LAM Pilot Study with Imatinib Mesylate (LAMP-1)

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2017-10-01

AWARD NUMBER: W81XWH-14-1-0132 TITLE: LAM Pilot Study with Imatinib Mesylate (LAMP-1) PRINCIPAL INVESTIGATOR: Charlie Strange, MD...regarding imatinib mesylate (imatinib) in the treatment of Lymphangioleiomyomatosis ( LAM ) sufficient to power and design a phase 3 imatinib vs. placebo...clinical trial. The hypothesis is that imatinib will be equivalent to rapamycin in short term efficacy and safety. Currently, most LAM patients are

Antitumor action of temozolomide, ritonavir and aprepitant against human glioma cells.

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Kast, Richard E; Ramiro, Susana; Lladó, Sandra; Toro, Salvador; Coveñas, Rafael; Muñoz, Miguel

2016-02-01

In the effort to find better treatments for glioblastoma we tested several currently marketed non-chemotherapy drugs for their ability to enhance the standard cytotoxic drug currently used to treat glioblastoma- temozolomide. We tested four antiviral drugs- acyclovir, cidofovir, maraviroc, ritonavir, and an anti-emetic, aprepitant. We found no cytotoxicity of cidofovir and discussed possible reasons for discrepancy from previous findings of others. We also found no cytotoxicity from acyclovir or maraviroc also in contradistinction to predictions. Cytotoxicity to glioma cell line GAMG for temozolomide alone was 14%, aprepitant alone 7%, ritonavir alone 14%, while temozolomide + aprepitant was 19%, temozolomide + ritonavir 34%, ritonavir + aprepitant 64 %, and all three, temozolomide + ritonavir + aprepitant 78%. We conclude that a remarkable synergy exists between aprepitant and ritonavir. Given the long clinical experience with these two well-tolerated drugs in treating non-cancer conditions, and the current median survival of glioblastoma of 2 years, a trial is warranted of adding these two simple drugs to current standard treatment with temozolomide.

Pd-Catalyzed Cross-Coupling Reactions of Amides and Aryl Mesylates

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Dooleweerdt, Karin; Fors, Brett P.; Buchwald, Stephen L.

2010-01-01

A catalyst, based on a biarylphosphine ligand, for the Pd-catalyzed cross-coupling reactions of amides and aryl mesylates is described. This system allows an array of aryl and heteroaryl mesylates to be transformed into the corresponding N-arylamides in moderate to excellent yields. PMID:20420379

Gemfibrozil Concentrations are Significantly Decreased in the Presence of Lopinavir/ritonavir

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Busse, Kristin H.; Hadigan, Colleen; Chairez, Cheryl; Alfaro, Raul M.; Formentini, Elizabeth; Kovacs, Joseph A.; Penzak, Scott R.

2009-01-01

Objective: To determine the influence of a two-week course of lopinavir-ritonavir on the pharmacokinetics of the triglyceride-lowering agent, gemfibrozil. Methods: The study was conducted as an open label, single-sequence pharmacokinetic study in healthy human volunteers. Gemfibrozil pharmacokinetic parameter values were compared using a students t test after a single 600 mg dose was administered to healthy volunteers before, and after two weeks of lopinavir-ritonavir (400/100 mg) twice daily. Results: Fifteen healthy volunteers (8 males) completed the study. All study drugs were generally well-tolerated and no subjects withdrew participation. The geometric mean ratio (GMR, 90% CI) for gemfibrozil area under the plasma concentration-time curve (AUC0-∞) after 14 days of lopinavir-ritonavir compared to baseline was 0.59 (0.52, 0.67) (P gemfibrozil AUC0-∞ after lopinavir-ritonavir (range: −6% to −74%). The GMRs for gemfibrozil apparent oral clearance (Cl/F) and maximum concentration (Cmax) were 1.69 (1.41, 1.97) and 0.67 (0.49, 0.86) after 14 days of lopinavir-ritonavir versus baseline, respectively (P Gemfibrozil elimination half-life did not change after lopinavir-ritonavir administration (P = 0.60). Conclusion: Lopinavir/ritonavir significantly reduced the systemic exposure of gemfibrozil by reducing gemfibrozil absorption. Clinicians treating HIV-infected patients with hypertriglyceridemia should be aware of this drug interaction. PMID:19648824

Gemfibrozil concentrations are significantly decreased in the presence of lopinavir-ritonavir.

