings imply that “moral disgust” influences consumption in ways similar to core disgust, and thus provide evidence for the associations between moral violations, emotions, and consumer behavior. PMID:25125931

  13. Moral Violations Reduce Oral Consumption.

    PubMed

    Chan, Cindy; Van Boven, Leaf; Andrade, Eduardo B; Ariely, Dan

    2014-07-01

    Consumers frequently encounter moral violations in everyday life. They watch movies and television shows about crime and deception, hear news reports of corporate fraud and tax evasion, and hear gossip about cheaters and thieves. How does exposure to moral violations influence consumption? Because moral violations arouse disgust and because disgust is an evolutionarily important signal of contamination that should provoke a multi-modal response, we hypothesize that moral violations affect a key behavioral response to disgust: reduced oral consumption. In three experiments, compared with those in control conditions, people drank less water and chocolate milk while (a) watching a film portraying the moral violations of incest, (b) writing about moral violations of cheating or theft, and (c) listening to a report about fraud and manipulation. These findings imply that "moral disgust" influences consumption in ways similar to core disgust, and thus provide evidence for the associations between moral violations, emotions, and consumer behavior.

  14. Interventions to reduce school bullying.

    PubMed

    Smith, Peter K; Ananiadou, Katerina; Cowie, Helen

    2003-10-01

    In the last 2 decades, school bullying has become a topic of public concern and research around the world. This has led to action to reduce the problem. We review interventions targeted at the school level (for example, whole school policy, classroom climate, peer support, school tribunal, and playground improvement), at the class level (for example, curriculum work), and at the individual level (for example, working with specific pupils). Effectiveness of interventions has been sporadically assessed. We review several systematically evaluated, large-scale, school-based intervention programs. Their effectiveness has varied, and we consider reasons for this. We suggest ways to improve the evaluation and comparability of studies, as well as the effectiveness of future interventions.

  15. Quench cooling under reduced gravity.

    PubMed

    Chatain, D; Mariette, C; Nikolayev, V S; Beysens, D

    2013-07-01

    We report quench cooling experiments performed with liquid O(2) under different levels of gravity, simulated with magnetic gravity compensation. A copper disk is quenched from 300 to 90 K. It is found that the cooling time in microgravity is very long in comparison with any other gravity level. This phenomenon is explained by the insulating effect of the gas surrounding the disk. A weak gas pressurization (which results in subcooling of the liquid with respect to the saturation temperature) is shown to drastically improve the heat exchange, thus reducing the cooling time (about 20 times). The effect of subcooling on the heat transfer is analyzed at different gravity levels. It is shown that this type of experiment cannot be used for the analysis of the critical heat flux of the boiling crisis. The film boiling heat transfer and the minimum heat flux of boiling are analyzed as functions of gravity and subcooling.

  16. Family planning is reducing abortions.

    PubMed

    Clinton, H R

    1997-01-01

    This news brief presents the US President's wife's statement on the association between use of family planning and a decline in abortions worldwide. Hillary Rodham Clinton attended the Sixth Conference of Wives of Heads of State and Government of the Americas held in La Paz, Bolivia. The conference was suitably located in Bolivia, a country with the highest rates of maternal mortality in South America. Bolivia has responded by launching a national family planning campaign coordinated between government, nongovernmental, and medical organizations. Half of Bolivian women experience pregnancy and childbirth without the support of trained medical staff. Mortality from abortion complications account for about half of all maternal deaths in Bolivia. Voluntary family planning workers teach women about the benefits of child spacing, breast feeding, nutrition, prenatal and postpartum care, and safe deliveries. Bolivia has succeeded in increasing its contraceptive use rates and decreasing the number of safe and unsafe abortions. Bolivia's program effort was supported by USAID. USAID provided technical assistance and funds for the establishment of a network of primary health care clinics. Mrs. Clinton visited one such clinic in a poor neighborhood in La Paz, which in its first six months of operation provided 2200 consultations, delivered 200 babies, registered 700 new family planning users, and immunized 2500 children. Clinics such as this one will be affected by the US Congress's harsh cuts in aid, which reduce funding by 35% and delay program funding by 9 months. These US government cuts in foreign aid are expected to result in an additional 1.6 million abortions, over 8000 maternal deaths, and 134,000 infant deaths in developing countries. An investment in population assistance represents a sensible, cost-effective, and long-term strategy for improving women's health, strengthening families, and reducing abortion.

  17. Breastfeeding Reduces Childhood Obesity Risks.

    PubMed

    Wang, Liang; Collins, Candice; Ratliff, Melanie; Xie, Bin; Wang, Youfa

    2017-06-01

    The present study examined the effects of breastfeeding and its duration on the development of childhood obesity from 24 months through grade 6. U.S. longitudinal data collected from 1234 children were analyzed using logistic regression models and generalized estimating equation (GEE). Child height and weight were measured six times at ages of 24 months, 36 months, 54 months, grade 1, grade 3, and grade 6. During the early 1990s, prevalence of breastfeeding was low in the United States, 60% and 48% at 1 and 6 months, respectively. Nonsmoking, white, married mothers with both parents in the household, and with income above the poverty line, were more likely to breastfeed at 1 month of age of their babies. Obesity rate of the children increased with age from 24 months to grade 6. Logistic regression showed that breastfeeding at month 1 was associated with 53% (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.30-0.73) and 47% (OR: 0.53, 95% CI: 0.36-0.78) decreased risks for childhood obesity at grades 1 and 6, respectively. GEE analysis showed that breastfeeding at 1 month reduced risk for childhood obesity by 36% (95% CI: 0.47-0.88) from ages 24 months through grade 6. Regarding breastfeeding duration, more than 6 months (vs. never) was associated with a decreased risk for childhood obesity by 42% (OR: 0.58, 95% CI: 0.36-0.94). Breastfeeding at 1 month and more than 6 months reduced the risk of childhood obesity. Rate of breastfeeding was low in the United States in the 1990s, which may have had long-term implications on children.

  18. Pegylated interferon β-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study.

    PubMed

    Calabresi, Peter A; Kieseier, Bernd C; Arnold, Douglas L; Balcer, Laura J; Boyko, Alexey; Pelletier, Jean; Liu, Shifang; Zhu, Ying; Seddighzadeh, Ali; Hung, Serena; Deykin, Aaron

    2014-07-01

    taking study drug every 2 weeks, and 71 (14%) patients taking study drug every 4 weeks reported serious adverse events; relapse, pneumonia, and urinary tract infection were the most common. After 48 weeks, peginterferon beta-1a significantly reduced relapse rate compared with placebo. The drug might be an effective treatment for relapsing-remitting multiple sclerosis with less frequent administration than available treatments. Biogen Idec. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Reducing stillbirths: interventions during labour

    PubMed Central

    Darmstadt, Gary L; Yakoob, Mohammad Yawar; Haws, Rachel A; Menezes, Esme V; Soomro, Tanya; Bhutta, Zulfiqar A

    2009-01-01

    Background Approximately one million stillbirths occur annually during labour; most of these stillbirths occur in low and middle-income countries and are associated with absent, inadequate, or delayed obstetric care. The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care, including prompt recognition and management of intrapartum complications. The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematically examined. Methods We undertook a systematic review of the published literature, searching PubMed and the Cochrane Library, of trials and reviews (N = 230) that reported stillbirth or perinatal mortality outcomes for eight interventions delivered during labour. Where eligible randomised controlled trials had been published after the most recent Cochrane review on any given intervention, we incorporated these new trial findings into a new meta-analysis with the Cochrane included studies. Results We found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality, especially on stillbirths. Available evidence suggests that operative delivery, especially Caesarean section, contributes to decreased stillbirth rates. Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact, though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour. Planned Caesarean section for term breech presentation has been shown in a large randomised trial to reduce stillbirths, but the feasibility and consequences of implementing this intervention routinely in low-/middle-income countries add caveats to recommending its use. Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures, but studies have not demonstrated impact

  20. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-05-01

    (-)-Gossypol; Abacavir sulfate/lamivudine, ACAM-1000, ACE-011, Agomelatine, AGS-004, Alemtuzumab, Alvocidib hydrochloride, AMG-317, Amlodipine, Aripiprazole, Atazanavir sulfate, Azacitidine; Becatecarin, Belinostat, Bevacizumab, BMS-387032, BMS-690514, Bortezomib; Casopitant mesylate, Cetuximab, Choline fenofibrate, CK-1827452, Clofarabine, Conivaptan hydrochloride; Dabigatran etexilate, DADMe-Immucillin-H, Darbepoetin alfa, Darunavir, Dasatinib, DC-WT1, Decitabine, Deferasirox, Degarelix acetate, Denenicokin, Denosumab, Dienogest, Duloxetine hydrochloride; Ecogramostim, Eculizumab, Edoxaban tosilate, Elacytarabine, Elesclomol, Eltrombopag olamine, Enfuvirtide, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Etravirine; Flibanserin, Fludarabine, Fondaparinux sodium, Fosamprenavir calcium; Gefitinib, Genistein; I-131-L19-SIP, Idrabiotaparinux sodium, Imatinib mesylate, IMGN-901, Ipilimumab; Laromustine, Lenalidomide, Liposomal cisplatin, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Lopinavir/ritonavir; Maraviroc, MDV-3100, Mecasermin rinfabate, MP-470, Mycophenolic acid sodium salt; Naproxcinod, NB-002, Nesiritide, Nilotinib hydrochloride monohydrate, NK-012; Palonosetron hydrochloride, Panobinostat, Pegfilgrastim, Peginterferon alfa-2a, Pitavastatin calcium, PL-3994, Plerixafor hydrochloride, Plitidepsin, PM-10450; Raltegravir potassium, Recombinant human soluble thrombomodulin, ReoT3D, RHAMM R3 peptide, Rivaroxaban, Romiplostim, Rosuvastatin calcium, Rozrolimupab; Sabarubicin hydrochloride, Salinosporamide A, Sirolimus-eluting stent, Smallpox (Vaccinia) Vaccine, Live, Sorafenib; Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Teriparatide, Tipifarnib, Tipranavir, Trabectedin, Trifluridine/TPI; Vardenafil hydrochloride hydrate, Vinflunine, Volociximab, Vorinostat; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, Zoledronic acid monohydrate

  1. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adalimumab, alefacept, alemtuzumab, almotriptan, AMGN-0007, anakinra, anti-CTLA-4 Mab, L-arginine hydrochloride, arzoxifene hydrochloride, astemizole, atazanavir sulfate, atlizumab; Belimumab, BG-9928, binodenoson, bosentan, botulinum toxin type B, bovine lactoferrin, BufferGel; Caspofungin acetate, ciclesonide,cilomilast, ciluprevir, clofarabine, CVT-3146; Darbepoetin alfa, desloratadine, diflomotecan, doripenem, dronedarone hydrochloride, drotrecogin alfa (activated), DT388-GM-CSF, duloxetine hydrochloride, E-5564, efalizumab, enfuvirtide, esomeprazole magnesium, estradiol acetate, ETC-642, exenatide, exisulind, ezetimib; Febuxostat; Gallium maltolate, ganirelix acetate, garenoxacin mesilate, gefitinib; H11, HuMax; IL-15, IDD-1, IGIV-C, imatinib mesylate, ISIS-14803, ITF-1697, ivabradine hydrochloride; KRN-5500; L-365260, levetiracetam, levosimendan, licofelone, linezolid, LJP-1082, lopinavir lumiracoxib; MCC-478, melatonin, morphine hydrochloride, morphine-6-glucuronide, moxidectin; N-Acetylcarnosine, natalizumab, NM-702, NNC-05-1869, NSC-703940; Ocinaplon OM-89, omalizumab, omeprazole/ sodium bicarbonate, OPC-28326, ospemifene; PEG-filgrastim peginterferon alfa-2a, pegsunercept, pirfenidone, pralmorelin, pregabalin; Recombinant glucagon-like peptide-1 (7-36) amide, repifermin, RSD-1235; S-8184, selodenoson, sodium dichloroacetate, suberanilohydroxamic acid; TAS-102, terfenadine, teriparatide, tipranavir troxacitabine; Ximelagatran; YM-337. (c) 2003 Prous Science

  2. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2003-06-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AdGVVEGF121.10, anakinra, andolast, anidulafungin, APC-2059, l-arginine hydrochloride, aripiprazole, arzoxifene hydrochloride, asimadoline; Bexarotene, bimatoprost, bimosiamose, bizelesin, BMS-188667, botulinum toxin type B, bromfenac sodium, bryostatin 1; Cannabidiol, cariporide mesilate, CCI-1004, CDP-571, cerivastatin sodium, clevudine; Dalbavancin, darbepoetin alfa, decitabine, deligoparin sodium, diethylnorspermine, drotrecogin alfa (activated), DTaP-HBV-IPV/Hib-vaccine; E-5564, eculizumab, edodekin alfa, emtricitabine, enfuvirtide, (-)-epigallocatechin gallate, eplerenone, esomeprazole magnesium, etaquine, etoricoxib, ezetimibe; Fesoterodine, fipamezole hydrochloride, fondaparinux sodium, fosamprenavir calcium, frovatriptan, fulvestrant; Gadofosveset sodium, galiximab, ghrelin (human), glufosfamide; Homoharringtonine; Idraparinux sodium, imatinib mesylate, INS-37217; KRN-7000; L-651582, lafutidine, lanthanum carbonate, lenercept, levetiracetam, lusupultide; Magnesium sulfate, melatonin, mepolizumab, midostaurin, morphine hydrochloride, mozavaptan; Natalizumab, nesiritide; OPC-51803, oregovomab, oritavancin; Peginterferon alfa-2(a), pleconaril, plevitrexed, prasterone, pregabalin; Ranibizumab, Ro-31-7453, roxifiban acetate, rubitecan; SCV-07, SHL-749, sho-saiko-to, soblidotin, solifenacin succinate; Tegaserod maleate, telithromycin, tenecteplase, theraCIM, tipifarnib, travoprost; Valdecoxib, vardenafil hydrochloride hydrate, voriconazole; Ximelagatran; Ziprasidone hydrochloride, ZYC-00101. (c) 2003 Prous Science. All rights reserved.

  3. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-12-01

    [Methoxy-(11)C]PD-153035, 2-Methoxyestradiol; Adalimumab, Adecatumumab, Adefovir dipivoxil, ADH-1, ADX-10059, Aflibercept, AIR-human growth hormone, Aliskiren fumarate, AMG-221, Amlodipine besylate/olmesartan medoxomil, Aprepitant; Bavituximab, Bevacizumab, Bexarotene, BIBW-2992, BMS-690514, Bortezomib, Bosentan, Briakinumab; Capecitabine, Certolizumab pegol, Cetuximab, Cholecalciferol, Choline fenofibrate, Chorionic gonadotropin (human), Cixutumumab, Clopidogrel, CP-690550 citrate; Dabigatran, Dacetuzumab, Daclizumab, Dapagliflozin, Darbepoetin alfa, Dasatinib, Denosumab; Efavirenz, Elisidepsin, Enoxaparin, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Everolimus, Exenatide; Fenobam, Figitumumab, Filibuvir, Fondaparinux sodium, Fresolimumab; Gefitinib, Golimumab, Golnerminogene pradenovec; Ifosfamide, Imatinib mesylate, Ipilimumab, Ivabradine hydrochloride, Ixabepilone; Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liposomal vincristine, Liraglutide; M-118, Masitinib mesylate, Metformin hydrochloride, Micafungin sodium, Moxifloxacin hydrochloride; Neratinib; Oblimersen sodium, Ofatumumab, Olmesartan medoxomil; Paclitaxel nanoparticles, Palifosfamide lysine, Panobacumab, Panobinostat, Patupilone, Peginterferon alfa-2a, Pegylated arginine deiminase 20000, Piclozotan hydrochloride hydrate, Pixantrone maleate, Prasterone, Prasugrel, Prednisone, Progesterone, Prucalopride, pVGI.1 (VEGF-2); Retigabine, rhFSH, Rituximab, Rivaroxaban, Rosuvastatin calcium; Salinosporamide A, Selumetinib, Sipuleucel-T, Somatropin, Sorafenib, SSR-244738, Sunitinib malate; Tamoxifen citrate, Teduglutide, Telavancin hydrochloride, Telmisartan, Telmisartan/amlodipine, Telmisartan/hydrochlorothiazide, Temsirolimus, Tenofovir disoproxil fumarate, Tipifarnib, Tolvaptan, Trastuzumab, Trastuzumab-MCC-DM1, Travoprost, Tremelimumab; Valsartan/amlodipine besylate, Valsartan/amlodipine besylate/hydrochlorothiazide, Valsartan/hydrochlorothiazide, Vandetanib

  4. Variational integrators for reduced magnetohydrodynamics

    SciTech Connect

    Kraus, Michael; Tassi, Emanuele; Grasso, Daniela

    2016-09-15

    Reduced magnetohydrodynamics is a simplified set of magnetohydrodynamics equations with applications to both fusion and astrophysical plasmas, possessing a noncanonical Hamiltonian structure and consequently a number of conserved functionals. We propose a new discretisation strategy for these equations based on a discrete variational principle applied to a formal Lagrangian. The resulting integrator preserves important quantities like the total energy, magnetic helicity and cross helicity exactly (up to machine precision). As the integrator is free of numerical resistivity, spurious reconnection along current sheets is absent in the ideal case. If effects of electron inertia are added, reconnection of magnetic field lines is allowed, although the resulting model still possesses a noncanonical Hamiltonian structure. After reviewing the conservation laws of the model equations, the adopted variational principle with the related conservation laws is described both at the continuous and discrete level. We verify the favourable properties of the variational integrator in particular with respect to the preservation of the invariants of the models under consideration and compare with results from the literature and those of a pseudo-spectral code.

  5. Reduced friction engine tappet construction

    SciTech Connect

    Pieprzak, J.M.; Wilermet, P.A.

    1989-09-19

    This patent describes a tappet construction for the valve train of an internal combustion engine having an element of the valve train engaged by the tappet for moving the same. The tappet having an outer cup-shaped case member with side walls and an essentially flat bottom wall adapted to be engaged by a rotating cam member. The cam member having a circumferential base circle no-load portion and a countoured cam circumferential load portion, the cam member engaging the bottom wall to one side of its center to impart a rotative torque on the case. The case slidably and rotatably receiving therein in back-to-back relationship first and second channel-like members each having spaced side walls joined by a continuous essentially flat end wall, the first member being engageable by a portion of the engine element. The flat end walls of the members being adjacent one another and movable relative to each other to at times form a fluid chamber therebetween, a fluid inlet to the chamber and a source of fluid lubricant under pressure connected to the inlet for supplying lubricant at a pressure level greater than the force of the element and cam member against the first member and case to thereby effect separation of the end walls by a film of lubricant thereby reducing frictional resistance to rotation between the parts.