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Busse, Kristin H; Hadigan, Colleen; Chairez, Cheryl; Alfaro, Raul M; Formentini, Elizabeth; Kovacs, Joseph A; Penzak, Scott R

2009-10-01

The objective of this study was to determine the influence of a 2-week course of lopinavir-ritonavir on the pharmacokinetics of the triglyceride-lowering agent, gemfibrozil. The study was conducted as an open label, single-sequence pharmacokinetic study in healthy human volunteers. Gemfibrozil pharmacokinetic parameter values were compared using a Student t test after a single 600-mg dose was administered to healthy volunteers before and after 2 weeks of lopinavir-ritonavir (400/100 mg) twice daily. Fifteen healthy volunteers (eight males) completed the study. All study drugs were generally well tolerated and no subjects withdrew participation. The geometric mean ratio (90% confidence interval) for gemfibrozil area under the plasma concentration-time curve after 14 days of lopinavir-ritonavir compared with baseline was 0.59 (0.52, 0.67) (P gemfibrozil area under the plasma concentration-time curve after lopinavir-ritonavir (range, -6% to -74%). The geometric mean ratios for gemfibrozil apparent oral clearance and maximum concentration were 1.69 (1.41, 1.97) and 0.67 (0.49, 0.86) after 14 days of lopinavir-ritonavir versus baseline, respectively (P Gemfibrozil elimination half-life did not change after lopinavir-ritonavir administration (P = 0.60). Lopinavir-ritonavir significantly reduced the systemic exposure of gemfibrozil by reducing gemfibrozil absorption. Clinicians treating HIV-infected patients with hypertriglyceridemia should be aware of this drug interaction.

Safety pharmacology of sibutramine mesylate, an anti-obesity drug.

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Kim, Eun-Joo; Park, Eun-Kyung; Suh, Kwee-Hyun

2005-03-01

Sibutramine mesylate is a new anti-obesity drug. It is a crystalline salt of sibutramine developed to improve the solubility of sibutramine hydrochloride. Methanesulfonic acid was used as a salt-forming acid instead of hydrochloric acid, resulting in a greatly improved solubility of 1000 mg/mL in water. Sibutramine mesylate was administered orally to ICR mice, Sprague-Dawley rats, and beagle dogs at dose levels of 1.15, 3.45, and 11.50 mg/kg to measure its effects on the central nervous system (CNS), general behaviour, cardiovascular-respiratory system and the other organ systems. Following administration of sibutramine mesylate, spontaneous locomotor activity was significantly increased from 120 min to 24 hours at 3.45 mg/kg and from 30 min to 24 hours at 11.50 mg/kg. Furthermore, there were a decrease in hexobarbital-induced sleep time, an increase in respiratory rate at 120 min, increases in intestinal transport capacity and gastric pH at 11.50 mg/kg, and decreases in gastric volume and total acidity at 3.45 and 11.50 mg/kg. However sibutramine mesylate caused no effects on general behaviour, motor coordination, body temperature, analgesia, convulsion, blood pressure, heart rate, electrocardiogram, cardiac functions of the isolated rat heart, isolated smooth muscles and renal function. Based on the above results, it was concluded that sibutramine mesylate caused effects on the spontaneous locomotor activity, hexobarbital-induced sleep time, respiration, gastrointestinal transport, and gastric secretion at a dose level of 3.45 mg/kg or greater but caused no effects on other general pharmacological reactions.

Pharmacokinetics, safety and efficacy of ritonavir-boosted atazanavir (300/100 mg once daily) in HIV-1-infected pregnant women.

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Lê, Minh P; Mandelbrot, Laurent; Descamps, Diane; Soulié, Cathia; Ichou, Houria; Bourgeois-Moine, Agnès; Damond, Florence; Lariven, Sylvie; Valantin, Marc-Antoine; Landman, Roland; Faucher, Philippe; Tubiana, Roland; Duro, Dominique; Meier, Françoise; Legac, Sylvie; Bourse, Patricia; Mortier, Emmanuel; Dommergues, Marc; Calvez, Vincent; Matheron, Sophie; Peytavin, Gilles

2015-01-01

Atazanavir/ritonavir (ATV/r) is a boosted protease inhibitor recommended to minimize the risk of mother-to-child HIV-1 transmission (MTCT). We aimed to assess the pharmacokinetics, safety and efficacy of ATV/r in HIV-1-infected pregnant women and their neonates. A multicentre, cross-sectional, non-interventional cohort of HIV-1-infected pregnant women receiving ATV/r (300/100 mg once daily) who delivered in three Paris hospitals from 2006 to 2013 was designed. We determined antiretroviral trough plasma concentrations using liquid chromatography-mass spectrometry at each of the three trimesters, delivery and post-partum. ATV concentrations at 24 h (C24h) were interpreted by the 150-850 ng/ml efficacy-tolerance thresholds. Safety data and newborn HIV status were recorded. A mother's virological failure was defined as two successive measurements of plasma HIV-1 RNA>50 copies/ml within the 2 months before delivery. 103 pregnant women were included, mostly from sub-Saharan Africa (88%). ATV C24h at each of the three trimesters and delivery remained similar to post-partum values. No dose adjustment was needed during pregnancy. The median plasma ratio of fetal/maternal ATV level was 0.19 (n=28). Only three patients showed two successive detectable viral loads but <400 copies/ml. Among 82 available newborn data, 16 were born preterm. Three in utero deaths occurred. Tolerance was good with one case of maternal grade 3 hyperbilirubinaemia, no cases in neonates at delivery and no clinically relevant adverse event. No case of MTCT was reported. In this population, an ATV/r-containing antiretroviral regimen demonstrated good pharmacokinetics, virological efficacy and safety. No significant impact of pregnancy on ATV C24h was found. No dose adjustment was required.

Phentolamine mesylate: It′s role as a reversal agent for unwarranted prolonged local analgesia

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Harpreet Singh Grover

2015-01-01

Full Text Available Administration of local anesthesia is an integral procedure prior to dental treatments to minimize the associated pain. It is learned that its effect stays more than the time required for the dental procedure to be completed. This prolonged soft tissue anesthesia (STA can be detrimental, inconvenient, and unnecessary. Phentolamine mesylate, a Food and Drug Administration-approved drug essentially serves the purpose of faster recovery from numbness at the site of local anesthesia. This article reviews the development of the drug phentolamine mesylate and its indication as a local anesthetic reversal agent. A literature search for phentolamine mesylate as a STA reversal agent was conducted in PubMed using the terms "dental local anesthesia reversal, phentolamine mesylate" up to March 2014. The search was limited to articles published in English. The search revealed 13 PubMed indexed articles stating the development and application of phentolamine mesylate. Phentolamine mesylate is an important step in the progress of developing patient care as well as an aid to the dental clinician.

[Efficacy of initial antiretroviral therapy based on lopinavir/ritonavir plus 2 nucleoside/nucleotide analogs in patients with human immunodeficiency virus type 1 infection].

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Zamora, Laura; Gatell, José M

2014-11-01

Triple combination regimens consisting of lopinavir/ritonavir (LPV/r) plus 2 nucleoside/nucleotide analogs continue to be a valid option in initial antiretroviral therapy. Other protease inhibitors boosted with ritonavir (and in future with cobicistat) have been introduced, as well as other non-nucleoside analogs (rilpivirin) and 3 integrase inhibitors. None of the new regimens have shown superiority over LPV/r or comparisons are lacking. Therefore, regimens including LPV/r continue to be recommended as initial first-line or alternative strategies in most treatment guidelines. Dual combinations with LPV/r (plus raltegravir or lamivudine) are described in another article and can provide a similar response rate to triple combinations, better tolerance, and an improved cost-efficacy ratio, both for initial therapy and in simplification strategies. In contrast, LPV/r or darunavir/r monotherapy does not seem an acceptable option in treatment-naïve patients and is becoming increasingly less acceptable in simplification strategies. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

EFFECT OF ULTRA-HIGH PRESSURE HOMOGENIZATION ON THE INTERACTION BETWEEN BOVINE CASEIN MICELLES AND RITONAVIR

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Corzo-Martínez, M.; Mohan, M.; Dunlap, J.; Harte, F.

2014-01-01

Purpose The aim of this work was to develop a milk-based powder formulation appropriate for pediatric delivery of ritonavir (RIT). Methods Ultra-high pressure homogenization (UHPH) at 0.1, 300 and 500 MPa was used to process a dispersion of pasteurized skim milk (SM) and ritonavir. Loading efficiency was determined by RP-HPLC-UV; characterization of RIT:SM systems was carried out by apparent average hydrodynamic diameter and rheological measurements as well as different analytical techniques including Trp fluorescence, UV spectroscopy, DSC, FTIR and SEM; and delivery capacity of casein micelles was determined by in vitro experiments promoting ritonavir release. Results Ritonavir interacted efficiently with milk proteins, especially, casein micelles, regardless of the processing pressure; however, results suggest that, at 0.1 MPa, ritonavir interacts with caseins at the micellar surface, whilst, at 300 and 500 MPa, ritonavir is integrated to the protein matrix during UHPH treatment. Likewise, in vitro experiments showed that ritonavir release from micellar casein systems is pH dependent; with a high retention of ritonavir during simulated gastric digestion and a rapid delivery under conditions simulating the small intestine environment. Conclusions Skim milk powder, especially, casein micelles are potentially suitable and efficient carrier systems to develop novel milk-based and low-ethanol powder formulations of ritonavir appropriate for pediatric applications. PMID:25270571

Physico-chemical stability of eribulin mesylate containing concentrate and ready-to-administer solutions.