  6. Yolk androgens reduce offspring survival.

    PubMed Central

    Sockman, K W; Schwabl, H

    2000-01-01

    Females may favour some offspring over others by differential deposition of yolk hormones. In American kestrels (Falco sparverius), we found that yolks of eggs laid late in the sequence of a clutch had more testosterone (T) and androstenedione (A4) than yolks of first-laid eggs. To investigate the effects of these yolk androgens on nestling 'fitness', we injected both T and A4 into the yolks of first-laid eggs and compared their hatching time, nestling growth and nestling survival with those of first-laid eggs in which we injected vehicle as a control. Compared to controls, injection of T and A4 at a dose intended to increase their levels to those of later-laid eggs delayed hatching and reduced nestling growth and survival rates. Yolk androgen treatment of egg 1 had no effect on survival of siblings hatching from subsequently laid eggs. The adverse actions of yolk androgen treatment in the kestrel are in contrast to the favourable actions of yolk T treatment found previously in canaries (Serinus canaria). Additional studies are necessary in order to determine whether the deposition of yolk androgens is an adaptive form of parental favouritism or an adverse by-product of endocrine processes during egg formation. Despite its adaptive significance, such 'transgenerational' effects of steroid hormones may have helped to evolutionarily shape the hormonal mechanisms regulating reproduction. PMID:10983830

  7. Variational integrators for reduced magnetohydrodynamics

    NASA Astrophysics Data System (ADS)

    Kraus, Michael; Tassi, Emanuele; Grasso, Daniela

    2016-09-01

    Reduced magnetohydrodynamics is a simplified set of magnetohydrodynamics equations with applications to both fusion and astrophysical plasmas, possessing a noncanonical Hamiltonian structure and consequently a number of conserved functionals. We propose a new discretisation strategy for these equations based on a discrete variational principle applied to a formal Lagrangian. The resulting integrator preserves important quantities like the total energy, magnetic helicity and cross helicity exactly (up to machine precision). As the integrator is free of numerical resistivity, spurious reconnection along current sheets is absent in the ideal case. If effects of electron inertia are added, reconnection of magnetic field lines is allowed, although the resulting model still possesses a noncanonical Hamiltonian structure. After reviewing the conservation laws of the model equations, the adopted variational principle with the related conservation laws is described both at the continuous and discrete level. We verify the favourable properties of the variational integrator in particular with respect to the preservation of the invariants of the models under consideration and compare with results from the literature and those of a pseudo-spectral code.

  8. Reducing waste in Big D

    SciTech Connect

    Woods, R.

    1994-03-01

    The city of Dallas is in a unique position among major metropolitan areas of the US. Despite boasting a population of more than 1 million, which grows by 1.3% each year, and a municipal solid waste (MSW) stream averaging 1.2 million tons per year, the city -- the eighth-largest in the country -- has another 50 years of landfill disposal capacity left. This fact is even more impressive when one considers that Dallas' only municipal facility, known as the McCommas Bluff Landfill, accepted 33% more MSW in 1993 than in 1992. The positive landfill situation, however, does not mean Dallas lacks ambition for recycling and waste reduction. Last, April, the city set an aggressive goal of reducing 40% of its MSW from the landfill by 1997. To help reach this mark over the next three years, the city has banned lead-acid batteries, grass clippings, and leaves from landfills, mandated news and office paper collection, and set up a composting operation at the landfill. At present, Dallas recycles about 13% of its waste. Surprisingly, most of the residential recycling effort has been based on voluntary participation through dozens of drop-off sites scattered around the city, rather than on curbside service. The only curbside program the city is conducting is a once-per-week, blue bag pilot program involving 2,000 Dallas homes.

  9. Reduced neutral XLPE cable design

    SciTech Connect

    Valli, G.F.; Zawadzki, J.A.; Orton, H.E. )

    1990-04-01

    This paper describes the theoretical, laboratory and economic analyses undertaken to determine the optimum metallic concentric neutral design for its single conductor 750 and 500 kcmil aluminum XLPE 15 kV insulated concentric-neutral type feeder cables. The results suggest that reducing the cross-sectional area of this concentric neutral from the currently-recognized industry standard of 20 percent of the central conductor to 7% results in overall present-worth system cost saving of approximately $3 per conductor meter or approximately 22% of the cable first cost. The neutral configuration ultimately chosen to replace the previous standard 37 - number 14 AWG wires was 2 - 1 inch {times} 5 mil tinned copper tapes overlapped by 25%. Line voltage fault test were run in the high-power laboratory on samples with various neutral configurations to confirm they would successfully pass our worst-case fault duty of 10 kA for 20 cycles (i.e., .33 sec) with no reclosing.

  10. Neuromuscular Adaptations to Reduced Use

    NASA Technical Reports Server (NTRS)

    Ploutz-Snyder, Lori

    2009-01-01

    This viewgraph presentation reviews the studies done to reduce neuromuscular strength loss during unilateral lower limb suspension (ULLS). Since there are animals that undergo fairly long periods of muscular disuse without any or minimal muscular atrophy, there is an answer to that might be applicable to human in situations that require no muscular use to diminish the effects of muscular atrophy. Three sets of ULLS studies were reviewed indicated that muscle strength decreased more than the muscle mass. The study reviewed exercise countermeasures to combat the atrophy, including: ischemia maintained during Compound muscle action potential (CMAP), ischemia and low load exercise, Japanese kaatsu, and the potential for rehabilitation or situations where heavy loading is undesirable. Two forms of countermeasures to unloading have been successful, (1) high-load resistance training has maintained muscle mass and strength, and low load resistance training with blood flow restriction (LL(sub BFR)). The LL(sub BFR) has been shown to increase muscle mass and strength. There has been significant interest in Tourniquet training. An increase in Growth Hormone(GH) has been noted for LL(sub BFR) exercise. An experimental study with 16 subjects 8 of whom performed ULLS, and 8 of whom performed ULLS and LL(sub BFR) exercise three times per week during the ULLS. Charts show the results of the two groups, showing that performing LL(sub BFR) exercise during 30 days of ULLS can maintain muscle size and strength and even improve muscular endurance.

  11. Restricted sample variance reduces generalizability.

    PubMed

    Lakes, Kimberley D

    2013-06-01

    One factor that affects the reliability of observed scores is restriction of range on the construct measured for a particular group of study participants. This study illustrates how researchers can use generalizability theory to evaluate the impact of restriction of range in particular sample characteristics on the generalizability of test scores and to estimate how changes in measurement design could improve the generalizability of the test scores. An observer-rated measure of child self-regulation (Response to Challenge Scale; Lakes, 2011) is used to examine scores for 198 children (Grades K through 5) within the generalizability theory (GT) framework. The generalizability of ratings within relatively developmentally homogeneous samples is examined and illustrates the effect of reduced variance among ratees on generalizability. Forecasts for g coefficients of various D study designs demonstrate how higher generalizability could be achieved by increasing the number of raters or items. In summary, the research presented illustrates the importance of and procedures for evaluating the generalizability of a set of scores in a particular research context.

  12. SRBF: Speckle reducing bilateral filtering.

    PubMed

    Balocco, Simone; Gatta, Carlo; Pujol, Oriol; Mauri, Josepa; Radeva, Petia

    2010-08-01

    Speckle noise negatively affects medical ultrasound image shape interpretation and boundary detection. Speckle removal filters are widely used to selectively remove speckle noise without destroying important image features to enhance object boundaries. In this article, a fully automatic bilateral filter tailored to ultrasound images is proposed. The edge preservation property is obtained by embedding noise statistics in the filter framework. Consequently, the filter is able to tackle the multiplicative behavior modulating the smoothing strength with respect to local statistics. The in silico experiments clearly showed that the speckle reducing bilateral filter (SRBF) has superior performances to most of the state of the art filtering methods. The filter is tested on 50 in vivo US images and its influence on a segmentation task is quantified. The results using SRBF filtered data sets show a superior performance to using oriented anisotropic diffusion filtered images. This improvement is due to the adaptive support of SRBF and the embedded noise statistics, yielding a more homogeneous smoothing. SRBF results in a fully automatic, fast and flexible algorithm potentially suitable in wide ranges of speckle noise sizes, for different medical applications (IVUS, B-mode, 3-D matrix array US).

  13. Reducing power usage on demand

    NASA Astrophysics Data System (ADS)

    Corbett, G.; Dewhurst, A.

    2016-10-01

    The Science and Technology Facilities Council (STFC) datacentre provides large- scale High Performance Computing facilities for the scientific community. It currently consumes approximately 1.5MW and this has risen by 25% in the past two years. STFC has been investigating leveraging preemption in the Tier 1 batch farm to save power. HEP experiments are increasing using jobs that can be killed to take advantage of opportunistic CPU resources or novel cost models such as Amazon's spot pricing. Additionally, schemes from energy providers are available that offer financial incentives to reduce power consumption at peak times. Under normal operating conditions, 3% of the batch farm capacity is wasted due to draining machines. By using preempt-able jobs, nodes can be rapidly made available to run multicore jobs without this wasted resource. The use of preempt-able jobs has been extended so that at peak times machines can be hibernated quickly to save energy. This paper describes the implementation of the above and demonstrates that STFC could in future take advantage of such energy saving schemes.

  14. Does thermophoresis reduce aggregate stability?

    NASA Astrophysics Data System (ADS)

    Sachs, Eyal; Sarah, Pariente

    2017-04-01

    Thermophoresis is mass flow driven by a thermal gradient. As a result of Seebeck effect and Soret effect, colloids can move from the hot to the cold region or vice versa, depending on the electrolyte composition and on the particle size. This migration of colloids can weaken aggregates. The effect of raindrop temperatures on runoff generation and erosion on clayey soil was investigated in sprinkling experiments with a laboratory rotating disk rain simulator. The experiments were applied to Rhodoxeralt (Terra Rossa) soil with two pre-prepared moisture contents: hygroscopic and field capacity. For each moisture content three rainfall temperatures were applied: 2, 20, and 35°C. Erosion was generally lower in the pre-wetted soil than in the dry soil (12.5 and 24.4 g m-2 per 40 mm of rain,respectively). Whereas there was no significant effect of raindrop temperature on the dry soil the soil that was pre-moistened to field capacity was affected by rainwater temperature: runoff and erosion were high when the temperature difference between rainfall and soil surface was high, sediment yields were 13.9, 5.2, and 18.3 g m-2 per 40 mm of rain, for rain temperature of 2, 20, and 35 °C, respectively. It is reasonable to conclude that thermophoresis caused by thermal gradients within the soil solution reduces the stability of aggregates and then increase the soil losses.

  15. Bioventing reduces soil cleanup costs

    SciTech Connect

    Leahy, M.C.; Erickson, G.P.

    1995-08-01

    An offshoot technology from soil venting, bioventing offers a win-win solution for soils contaminated with volatile organic compounds (VOCs) and nonvolatile contaminants such as diesel and fuel oil. Using low air flowrates through permeable soils, bioventing injects sufficient oxygen to support naturally-occurring bacteria, which biodegraded the VOCs and other contaminants into benign byproducts. Waste gas can be directly discharged to atmosphere without further treatment. This results in no offgas treatment required. Bioventing is a cost-effective alternative to traditional soil-venting techniques. Soil venting uses air to volatilize organic-compound contamination from the vadose zone, the unsaturated soil layer above groundwater. Unfortunately, this simple-and-fast approach creates a waste offgas that requires further treatment before discharge, thus adding significantly to overall project costs. In contrast, bioventing uses low air flowrates, which require lower capital and operating costs. No offgas treatment further reduces equipment and operating costs and often eliminates air permitting. As in all treatment strategies, the process must meet the cleanup objectives. Bioventing is an alternative technique making inroads into refining and petrochemical soil-remediation applications.

  16. Regulating environments to reduce obesity.

    PubMed

    Hayne, Cheryl L; Moran, Patricia A; Ford, Mary M

    2004-01-01

    The marked increase in the prevalence of obesity appears to be attributable to environmental conditions that implicitly discourage physical activity while explicitly encouraging the consumption of greater quantities of energy-dense, low-nutrient foods. In the United States food environment, consumers are bombarded with advertising for unhealthy food, and receive inadequate nutritional information, especially at restaurants. In the US school environment children have access to sugary sodas and unhealthy a la carte foods in their cafeterias, at the same time getting inadequate physical activity and nutrition education. In the built environment, sprawl has reduced active living. We describe these environments and explore the potential effects of regulatory measures on these environments. In the United States, regulatory opportunities exist at the national, state and local levels to mandate action and to allocate funds for promising health-promoting strategies. Regulatory approaches, much like litigation, can transform the entire environment in which corporations operate. Even with incomplete enforcement of rules, they send a public message about what is acceptable behavior for corporations and individuals. Additionally, because the United States is party to many multilateral and bilateral trade agreements and is an active participant in the GATT/WTO framework, US regulatory actions promise to have a beneficial impact both domestically and globally.

  17. Peg-Interferon Lambda Treatment Induces Robust Innate and Adaptive Immunity in Chronic Hepatitis B Patients.

    PubMed

    Phillips, Sandra; Mistry, Sameer; Riva, Antonio; Cooksley, Helen; Hadzhiolova-Lebeau, Tanya; Plavova, Slava; Katzarov, Krum; Simonova, Marieta; Zeuzem, Stephan; Woffendin, Clive; Chen, Pei-Jer; Peng, Cheng-Yuan; Chang, Ting-Tsung; Lueth, Stefan; De Knegt, Robert; Choi, Moon-Seok; Wedemeyer, Heiner; Dao, Michael; Kim, Chang-Wook; Chu, Heng-Chen; Wind-Rotolo, Megan; Williams, Roger; Cooney, Elizabeth; Chokshi, Shilpa

    2017-01-01

    IFN-lambda (IFNλ) is a member of the type III IFN family and is reported to possess anti-pathogen, anti-cancer, and immunomodulatory properties; however, there are limited data regarding its impact on host immune responses in vivo. We performed longitudinal and comprehensive immunosurveillance to assess the ability of pegylated (peg)-IFNλ to augment antiviral host immunity as part of a clinical trial assessing the efficacy of peg-IFNλ in chronic hepatitis B (CHB) patients. These patients were pretreated with directly acting antiviral therapy (entecavir) for 12 weeks with subsequent addition of peg-IFNλ for up to 32 weeks. In a subgroup of patients, the addition of peg-IFNλ provoked high serum levels of antiviral cytokine IL-18. We also observed the enhancement of natural killer cell polyfunctionality and the recovery of a pan-genotypic HBV-specific CD4(+) T cells producing IFN-γ with maintenance of HBV-specific CD8(+) T cell antiviral and cytotoxic activities. It was only in these patients that we observed strong virological control with reductions in both viral replication and HBV antigen levels. Here, we show for the first time that in vivo peg-IFNλ displays significant immunostimulatory properties with improvements in the main effectors mediating anti-HBV immunity. Interestingly, the maintenance in HBV-specific CD8(+) T cells in the presence of peg-IFNλ is in contrast to previous studies showing that peg-IFNα treatment for CHB results in a detrimental effect on the functionality of this important antiviral T cell compartment. ClinicalTrials.gov NCT01204762.

  18. Interstitial pneumonia associated to peginterferon alpha-2a: A focus on lung function

    PubMed Central

    Cortés-Telles, Arturo

    2016-01-01

    Pulmonary toxicity related to the use of pegylated interferon alpha-2a during treatment of hepatitis C infections is rare; nonetheless, some cases with fatal outcomes have been reported. Evaluating patients’ pulmonary function is a key to diagnosis, follow-up and prognosis of several respiratory diseases, but case reports of respiratory manifestations related to the use of pegylated interferon alpha-2a have limited their findings to only baseline measurements. This paper examines the case of a 65-year-old woman with chronic hepatitis C virus infection who developed interstitial pneumonitis associated with pegylated interferon alpha-2a. Initial lung function evaluation revealed a marked reduction compared to an earlier assessment; the results were consistent with a moderate restricted pattern. Fortunately, over the ensuing 8 weeks of follow-up after discontinuing the drug, the patient recovered her lung function and experienced an overall improvement in her respiratory symptoms. PMID:27051119

  19. Bell's palsy associated with chronic HCV infection before and during peginterferon alfa and ribavirin therapy.

    PubMed

    Jabbari, Hossain; Fakharzadeh, Elham; Merat, Shahin; Zamini, Hedyeh; Sharifi, Amir Houshang

    2011-05-01

    Neuropsychiatric side effects of peg interferon-α (PEG-IFN-α) therapy consist of a large spectrum of symptoms. Organic personality syndrome, organic affective syndrome, psychotic manifestations and seizures are more common side effects of PEG-IFN-α whereas cranial neuropathy and movement disorders are less common. Bell's palsy is often idiopathic, but has been linked to some viral infections, particularly with herpes viruses. Other infections, such as human immunodeficiency virus infection and Lyme disease, may also lead to idiopathic facial paralysis. Neither acute nor chronic Hepatitis C infection has been implicated previously in Bell's palsy, but PEG-IFN-α may play a role. Two patients with CHC who developed Bell's palsy before and during treatment with PEG-IFN-α and Ribavirin are presented here.

  20. Simeprevir with peginterferon and ribavirin induced interstitial pneumonitis: first case report.

    PubMed

    Tamaki, Katsuyoshi; Okubo, Akihiko

    2015-01-21

    The effectiveness of hepatitis C treatment has improved with the development of interferon (IFN), and it has drastically improved with the development of peg-interferon-α (PEG-IFN) in combination with ribavirin (RBV) and, more recently, with the addition of a protease inhibitor. Simeprevir, which is a second-generation protease inhibitor, has shown clinically favorable safety and tolerability profiles. Simeprevir received its first global approval in Japan in September 2013 for the treatment of genotype 1 chronic hepatitis C in combination with PEG-IFN and RBV. One serious adverse event associated with IFN therapy is interstitial pneumonitis, which can be fatal. We experienced a patient with interstitial pneumonitis that was induced by simeprevir with PEG-IFN and RBV therapy for chronic hepatitis C in the early stages of therapy (8 wk after initiating therapy). This is the first case report of interstitial pneumonitis with simeprevir with PEG-IFN and RBV in the world. In addition, it is very interesting that the onset of interstitial pneumonitis was earlier than that in conventional PEG-IFN and RBV therapy. This finding suggests that simeprevir augments the adverse event. We present this case report in light of relevant literature on interstitial pneumonitis with conventional PEG-IFN and RBV therapy.

  1. Clearance of Hepatitis C Virus Improves Insulin Resistance During and After Peginterferon and Ribavirin Therapy.

    PubMed

    Chien, Cheng-Hung; Lin, Chih-Lang; Hu, Ching-Chih; Chang, Jia-Jang; Chien, Rong-Nan

    2015-12-01

    Patients with chronic hepatitis C virus (HCV) infection are at a greater risk of developing insulin resistance (IR). However, little is known about when insulin sensitivity may improve during or after treatment for hepatitis C. In this study, we examined the effect of combination therapy with pegylated interferon-α and ribavirin on IR in patients with chronic HCV infection. We also analyzed factors associated with changes in insulin sensitivity. IR was estimated by homeostasis model assessment (HOMA-IR). HOMA-IR was measured before therapy, during therapy (12 and 24 weeks), and at the end of therapy (EOT; 24 or 48 weeks). We analyzed 78 HCV patients receiving combination therapy. Twenty-two patients (28.2%) exhibited pretreatment IR (HOMA-IR >2.5). In all patients, HOMA-IR was not significantly different from baseline values at 12 weeks (P = 0.823), 24 weeks (P = 0.417), or at EOT (P = 0.158). In patients with pretreatment IR, a significant decrease in HOMA-IR was observed at 12 weeks (P = 0.023), 24 weeks (P = 0.008), and at EOT (P = 0.002). Multivariate analysis using a logistic regression model showed that baseline HOMA-IR is the only factor associated with the decline in HOMA-IR during and after therapy. The eradication of HCV infection was associated with improved insulin sensitivity among patients with pretreatment IR. This significant improvement in insulin sensitivity may occur as early as 12 weeks after the initiation of antiviral therapy.