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Spindeldreier, Kirsten; Thiesen, Judith; Lipp, Hans-Peter; Krämer, Irene

2014-06-01

The aim of this study was to determine the stability of commercially available eribulin mesylate containing injection solution as well as diluted ready-to-administer solutions stored under refrigeration or at room temperature. Stability was studied by a novel developed stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) assay with ultraviolet detection (detection wavelength 200 nm). Triplicate test solutions of eribulin mesylate containing injection concentrate (0.5 mg/mL) and with 0.9% sodium chloride solution diluted ready-to-administer preparations (0.205 mg/mL eribulin mesylate in polypropylene (PP) syringes, 0.020 mg/mL eribulin mesylate in polypropylene/polyethylene (PE) bags) were stored protected from light either at room temperature (25) or under refrigeration (2-8). Samples were withdrawn on day 0 (initial), 1, 3, 5, 7, 14, 21 and 28 of storage and assayed. Physical stability was determined by measuring the pH value once a week and checking for visible precipitations or colour changes. The stability tests revealed that concentrations of eribulin mesylate remained unchanged over a period of 28 days irrespective of concentration, container material or storage temperature. Neither colour changes nor visible particles have been observed. The pH value varied slightly over time but remained in the stability favourable range of 5-9. Eribulin mesylate injection (0.5 mg/mL) is physico-chemically stable over a period of 28 days after first puncture of the vial. After dilution with 0.9% NaCl vehicle solution, ready-to-administer eribulin mesylate injection solutions (0.205 mg/mL in PP syringe) and infusion solutions (0.02 mg/mL in prefilled PP/PE bags) are physico-chemically stable for a period of at least four weeks either refrigerated or stored at room temperature. For microbiological reasons storage under refrigeration is recommended.

Cerebrospinal fluid analysis for HIV replication and biomarkers of immune activation and neurodegeneration in long-term atazanavir/ritonavir monotherapy treated patients.

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Ferretti, Francesca; Bigoloni, Alba; Passeri, Laura; Galli, Laura; Longo, Valeria; Gerevini, Simonetta; Spagnuolo, Vincenzo; Gisslen, Magnus; Zetterberg, Henrik; Fuchs, Dietmar; Cattaneo, Dario; Caramatti, Giada; Lazzarin, Adriano; Cinque, Paola; Castagna, Antonella

2016-07-01

Cerebrospinal fluid (CSF) viral escape is a concern in ritonavir-boosted protease inhibitors monotherapy. The aim was to assess HIV-RNA, biomarkers of immune activation and neurodegeneration, and atazanavir concentrations in CSF of patients on successful long-term atazanavir/ritonavir (ATV/r) monotherapy. This is a substudy of the multicentric, randomized, open-label, noninferiority trial monotherapy once a day with atazanavir/ritonavir (NCT01511809), comparing the ongoing ATV/r along with 2 nucleoside retrotranscriptase inhibitors (NRTIs) regimen to a simplified ATV/r monotherapy. Patients with plasma HIV-RNA < 50 copies/mL after at least 96 study weeks were eligible.We assessed HIV-RNA, soluble (s)CD14, sCD163, CCL2, CXCL10, interleukin-6, and YKL40 by enzyme-linked immunosorbent assay; neopterin, tryptophan, kynurenine, and neurofilament by immunoassays; and ATV concentrations by liquid chromatography-mass spectrometry in paired plasma and CSF samples. Variables were compared with Wilcoxon rank-sum or Fisher exact test, as appropriate. HIV-RNA was detected in the CSF of 1/11 patients on ATV/r monotherapy (114 copies/mL), without neurological symptoms, who was successfully reintensified with his previous 2NRTIs, and in none of the 12 patients on ATV/r + 2NRTIs. CSF biomarkers and ATV concentrations did not differ between the 2 arms. CSF escape was uncommon in patients on long-term ATV/r monotherapy and was controlled with reintensification.

The synthesis of [[sup 2]H],[[sup 3]H], and [[sup 14]C]-labeled 8[beta]-[(methylthio)methyl]-6-propylergoline mesylate (pergolide mesylate), a potent, long-acting dopamine agonist

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Wheeler, W.J.; Kau, D.L.K.; Bach, N.J. (Lilly (Eli) and Co., Indianapolis, IN (United States). Lilly Research Labs.)

1990-03-01

The [[sup 3]H]- and two[[sup 14]C]-isopomers of 8[beta]-[(methylthio)methyl]-6-propylergoline mesylate (pergolide mesylate) have been synthesized. The [[sup 3]H]-derivative was synthesized by the palladium catalyzed tritiation of the corresponding 6-allyl derivative. Reaction of 8[beta]-[(methylthio)methyl]-ergoline with 1-[[sup 14]C]-1-propyl bromide yielded pergolide labeled in the 6-propyl group. Alternatively, reaction of 8[beta]-mesyloxy-6-propylergoline with [[sup 14]C]-sodium cyanide, followed by base hydrolysis, yielded 8 [beta]-carboxy-6-propylergoline-[[sup 14]C], which was subsequently converted to pergolide mesylate radiolabeled in the 17-position via a four step sequence. (Author).

Estimation of population pharmacokinetic parameters of saquinavir in HIV patients with the MONOLIX software.

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Lavielle, Marc; Mentré, France

2007-04-01

In nonlinear mixed-effects models, estimation methods based on a linearization of the likelihood are widely used although they have several methodological drawbacks. Kuhn and Lavielle (Comput. Statist. Data Anal. 49:1020-1038 (2005)) developed an estimation method which combines the SAEM (Stochastic Approximation EM) algorithm, with a MCMC (Markov Chain Monte Carlo) procedure for maximum likelihood estimation in nonlinear mixed-effects models without linearization. This method is implemented in the Matlab software MONOLIX which is available at http://www.math.u-psud.fr/~lavielle/monolix/logiciels. In this paper we apply MONOLIX to the analysis of the pharmacokinetics of saquinavir, a protease inhibitor, from concentrations measured after single dose administration in 100 HIV patients, some with advance disease. We also illustrate how to use MONOLIX to build the covariate model using the Bayesian Information Criterion. Saquinavir oral clearance (CL/F) was estimated to be 1.26 L/h and to increase with body mass index, the inter-patient variability for CL/F being 120%. Several methodological developments are ongoing to extend SAEM which is a very promising estimation method for population pharmacockinetic/pharmacodynamic analyses.

Body composition and metabolic outcomes after 96 weeks of treatment with ritonavir-boosted lopinavir plus either nucleoside or nucleotide reverse transcriptase inhibitors or raltegravir in patients with HIV with virological failure of a standard first-line antiretroviral therapy regimen: a substudy of the randomised, open-label, non-inferiority SECOND-LINE study.

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Boyd, Mark A; Amin, Janaki; Mallon, Patrick W G; Kumarasamy, Nagalingeswaran; Lombaard, Johan; Wood, Robin; Chetchotisakd, Ploenchan; Phanuphak, Praphan; Mohapi, Lerato; Azwa, Iskandar; Belloso, Waldo H; Molina, Jean-Michel; Hoy, Jennifer; Moore, Cecilia L; Emery, Sean; Cooper, David A

2017-01-01

Lipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological failure of a first-line antiretroviral (ART) regimen containing a non-nucleoside reverse transcriptase inhibitor plus two N(t)RTIs and were randomly assigned to receive a second-line regimen containing a boosted protease inhibitor given with either N(t)RTIs or raltegravir. Of the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122. Between Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N

Lopinavir/ritonavir in the treatment of HIV-1 infection: a review

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Ashish Chandwani

2008-09-01

Full Text Available Ashish Chandwani1, Jonathan Shuter21Division of Infectious Diseases, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY, USA; 2AIDS Center and Division of Infectious Diseases, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY, USAAbstract: Lopinavir/ritonavir is the first and only coformulated HIV-1 protease inhibitor (PI. Large clinical trials have demonstrated lopinavir/ritonavir’s clinical efficacy in both antiretroviral-naïve and -experienced patients. The immunologic and virologic benefits of treatment with this agent have been proven in HIV-infected adults, adolescents, and children. Smaller studies support the use of lopinavir/ritonavir monotherapy as a therapeutic option in certain patients. The drug is characterized by a high genetic barrier to resistance, and appears to be more forgiving of non-adherence than earlier, unboosted PIs. The most frequent side effects observed are diarrhea, nausea, and vomiting. These gastrointestinal adverse effects are generally mild to moderate. Metabolic derangements, including hyperlipidemia and glucose intolerance, have also been observed in lopinavir/ritonavir recipients. As the menu of available antiretroviral agents continues to expand, lopinavir/ritonavir remains a proven and effective drug for the treatment of HIV infection.Keywords: lopinavir/ritonavir, protease inhibitor, HIV, antiretroviral, Kaletra®

Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

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Reardon, David A; Egorin, Merrill J; Quinn, Jennifer A; Rich, Jeremy N; Rich, Jeremy N; Gururangan, Sridharan; Gururangan, Idharan; Vredenburgh, James J; Desjardins, Annick; Sathornsumetee, Sith; Provenzale, James M; Herndon, James E; Dowell, Jeannette M; Badruddoja, Michael A; McLendon, Roger E; Lagattuta, Theodore F; Kicielinski, Kimberly P; Dresemann, Gregor; Sampson, John H; Friedman, Allan H; Salvado, August J; Friedman, Henry S

2005-12-20

We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

HIV protease inhibitors in pregnancy : pharmacology and clinical use.