  2. DO SONS REDUCE PARENTAL MORTALITY?

    PubMed Central

    Pham-Kanter, Genevieve; Goldman, Noreen

    2013-01-01

    BACKGROUND Although sons are thought to impose greater physiological costs on mothers than daughters, sons may be advantageous for parental survival in some social contexts. We examined the relationship between the sex composition of offspring and parental survival in contemporary China and Taiwan. Because of the importance of sons for the provision of support to elderly parents in these populations, we hypothesized that sons would have a beneficial effect on parental survival relative to daughters. METHODS We used data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) and the Taiwan Longitudinal Study of Aging (TLSA). Our CLHLS sample consisted of 4132 individuals ages 65+ in 2002. Our TLSA sample comprised two cohorts: 3409 persons aged 60+ in 1989 and 2193 persons aged 50–66 in 1996.These cohorts were followed for 3, 18, and 11 years, respectively. We used Cox proportional hazards models to estimate the relationship between the sex composition of offspring and parental mortality. RESULTS Based on 7 measures of sex composition, we find no protective effect of sons in either China or Taiwan. For example, in the 1989 Taiwan sample, the hazard ratio for maternal mortality associated with having an eldest son is 0.979 (95% CI (0.863, 1.111)). In Taiwan, daughters may have been more beneficial than sons in reducing mortality in recent years. CONCLUSION We offer several explanations for these findings, including possible benefits associated with emotional and interpersonal forms of support provided by daughters and negative impacts of conflicts arising between parents and resident daughters-in-law. PMID:21551178

  3. Reducing lead exposure in children

    SciTech Connect

    Farfel, M.R.

    1985-01-01

    The near elimination of lead-related childhood fatalities and encephalopathy by the 1970s and the sharp decline in mean blood lead levels nationwide documented between 1976 and 1980 are two milestones in the fight against lead poisoning. In the case of the latter, we know the antecedents, such as controls on the sale, use, and lead content of lead paint, improved chelation therapy, and increased awareness and case finding; however, the antecedents' relative contributions are not known due to a lack of evaluation. Similarly, the effect of a variety of social-welfare programs has not been evaluated. Since the 1970s, our perception of the problem of lead toxicity and consequently its control has changed. First steps have been made toward attaining one primary preventive objective, controlling the multiple sources of new inputs of lead to the biosphere that contribute to asymptomatic lead toxicity. The lead content of widely used commodities has been reduced (canned foods and gasoline) or virtually eliminated (paint). The benefits of passive measures used to attain reductions in lead exposure have been documented to a greater extent than those of active programs. The best example of a successful primary and passive preventive measure is the availability of lead-free gasoline since 1974, which largely accounts for decreases in ambient air lead concentrations nationwide and the recent shift to lower values in the distribution curve of children's blood lead levels. The latter provides a margin of safety for children before known toxic levels are reached. The contribution of reductions in dietary lead to changes in blood lead levels has not been well documented. Studies also show the benefits of the use of lead-free paint in new housing. Compared to children living in older homes with deteriorating lead paint, those living in lead-free homes are at low risk for lead toxicity.

  4. Reducing abortion: the Danish experience.

    PubMed

    Risor, H

    1989-01-01

    In 1987, 20,830 legal abortions were performed in Denmark. 2,845 involved women below the age of 20, and 532 involved women terminating pregnancy after the 12th week. Danish law permits all of its female citizens to have an abortion free-of-charge before the 12th week of pregnancy. After the 12th week, the abortion must be applied for through a committee of 3 members, and all counties in Denmark have a committee. It is felt in Denmark that a woman has a right to an abortion if she decides to have one. It she makes that choice, doctors and nurses are supportive. Since 1970, sex education has been mandatory in Danish schools. Teachers often collaborate closely with school doctors and nurses in this education. All counties are required to have at least 1 clinic that provides contraceptive counselling. It was recently found that the lowest number of pregnancies among teenaged girls was found in a county in Jutland where all 9th grade students visit the county clinic to learn about contraceptives, pregnancy, and abortion. Within 1 year after Copenhagen had adopted this practice, the number of abortions among teenagers declined by 20%. One fourth of all pharmacies also collaborate with schools to promote sex education, instructing students about contraceptives and pregnancy tests. The Danish Family Planning Association has produced a film on abortion, and plans to produce videos on abortion for use in schools. The organization also holds training programs for health care personnel on contraception, pregnancy, and abortion. By means of the practices described above, it is hoped that the number of abortions and unwanted pregnancies in Denmark will be reduced.

  5. Meditation can reduce habitual responding.

    PubMed

    Wenk-Sormaz, Heidi

    2005-01-01

    Although cognitive aspects of meditation underlie much of its clinical application, very little research has examined meditation's cognitive consequences. This investigation provides experimental support for the idea that meditation leads to a reduction in habitual responding using randomly selected subjects, a secular form of meditation, and a full experimental design. To test the hypothesis that meditation leads to a reduction in habitual responding. Studies 1 and 2 each incorporated pre-test and post-test designs with a 20-minute intervening attention task (meditation, rest, or a cognitive control). Yale University in New Haven, Conn, and the University of California, Berkeley. One hundred and twenty and 90 undergraduates participated in Studies 1 and 2, respectively. Stroop and Word Production (category generation and stem-completion) tasks assessed habitual responding in Study 1. Galvanic Skin response measured arousal in Study 1. The category generation task assessed habitual responding in Study 2. Tellegen's Absorption Scale (TAS) measured attention ability. In Study 1, meditation participants showed a reduction in habitual responding on the Stroop task as compared to controls. Study 1 revealed no statistically significant effects in the word production task. Stroop task performance was not mediated by arousal reduction. In Study 2, meditation participants showed a reduction in habitual responding on the category production task. Specifically, when participants generated either typical or atypical items, on average, meditation participants produced more atypical items than controls. Category production performance was not mediated by Tellegen's Absorption Scale (TAS) scores. Overall, high TAS scores were related to atypical responding. Across cognitive tasks, when participants understood that the goal was to respond non-habitually, meditation reduced habitual responding.

  6. Hyaluronidase for reducing perineal trauma.

    PubMed

    Zhou, Fan; Wang, Xiao Dong; Li, Jing; Huang, Gui Qiong; Gao, Bing Xin

    2014-02-05

    Perineal hyaluronidase (HAase) injection was widely used to reduce the occurrence of perineal trauma, pain and need for episiotomy in the 1950s to 1960s. Reports suggested that the administration of HAase was a simple, low risk, low cost and effective way to decrease perineal trauma without adverse effects. The objective of this review was to assess the effectiveness and safety of perineal HAase injection for reducing spontaneous perineal trauma, episiotomy and perineal pain in vaginal deliveries. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2013), the International Clinical Trials Registry Platform (ICTRP) and the Networked Digital Library of Theses and Dissertations (both on 1 April 2013), and reference lists of retrieved studies. We also contacted relevant organisations. Published and unpublished randomised and quasi-randomised controlled trials comparing perineal HAase injection with placebo injection or no intervention in vaginal deliveries. Two review authors independently assessed trials for inclusion, extracted data and evaluated methodological quality. Data were checked for accuracy. The search strategy identified six potentially eligible studies. Two studies were excluded. We included four randomised controlled trials that randomised a total of 599 women (data were available for 595 women).Two trials (283 women) compared the effects of perineal HAase injection during the second stage of labour with placebo injection and were at low risk of bias. Three trials (one three-armed trial was analysed twice) (373 women) compared the effects of perineal HAase injection during second stage of labour with no intervention and two out of the three trials were at high risk of bias. Data from four trials involving 599 women suggested that perineal HAase injection during second stage of labour had a lower incidence of perineal trauma (average risk ratio (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.95,Tau² = 0.08, I² = 82

  7. 40 CFR 1500.4 - Reducing paperwork.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Reducing paperwork. 1500.4 Section 1500.4 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY PURPOSE, POLICY, AND MANDATE § 1500.4 Reducing paperwork. Agencies shall reduce excessive paperwork by: (a) Reducing the length of environmental...

  8. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-01-01

    4; NBI-56418, NCX-4016, nesiritide, nicotine conjugate vaccine, NSC-330507; Oglufanide, omalizumab, oxipurinol; Palifermin, palonosetron hydrochloride, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, PEGylated interferon alfacon-1, perospirone hydrochloride, pimecrolimus, pixantrone maleate, plerixafor hydrochloride, PowderJect lidocaine, pradefovir mesylate, prasterone, pregabalin, Prostvac VF, PT-141, PTC-124, pyridoxamine; QS-21, quercetin; R-126638, R-411, ralfinamide, rasagiline mesilate, rF-PSA, RG-2077, rhThrombin, rimonabant hydrochloride, rofecoxib, rosuvastatin calcium, rotigotine hydrochloride, rV-PSA; S-18886, S-303, seocalcitol, SGN-40, sitaxsentan sodium, SPP-301, St. John's Wort extract; Tadalafil, taxus, telithromycin, tenatoprazole, tenofovir disoproxil fumarate, testosterone MDTS, testosterone transdermal patch, tgAAC-09, TH-9507, thioacetazone, tipifarnib, TQ-1011, trabectedin, travoprost, trimethoprim; Valdecoxib, valganciclovir hydrochloride, valopicitabine, voriconazole; Xcellerated T cells.

  9. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-03-01

    , mycophenolate mofetil, mycophenolic acid sodium salt; Nitisinone; Omalizumab, omapatrilat, ONYX-015, oxaliplatin; Paclitaxel, paclitaxel nanoparticles, panitumumab, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pertuzumab, phosphatidylcholine-rich phospholipid mixture, pimecrolimus, pioglitazone hydrochloride, pramlintide acetate, prasterone; QR-333; Ranelic acid distrontium salt, ranolazine, rasagiline mesilate, RFB4(dsFv)-PE38, ribavirin, rifabutin, risperidone, rituximab, rofecoxib, rosiglitazone maleate, rosiglitazone maleate/metformin hydrochloride, rotavirus vaccine; S-236, salmeterol xinafoate, sarizotan hydrochloride, sildenafil, sildenafil citrate, sunitinib malate; Tadalafil, tegaserod maleate, temozolomide, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, trabectedin, treprostinil sodium; Vandetanib, vardenafil hydrochloride hydrate, vatalanib succinate, vinflunine, virosome influenza vaccine, voriconazole; Zidovudine.

  10. Reducing Sugar in Children's Diets: Why? How?

    ERIC Educational Resources Information Center

    Rogers, Cosby S.; Morris, Sandra S.

    1986-01-01

    Maintains that sugar intake should be reduced in young children's diets because of its link to dental cavities, poor nutrition, and obesity. Reducing the focus on sweetness, limiting sugar consumption, and using natural sources of sweetness and other treats are ways to help reduce sugar intake. (BB)

  11. 21 CFR 582.5375 - Iron reduced.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Iron reduced. 582.5375 Section 582.5375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5375 Iron reduced. (a) Product. Iron reduced. (b) Conditions of use. This substance is...

  12. 21 CFR 582.5375 - Iron reduced.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Iron reduced. 582.5375 Section 582.5375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5375 Iron reduced. (a) Product. Iron reduced. (b) Conditions of use. This substance is...

  13. 21 CFR 582.5375 - Iron reduced.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Iron reduced. 582.5375 Section 582.5375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5375 Iron reduced. (a) Product. Iron reduced. (b) Conditions of use. This substance is...

  14. Reducing Sugar in Children's Diets: Why? How?

    ERIC Educational Resources Information Center

    Rogers, Cosby S.; Morris, Sandra S.

    1986-01-01

    Maintains that sugar intake should be reduced in young children's diets because of its link to dental cavities, poor nutrition, and obesity. Reducing the focus on sweetness, limiting sugar consumption, and using natural sources of sweetness and other treats are ways to help reduce sugar intake. (BB)

  15. 40 CFR 1500.4 - Reducing paperwork.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... environmental issues deserving of study, but also to deemphasize insignificant issues, narrowing the scope of... 1500.4 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY PURPOSE, POLICY, AND MANDATE § 1500.4 Reducing paperwork. Agencies shall reduce excessive paperwork by: (a) Reducing the length of...

  16. 40 CFR 1500.4 - Reducing paperwork.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... environmental issues deserving of study, but also to deemphasize insignificant issues, narrowing the scope of... 1500.4 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY PURPOSE, POLICY, AND MANDATE § 1500.4 Reducing paperwork. Agencies shall reduce excessive paperwork by: (a) Reducing the length of...

  17. 40 CFR 1500.4 - Reducing paperwork.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... environmental issues deserving of study, but also to deemphasize insignificant issues, narrowing the scope of... 1500.4 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY PURPOSE, POLICY, AND MANDATE § 1500.4 Reducing paperwork. Agencies shall reduce excessive paperwork by: (a) Reducing the length of...

  18. 40 CFR 1500.4 - Reducing paperwork.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... environmental issues deserving of study, but also to deemphasize insignificant issues, narrowing the scope of... 1500.4 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY PURPOSE, POLICY, AND MANDATE § 1500.4 Reducing paperwork. Agencies shall reduce excessive paperwork by: (a) Reducing the length of...

  19. 31 CFR 561.328 - Reduce significantly, significantly reduced, and significant reduction.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Reduce significantly, significantly reduced, and significant reduction. 561.328 Section 561.328 Money and Finance: Treasury Regulations... reduced, and significant reduction. The terms reduce significantly, significantly reduced, and significant...

  20. 31 CFR 561.328 - Reduce significantly, significantly reduced, and significant reduction.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Reduce significantly, significantly reduced, and significant reduction. 561.328 Section 561.328 Money and Finance: Treasury Regulations... reduced, and significant reduction. The terms reduce significantly, significantly reduced, and significant...

  1. Reduced Toxicity Fuel Satellite Propulsion System

    NASA Technical Reports Server (NTRS)

    Schneider, Steven J. (Inventor)

    2001-01-01

    A reduced toxicity fuel satellite propulsion system including a reduced toxicity propellant supply for consumption in an axial class thruster and an ACS class thruster. The system includes suitable valves and conduits for supplying the reduced toxicity propellant to the ACS decomposing element of an ACS thruster. The ACS decomposing element is operative to decompose the reduced toxicity propellant into hot propulsive gases. In addition the system includes suitable valves and conduits for supplying the reduced toxicity propellant to an axial decomposing element of the axial thruster. The axial decomposing element is operative to decompose the reduced toxicity propellant into hot gases. The system further includes suitable valves and conduits for supplying a second propellant to a combustion chamber of the axial thruster, whereby the hot gases and the second propellant auto-ignite and begin the combustion process for producing thrust.

  2. Escherichia coli growth under modeled reduced gravity

    NASA Technical Reports Server (NTRS)

    Baker, Paul W.; Meyer, Michelle L.; Leff, Laura G.

    2004-01-01

    Bacteria exhibit varying responses to modeled reduced gravity that can be simulated by clino-rotation. When Escherichia coli was subjected to different rotation speeds during clino-rotation, significant differences between modeled reduced gravity and normal gravity controls were observed only at higher speeds (30-50 rpm). There was no apparent affect of removing samples on the results obtained. When E. coli was grown in minimal medium (at 40 rpm), cell size was not affected by modeled reduced gravity and there were few differences in cell numbers. However, in higher nutrient conditions (i.e., dilute nutrient broth), total cell numbers were higher and cells were smaller under reduced gravity compared to normal gravity controls. Overall, the responses to modeled reduced gravity varied with nutrient conditions; larger surface to volume ratios may help compensate for the zone of nutrient depletion around the cells under modeled reduced gravity.

  3. Escherichia coli growth under modeled reduced gravity

    NASA Technical Reports Server (NTRS)

    Baker, Paul W.; Meyer, Michelle L.; Leff, Laura G.

    2004-01-01

    Bacteria exhibit varying responses to modeled reduced gravity that can be simulated by clino-rotation. When Escherichia coli was subjected to different rotation speeds during clino-rotation, significant differences between modeled reduced gravity and normal gravity controls were observed only at higher speeds (30-50 rpm). There was no apparent affect of removing samples on the results obtained. When E. coli was grown in minimal medium (at 40 rpm), cell size was not affected by modeled reduced gravity and there were few differences in cell numbers. However, in higher nutrient conditions (i.e., dilute nutrient broth), total cell numbers were higher and cells were smaller under reduced gravity compared to normal gravity controls. Overall, the responses to modeled reduced gravity varied with nutrient conditions; larger surface to volume ratios may help compensate for the zone of nutrient depletion around the cells under modeled reduced gravity.

  4. Reducing energy costs in nursing homes

    SciTech Connect

    Not Available

    1981-01-01

    The handbook presents ideas and techniques for energy conservation in nursing homes. Case studies were developed of nursing homes located in different parts of the US. The typical nursing home assessed was proprietary, of intermediate-care level, medicaid-certified, and had less than 200 beds. Specific energy conservation measures were analyzed to determine the energy and dollar savings that could be realized. These include reducing heat loss through the building shell; reducing hot water costs; recovering the heat generated by dryers; reducing lighting costs; reducing heating and cooling costs, and analyzing fuels and fuel rates. A case for converting electric clothes dryers to gas was analyzed. (MCW)

  5. Reducing pawing in horses using positive reinforcement.

    PubMed

    Fox, Adam E; Belding, Devon L

    2015-12-01

    Aversive control is a common method to reduce undesirable behavior in horses. However, it often results in unintended negative side effects, including potential abuse of the animal. Procedures based on positive reinforcement, such as differential reinforcement of other behavior (DRO), may reduce undesirable behaviors with fewer negative consequences. The current study used DRO schedules to reduce pawing using a multiple baseline design across 3 horses. Results indicated that DRO schedules were effective at reducing pawing. However, individual differences in sensitivity to DRO and reinforcer efficacy may be important considerations.

  6. Mesenchymal Stem Cells Reduce Murine Atherosclerosis Development

    PubMed Central

    Frodermann, Vanessa; van Duijn, Janine; van Pel, Melissa; van Santbrink, Peter J.; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C. A.

    2015-01-01

    Mesenchymal stem cells (MSCs) have regenerative properties, but recently they were also found to have immunomodulatory capacities. We therefore investigated whether MSCs could reduce atherosclerosis, which is determined by dyslipidaemia and chronic inflammation. We adoptively transferred MSCs into low-density lipoprotein-receptor knockout mice and put these on a Western-type diet to induce atherosclerosis. Initially after treatment, we found higher levels of circulating regulatory T cells. In the long-term, overall numbers of effector T cells were reduced by MSC treatment. Moreover, MSC-treated mice displayed a significant 33% reduction in circulating monocytes and a 77% reduction of serum CCL2 levels. Most strikingly, we found a previously unappreciated effect on lipid metabolism. Serum cholesterol was reduced by 33%, due to reduced very low-density lipoprotein levels, likely a result of reduced de novo hepatic lipogenesis as determined by a reduced expression of Stearoyl-CoA desaturase-1 and lipoprotein lipase. MSCs significantly affected lesion development, which was reduced by 33% in the aortic root. These lesions contained 56% less macrophages and showed a 61% reduction in T cell numbers. We show here for the first time that MSC treatment affects not only inflammatory responses but also significantly reduces dyslipidaemia in mice. This makes MSCs a potent candidate for atherosclerosis therapies. PMID:26490642

  7. Reducing Aerodynamic Drag Of Bluff Bodies

    NASA Technical Reports Server (NTRS)

    Taylor, Lawrence W., Jr.; Pamadi, Bandu N.