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Andany, Nisha; Loutfy, Mona R

2013-03-01

The impact of antiretroviral therapy (ART) on the natural history of HIV-1 infection has resulted in dramatic reductions in disease-associated morbidity and mortality. Additionally, the epidemiology of HIV-1 infection worldwide is changing, as women now represent a substantial proportion of infected adults. As more highly effective and tolerable antiretroviral regimens become available, and as the prevention of mother-to-child transmission becomes an attainable goal in the management of HIV-infected individuals, more and more HIV-positive women are choosing to become pregnant and have children. Consequently, it is important to consider the efficacy and safety of antiretroviral agents in pregnancy. Protease inhibitors are a common class of medication used in the treatment of HIV-1 infection and are increasingly being used in pregnancy. However, several studies have raised concerns regarding pharmacokinetic alterations in pregnancy, particularly in the third trimester, which results in suboptimal drug concentrations and a theoretically higher risk of virologic failure and perinatal transmission. Drug level reductions have been observed with each individual protease inhibitor and dose adjustments in pregnancy are suggested for certain agents. Furthermore, studies have also raised concerns regarding the safety of protease inhibitors in pregnancy, particularly as they may increase the risk of pre-term birth and metabolic disturbances. Overall, protease inhibitors are safe and effective for the treatment of HIV-infected pregnant women. Specifically, ritonavir-boosted lopinavir- and atazanavir-based regimens are preferred in pregnancy, while ritonavir-boosted darunavir- and saquinavir-based therapies are reasonable alternatives. This paper reviews the use of protease inhibitors in pregnancy, focusing on pharmacokinetic and safety considerations, and outlines the recommendations for use of this class of medication in the HIV-1-infected pregnant woman.

The human immunodeficiency virus protease inhibitor ritonavir is potentially active against urological malignancies

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Sato A

2015-04-01

Full Text Available Akinori Sato Department of Urology, National Defense Medical College, Tokorozawa, Japan Abstract: The human immunodeficiency virus protease inhibitor ritonavir has recently been shown to have antineoplastic activity, and its use in urological malignancies is under investigation with an eye toward drug repositioning. Ritonavir is thought to exert its antineoplastic activity by inhibiting multiple signaling pathways, including the Akt and nuclear factor-kappaB pathways. It can increase the amount of unfolded proteins in the cell by inhibiting both the proteasome and heat shock protein 90. Combinations of ritonavir with agents that increase the amount of unfolded proteins, such as proteasome inhibitors, histone deacetylase inhibitors, or heat shock protein 90 inhibitors, therefore, induce endoplasmic reticulum stress cooperatively and thereby kill cancer cells effectively. Ritonavir is also a potent cytochrome P450 3A4 and P-glycoprotein inhibitor, increasing the intracellular concentration of combined drugs by inhibiting their degradation and efflux from cancer cells and thereby enhancing their antineoplastic activity. Furthermore, riotnavir’s antineoplastic activity includes modulation of immune system activity. Therapies using ritonavir are thus an attractive new approach to cancer treatment and, due to their novel mechanisms of action, are expected to be effective against malignancies that are refractory to current treatment strategies. Further investigations using ritonavir are expected to find new uses for clinically available drugs in the treatment of urological malignancies as well as many other types of cancer. Keywords: drug repositioning, novel treatment

Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

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Bérengère Gobin

Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

Solution-mediated phase transformation of haloperidol mesylate in the presence of sodium lauryl sulfate.

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Greco, Kristyn; Bogner, Robin

2011-09-01

Forming a salt is a common way to increase the solubility of a poorly soluble compound. However, the solubility enhancement gained by salt formation may be lost due to solution-mediated phase transformation (SMPT) during dissolution. The SMPT of a salt can occur due to a supersaturated solution near the dissolving surface caused by pH or other solution conditions. In addition to changes in pH, surfactants are also known to affect SMPT. In this study, SMPT of a highly soluble salt, haloperidol mesylate, at pH 7 in the presence of a commonly used surfactant, sodium lauryl sulfate (SLS), was investigated. Dissolution experiments were performed using a flow-through dissolution apparatus with solutions containing various concentrations of SLS. Compacts of haloperidol mesylate were observed during dissolution in the flow-through apparatus using a stereomicroscope. Raman microscopy was used to characterize solids. The dissolution of haloperidol mesylate was significantly influenced by the addition of sodium lauryl sulfate. In conditions where SMPT was expected, the addition of SLS at low concentrations (0.1-0.2 mM) reduced the dissolution of haloperidol mesylate. In solutions containing concentrations of SLS above the critical micelle concentration (CMC) (10-15 mM), the dissolution of haloperidol mesylate increased compared to below the CMC. The solids recovered from solubility experiments of haloperidol mesylate indicated that haloperidol free base precipitated at all concentrations of SLS. Above 5 mM of SLS, Raman microscopy suggested a new form, perhaps the estolate salt. The addition of surfactant in solids that undergo solution-mediated phase transformation can add complexity to the dissolution profiles and conversion.

Improved Oral Bioavailability and Brain Transport of Saquinavir Upon Administration in Novel Nanoemulsion Formulations

OpenAIRE

Vyas, Tushar K.; Shahiwala, Aliasgar; Amiji, Mansoor M.