    1990-01-01

    New method found to reduce aerodynamic drag of noncircular bluff bodies like road-transport vehicles. Consists of installation of thin, flat panels on forward side of body, facing airstream. Produces streamlining effect over body. Width of wake reduced, and vortex shedding is greatly suppressed.

  8. Simple Potentiometric Determination of Reducing Sugars

    ERIC Educational Resources Information Center

    Moresco, Henry; Sanson, Pedro; Seoane, Gustavo

    2008-01-01

    In this article a potentiometric method for reducing sugar quantification is described. Copper(II) ion reacts with the reducing sugar (glucose, fructose, and others), and the excess is quantified using a copper wire indicator electrode. In order to accelerate the kinetics of the reaction, working conditions such as pH and temperature must be…

  9. 40 CFR 1500.5 - Reducing delay.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Reducing delay. 1500.5 Section 1500.5 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY PURPOSE, POLICY, AND MANDATE § 1500.5 Reducing...). (b) Emphasizing interagency cooperation before the environmental impact statement is prepared, rather...

  10. Partial turbo detection with reduced complexity

    NASA Astrophysics Data System (ADS)

    Ouardi, Aissa; Djebbari, A.; Bouazza, B. S.

    2011-06-01

    In this article, we propose a novel method for reducing the complexity of the turbo detector MAP (maximum a posteriori). The basic idea consists in turbo detecting a part of intersymbol interference (ISI) after decomposing the channel in two parts. We show that we can reduce the trellis complexity in the turbo process at a certain cost, i.e. performance loss.

  11. The Consumer's Handbook for Reducing Solid Waste.

    ERIC Educational Resources Information Center

    Environmental Protection Agency, Washington, DC.

    This profusely illustrated and informally written booklet describes how people can help solve a growing problem--garbage. The following 12 tips are presented: (1) Reduce the amount of unnecessary packaging; (2) Adopt practices that reduce waste toxicity; (3) Consider reusable products; (4) Maintain and repair durable products; (5) Reuse bags,…

  12. Welfare Reform and Reducing Teen Pregnancy.

    ERIC Educational Resources Information Center

    Sawhill, Isabel V.

    2000-01-01

    Most adolescent mothers are unmarried and on welfare. Congress enacted new welfare legislation that emphasizes reducing teen pregnancy and requiring work, but states are reluctant to meet this challenge. Discusses child poverty's new face, public policy and culture wars, welfare reform, and social norms. Concludes that reducing unwed parenthood…

  13. Simple Potentiometric Determination of Reducing Sugars

    ERIC Educational Resources Information Center

    Moresco, Henry; Sanson, Pedro; Seoane, Gustavo

    2008-01-01

    In this article a potentiometric method for reducing sugar quantification is described. Copper(II) ion reacts with the reducing sugar (glucose, fructose, and others), and the excess is quantified using a copper wire indicator electrode. In order to accelerate the kinetics of the reaction, working conditions such as pH and temperature must be…

  14. Soluble calcium amendments: reducing pathogen losses

    USDA-ARS?s Scientific Manuscript database

    Flue gas desulfurization (FGD) gypsum is a byproduct of coal-fired power plants. Its application to agricultural fields may increase water infiltration, reduce soil erosion, and decrease nutrient losses from applications of animal manures. It may also reduce fecal bacterial contamination of surface ...

  15. Tools to Reduce Waste in Schools

    ERIC Educational Resources Information Center

    US Environmental Protection Agency, 2007

    2007-01-01

    This guide was produced to help schools and school districts reduce the amount of waste they generate It shows how to start a waste reduction program or expand an existing one. The booklet shows how such programs can benefit schools, communities, and the environment by reducing, reusing, and recycling waste. Each section--schools, school…

  16. Social Work Practice to Reduce Underachievement.

    ERIC Educational Resources Information Center

    Barth, Richard P.

    1988-01-01

    Social workers' direct work with students can help to reduce the disparity between educational ability and achievement. Interventions with low achievers must include fostering linkages between home and school. Consultation and followup are necessary components for reducing underachievement. The intervention must be done in conjunction with school…

  17. Optimizing Reduced-Order Transfer Functions

    NASA Technical Reports Server (NTRS)

    Spanos, John T.; Milman, Mark H.; Mingori, D. Lewis

    1992-01-01

    Transfer-function approximations made optimal in special least-squares sense. Algorithm computes reduced-order rational-fraction approximates to single-input/single-output transfer functions. Reduces amount of computation needed for such purposes as numerical simulation of dynamics and design of control subsystems.

  18. [Chest physiotherapy techniques - can they reduce hyperinflation].

    PubMed

    Perez Bogerd, S; Selleron, B; Hotton, R; Ferrali, O; Sergysels, R

    2009-12-01

    The authors review the literature concerning the possibilities of modifying the mechanical characteristics of the respiratory system with breathing retraining and other chest physiotherapy intervention. Breathing retraining techniques with prolonged and active expiration induce increased work of breathing and do not help diaphragmatic function. Only pursed lips breathing seems to produce some mechanical advantages. The seated and forward position with fixed arms may reduce dyspnea but this does not appear to be caused by a decrease in operating lung volumes. By contrast, the dorsal decubitus position may reduce hyperinflation, giving some mechanical advantage to the diaphragm but does not reduce dyspnea and is not a position spontaneously adopted by patients. General muscular training may reduce ventilatory demand, and by reducing respiratory frequency lead to a decrease in the end expiratory lung volume; therefore inducing improvement in exercise tolerance.

  19. Uranium reduction and resistance to reoxidation under iron-reducing and sulfate-reducing conditions.

    PubMed

    Boonchayaanant, Benjaporn; Nayak, Dipti; Du, Xin; Criddle, Craig S

    2009-10-01

    Oxidation and mobilization of microbially-generated U(IV) is of great concern for in situ uranium bioremediation. This study investigated the reoxidation of uranium by oxygen and nitrate in a sulfate-reducing enrichment and an iron-reducing enrichment derived from sediment and groundwater from the Field Research Center in Oak Ridge, Tennessee. Both enrichments were capable of reducing U(VI) rapidly. 16S rRNA gene clone libraries of the two enrichments revealed that Desulfovibrio spp. are dominant in the sulfate-reducing enrichment, and Clostridium spp. are dominant in the iron-reducing enrichment. In both the sulfate-reducing enrichment and the iron-reducing enrichment, oxygen reoxidized the previously reduced uranium but to a lesser extent in the iron-reducing enrichment. Moreover, in the iron-reducing enrichment, the reoxidized U(VI) was eventually re-reduced to its previous level. In both, the sulfate-reducing enrichment and the iron-reducing enrichment, uranium reoxidation did not occur in the presence of nitrate. The results indicate that the Clostridium-dominated iron-reducing communities created conditions that were more favorable for uranium stability with respect to reoxidation despite the fact that fewer electron equivalents were added to these systems. The likely reason is that more of the added electrons are present in a form that can reduce oxygen to water and U(VI) back to U(IV).

  20. Rosa's roses: Reduced vowels in American English

    NASA Astrophysics Data System (ADS)

    Flemming, Edward

    2004-05-01

    Beginning phonetics students are taught that American English has two contrasting reduced vowels, transcribed as [squflg] and [squflg], illustrated by the unstressed vowels in the minimal pair Rosa's versus roses. However, little seems to be known about the precise nature or distribution of these vowels. This study explores these questions through acoustic analysis of reduced vowels in the speech of 12 American English speakers. The results show that there is a fundamental distinction between the mid central [squflg] vowel that can occur in unstressed word-final position (e.g., in Rosa), and high reduced vowels that occur in most other unstressed positions, and might be transcribed as [squflg]. The contrast between pairs like Rosa's and roses derives from this difference because the word-final [squflg] is preserved when an inflectional suffix is added, so the schwa of Rosa's is similar to the final vowel of Rosa, whereas the unstressed vowel of roses is the high [squflg] reduced vowel quality found elsewhere. So the standard transcription of the reduced vowel contrast is justified, but the widespread use of [squflg] to transcribe word-internal reduced vowels is misleading-mid reduced vowels are generally only found in stem-final position.

  1. Multiclass Reduced-Set Support Vector Machines

    NASA Technical Reports Server (NTRS)

    Tang, Benyang; Mazzoni, Dominic

    2006-01-01

    There are well-established methods for reducing the number of support vectors in a trained binary support vector machine, often with minimal impact on accuracy. We show how reduced-set methods can be applied to multiclass SVMs made up of several binary SVMs, with significantly better results than reducing each binary SVM independently. Our approach is based on Burges' approach that constructs each reduced-set vector as the pre-image of a vector in kernel space, but we extend this by recomputing the SVM weights and bias optimally using the original SVM objective function. This leads to greater accuracy for a binary reduced-set SVM, and also allows vectors to be 'shared' between multiple binary SVMs for greater multiclass accuracy with fewer reduced-set vectors. We also propose computing pre-images using differential evolution, which we have found to be more robust than gradient descent alone. We show experimental results on a variety of problems and find that this new approach is consistently better than previous multiclass reduced-set methods, sometimes with a dramatic difference.

  2. Reducibility of Matrix Equations Containing Several Parameters.

    DTIC Science & Technology

    1981-12-01

    AD-AI15 568 AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB OH SCHOO;-ETC EF G 12 1ADA1551 REDUCIBILITY OF MATRIX EQUATIONS CONTAINING SEVERAL...PARAMETERS.E U)CA E UNCLASSIFIED AFIT/GE/RA/81D-1 N P11111111II soonhh Eu;o I. ’Trm * a, ~t- NMI 4 i’- 00Nt. met r~ REDUCIBILITY OF MATRIX EQUATIONS CONTAINING...1 REDUCIBILITY OF MATRIX EQUATIONS CONTAINING SEVERAL PARAMETERS THESIS Presented to the Faculty of the School of Engineering of the Air Force

  3. Reduced Baroclinicity During Martian Global Dust Storms

    NASA Astrophysics Data System (ADS)

    Battalio, Joseph; Szunyogh, Istvan; Lemmon, Mark

    2015-11-01

    The eddy kinetic energy equation is applied to the Mars Analysis Correction Data Assimilation (MACDA) dataset during the pre-winter solstice period for the northern hemisphere of Mars. Traveling waves are triggered by geopotential flux convergence, grow baroclinically, and decay barotropically. Higher optical depth increases the static stability, which reduces vertical and meridional heat fluxes. Traveling waves during a global dust storm year develop a mixed baroclinic/barotropic growth phase before decaying barotropically. Baroclinic energy conversion is reduced during the global dust storm, but eddy intensity is undiminished. Instead, the frequency of storms is reduced due to a stabilized vertical profile.

  4. Reducing urinary tract infections in catheterised patients.

    PubMed

    Howe, Pam; Adams, John

    2015-01-20

    Urinary tract infections in catheterised patients continue to present a challenge in reducing healthcare-associated infection. In this article, an infection prevention and control team in one NHS trust reports on using audit results to focus attention on measures to reduce bacterial infections. Educational initiatives have an important role in reducing infection, but there is no single solution to the problem. Practice can be improved using a multi-targeted approach, peer review and clinical audit to allow for shared learning and experiences. These, along with informal education in the clinical area and more formal classroom lectures, can ultimately lead to improved patient outcomes.

  5. Reducing the atmospheric impact of wet slaking

    SciTech Connect

    B.D. Zubitskii; G.V. Ushakov; B.G. Tryasunov; A.G.Ushakov

    2009-05-15

    Means of reducing the atmospheric emissions due to the wet slaking of coke are considered. One option, investigated here, is to remove residual active silt and organic compounds from the biologically purified wastewater sent for slaking, by coagulation and flocculation.

  6. Auto Accidents: Reducing Frequency, Increasing Recovery.

    ERIC Educational Resources Information Center

    Comeaux, Linda Atkins

    1988-01-01

    Careful hiring, monitoring, training, discipline, and safety policies will reduce school automobile and bus accidents. Guidelines are offered for accident reporting, claim handling, and dealing with insurance adjusters. (MLF)

  7. Vaccine Reduces HPV Infections in Young Men

    Cancer.gov

    An international randomized clinical trial has shown that the vaccine Gardasil can reduce the incidence of anogenital human papillomavirus (HPV) infections in young men 16 to 26 years of age at the time of vaccination.

  8. Auto Accidents: Reducing Frequency, Increasing Recovery.

    ERIC Educational Resources Information Center

    Comeaux, Linda Atkins

    1988-01-01

    Careful hiring, monitoring, training, discipline, and safety policies will reduce school automobile and bus accidents. Guidelines are offered for accident reporting, claim handling, and dealing with insurance adjusters. (MLF)

  9. Electronic states in systems of reduced dimensionality

    SciTech Connect

    Ulloa, S.E.

    1992-04-15

    This report briefly discusses the following research: magnetically modulated systems, inelastic magnetotunneling, ballistic transport review, screening in reduced dimensions, raman and electron energy loss spectroscopy; and ballistic quantum interference effects. (LSP).

  10. Reducing Risks Associated with Medical Device Misconnections

    MedlinePlus

    ... partners, professional societies, advocacy groups, patients and other stakeholders to reduce the chance of medical device misconnections. ... medical device misconnections; Communicating with patients and other stakeholders to understand the impact of new connector designs. ...

  11. ENDOCRINE FUNCTION OF THE SURGICALLY REDUCED PANCREAS

    PubMed Central

    Houssay, B. A.; Foglia, V. G.; Smyth, F. S.

    1941-01-01

    The pancreas reduced to 4 or 10 gm. weeks or months previously by partial resection, is able to maintain a normal glycemic level in dogs of about 10 kilos in good condition. When the pancreas is reduced to 4 gm. the capacity for secreting insulin under certain conditions of strain is diminished whereas a pancreas reduced to 10 gm. may have a normal or decreased capacity. This decreased functional capacity is shown: (1) by a longer hyperglycemic curve after the intravenous injection of 1 gm. of glucose per kilo; (2) by the requirement of smaller doses of extract of anterior hypophysis to produce diabetes; and (3) by the longer time required to correct the diabetic hyperglycemia if reduced pancreas is grafted in the neck of pancreatectomized animals. The time to recover is in inverse ratio to the weight of the transplanted pancreatic tissue. PMID:19871135

  12. Deep brain stimulation to reduce sexual drive

    PubMed Central

    Fuss, Johannes; Auer, Matthias K.; Biedermann, Sarah V.; Briken, Peer; Hacke, Werner

    2015-01-01

    To date there are few treatment options to reduce high sexual drive or sexual urges in paraphilic patients with a risk for sexual offending. Pharmacological therapy aims to reduce sexual drive by lowering testosterone at the cost of severe side effects. We hypothesize that high sexual drive could also be reduced with deep brain stimulation (DBS) of circuits that generate sexual drive. This approach would help to avoid systemic side effects of antiandrogenic drug therapies. So far the best investigated target to reduce sexual drive is the ventromedial hypothalamus, which was lesioned unilaterally and bilaterally by stereotaxic interventions in paraphilic patients in the 1970s. Here, we discuss DBS as a treatment strategy in patients with severe paraphilic disorders with a serious risk of sexual offending. There are profound ethical and practical issues associated with DBS treatment of paraphilic patients that must be solved before considering such a treatment approach. PMID:26057198

  13. REDUCING CHILDREN'S RISK FROM LEAD IN SOIL

    EPA Science Inventory

    Traditional methods for reducing risk from elevated levels of soil Pb involves removal, covering, or dilution by mixing with uncontaminated soil. Believing that in situ remediation techniques are viable alternatives, the EPA=s National Risk Management Research Laboratory (NRMRL) ...

  14. 49 CFR 609.23 - Reduced fare.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... TRANSPORTATION TRANSPORTATION FOR ELDERLY AND HANDICAPPED PERSONS § 609.23 Reduced fare. Applicants for financial... Administrator may prescribe, that the rates charged elderly and handicapped persons during non-peak hours...

  15. 49 CFR 609.23 - Reduced fare.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... TRANSPORTATION TRANSPORTATION FOR ELDERLY AND HANDICAPPED PERSONS § 609.23 Reduced fare. Applicants for financial... Administrator may prescribe, that the rates charged elderly and handicapped persons during non-peak hours...

  16. Technique simulates effect of reduced gravity

    NASA Technical Reports Server (NTRS)

    Hewes, D. E.; Spady, A. A., Jr.

    1964-01-01

    To simulate the effects of lunar gravity, an arrangement of near-vertical cables has been devised. These suspend the test subject perpendicular to an inclined walkway to give the effect of reduced gravitational pull.

  17. Optimal Microstructures Drag Reducing Mechanism of Riblets

    NASA Astrophysics Data System (ADS)

    Friedmann, Elfriede; Richter, Thomas

    2011-09-01

    We consider an optimal shape design problem of periodically distributed three-dimensional microstructures on surfaces of swimming bodies in order to reduce their drag. Our model is restricted to the flow in the viscous sublayer of the boundary layer of a turbulent flow. The costs for the optimization problem are very high because the three-dimensional flow equations have to be solved several times. We avoid this problem by approximations: the microscopic optimization problem is reduced applying homogenization. Considering a special geometry (riblets) the resulting so-called macroscopic optimization problem can be additionally reduced to a two-dimensional problem. We analyze the drag reducing mechanism of riblets which are believed to be optimal structures. Therefore we perform direct simulations on the total rough channel for different shapes of microstructures: riblets and fully three-dimensional structures.

  18. Reducing health inequalities for older LGBTQ+ people.

    PubMed

    Thomas, Ben

    2016-10-26

    The recent LGBTQ+ history exhibition Speak Out London, Diversity City presented a fantastic collection of stories, documents and photographs from LGBTQ+ Londoners. It also provided a reminder of how far we have come in reducing stigma, prejudice and discrimination.

  19. Dual photochemical replenisher system reduces chemical losses

    NASA Technical Reports Server (NTRS)

    Kolber, J. M.

    1967-01-01

    Dual replenisher system reduces chemical losses and maintains optimum solution concentration during long nonprocessing cycles of photo processing machines. Using a single 3-position switch and solenoid control valves, the system provides instantaneous flow control to each processing tank.

  20. Reducing Peak Power in Automated Weapon Laying

    DTIC Science & Technology

    2016-02-01

    UNCLASSIFIED UNCLASSIFIED AD-E403 AD-E403 737 Technical Report ARWSE-TR-15036 REDUCING PEAK POWER IN AUTOMATED WEAPON...PEAK POWER IN AUTOMATED WEAPON LAYING 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHORS Joshua Stapp and...amount of time while reducing the amount of peak power required and, therefore, minimizing the forces caused by acceleration. 15. SUBJECT TERMS

  1. New approaches to reduce radiation exposure

    PubMed Central

    Hill, Kevin D.; Einstein, Andrew J.

    2015-01-01

    Exposure to ionizing radiation is associated with a long term risk of health effects including cancer. Radiation exposure to the U.S. population from cardiac imaging has increased markedly over the past three decades. Initiatives to reduce radiation exposure have focused on the tenets of appropriate study “justification” and “optimization” of imaging protocols. This article reviews ways to optimally reduce radiation dose across the spectrum of cardiac imaging. PMID:25962784

  2. Solar geoengineering reduces atmospheric carbon burden

    NASA Astrophysics Data System (ADS)

    Keith, David W.; Wagner, Gernot; Zabel, Claire L.