2007-01-01

The aim of this investigation was to develop novel oil-in-water (o/w) nanoemulsions containing saquinavir (SQV), an anti-HIV protease inhibitor, for enhanced oral bioavailability and brain disposition. SQV was dissolved in different types of edible oils rich in essential polyunsaturated fatty acids (PUFA) to constitute the internal oil phase of the nanoemulsions. The external phase consisted of surfactants Lipoid®-80 and deoxycholic acid dissolved in water. The nanoemulsions with an average o...

Influence of Carrier (Polymer Type and Drug-Carrier Ratio in the Development of Amorphous Dispersions for Solubility and Permeability Enhancement of Ritonavir

Directory of Open Access Journals (Sweden)

Vivek S. Dave

2017-09-01

Full Text Available The influence of the ratio of Eudragit® L100-55 or Kolliphor® P188 on the solubility, dissolution, and permeability of ritonavir was studied with a goal of preparing solid dispersions (SDs of ritonavir. SDs were formulated using solvent evaporation or lyophilization techniques, and evaluated for their physical-chemical properties. The dissolution and permeability assessments of the functionality of the SDs were carried out. The preliminary functional stability of these formulations was assessed at accelerated storage conditions for a period of six months. Ritonavir: Eudragit® L100-55 (RE, 1:3 SD showed a 36-fold higher ritonavir solubility compared to pure ritonavir. Similarly, ritonavir: Kolliphor® P188 (RP, 1:2 SD exhibited a 49-fold higher ritonavir solubility compared to pure ritonavir. Ritonavir dissolution from RE formulations increased with increasing ratios of Eudragit® L100-55, up to a ritonavir: carrier ratio of 1:3. The ritonavir dissolution from RP formulations was highest at ritonavir: Kolliphor® P188 ratio of 1:2. Dissolution efficiencies of these formulations were found to be in line with, and supported the dissolution results. The permeability of ritonavir across the biological membrane from the optimized formulations RE (1:3 and RP (1:2 were ~76 % and ~97 %, respectively; and were significantly higher compared to that of pure ritonavir (~20 %. A preliminary (six-month stability study demonstrated the functional stability of prepared solid dispersions. The present study demonstrates that ritonavir solubility, dissolution, and permeability improvement can be achieved with a careful choice of the carrier polymer, and optimizing the amount of polymer in a SD formulation.

New use of an old drug: inhibition of breast cancer stem cells by benztropine mesylate.

Science.gov (United States)

Cui, Jihong; Hollmén, Maija; Li, Lina; Chen, Yong; Proulx, Steven T; Reker, Daniel; Schneider, Gisbert; Detmar, Michael

2017-01-03

Cancer stem cells (CSCs) play major roles in cancer initiation, metastasis, recurrence and therapeutic resistance. Targeting CSCs represents a promising strategy for cancer treatment. The purpose of this study was to identify selective inhibitors of breast CSCs (BCSCs). We carried out a cell-based phenotypic screening with cell viability as a primary endpoint, using a collection of 2,546 FDA-approved drugs and drug-like molecules in spheres formed by malignant human breast gland-derived cells (HMLER-shEcad cells, representing BCSCs) and control immortalized non-tumorigenic human mammary cells (HMLE cells, representing normal stem cells). 19 compounds were identified from screening. The chemically related molecules benztropine mesylate and deptropine citrate were selected for further validation and both potently inhibited sphere formation and self-renewal of BCSCs in vitro. Benztropine mesylate treatment decreased cell subpopulations with high ALDH activity and with a CD44+/CD24- phenotype. In vivo, benztropine mesylate inhibited tumor-initiating potential in a 4T1 mouse model. Functional studies indicated that benztropine mesylate inhibits functions of CSCs via the acetylcholine receptors, dopamine transporters/receptors, and/or histamine receptors. In summary, our findings identify benztropine mesylate as an inhibitor of BCSCs in vitro and in vivo. This study also provides a screening platform for identification of additional anti-CSC agents.

Clinical studies with oral lipid based formulations of poorly soluble compounds

DEFF Research Database (Denmark)

Fatouros, Dimitrios; Karpf, Ditte M; Nielsen, Flemming S

2007-01-01

. Several drug products intended for oral administration have been marketed utilizing lipid and surfactant based formulations. Sandimmune((R)) and Sandimmune Neoral((R)) (cyclosporin A, Novartis), Norvir((R)) (ritonavir), and Fortovase((R)) (saquinavir) have been formulated in self-emulsifying drug delivery...... systems (SEDDS). This review summarizes published pharmacokinetic studies of orally administered lipid based formulations of poorly aqueous soluble drugs in human subjects. Special attention has been paid to the physicochemical characteristics of the formulations, when available and the impact...

Real-world efficacy and safety of ritonavir-boosted paritaprevir, ombitasvir, dasabuvir ± ribavirin for hepatitis C genotype 1 - final results of the REV1TAL study.