    2017-09-01

    Solar geoengineering is no substitute for cutting emissions, but could nevertheless help reduce the atmospheric carbon burden. In the extreme, if solar geoengineering were used to hold radiative forcing constant under RCP8.5, the carbon burden may be reduced by ~100 GTC, equivalent to 12-26% of twenty-first-century emissions at a cost of under US$0.5 per tCO2.

  3. Laser welding in a reduced gravity environment

    NASA Technical Reports Server (NTRS)

    Workman, Gary L.; Kaukler, William F.

    1992-01-01

    Preliminary results on the effects of reduced gravity on laser welding of stainless steel and other materials are reported. Laser welding experiments using a low power (10-18 watts) Nd-YAG laser have been performed on the NASA KC-135, which flies parabolic maneuvers to simulate reduced gravity conditions. Experiments on 0.005-0.010 inch thick stainless steel samples displayed a pronounced change in weld bead width, depth of penetration and surface ripple with changes in gravity level.

  4. Boiler burden reduced at Bedford site.

    PubMed

    Horsley, Chris

    2011-10-01

    With the NHS aiming to reduce its 2007 carbon footprint by 10% by 2015, Chris Horsley, managing director of Babcock Wanson UK, a provider of industrial boilers and burners, thermal oxidisers, air treatment, water treatment, and associated services, looks at how one NHS Trust has approached the challenge, and considerably reduced its carbon emissions, by refurbishing its boiler house and moving from oil to gas-fired steam generation.

  5. Reducing mode circulating fluid bed combustion

    DOEpatents

    Lin, Yung-Yi; Sadhukhan, Pasupati; Fraley, Lowell D.; Hsiao, Keh-Hsien

    1986-01-01

    A method for combustion of sulfur-containing fuel in a circulating fluid bed combustion system wherein the fuel is burned in a primary combustion zone under reducing conditions and sulfur captured as alkaline sulfide. The reducing gas formed is oxidized to combustion gas which is then separated from solids containing alkaline sulfide. The separated solids are then oxidized and recycled to the primary combustion zone.

  6. Reduced gravity - A new biomedical research environment

    NASA Technical Reports Server (NTRS)

    Snyder, Robert S.

    1989-01-01

    Experiment programs for continuous flow electrophoresis and protein crystal growth are described to demonstrate the utility of the reduced gravity environment for scientific research. The advantages of the reduced gravity environment are outlined. The results of experiments on the Space Shuttle using the Continuous Flow Electrophoresis System and crystal growth experiments on Spacelab-1 and the Space Shuttle are examined, noting the importance of microgravity research.

  7. Reduced waste generation technical work plan

    SciTech Connect

    Not Available

    1987-05-01

    The United States Department of Energy has established policies for avoiding plutonium losses to the waste streams and minimizing the generation of wastes produced at its nuclear facilities. This policy is evidenced in DOE Order 5820.2, which states Technical and administrative controls shall be directed towards reducing the gross volume of TRU waste generated and the amount of radioactivity in such waste.'' To comply with the DOE directive, the Defense Transuranic Waste Program (DTWP) supports and provides funding for specific research and development tasks at the various DOE sites to reduce the generation of waste. This document has been prepared to give an overview of current and past Reduced Waste Generation task activities which are to be based on technical and cost/benefit factors. The document is updated annually, or as needed, to reflect the status of program direction. Reduced Waste Generation (RWG) tasks encompass a wide range of goals which are basically oriented toward (1) avoiding the generation of waste, (2) changing processes or operations to reduce waste, (3) converting TRU waste into LLW by sorting or decontamination, and (4) reducing volumes through operations such as incineration or compaction.

  8. Reduced-order modeling for hyperthermia control.

    PubMed

    Potocki, J K; Tharp, H S

    1992-12-01

    This paper analyzes the feasibility of using reduced-order modeling techniques in the design of multiple-input, multiple-output (MIMO) hyperthermia temperature controllers. State space thermal models are created based upon a finite difference expansion of the bioheat transfer equation model of a scanned focused ultrasound system (SFUS). These thermal state space models are reduced using the balanced realization technique, and an order reduction criterion is tabulated. Results show that a drastic reduction in model dimension can be achieved using the balanced realization. The reduced-order model is then used to design a reduced-order optimal servomechanism controller for a two-scan input, two thermocouple output tissue model. In addition, a full-order optimal servomechanism controller is designed for comparison and validation purposes. These two controllers are applied to a variety of perturbed tissue thermal models to test the robust nature of the reduced-order controller. A comparison of the two controllers validates the use of open-loop balanced reduced-order models in the design of MIMO hyperthermia controllers.

  9. Interventions to Reduce Myopia Progression in Children.

    PubMed

    Tay, Su Ann; Farzavandi, Sonal; Tan, Donald

    2017-03-01

    Efforts to reduce the progression of myopia in childhood are on the rise, due to an increasing incidence of myopia worldwide and its associated sight-threatening complications. Interventions are aimed at reducing myopia in childhood and include environmental considerations, spectacles, contact lenses, and pharmacological agents. We reviewed recent literature with interventions aimed at reducing myopia progression in children and found that a number of interventions were significant in reducing the progression of myopia. Of these interventions, atropine showed the largest dose-related effect on myopia progression control. Although higher doses are associated with side effects of pupil dilatation, loss of accommodation, near vision blur, and rebound phenomenon, low-dose atropine has also been shown to provide effective myopia control with minimal side effects and rebound. To a lesser degree, bifocal soft contact lenses have also been shown to be effective in reducing the progression of myopia, though compliance is an issue. Similarly, orthokeratology lenses have also been shown to be effective in reducing axial length elongation and myopia progression, though long-term data on its rebound effects are unavailable.

  10. Evolution of technetium speciation in reducing grout

    SciTech Connect

    Lukens, Wayne W.; Bucher, Jerome J.; Shuh, David K.; Edelstein,Norman M.

    2003-11-24

    Cementitious waste forms (CWFs) are an important component of the strategy to immobilize high-level nuclear waste resulting from plutonium production by the U.S. Department of Energy (DOE). Technetium (99Tc) is an abundant fission product of particular concern in CWFs due to the high solubility and mobility of pertechnetate, TcO4-, the stable form of technetium in aerobic environments. CWFs can more effectively immobilize 99Tc if they contain additives that reduce mobile TcO4- to immobile Tc(IV) species. Leaching of 99Tc from reducing CWFs that contain Tc(IV) is much slower than for CWFs containing TcO4-. Previous X-ray absorption fine structure (XAFS) studies showed that the Tc(IV) species were oxidized to TcO4- in reducing grout samples prepared on a laboratory scale. Whether the oxidizer was atmospheric O2 or NO3- in the waste simulant was not determined. In actual CWFs, rapid oxidation of Tc(IV) by NO3- would be a concern, whereas oxidation by atmospheric O2 would be of less concern due to the slow diffusion and reaction of O2 with the reducing CWF. To address this uncertainty, two series of reducing grouts were prepared using TcO4- containing waste simulants with and without NO3-. In the first series of samples, the TcO4- was completely reduced using Na2S, and the samples were placed in containers that permitted O2 diffusion. In these samples, all of the technetium was initially present as aTc(IV) sulfide compound, TcSx, which was characterized using extended X-ray absorption fine structure (EXAFS) spectroscopy, and is likely Tc2S7. The TcSx initially present in the grout samples was steadily oxidized over 4 years. In the second series of samples, all of the TcO4- was not initially reduced, and the grout samples were placed in airtight containers. In these samples, the remaining TcO4- continued to be reduced as the samples aged, presumably due to the presence of reducing blast furnace slag. When samples in the second series were exposed to atmosphere, the

  11. Advanced flow noise reducing acoustic sensor arrays

    NASA Astrophysics Data System (ADS)

    Fine, Kevin; Drzymkowski, Mark; Cleckler, Jay

    2009-05-01

    SARA, Inc. has developed microphone arrays that are as effective at reducing flow noise as foam windscreens and sufficiently rugged for tough battlefield environments. These flow noise reducing (FNR) sensors have a metal body and are flat and conformally mounted so they can be attached to the roofs of land vehicles and are resistant to scrapes from branches. Flow noise at low Mach numbers is created by turbulent eddies moving with the fluid flow and inducing pressure variations on microphones. Our FNR sensors average the pressure over the diameter (~20 cm) of their apertures, reducing the noise created by all but the very largest eddies. This is in contrast to the acoustic wave which has negligible variation over the aperture at the frequencies of interest (f less or equal than 400 Hz). We have also post-processed the signals to further reduce the flow noise. Two microphones separated along the flow direction exhibit highly correlated noise. The time shift of the correlation corresponds to the time for the eddies in the flow to travel between the microphones. We have created linear microphone arrays parallel to the flow and have reduced flow noise as much as 10 to 15 dB by subtracting time-shifted signals.

  12. Model diagnostics in reduced-rank estimation

    PubMed Central

    Chen, Kun

    2016-01-01

    Reduced-rank methods are very popular in high-dimensional multivariate analysis for conducting simultaneous dimension reduction and model estimation. However, the commonly-used reduced-rank methods are not robust, as the underlying reduced-rank structure can be easily distorted by only a few data outliers. Anomalies are bound to exist in big data problems, and in some applications they themselves could be of the primary interest. While naive residual analysis is often inadequate for outlier detection due to potential masking and swamping, robust reduced-rank estimation approaches could be computationally demanding. Under Stein's unbiased risk estimation framework, we propose a set of tools, including leverage score and generalized information score, to perform model diagnostics and outlier detection in large-scale reduced-rank estimation. The leverage scores give an exact decomposition of the so-called model degrees of freedom to the observation level, which lead to exact decomposition of many commonly-used information criteria; the resulting quantities are thus named information scores of the observations. The proposed information score approach provides a principled way of combining the residuals and leverage scores for anomaly detection. Simulation studies confirm that the proposed diagnostic tools work well. A pattern recognition example with hand-writing digital images and a time series analysis example with monthly U.S. macroeconomic data further demonstrate the efficacy of the proposed approaches. PMID:28003860

  13. Coal ash behavior in reducing environments

    SciTech Connect

    Benson, S.A.; Erickson, T.A.; Brekke, D.W.; Folkedahl, B.C.; Tibbetts, J.E.; Nowok, J.W.

    1994-10-01

    This project is a four-year program designed to investigate the transformations and properties of coal ash in reducing environment systems. This project is currently midway through its third year. The work to date has emphasized four areas of research: (1) the development of quantitative techniques to analyze reduced species, (2) the production of gasification-type samples under closely controlled conditions, (3) the systematic gasification of specific coals to produce information about their partitioning during gasification, and (4) the study of the physical properties of ashes and slags under reducing atmospheres. The project is organized into three tasks which provide a strong foundation for the project. Task 1, Analytical Methods Development, has concentrated on the special needs of analyzing samples produced under a reducing atmosphere as opposed to the more often studied combustion systems. Task 2, Inorganic Partitioning and Ash Deposition, has focused on the production of gasification-type samples under closely controlled conditions for the study of inorganic partitioning that may lead to deposition. Task 3, Ash and Slag Physical Properties, has made large gains in the areas of sintering and strength development of coal ashes under reducing atmospheres for the evaluation of deposition problems. Results are presented for all three tasks.

  14. Infrared photoemitting diode having reduced work function

    DOEpatents

    Hirschfeld, Tomas B.

    1984-01-01

    In electro-optical detectors which include as elements a photoemitting photocathode and anode, a photoemitting diode is fabricated which lowers the diode's work function, thus reducing the cooling requirement typically needed for this type of device. The work function is reduced by sandwiching between the photocathode and anode a liquid medium of the formula NR.sub.3 and having an electron affinity for the electrons of the photocathode, which liquid medium permits free electrons leaving the photocathode to remain as stable solvated species in the liquid medium. Thus, highly light-absorbent, and therefore thin, metallic layers can be used for detection, thereby reducing dark current at a given temperature, with a consequent reduction in cooling requirements at constant detector performance.

  15. Infrared photoemitting diode having reduced work function

    DOEpatents

    Hirschfeld, T.B.

    1982-05-06

    In electro-optical detectors which include as elements a photoemitting photocathode and anode, a photoemitting diode is fabricated which lowers the diode's work function, thus reducing the cooling requirement typically needed for this type of device. The work function is reduced by sandwiching between the photocathode and anode a liquid meidum of the formula NR/sub 3/ and having an electron affinity for the electrons of the photocathode, which liquid medium permits free electrons leaving the photocathode to remain as stable solvated species in the liquid medium. Thus, highly light-absorbent, and therefore thin, metallic layers can be used for detection, thereby reducing dark current at a given temperature, with a consequent reduction in cooling requirements at constant detector performance.

  16. Arbuscular mycorrhizas reduce nitrogen loss via leaching.

    PubMed

    Asghari, Hamid R; Cavagnaro, Timothy R

    2012-01-01

    The capacity of mycorrhizal and non-mycorrhizal root systems to reduce nitrate (NO₃⁻) and ammonium (NH₄⁺) loss from soils via leaching was investigated in a microcosm-based study. A mycorrhiza defective tomato mutant and its mycorrhizal wildtype progenitor were used in this experiment in order to avoid the indirect effects of establishing non-mycorrhizal control treatments on soil nitrogen cycling and the wider soil biota. Mycorrhizal root systems dramatically reduced nitrate loss (almost 40 times less) via leaching, compared to their non-mycorrhizal counterparts, following a pulse application of ammonium nitrate to experimental microcosms. The capacity of AM to reduce nutrient loss via leaching has received relatively little attention, but as demonstrated here, can be significant. Taken together, these data highlight the need to consider the potential benefits of AM beyond improvements in plant nutrition alone.

  17. Targets set to reduce Lake Erie algae

    USGS Publications Warehouse

    Evans, Mary

    2016-01-01

    In February 2016, the Great Lakes Executive Committee, which oversees the implementation of the Great Lakes Water Quality Agreement (GLWQA) between the U.S. and Canada, approved phosphorus loading targets for Lake Erie to reduce the size of harmful algal blooms (HABs), reduce the presence of the low oxygen zone in the central basin, and protect nearshore water quality. The targets are set with respect to the nutrient loads calculated for 2008. To reduce the impacts of HABs on Lake Erie a target was set of a 40 percent reduction in total and soluble reactive phosphorus loads in the spring from two Canadian rivers and several Michigan and Ohio rivers, especially the Maumee River (https://binational.net/2016/02/22/ finalptargets-ciblesfinalesdep/). States and the province of Ontario are already developing Domestic Action Plans to accomplish the reductions and scientists are developing research and monitoring plans to assess progress.

  18. Arbuscular Mycorrhizas Reduce Nitrogen Loss via Leaching

    PubMed Central

    Asghari, Hamid R.; Cavagnaro, Timothy R.

    2012-01-01

    The capacity of mycorrhizal and non-mycorrhizal root systems to reduce nitrate (NO3−) and ammonium (NH4+) loss from soils via leaching was investigated in a microcosm-based study. A mycorrhiza defective tomato mutant and its mycorrhizal wildtype progenitor were used in this experiment in order to avoid the indirect effects of establishing non-mycorrhizal control treatments on soil nitrogen cycling and the wider soil biota. Mycorrhizal root systems dramatically reduced nitrate loss (almost 40 times less) via leaching, compared to their non-mycorrhizal counterparts, following a pulse application of ammonium nitrate to experimental microcosms. The capacity of AM to reduce nutrient loss via leaching has received relatively little attention, but as demonstrated here, can be significant. Taken together, these data highlight the need to consider the potential benefits of AM beyond improvements in plant nutrition alone. PMID:22253790

  19. Reducing online identity disclosure using warnings.

    PubMed

    Carpenter, Sandra; Zhu, Feng; Kolimi, Swapna

    2014-09-01

    In an experimental design, we tested whether written warnings can reduce the amount of identity information exposure online. A psychological attack on information privacy that has been shown to be effective in previous research was launched. This attack took advantage of the fact that people respond to certain types of requests in a relatively automatic, or mindless, fashion. The experiment manipulated the word that was used in the alert header: "warning", "caution", or "hazard". All warnings proved to be effective in reducing disclosure, but "hazard" proved to be most effective. Also warnings were more effective in reducing disclosure of driver's license numbers than email addresses. The discussion (a) provides tentative conclusions why these patterns were obtained, (b) suggests how to design warnings in cyber-environments, and (c) addresses future possibilities for research on this topic.

  20. Process for reducing beta activity in uranium

    DOEpatents

    Briggs, G.G.; Kato, T.R.; Schonegg, E.

    1985-04-11

    This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed. 5 tabs.

  1. Reduced-energy decoding of MPEG streams

    NASA Astrophysics Data System (ADS)

    Mesarina, Melena; Turner, Yoshio

    2001-12-01

    Long battery life and high performance multimedia decoding are competing design goals for portable appliances. For a target level of QoS, the achievable battery life can be increased by dynamically adjusting the supply voltage throughout execution. In this paper, an efficient offline scheduling algorithm is proposed for preprocessing stored MPEG audio and video streams. It computes the order and voltage settings at which the appliance's CPU decodes the frames, reducing energy consumption without violating timing or buffering constraints. Our experimental results elucidate the tradeoff of QoS and energy consumption. They demonstrate that the scheduler reduces CPU energy consumption by 19%, without any sacrifice of quality, and by nearly 50%, with only slightly reduced quality. The results also explore how the QoS/energy tradeoff is affected by buffering and processor speed.

  2. Alternatives for reducing hot-water bills

    SciTech Connect

    Bennington, G.E.; Spewak, P.C.

    1981-06-01

    A two stage approach to reducing residential water heating bills is described. In Stage I, simple conservation measures were included to reduce the daily hot water energy consumption and the energy losses from the water tank. Once these savings are achieved, Stage II considers more costly options for further reducing the water heating bill. Four alternatives are considered in Stage II: gas water heaters; solar water heaters (two types); heat pump water heaters; and heat recovery from a heat pump or air conditioner. To account for variations within the MASEC region, information on water heating in Rapid City, Minneapolis, Chicago, Detroit, and Kansas City is presented in detail. Information on geography, major population centers, fuel prices, climate, and state solar incentives is covered. (MCW)

  3. Barriers to reducing burden of affective disorders.

    PubMed

    Bruce, Martha L; Wells, Kenneth B; Miranda, Jeanne; Lewis, Lydia; Gonzalez, Junius L

    2002-12-01

    This paper summarizes 3 sets of barriers to reducing burden of affective disorders including factors that contribute to 1) the risk, course, and outcomes of affective disorders; 2) help-seeking and use of health and mental health services for affective and other mental disorders; and 3) the appropriateness of treatments used for affective disorders. On the basis of this review, the authors recommend research needed to identify modifiable barriers to reducing the burden of affective disorders and to identifying opportunities to reduce these barriers. This new research should focus on clarifying societal, family, and consumer, clinician, and system barriers to recognizing disorders, seeking and providing care, and adhering with guideline concordant care, and should include barriers that apply to both treatment and prevention services.

  4. Reducing the environmental impact of global diets.

    PubMed

    Swain, Marian; Blomqvist, Linus; McNamara, James; Ripple, William J

    2017-08-25

    It is well established in the literature that reducing the amount of meat in global diets would reduce the environmental impacts of food production. However, changes to livestock production systems also have significant potential to reduce environmental impacts from meat production, and yet are not as widely discussed in the literature. Modern, intensive livestock systems, especially for beef, offer substantially lower land requirements and greenhouse gas emissions per kilogram of meat than traditional, extensive ones. The land sparing potential of beef sector intensification is especially relevant for high priority conservation regions like the Brazilian Amazon. Leveraging livestock production systems in addition to dietary change greatly expands the opportunity to achieve conservation and climate goals in the coming decades. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Moral elevation reduces prejudice against gay men.

    PubMed

    Lai, Calvin K; Haidt, Jonathan; Nosek, Brian A

    2014-01-01

    Disgust is linked to social evaluation. People with higher disgust sensitivity exhibit more sexual prejudice, and inducing disgust increases sexual prejudice. We tested whether inducing moral elevation, the theoretical opposite of disgust, would reduce sexual prejudice. In four studies (N = 3622), we induced elevation with inspiring videos and then measured sexual prejudice with implicit and explicit measures. Compared to control videos that elicited no particular affective state, we found that elevation reduced implicit and explicit sexual prejudice, albeit very slightly. No effect was observed when the target of social evaluation was changed to race (Black-White). Inducing amusement, another positive emotion, did not significantly affect sexual prejudice. We conclude that elevation weakly but reliably reduces prejudice towards gay men.

  6. Mistake proofing: changing designs to reduce error

    PubMed Central

    Grout, J R

    2006-01-01

    Mistake proofing uses changes in the physical design of processes to reduce human error. It can be used to change designs in ways that prevent errors from occurring, to detect errors after they occur but before harm occurs, to allow processes to fail safely, or to alter the work environment to reduce the chance of errors. Effective mistake proofing design changes should initially be effective in reducing harm, be inexpensive, and easily implemented. Over time these design changes should make life easier and speed up the process. Ideally, the design changes should increase patients' and visitors' understanding of the process. These designs should themselves be mistake proofed and follow the good design practices of other disciplines. PMID:17142609

  7. Process for reducing beta activity in uranium

    DOEpatents

    Briggs, Gifford G.; Kato, Takeo R.; Schonegg, Edward

    1986-10-07

    This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which have undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed.

  8. Process for reducing beta activity in uranium

    DOEpatents

    Briggs, Gifford G.; Kato, Takeo R.; Schonegg, Edward

    1986-01-01

    This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which have undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed.

  9. Lasercom system architecture with reduced complexity

    NASA Technical Reports Server (NTRS)

    Lesh, James R. (Inventor); Chen, Chien-Chung (Inventor); Ansari, Homayoon (Inventor)

    1994-01-01

    Spatial acquisition and precision beam pointing functions are critical to spaceborne laser communication systems. In the present invention, a single high bandwidth CCD detector is used to perform both spatial acquisition and tracking functions. Compared to previous lasercom hardware design, the array tracking concept offers reduced system complexity by reducing the number of optical elements in the design. Specifically, the design requires only one detector and one beam steering mechanism. It also provides the means to optically close the point-ahead control loop. The technology required for high bandwidth array tracking was examined and shown to be consistent with current state of the art. The single detector design can lead to a significantly reduced system complexity and a lower system cost.

  10. Study examines sulfate-reducing bacteria activity

    SciTech Connect

    McElhiney, J.E.; Hardy, J.A.; Rizk, T.Y.; Stott, J.F.D.; Eden, R.D.

    1996-12-09

    Low-sulfate seawater injection can reduce the potential of an oil reservoir turning sour because of sulfate-reducing bacteria. Sulfate-reducing bacteria (SRB) convert sulfate ions in seawater used in waterflooding into sulfide with the concomitant oxidation of a carbon source. A recent study at Capcis investigated the efficiency of SRB under various conditions of sulfate limitation. This study was conducted in a flowing bioreactor at 2,000 psia with different temperature zones (mesophilic 35 C and thermophilic 60--80 C). The study mixed microfloral populations derived from real North Sea-produced fluids, and included an active population of marine methanogenic bacteria present to provide competition for the available carbon sources. In general, results showed that SRB continue to convert sulfate to sulfide in stoichiometric quantities without regard to absolute concentrations. The paper discusses the results and recommends nanofiltration of seawater for ``sweet`` reservoirs.

  11. Local stressors reduce coral resilience to bleaching.

    PubMed

    Carilli, Jessica E; Norris, Richard D; Black, Bryan A; Walsh, Sheila M; McField, Melanie

    2009-07-22

    Coral bleaching, during which corals lose their symbiotic dinoflagellates, typically corresponds with periods of intense heat stress, and appears to be increasing in frequency and geographic extent as the climate warms. A fundamental question in coral reef ecology is whether chronic local stress reduces coral resistance and resilience from episodic stress such as bleaching, or alternatively promotes acclimatization, potentially increasing resistance and resilience. Here we show that following a major bleaching event, Montastraea faveolata coral growth rates at sites with higher local anthropogenic stressors remained suppressed for at least 8 years, while coral growth rates at sites with lower stress recovered in 2-3 years. Instead of promoting acclimatization, our data indicate that background stress reduces coral fitness and resilience to episodic events. We also suggest that reducing chronic stress through local coral reef management efforts may increase coral resilience to global climate change.

  12. Reduced pressure quenching oil and distortion

    SciTech Connect

    Asada, S.; Ogino, M.

    1996-12-31

    Cooling process observed in a quenching oil`s cooling curve determination by JIS silver probe method, has been divided into three stages, vapor blanket stage, boiling stage and convection stage. Under reduced pressure vaporization is accelerated and extend the vapor blanket stage which shift the position of boiling stage the fastest of cooling speed among the cooling process toward low temperature side. Taking advantage of this behavior in quenching under reduced pressure, it is possible to improve quench hardenability by controlling reduced pressure. Vapor pressure of quenching oil increases under very high vacuum and accelerates vapor blanket formation and covers the material with more vapor blanket, resulting in reduction of cooling speed. Excessive vapor blanket covering the material will lead to partially uneven quenching of the treated material caused by uneven conditions by partial decomposition. Making vapor blanket distribution more even and to optimize uniform coating condition enables to prevent heat treatment distortion caused by uneven quenching conditions.

  13. Nature of Reduced Carbon in Martian Meteorites

    NASA Technical Reports Server (NTRS)

    Gibson, Everett K., Jr.; McKay, D. S.; Thomas-Keprta, K. L.; Clemett, S. J.; White, L. M.

    2012-01-01

    Martian meteorites provide important information on the nature of reduced carbon components present on Mars throughout its history. The first in situ analyses for carbon on the surface of Mars by the Viking landers yielded disappointing results. With the recognition of Martian meteorites on Earth, investigations have shown carbon-bearing phases exist on Mars. Studies have yielded presence of reduced carbon, carbonates and inferred graphitic carbon phases. Samples ranging in age from the first approximately 4 Ga of Mars history [e.g. ALH84001] to nakhlites with a crystallization age of 1.3 Ga [e.g. Nakhla] with aqueous alteration processes occurring 0.5-0.7 Ga after crystallizaton. Shergottites demonstrate formation ages around 165-500 Ma with younger aqueous alterations events. Only a limited number of the Martian meteorites do not show evidence of significance terrestrial alterations. Selected areas within ALH84001, Nakhla, Yamato 000593 and possibly Tissint are suitable for study of their indigenous reduced carbon bearing phases. Nakhla possesses discrete, well-defined carbonaceous phases present within iddingsite alteration zones. Based upon both isotopic measurements and analysis of Nakhla's organic phases the presence of pre-terrestrial organics is now recognized. The reduced carbon-bearing phases appear to have been deposited during preterrestrial aqueous alteration events that produced clays. In addition, the microcrystalline layers of Nakhla's iddingsite have discrete units of salt crystals suggestive of evaporation processes. While we can only speculate on the origin of these unique carbonaceous structures, we note that the significance of such observations is that it may allow us to understand the role of Martian carbon as seen in the Martian meteorites with obvious implications for astrobiology and the pre-biotic evolution of Mars. In any case, our observations strongly suggest that reduced organic carbon exists as micrometer- size, discrete structures

  14. Stress, burnout, and strategies for reducing them

    PubMed Central

    Lee, F. Joseph; Stewart, Moira; Brown, Judith Belle

    2008-01-01

    OBJECTIVE To ascertain Canadian family physicians’ levels of stress and burnout and the strategies they use to reduce these problems. DESIGN Census survey. SETTING Kitchener-Waterloo, an urban area with a population of approximately 300 000 in southwestern Ontario. PARTICIPANTS Family physicians. MAIN OUTCOME MEASURES Scores on the Family Physician Stress Inventory, scores on strategies to reduce personal stress, scores on strategies to reduce stress on the job, and scores on the Maslach Burnout Inventory. RESULTS Participation rate was 77.8% (123 of 158 surveys returned). About 42.5% of participants had high stress levels. Burnout was defined by 3 components: emotional exhaustion, depersonalization (going through the day like an “automaton”), and perceived lack of personal accomplishment. Many respondents scored high on the burnout inventory, and almost half had high levels of emotional exhaustion and depersonalization (47.9% and 46.3%, respectively). No demographic factors were associated with high scores on these components. Use of strategies to reduce personal and occupational stress was associated with lower levels of burnout. Scores on the Family Physician Stress Inventory correlated highly with scores on the Maslach Burnout Inventory. CONCLUSION Regardless of demographic factors, family physicians are at risk of having high levels of stress and burnout. Classic burnout is related to stress brought on by factors such as too much paperwork, long waits for specialists and tests, feeling undervalued, feeling unsupported, and having to abide by rules and regulations. Common strategies for reducing personal stress included eating nutritiously and spending time with family and friends. Common strategies for reducing stress on the job included valuing relationships with patients and participating in continuing medical education. Stress and burnout are related to the desire to give up practice and are, therefore, a human resources issue for the entire health

  15. Pathogenesis of reduced or increased bladder sensation.

    PubMed

    Tsunoyama, Kuniko; Sakakibara, Ryuji; Yamaguchi, Chiharu; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori; Takahashi, Osamu; Sugiyama, Megumi; Kishi, Masahiko; Ogawa, Emina

    2011-03-01

    Pathogenesis of reduced or increased bladder sensation is not well known. Hence, we systematically investigated the frequency of reduced or increased bladder sensation in neurologic/mental diseases. We analyzed 911 patients who were referred from within our hospital. Data registries included a diagnosis, a lower urinary tract symptom questionnaire, a urodynamic study, and neurological examinations. Reduced bladder sensation is defined as bladder volume at the first sensation >300 ml. Increased bladder sensation is defined as bladder volume at the first sensation <100 ml. These patients were stratified into those with and without DO. Neuropathies are the most common cause of reduced bladder sensation (33.3-43.8% in diabetic neuropathy, etc.). Myelopathies are the second most common cause (17.4-25.0% in multiple sclerosis, etc.). Less common is brain diseases (9.6% in multiple system atrophy, etc.). In contrast, myelopathies are the most common cause of increased bladder sensation without DO (25.0-40.0% in spinal forms of systemic lupus erythematosus, Sjogren's syndrome, etc.). Neuropathies are the second most common (17.3-22.2% in post-pelvic organ surgery, diabetic neuropathy, etc.). Less common is brain/mental diseases (20.0% in psychogenic bladder dysfunction, 8.1% in Parkinson's disease, etc.). The present study revealed that neuropathies are the most common cause of reduced bladder sensation in neurologic/mental diseases. Increased bladder sensation without DO occurs mainly in peripheral and central sensory pathway lesions, as well as in basal ganglia lesions and psychogenic bladder dysfunction. Reduced and increased bladder sensation should be a major treatment target for maximizing patients' quality of life. Copyright © 2011 Wiley-Liss, Inc.

  16. Reducing the capacitance of piezoelectric film sensors

    SciTech Connect

    González, Martín G.; Sorichetti, Patricio A.; Santiago, Guillermo D.

    2016-04-15

    We present a novel design for large area, wideband, polymer piezoelectric sensor with low capacitance. The large area allows better spatial resolution in applications such as photoacoustic tomography and the reduced capacitance eases the design of fast transimpedance amplifiers. The metalized piezoelectric polymer thin film is segmented into N sections, electrically connected in series. In this way, the total capacitance is reduced by a factor 1/N{sup 2}, whereas the mechanical response and the active area of the sensor are not modified. We show the construction details for a two-section sensor, together with the impedance spectroscopy and impulse response experimental results that validate the design.

  17. Method of reducing drag in aerodynamic systems

    NASA Technical Reports Server (NTRS)

    Hrach, Frank J. (Inventor)

    1993-01-01

    In the present method, boundary layer thickening is combined with laminar flow control to reduce drag. An aerodynamic body is accelerated enabling a ram turbine on the body to receive air at velocity V sub 0. The discharge air is directed over an aft portion of the aerodynamic body producing boundary layer thickening. The ram turbine also drives a compressor by applying torque to a shaft connected between the ram turbine and the compressor. The compressor sucks in lower boundary layer air through inlets in the shell of the aircraft producing laminar flow control and reducing drag. The discharge from the compressor is expanded in a nozzle to produce thrust.

  18. Reduced variable technique for predicting grain behavior

    NASA Technical Reports Server (NTRS)

    Lewis, G. W.; Fedors, R. F.; Landel, R. F.

    1977-01-01

    The use of reduced variables to account for the time-temperature dependence of the relaxation modulus is a standard and universally adopted technique in the stress analysis of solid propellant grains. Recent work has suggested that the reduced variable technique can also be used to account for the dependence of the relaxation modulus on the crosslink density of an elastomer system. By combining variables, it is now possible to determine the relaxation modulus as a function of both mechanical and chemical parameters over a long period of time. The problems involved, the pitfalls to be avoided, and suggested techniques to be used in acquiring data are discussed.

  19. Natural genetic variability reduces recalcitrance in poplar

    SciTech Connect

    Bhagia, Samarthya; Muchero, Wellington; Kumar, Rajeev; Tuskan, Gerald A.; Wyman, Charles E.

    2016-05-20

    Here, lignin content and structure are known to affect recalcitrance of lignocellulosic biomass to chemical/biochemical conversion. Previously, we identified rare Populus trichocarpa natural variants with significantly reduced lignin content. Because reduced lignin content may lower recalcitrance, 18 rare variants along with 4 comparators, and BESC standard Populus was analyzed for composition of structural carbohydrates and lignin. Sugar yields from these plants were measured at 5 process conditions: one for just enzymatic hydrolysis without pretreatment and four via our combined high-throughput hot water pretreatment and co-hydrolysis (HTPH) technique.

  20. Viscous damped space structure for reduced jitter

    NASA Technical Reports Server (NTRS)

    Wilson, James F.; Davis, L. Porter

    1987-01-01

    A technique to provide modal vibration damping in high performance space structures was developed which uses less than one once of incompressible fluid. Up to 50 percent damping can be achieved which can reduce the settling times of the lowest structural mode by as much as 50 to 1. This concept allows the designers to reduce the weight of the structure while improving its dynamic performance. Damping by this technique is purely viscous and has been shown by test to be linear over 5 orders of input magnitude. Amplitudes as low as 0.2 microinch were demonstrated. Damping in the system is independent of stiffness and relatively insensitive to temperature.

  1. Reducing the cost of HIV antibody testing.

    PubMed

    Tamashiro, H; Maskill, W; Emmanuel, J; Fauquex, A; Sato, P; Heymann, D

    1993-07-10

    Available tests to detect antibody to human immunodeficiency virus (HIV) have a range of applications, and injudicious selection and inappropriate use can add a significant financial burden to budgets for AIDS programmes in developing countries. There are several ways by which the cost of HIV antibody testing can be reduced; they include use of tests appropriate for existing laboratory capabilities; adoption of cost-effective testing strategies; pooling of serum samples before testing; and ensuring best possible purchase prices. Each approach can significantly reduce the cost of HIV antibody testing alone or in combination, which increases the potential sustainability of antibody testing programmes, even in settings of limited resources.

  2. Vacancy ordering in reduced barium titanate

    NASA Astrophysics Data System (ADS)

    Woodward, David I.; Reaney, Ian M.; Yang, Gaiying Y.; Dickey, Elizabeth C.; Randall, Clive A.

    2004-06-01

    A crystal structure is proposed for reduced barium titanate, BaTiO3-δ, δ≈0.33, formed during the degradation of Ni-BaTiO3 X7R multilayer ceramic capacitors. High-resolution transmission electron microscopy and selected-area electron diffraction have been used in combination with computer simulations to show that oxygen vacancies accrete on every third pseudocubic {111} plane, resulting in a cell with space group P3m1. Additionally, from electron energy loss spectroscopy, it is proposed that Ti4+ is reduced to Ti3+ as a mechanism of charge compensation within oxygen-deficient octahedra.

  3. Reducing the capacitance of piezoelectric film sensors.

    PubMed

    González, Martín G; Sorichetti, Patricio A; Santiago, Guillermo D

    2016-04-01

    We present a novel design for large area, wideband, polymer piezoelectric sensor with low capacitance. The large area allows better spatial resolution in applications such as photoacoustic tomography and the reduced capacitance eases the design of fast transimpedance amplifiers. The metalized piezoelectric polymer thin film is segmented into N sections, electrically connected in series. In this way, the total capacitance is reduced by a factor 1/N(2), whereas the mechanical response and the active area of the sensor are not modified. We show the construction details for a two-section sensor, together with the impedance spectroscopy and impulse response experimental results that validate the design.

  4. Natural genetic variability reduces recalcitrance in poplar

    DOE PAGES

    Bhagia, Samarthya; Muchero, Wellington; Kumar, Rajeev; ...

    2016-05-20

    Here, lignin content and structure are known to affect recalcitrance of lignocellulosic biomass to chemical/biochemical conversion. Previously, we identified rare Populus trichocarpa natural variants with significantly reduced lignin content. Because reduced lignin content may lower recalcitrance, 18 rare variants along with 4 comparators, and BESC standard Populus was analyzed for composition of structural carbohydrates and lignin. Sugar yields from these plants were measured at 5 process conditions: one for just enzymatic hydrolysis without pretreatment and four via our combined high-throughput hot water pretreatment and co-hydrolysis (HTPH) technique.

  5. A Review of Focal Reducer Interferometer Systems

    DTIC Science & Technology

    1986-06-01

    searches. G.Courtes has also proposed a design for a focal reducer for the E.S.O. 3.6m. Ritchey -Chretien telescope (Fig. 4b). He uses a Schmidt camera...spaced components, with a modified Wynne camera design (Fig. 7). The instrument proposed used folded optics and would operate at the F/8 Ritchey Cretien ...G.Courtes for the 3.6m Ritchey Chretien telescope . a, telescope focal plane and field lens; b, collimator; c, camera. Figure 5 The focal reducer of A.B

  6. Reduced Basis Method for Nanodevices Simulation

    SciTech Connect

    Pau, George Shu Heng

    2008-05-23

    Ballistic transport simulation in nanodevices, which involves self-consistently solving a coupled Schrodinger-Poisson system of equations, is usually computationally intensive. Here, we propose coupling the reduced basis method with the subband decomposition method to improve the overall efficiency of the simulation. By exploiting a posteriori error estimation procedure and greedy sampling algorithm, we are able to design an algorithm where the computational cost is reduced significantly. In addition, the computational cost only grows marginally with the number of grid points in the confined direction.

  7. Quantum Gauge Symmetry of Reducible Gauge Theory

    NASA Astrophysics Data System (ADS)

    Dwivedi, Manoj Kumar

    2017-05-01

    We derive the gaugeon formalism of the Kalb-Ramond field theory, a reducible gauge theory, which discusses the quantum gauge freedom. In gaugeon formalism, theory admits quantum gauge symmetry which leaves the action form-invariant. The BRST symmetric gaugeon formalism is also studied which introduces the gaugeon ghost fields and gaugeon ghosts of ghosts fields. To replace the Yokoyama subsidiary conditions by a single Kugo-Ojima type condition the virtue of BRST symmetry is utilized. Under generalized BRST transformations, we show that the gaugeon fields appear naturally in the reducible gauge theory.

  8. Tests of Reduced Redundancy--Theory.

    ERIC Educational Resources Information Center

    Klein-Braley, Christine

    One solution to the problems of discrete-point testing are tests of reduced redundancy, that is, tests that introduce interference into the communication through actual introduction of noise or through deletion of text and that ask the learner to perform in spite of the noise. Three test types were originally developed to operationalize the…

  9. Estimating Reduced Consumption for Dynamic Demand Response

    SciTech Connect

    Chelmis, Charalampos; Aman, Saima; Saeed, Muhammad Rizwan; Frincu, Marc; Prasanna, Viktor K.

    2015-01-30

    Growing demand is straining our existing electricity generation facilities and requires active participation of the utility and the consumers to achieve energy sustainability. One of the most effective and widely used ways to achieve this goal in the smart grid is demand response (DR), whereby consumers reduce their electricity consumption in response to a request sent from the utility whenever it anticipates a peak in demand. To successfully plan and implement demand response, the utility requires reliable estimate of reduced consumption during DR. This also helps in optimal selection of consumers and curtailment strategies during DR. While much work has been done on predicting normal consumption, reduced consumption prediction is an open problem that is under-studied. In this paper, we introduce and formalize the problem of reduced consumption prediction, and discuss the challenges associated with it. We also describe computational methods that use historical DR data as well as pre-DR conditions to make such predictions. Our experiments are conducted in the real-world setting of a university campus microgrid, and our preliminary results set the foundation for more detailed modeling.

  10. A Plan To Reduce Library Book Losses.

    ERIC Educational Resources Information Center

    Craig, Darlene S.

    The author researched and adapted ways to promote responsibility for library books. The program's aims were to reduce and retrieve lost library books that were reported on the inventory check and to make students, parents, and teachers aware of the problems and the importance of being responsible library users. Introduction to the project was done…

  11. Reducing Research Anxiety among MSW Students

    ERIC Educational Resources Information Center

    Einbinder, Susan Dana

    2014-01-01

    Research anxiety significantly declined in a diverse sample of 59 MSW students in their first-year hybrid online research course in which the instructor used an array of innovative educational techniques empirically proven to reduce this phenomenon. The pretest/posttest study, the standardized survey instruments used, and a summary of these…

  12. Policy Options for Reducing CO2 Emissions

    DTIC Science & Technology

    2008-02-01

    that they reduce emissions by more than one ton when they pay back the allowance loan. 35. See Catherine Kling and Jonathan Rubin, “ Bankable Permits...emissions and allowances (to determine compliance) at the end of each year. As under the SO2 trading program, the NOx allowances are bankable . In addition

  13. Reducing the diameters of computer networks

    NASA Technical Reports Server (NTRS)

    Bokhari, S. H.; Raza, A. D.

    1986-01-01

    Three methods of reducing the diameters of computer networks by adding additional processor to processor links under the constraint that no more than one I/O port be added to each processor are discussed. This is equivalent to adding edges to a given graph under the constraint that the degree of any node be increased, at most, by one.

  14. Projection screen having reduced ambient light scattering

    DOEpatents

    Sweatt, William C [Albuquerque, NM

    2010-05-11

    An apparatus and method for improving the contrast between incident projected light and ambient light reflected from a projection screen are described. The efficiency of the projection screen for reflection of the projected light remains high, while permitting the projection screen to be utilized in a brightly lighted room. Light power requirements from the projection system utilized may be reduced.

  15. Novel tactile feedback to reduce overt stuttering.

    PubMed

    Waddell, Dwight E; Goggans, Paul M; Snyder, Gregory J

    2012-08-22

    Stuttering is generally considered to be a speech disorder that affects ∼1% of the global population. Various forms of speech feedback have been shown to reduce overt stuttered speaking, and in particular, second speech signal through speech feedback has drastically reduced utterances of stuttered speech in adults with persistent stuttering. This study reports data for increased overt fluency of speech in an adult stuttering population, whereby the vocalization of the speaker is captured by a microphone or an accelerometer, signal processed, and returned as mechanical tactile speech feedback to the speaker's skin. A repeated measures analysis of variance was used to show that both the microphone and the accelerometer speaking conditions were significantly more fluent than a control (no feedback) condition, with the microphone-driven tactile feedback reducing instances of stuttering by 71% and the accelerometer-driven tactile feedback reducing instances of stuttering by 80%. It is apparent that self-generated tactile feedback can be used to enhance fluency significantly in those who stutter.

  16. Does zoning winter recreationists reduce recreation conflict?

    Treesearch

    Aubrey Miller; Jerry J. Vaske; John R. Squires; Lucretia E. Olson

    2016-01-01

    Parks and protected area managers use zoning to decrease interpersonal conflict between recreationists. Zoning, or segregation, of recreation - often by nonmotorized and motorized activity - is designed to limit physical interaction while providing recreation opportunities to both groups. This article investigated the effectiveness of zoning to reduce recreation...

  17. Reducing grain storage losses in developing countries

    USDA-ARS?s Scientific Manuscript database

    We investigated the use of insecticide-treated material and modified atmosphere storage for reducing insect damage in stored maize. Results showed that insecticide treated netting and insecticide treated seed bags protected grain from insect damage for up to nine months if the grain was free from i...

  18. Does zoning winter recreationists reduce recreation conflict?

    Treesearch

    Aubrey D. Miller; Jerry J. Vaske; John R. Squires; Lucretia E. Olson; Elizabeth K. Roberts

    2017-01-01

    Parks and protected area managers use zoning to decrease interpersonal conflict between recreationists. Zoning, or segregation, of recreation - often by nonmotorized and motorized activity - is designed to limit physical interaction while providing recreation opportunities to both groups. This article investigated the effectiveness of zoning to reduce recreation...

  19. Reducing exhaust gas emissions from Citydiesel busses

    NASA Astrophysics Data System (ADS)

    Mikkonen, Seppo

    The effect of fuel composition and exhaust gas aftertreatment on the emissions was measured from truck and bus engines. Possibilities to measure unregulated emissions (aldehydes, polyaromatic hydrocarbons, mutagenicity) were built. A reformulated diesel fuel 'Citydiesel' was developed. Citydiesel was able to reduce emissions compared to standard diesel fuel as follows: particulates by 10 to 30%, nitrogen oxides by 2 to 10%, sulphur dioxide by 97%, polyaromatic hydrocarbons (PAH) over 50%, mutagenicity of the exhaust particulates clearly, odor of the exhaust, and smoke after a cold start. The use of Citydiesel fuel reduces emissions of the existing vehicles immediately which is a remarkable benefit. The very low sulphur content (below 50 ppm) makes it possible to use oxidation. catalytic converters to reduce emissions of diesel vehicles. The new Euro 2 exhaust regulations coming into force during 1996 can be met with a modern diesel engine, Citydiesel fuel, and exhaust gas aftertreatment. Properties of Citydiesel fuel were verified in a three year field test with 140 city buses. Experience was good; e.g., engine oil change interval could be lengthened. Total value of the exhaust was estimated with different fuels and aftertreatment device in order to find out cheap ways to reduce emissions.

  20. Reducing social losses from forest fires

    Treesearch

    Gregory S. Amacher; Arun S. Malik; Robert G. Haight

    2006-01-01

    We evaluate two financial incentives to encourage nonindustrial forest landowners to undertake activities that mitigate fire losses: sharing of fire suppression costs by the landowner and sharing of fuel reduction costs by the government. First and second best outcomes are identified and compared to assess the effectiveness of these incentives in reducing social...

  1. Attributional Retraining: Reducing the Likelihood of Failure

    ERIC Educational Resources Information Center

    Haynes Stewart, Tara L.; Clifton, Rodney A.; Daniels, Lia M.; Perry, Raymond P.; Chipperfield, Judith G.; Ruthig, Joelle C.

    2011-01-01

    Failing a course is an acutely negative event for first-year university students, and a major contributor to high attrition rates at North American universities. Despite its prevalence, course failure receives relatively little research attention. What can be done to reduce course failure and help first-year students remain in university? This…

  2. Reducing Class Size: Promises and Perils

    ERIC Educational Resources Information Center

    Bascia, Nina; Fredua-Kwarteng, Eric

    2008-01-01

    Reducing class size, especially in primary grades, can have tremendous academic and social benefits for children--benefits that endure well beyond those first years of school. But smaller class sizes are not a cure-all. Beyond the hoopla of enthusiasm for this seemingly simple change in educational practice lie serious consequences for students…

  3. Headaches: Reduce Stress to Prevent the Pain

    MedlinePlus

    ... such as listening to music, dancing, playing a sport, reading a book or playing with your pet can help. In addition, set aside time, even if it's just 10 minutes a day, to practice relaxation. Techniques include: Meditation Yoga Tai chi Deep breathing Also, to reduce stress ...

  4. Light gas gun with reduced timing jitter

    DOEpatents

    Laabs, G.W.; Funk, D.J.; Asay, B.W.

    1998-06-09

    Gas gun with reduced timing jitter is disclosed. A gas gun having a prepressurized projectile held in place with a glass rod in compression is described. The glass rod is destroyed with an explosive at a precise time which allows a restraining pin to be moved and free the projectile. 4 figs.

  5. Reducing Procrastination through Required Course Involvement.

    ERIC Educational Resources Information Center

    Wesp, Richard

    1986-01-01

    Students in two introductory psychology classes using a personalized system of instruction were assigned to either daily quizzing or self-initiated quizzing treatment conditions. Results showed students in the daily quizzing section completed course work more rapidly and earned higher grades by reducing procrastination. (Author/JDH)

  6. Reducing Radon in Schools: A Team Approach.

    ERIC Educational Resources Information Center

    Ligman, Bryan K.; Fisher, Eugene J.

    This document presents the process of radon diagnostics and mitigation in schools to help educators determine the best way to reduce elevated radon levels found in a school. The guidebook is designed to guide school leaders through the process of measuring radon levels, selecting the best mitigation strategy, and directing the efforts of a…

  7. Software system for reducing PAM-2 data

    NASA Technical Reports Server (NTRS)

    Pepin, T. J.

    1982-01-01

    A software system for reducing PAM-II data was constructed. The data reduction process concatenates data tapes; determines ephemeris; and inverts full sun extinction data. Tests of this data reduction process show that PAM-II data can be compared with data from other, similar satellites.

  8. Gold nanoparticle hyperthermia reduces radiotherapy dose.

    PubMed

    Hainfeld, James F; Lin, Lynn; Slatkin, Daniel N; Avraham Dilmanian, F; Vadas, Timothy M; Smilowitz, Henry M

    2014-11-01

    Gold nanoparticles can absorb near infrared light, resulting in heating and ablation of tumors. Gold nanoparticles have also been used for enhancing the X-ray dose to tumors. The combination of hyperthermia and radiotherapy is synergistic, importantly allowing a reduction in X-ray dose with improved therapeutic results. Here we intratumorally infused small 15 nm gold nanoparticles engineered to be transformed from infrared-transparent to infrared-absorptive by the tumor, then heated by infrared followed by X-ray treatment. Synergy was studied using a very radioresistant subcutaneous squamous cell carcinoma (SCCVII) in mice. It was found that the dose required to control 50% of the tumors, normally 55 Gy, could be reduced to <15 Gy (a factor of >3.7). Gold nanoparticles therefore provide a method to combine hyperthermia and radiotherapy to drastically reduce the X-ray radiation needed, thus sparing normal tissue, reducing side effects, and making radiotherapy more effective. Gold nanoparticles are known to enhance the efficacy of X-ray in tumor irradiation resulting in tumor heating and ablation. They also absorb near infrared light. This dual property was studied using a very radioresistant subcutaneous squamous cell carcinoma in mice, demonstrating that the dose required to control 50% of the tumors could be reduced by a factor of > 3.7, paving the way to potential future clinical applications. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Chemicals Reduce Need To Mow Grass

    NASA Technical Reports Server (NTRS)

    Humphrys, Brooks; Farley, Max; Gast, Larry J.

    1993-01-01

    Brief report discusses use of herbicides Roundup(R), Campaign(R), and Oust(R) to retard growth of Argentine bahia grass. Herbicide applied by use of spraying apparatus pulled by tractor. "Chemical mowing" keeps grass at "freshly mowed" height with less mechanical mowing. Applied to grass on shoulders of roads, reducing time spent on mowing.

  10. Teachers: Recognize Important Steps to Reduce Cheating

    ERIC Educational Resources Information Center

    Supon, Viola

    2008-01-01

    Teachers must walk the steps and live the steps if reducing cheating is going to occur. Teachers begin this process by being cognizant and vigilant relative to administering means of measurement and assigning written work. This process includes skill acquisition in regards to: (1) acknowledging cheating, (2) purposeful planning, (3) electronic…

  11. Reducing Children's Littering on a Nature Trail

    ERIC Educational Resources Information Center

    LaHart, David E.; Bailey, Jon S.

    1975-01-01

    This study compared incentives and educational methods to motivate children to pick up litter and to prevent littering. Incentives did aid in getting litter picked up. One-sentence anti-litter statements, educational materials, and lectures reduced littering, but incentives did not. (MR)

  12. Reducing Test Anxiety: A Right Brain Approach.

    ERIC Educational Resources Information Center

    Cohen, Ruth I.

    Methods of helping students reduce test anxiety are discussed, including guided fantasy which leads students to imagine a setting in which they feel competent and relaxed. Catastrophic-anastrophic expectations teach that different expectations create different feelings and make students aware that they are in charge of their own attitudes. Anxiety…

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

    PubMed

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

    2014-10-01

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

  14. Reducing Incidents of Cheating in Adolescence.

    ERIC Educational Resources Information Center

    Bopp, Mary; Gleason, Patricia; Misicka, Stacey

    This report describes a program implemented to raise the awareness of the dramatic increases of reported academic cheating, to influence the attitudes of the targeted students towards cheating, and ultimately to reduce incidents of cheating in the targeted classrooms. The targeted populations consisted of middle school students in growing…

  15. Reducing the Negative Effects of Large Schools.

    ERIC Educational Resources Information Center

    Duke, Daniel L.; Trautvetter, Sara

    This report presents an overview of recent efforts to promote small schools by first reviewing the rationale for small schools based on recent studies linking school size and various educational outcomes, followed by arguments supporting larger schools. Succeeding sections explore the following four ways to reduce the negative effects of school…

  16. Cost-reducing multipurpose microfilm card

    NASA Technical Reports Server (NTRS)

    Smith, A. V.

    1970-01-01

    Microfilm-aperture card is printed in the same format on both sides which enables the use of one card for mounting films that are ''right reading'' on both the base side and the emulsion side. This reduces the number of microfilm-card formats.

  17. Reducing Error in Mail Surveys. ERIC Digest.

    ERIC Educational Resources Information Center

    Cui, Weiwei

    This Digest describes four types of errors in mail surveys and summarizes the ways they can be reduced. Any one of these sources of error can make survey results unacceptable. Sampling error is examined through inferential statistics applied to sample survey results. In general, increasing sample size will decrease sampling error when simple…

  18. Reducing Alcohol Consumption through Television Advertising.

    ERIC Educational Resources Information Center

    Barber, James G.; And Others

    1989-01-01

    Assessed impact of television commercial based on controlled-drinking principles. Measures were taken 12 months prior to start of campaign and 3 weeks after campaign from regular drinkers of general public whose drinking behavior was known to be unaffected by previous antidrug advertising campaign. Found that advertisement reduced intake provided…

  19. How to reduce your fire insurance rates

    NASA Technical Reports Server (NTRS)

    Dubain, M.

    1971-01-01

    Construction procedures and utilization of materials to reduce the cost of insuring large buildings against losses from fire are discussed. Examples of good and bad techniques in building construction and fire safety management are provided. The inadequacies of building codes and the hazards resulting from improper construction are examined.

  20. Soldering iron temperature is automatically reduced

    NASA Technical Reports Server (NTRS)

    Lum, J. Y.

    1966-01-01

    Hinged cradle-microswitch arrangement maintains a soldering iron at less than peak temperature when not in use. The microswitch introduces a voltage reducing element into the soldering iron power circuit when the iron is placed on the cradle. The iron, when removed from the cradle, returns to operating temperature in 15 to 30 seconds.

  1. Reducing Heating In High-Speed Cinematography

    NASA Technical Reports Server (NTRS)

    Slater, Howard A.

    1989-01-01

    Infrared-absorbing and infrared-reflecting glass filters simple and effective means for reducing rise in temperature during high-speed motion-picture photography. "Hot-mirror" and "cold-mirror" configurations, employed in projection of images, helps prevent excessive heating of scenes by powerful lamps used in high-speed photography.

  2. The Three Rs: Reduce, Reuse, Recycle.

    ERIC Educational Resources Information Center

    Science Activities, 1991

    1991-01-01

    A student hand-out for a recycling unit defines the terms reduce, recycle, and reuse as they relate to solid waste management. Presents the characteristics of recyclable items such as yard wastes, metals, glass, and paper. Lists organizations through which more information about recycling can be obtained. (MCO)

  3. Microwave Oscillator Would Have Reduced Phase Noise

    NASA Technical Reports Server (NTRS)

    Dick, G. John; Saunders, Jon

    1991-01-01

    Microwave oscillators of proposed new type incorporate suppressed-carrier/negative-feedback feature to reduce phase noise near their carrier frequencies. Concept results in phase noise less than achievable by cryogenically stabilized microwave components or by room-temperature oscillators stabilized by quartz crystals. Implemented in three different versions.

  4. Reducing Adverse Impact: One City's Efforts.

    ERIC Educational Resources Information Center

    Prewitt, Jeff

    Following a workshop on "Innovations in Employment Testing that Improve Validity and Reduce Adverse Impact," the City of Louisville (Kentucky) implemented a strategy to develop a comprehensive testing and recruiting program for police recruits. To improve candidate expectations and preparation, the following activities were undertaken:…

  5. Reducing Skin Picking via Competing Activities

    ERIC Educational Resources Information Center

    Lane, Kathleen Lynne; Thompson, Ada; Reske, Cara L.; Gable, Lauren M.; Barton-Arwood, Sally

    2006-01-01

    This study examined the outcomes of a competing activities intervention to decrease skin picking exhibited by a 9-year-old student with comorbid diagnoses. Results of an ABCBAB design revealed that the use of student-selected manipulatives resulted in reduced skin picking. (Contains 1 figure.)

  6. Reducing the diameters of computer networks

    NASA Technical Reports Server (NTRS)

    Bokhari, S. H.; Raza, A. D.

    1986-01-01

    Three methods of reducing the diameters of computer networks by adding additional processor to processor links under the constraint that no more than one I/O port be added to each processor are discussed. This is equivalent to adding edges to a given graph under the constraint that the degree of any node be increased, at most, by one.

  7. Light gas gun with reduced timing jitter

    DOEpatents

    Laabs, Gary W.; Funk, David J.; Asay, Blaine W.

    1998-01-01

    Gas gun with reduced timing jitter. A gas gun having a prepressurized projectile held in place with a glass rod in compression is described. The glass rod is destroyed with an explosive at a precise time which allows a restraining pin to be moved and free the projectile.

  8. Reduced-impact logging: challenges and opportunities

    Treesearch

    F.E. Putz; P. Sist; T. Fredericksen; D. Dykstra

    2008-01-01

    Over the past two decades, sets of timber harvesting guidelines designed to mitigate the deleterious environmental impacts of tree felling, yarding, and hauling have become known as "reduced-impact logging" (RIL) techniques. Although none of the components of RIL are new, concerns about destructive logging practices and worker safety in the tropics stimulated...

  9. Coatings to reduce wood preservative leaching.

    PubMed

    Nejad, Mojgan; Cooper, Paul

    2010-08-15

    The efficiency of semitransparent penetrating stains to reduce leaching of wood preservative components was evaluated. Five commercial wood deck finishes were applied to untreated and chromated copper arsenate (CCA), alkaline copper quat (ACQ), and copper azole (CA) treated wood, and leachates were collected and analyzed during 3 years of natural weathering exposure in Toronto, Canada. All stains evaluated effectively reduced the cumulative leaching of all inorganic preservative components by about 60% on average. Although most coatings showed significant film degradation starting around 12 months, the reduced leaching persisted even after 3 years. This suggests that temporary protection of wood with a coating during the early stages of use resulted in long-term reduction in preservative leaching potential. A two-week screening leaching test was able to predict the long-term leaching performance of different coatings reasonably well. Cured coating glass transition temperature (Tg) and liquid coating viscosity were the most important variables affecting a leaching prediction model. To effectively reduce leaching of preservative components from treated wood, coatings should have Tg low enough to withstand stresses caused by freezing in winter and have adequate viscosity to form a barrier film layer on the wood surface.

  10. Reduced No.sub.x combustion method

    DOEpatents

    Delano, Mark A.

    1991-01-01

    A combustion method enabling reduced NO.sub.x formation wherein fuel and oxidant are separately injected into a combustion zone in a defined velocity relation, combustion gases are aspirated into the oxidant stream prior to intermixture with the fuel, and the fuel is maintained free from contact with oxygen until the intermixture.

  11. Reducing Abstraction When Learning Graph Theory

    ERIC Educational Resources Information Center

    Hazzan, Orit; Hadar, Irit

    2005-01-01

    This article presents research on students' understanding of basic concepts in Graph Theory. Students' understanding is analyzed through the lens of the theoretical framework of reducing abstraction (Hazzan, 1999). As it turns out, in spite of the relative simplicity of the concepts that are introduced in the introductory part of a traditional…

  12. Sodium Valproate Withdrawal Correlates with Reduced Aggression

    ERIC Educational Resources Information Center

    Pritchard, Duncan; Hoerger, Marguerite; Dyer, Tim; Graham, Nicola; Penney, Heather; Mace, F. Charles

    2014-01-01

    People with learning disabilities are sometimes prescribed psychotropic medication to help manage their challenging behaviour. This case study describes how a multicomponent behavioural intervention in conjunction with the systematic withdrawal of sodium valproate was strongly correlated with reduced aggression. No symptoms of bipolar disorder or…

  13. Nitric oxide reduces seed dormancy in Arabidopsis.

    PubMed

    Bethke, Paul C; Libourel, Igor G L; Jones, Russell L

    2006-01-01

    Dormancy is a property of many mature seeds, and experimentation over the past century has identified numerous chemical treatments that will reduce seed dormancy. Nitrogen-containing compounds including nitrate, nitrite, and cyanide break seed dormancy in a range of species. Experiments are described here that were carried out to further our understanding of the mechanism whereby these and other compounds, such as the nitric oxide (NO) donor sodium nitroprusside (SNP), bring about a reduction in seed dormancy of Arabidopsis thaliana. A simple method was devised for applying the products of SNP photolysis through the gas phase. Using this approach it was shown that SNP, as well as potassium ferricyanide (Fe(III)CN) and potassium ferrocyanide (Fe(II)CN), reduced dormancy of Arabidopsis seeds by generating cyanide (CN). The effects of potassium cyanide (KCN) on dormant seeds were tested and it was confirmed that cyanide vapours were sufficient to break Arabidopsis seed dormancy. Nitrate and nitrite also reduced Arabidopsis seed dormancy and resulted in substantial rates of germination. The effects of CN, nitrite, and nitrate on dormancy were prevented by the NO scavenger c-PTIO. It was confirmed that NO plays a role in reducing seed dormancy by using purified NO gas, and a model to explain how nitrogen-containing compounds may break dormancy in Arabidopsis is presented.

  14. Fluidized-bed combustion reduces atmospheric pollutants

    NASA Technical Reports Server (NTRS)

    Jonke, A. A.

    1972-01-01

    Method of reducing sulfur and nitrogen oxides released during combustion of fossil fuels is described. Fuel is burned in fluidized bed of solids with simultaneous feeding of crushed or pulverized limestone to control emission. Process also offers high heat transfer rates and efficient contacting for gas-solid reactions.

  15. Preventive Intervention to Reduce Conflicts among Students.

    ERIC Educational Resources Information Center

    Dragoon, Marion; Klein, Robert

    1979-01-01

    Describes an intervention program at the Herbert H. Lehman High School in Bronx, New York. A conflicts class was introduced to reduce violence and tensions among students. Trust and openness increased, and fear of the loss of control was allayed through counseling, interpersonal relationships and activities, and video tape feedback. (BEF)

  16. A reduced volumetric expansion factor plot

    NASA Technical Reports Server (NTRS)

    Hendricks, R. C.

    1979-01-01

    A reduced volumetric expansion factor plot was constructed for simple fluids which is suitable for engineering computations in heat transfer. Volumetric expansion factors were found useful in correlating heat transfer data over a wide range of operating conditions including liquids, gases and the near critical region.

  17. A reduced volumetric expansion factor plot

    NASA Technical Reports Server (NTRS)

    Hendricks, R. C.

    1979-01-01

    A reduced volumetric expansion factor plot has been constructed for simple fluids which is suitable for engineering computations in heat transfer. Volumetric expansion factors have been found useful in correlating heat transfer data over a wide range of operating conditions including liquids, gases and the near critical region.

  18. Speak Up: Reduce Your Risk of Falling

    MedlinePlus

    ... sluggish or confused. Ask how to reduce these side effects or if you can take another medicine. The goal of the Speak Up ™ program is to help patients and their advocates become more informed and involved in their health care.

  19. Reducing Depression in Pregnancy: Designing Multimodel Interventions.

    ERIC Educational Resources Information Center

    Cunningham, Maddy; Zayas, Luis H.

    2002-01-01

    High levels of stress on low-income, inner-city women from ethnic minority groups often causes both poor maternal functioning and infant development outcomes. This article reviews literature that proposes using several social work treatment options instead a single approach to reduce maternal depression, expand mothers' social networks, and…

  20. A Health Plan to Reduce Poverty

    ERIC Educational Resources Information Center

    Weil, Alan

    2007-01-01

    Noting that the failures of the U.S. health care system are compounding the problems faced by low-income Americans, Alan Weil argues that any strategy to reduce poverty must provide access to health care for all low-income families. Although nearly all children in families with incomes under 200 percent of poverty are eligible for either Medicaid…

  1. Reducing sucrose loss in sugarbeet storage

    USDA-ARS?s Scientific Manuscript database

    Sucrose loss in sugarbeet storage is a considerable problem which is negatively influenced by environmental conditions, stress on roots from disease problems in the field, rough handling during harvest and transport, and microbial growth. To reduce sucrose loss in sugarbeet storage, studies were in...

  2. Reducible cationic lipids for gene transfer.

    PubMed Central

    Wetzer, B; Byk, G; Frederic, M; Airiau, M; Blanche, F; Pitard, B; Scherman, D

    2001-01-01

    One of the main challenges of gene therapy remains the increase of gene delivery into eukaryotic cells. We tested whether intracellular DNA release, an essential step for gene transfer, could be facilitated by using reducible cationic DNA-delivery vectors. For this purpose, plasmid DNA was complexed with cationic lipids bearing a disulphide bond. This reduction-sensitive linker is expected to be reduced and cleaved in the reducing milieu of the cytoplasm, thus potentially improving DNA release and consequently transfection. The DNA--disulphide-lipid complexation was monitored by ethidium bromide exclusion, and the size of complexes was determined by dynamic light scattering. It was found that the reduction kinetics of disulphide groups in DNA--lipid complexes depended on the position of the disulphide linker within the lipid molecule. Furthermore, the internal structure of DNA--lipid particles was examined by small-angle X-ray scattering before and after lipid reduction. DNA release from lipid complexes was observed after the reduction of disulphide bonds of several lipids. Cell-transfection experiments suggested that complexes formed with selected reducible lipids resulted in up to 1000-fold higher reporter-gene activity, when compared with their analogues without disulphide bonds. In conclusion, reduction-sensitive groups introduced into cationic lipid backbones potentially allow enhanced DNA release from DNA--lipid complexes after intracellular reduction and represent a tool for improved vectorization. PMID:11389682

  3. Reducible cationic lipids for gene transfer.

    PubMed

    Wetzer, B; Byk, G; Frederic, M; Airiau, M; Blanche, F; Pitard, B; Scherman, D

    2001-06-15

    One of the main challenges of gene therapy remains the increase of gene delivery into eukaryotic cells. We tested whether intracellular DNA release, an essential step for gene transfer, could be facilitated by using reducible cationic DNA-delivery vectors. For this purpose, plasmid DNA was complexed with cationic lipids bearing a disulphide bond. This reduction-sensitive linker is expected to be reduced and cleaved in the reducing milieu of the cytoplasm, thus potentially improving DNA release and consequently transfection. The DNA--disulphide-lipid complexation was monitored by ethidium bromide exclusion, and the size of complexes was determined by dynamic light scattering. It was found that the reduction kinetics of disulphide groups in DNA--lipid complexes depended on the position of the disulphide linker within the lipid molecule. Furthermore, the internal structure of DNA--lipid particles was examined by small-angle X-ray scattering before and after lipid reduction. DNA release from lipid complexes was observed after the reduction of disulphide bonds of several lipids. Cell-transfection experiments suggested that complexes formed with selected reducible lipids resulted in up to 1000-fold higher reporter-gene activity, when compared with their analogues without disulphide bonds. In conclusion, reduction-sensitive groups introduced into cationic lipid backbones potentially allow enhanced DNA release from DNA--lipid complexes after intracellular reduction and represent a tool for improved vectorization.

  4. Quasi-equilibria in reduced Liouville spaces.

    PubMed

    Halse, Meghan E; Dumez, Jean-Nicolas; Emsley, Lyndon

    2012-06-14

    The quasi-equilibrium behaviour of isolated nuclear spin systems in full and reduced Liouville spaces is discussed. We focus in particular on the reduced Liouville spaces used in the low-order correlations in Liouville space (LCL) simulation method, a restricted-spin-space approach to efficiently modelling the dynamics of large networks of strongly coupled spins. General numerical methods for the calculation of quasi-equilibrium expectation values of observables in Liouville space are presented. In particular, we treat the cases of a time-independent Hamiltonian, a time-periodic Hamiltonian (with and without stroboscopic sampling) and powder averaging. These quasi-equilibrium calculation methods are applied to the example case of spin diffusion in solid-state nuclear magnetic resonance. We show that there are marked differences between the quasi-equilibrium behaviour of spin systems in the full and reduced spaces. These differences are particularly interesting in the time-periodic-Hamiltonian case, where simulations carried out in the reduced space demonstrate ergodic behaviour even for small spins systems (as few as five homonuclei). The implications of this ergodic property on the success of the LCL method in modelling the dynamics of spin diffusion in magic-angle spinning experiments of powders is discussed.

  5. Reducing Class Size: Promises and Perils

    ERIC Educational Resources Information Center

    Bascia, Nina; Fredua-Kwarteng, Eric

    2008-01-01

    Reducing class size, especially in primary grades, can have tremendous academic and social benefits for children--benefits that endure well beyond those first years of school. But smaller class sizes are not a cure-all. Beyond the hoopla of enthusiasm for this seemingly simple change in educational practice lie serious consequences for students…

  6. How Does Distinctive Processing Reduce False Recall?

    ERIC Educational Resources Information Center

    Hunt, R. Reed; Smith, Rebekah E.; Dunlap, Kathryn R.

    2011-01-01

    False memories arising from associatively related lists are a robust phenomenon that resists many efforts to prevent it. However, a few variables have been shown to reduce this form of false memory. Explanations for how the reduction is accomplished have focused on either output monitoring processes or constraints on access, but neither idea alone…

  7. Sodium Valproate Withdrawal Correlates with Reduced Aggression

    ERIC Educational Resources Information Center

    Pritchard, Duncan; Hoerger, Marguerite; Dyer, Tim; Graham, Nicola; Penney, Heather; Mace, F. Charles

    2014-01-01

    People with learning disabilities are sometimes prescribed psychotropic medication to help manage their challenging behaviour. This case study describes how a multicomponent behavioural intervention in conjunction with the systematic withdrawal of sodium valproate was strongly correlated with reduced aggression. No symptoms of bipolar disorder or…

  8. Perioperative Interventions to Reduce Chronic Postsurgical Pain

    PubMed Central

    Carroll, Ian; Hah, Jennifer; Mackey, Sean; Ottestad, Einar; Kong, Jiang Ti; Lahidji, Sam; Tawfik, Vivianne; Younger, Jarred; Curtin, Catherine

    2016-01-01

    Approximately 10% of patients following a variety of surgeries develop chronic postsurgical pain. Reducing chronic postoperative pain is especially important to reconstructive surgeons because common operations such as breast and limb reconstruction have even higher risk for developing chronic postsurgical pain. Animal studies of posttraumatic nerve injury pain demonstrate that there is a critical time frame before and immediately after nerve injury in which specific interventions can reduce the incidence and intensity of chronic neuropathic pain behaviors–so called “preventative analgesia.” In animal models, perineural local anesthetic, systemic intravenous local anesthetic, perineural clonidine, systemic gabapentin, systemic tricyclic antidepressants, and minocycline have each been shown to reduce pain behaviors days to weeks after treatment. The translation of this work to humans also suggests that brief perioperative interventions may protect patients from developing new chronic postsurgical pain. Recent clinical trial data show that there is an opportunity during the perioperative period to dramatically reduce the incidence and severity of chronic postsurgical pain. The surgeon, working with the anesthesiologist, has the ability to modify both early and chronic postoperative pain by implementing an evidence-based preventative analgesia plan. PMID:23463498

  9. Reducing Dropout Rates. Educational Benchmark 2000 Series.

    ERIC Educational Resources Information Center

    Creech, Joseph D.

    This report describes and compares different methods used to calculate and report dropout rates; discusses advantages and disadvantages of each method; explains what is known about dropout students; and outlines actions states are taking to reduce dropout rates. Data are presented on whether dropout rates are lower now than in the 1980s in…

  10. A reduced gravity fiber pulling apparatus

    NASA Technical Reports Server (NTRS)

    Tucker, D. S.

    1992-01-01

    A reduced gravity fiber pulling apparatus (FPA) was constructed in order to study the effects of gravity on glass fiber formation. The apparatus was specifically designed and built for use on NASA's KC-135 aircraft. To date, four flights have been completed during which E-glass fiber was successfully produced in simulated lunar gravity.

  11. How Does Distinctive Processing Reduce False Recall?

    ERIC Educational Resources Information Center

    Hunt, R. Reed; Smith, Rebekah E.; Dunlap, Kathryn R.

    2011-01-01

    False memories arising from associatively related lists are a robust phenomenon that resists many efforts to prevent it. However, a few variables have been shown to reduce this form of false memory. Explanations for how the reduction is accomplished have focused on either output monitoring processes or constraints on access, but neither idea alone…

  12. Using Technology To Reduce Public School Violence.

    ERIC Educational Resources Information Center

    Brown, John A.; Brown, Robert C.; Ledford, Bruce R.

    1996-01-01

    Describes technology-driven strategies for reducing school violence: (1) commitment communicated by newsletters and cable television; (2) elimination of weapons using metal detectors, surveillance cameras, breathalyzers, student passes, alarm systems, and school emergency plans; (3) two-way communications and low technology; (4) educational…

  13. Reducing Research Anxiety among MSW Students

    ERIC Educational Resources Information Center

    Einbinder, Susan Dana

    2014-01-01

    Research anxiety significantly declined in a diverse sample of 59 MSW students in their first-year hybrid online research course in which the instructor used an array of innovative educational techniques empirically proven to reduce this phenomenon. The pretest/posttest study, the standardized survey instruments used, and a summary of these…

  14. Strategies for Reducing Text Book Costs

    ERIC Educational Resources Information Center

    Board of Governors, State University System of Florida, 2008

    2008-01-01

    In recent years, the price of college textbooks has become a growing concern for students and others who care about keeping college costs affordable. As policymakers and higher education systems explore the issue further, there are actions that can be taken immediately on college campuses to reduce the cost of textbooks. This brief presents…

  15. Reflecting layers reduce weight of insulation

    NASA Technical Reports Server (NTRS)

    Cole, J. D.; Schlessinger, E. D.; Rockoff, H. J.

    1981-01-01

    Metalized films placed between layers of fibrous material maintain equivalent thermal conductivity while cutting blanket density in half. Tests indicate that insulation with 1 lb/cu ft density with goldized films has thermal conductivity equal to 2 lb/cu ft of conventional insulation. Concept reduces weight in commercial aircraft and increases cargo space.

  16. 21 CFR 582.5375 - Iron reduced.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Iron reduced. 582.5375 Section 582.5375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements...

  17. 21 CFR 582.5375 - Iron reduced.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Iron reduced. 582.5375 Section 582.5375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements...

  18. Reducing Infant Mortality. KIDS COUNT Indicator Brief

    ERIC Educational Resources Information Center

    Shore, Rima; Shore, Barbara

    2009-01-01

    Despite the wide range of expertise that has been brought to bear on reducing infant mortality across the nation, the first year of life remains a time of considerable risk for many babies. Although the U.S. spends more on health care than any other country, its infant mortality rate remains higher than that of most other industrialized nations.…

  19. Method for reducing snap in magnetic amplifiers

    NASA Technical Reports Server (NTRS)

    Fischer, R. L. E.; Word, J. L.

    1968-01-01

    Method of reducing snap in magnetic amplifiers uses a degenerative feedback circuit consisting of a resistor and a separate winding on a magnetic core. The feedback circuit extends amplifier range by allowing it to be used at lower values of output current.

  20. Reducing the Deficit; Spending and Revenue Options

    DTIC Science & Technology

    1988-03-01

    income Social insurance Other Total Outlays National defense Nondefense discre- tionary spending Entitlements and other mandatory spending ...Total Outlays National defense Nondefense discre- tionary spending Entitlements and other mandatory spending Net interest Offsetting receipts...Fiscal Years SOURCE: Congressional Budget Office. CHAPTER I REDUCING THE DEFICIT: AN OVERVIEW 5 titlements and national defense spending tell the