Science.gov (United States)

Lubel, John; Strasser, Simone; Stuart, Katherine A; Dore, Gregory; Thompson, Alexander; Pianko, Stephen; Bollipo, Steven; Mitchell, Joanne L; Fragomeli, Vincenzo; Jones, Tracey; Chivers, Sarah; Gow, Paul; Iser, David; Levy, Miriam; Tse, Edmund; Gazzola, Alessia; Cheng, Wendy; Nazareth, Saroj; Galhenage, Sam; Wade, Amanda; Weltman, Martin; Wigg, Alan; MacQuillan, Gerry; Sasadeusz, Joe; George, Jacob; Zekry, Amany; Roberts, Stuart K

2017-01-01

Limited data exist on the outcomes of ritonavir-boosted paritaprevir with ombitasvir and dasabuvir (PrOD) ± ribavirin in a real-world setting. The aim of this study was to compare the efficacy and safety of PrOD-based therapy in hepatitis C genotype 1 patients with and without cirrhosis, and to explore pre-treatment factors predictive of sustained viral response (SVR) and serious adverse events (SAEs) on treatment. 451 patients with hepatitis C genotype 1 treated in 20 centres across Australia were included. Baseline demographic, clinical and laboratory information, on-treatment biochemical, virological and haematological indices and details on serious adverse events were collected locally. Cirrhosis was present in 340 patients (75.4%). Overall SVR was 95.1% with no differences in SVR between the cirrhosis and non-cirrhosis groups (94.7% versus 96.4%). SVR in subgenotypes 1a and 1b was 93.1% and 99.2%, respectively. On multivariate analysis, baseline bilirubin level and early treatment cessation predicted SVR. SAEs occurred in 10.9% of patients including hepatic decompensation (2.7%) and hepatocellular carcinoma (1.8%). On multivariate analysis of factors predictive of SAEs in the overall group, Child-Turcotte-Pugh (CTP) B was the only significant factor, while in those with cirrhosis, baseline albumin and creatinine levels were significant. In this large real-world cohort of HCV genotype 1 subjects, treatment with PrOD was highly effective and similar to clinical trials. Important determinants of reduced SVR include early cessation of therapy and baseline bilirubin concentration. SAEs were not infrequent with CTP B patients being at greatest risk.

Tirilazad mesylate protects stored erythrocytes against osmotic fragility.

Science.gov (United States)

Epps, D E; Knechtel, T J; Bacznskyj, O; Decker, D; Guido, D M; Buxser, S E; Mathews, W R; Buffenbarger, S L; Lutzke, B S; McCall, J M

1994-12-01

The hypoosmotic lysis curve of freshly collected human erythrocytes is consistent with a single Gaussian error function with a mean of 46.5 +/- 0.25 mM NaCl and a standard deviation of 5.0 +/- 0.4 mM NaCl. After extended storage of RBCs under standard blood bank conditions the lysis curve conforms to the sum of two error functions instead of a possible shift in the mean and a broadening of a single error function. Thus, two distinct sub-populations with different fragilities are present instead of a single, broadly distributed population. One population is identical to the freshly collected erythrocytes, whereas the other population consists of osmotically fragile cells. The rate of generation of the new, osmotically fragile, population of cells was used to probe the hypothesis that lipid peroxidation is responsible for the induction of membrane fragility. If it is so, then the antioxidant, tirilazad mesylate (U-74,006f), should protect against this degradation of stored erythrocytes. We found that tirilazad mesylate, at 17 microM (1.5 mol% with respect to membrane lecithin), retards significantly the formation of the osmotically fragile RBCs. Concomitantly, the concentration of free hemoglobin which accumulates during storage is markedly reduced by the drug. Since the presence of the drug also decreases the amount of F2-isoprostanes formed during the storage period, an antioxidant mechanism must be operative. These results demonstrate that tirilazad mesylate significantly decreases the number of fragile erythrocytes formed during storage in the blood bank.

Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg, plus tenofovir/emtricitabine, for the initial treatment of HIV infection: 48-week results of ALERT

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Ross Lisa L

2008-03-01

Full Text Available Abstract Background Once-daily (QD ritonavir 100 mg-boosted fosamprenavir 1400 mg (FPV/r100 or atazanavir 300 mg (ATV/r100, plus tenofovir/emtricitabine (TDF/FTC 300 mg/200 mg, have not been compared as initial antiretroviral treatment. To address this data gap, we conducted an open-label, multicenter 48-week study (ALERT in 106 antiretroviral-naïve, HIV-infected patients (median HIV-1 RNA 4.9 log10 copies/mL; CD4+ count 191 cells/mm3 randomly assigned to the FPV/r100 or ATV/r100 regimens. Results At baseline, the FPV/r100 or ATV/r100 arms were well-matched for HIV-1 RNA (median, 4.9 log10 copies/mL [both], CD4+ count (mean, 176 vs 205 cells/mm3. At week 48, intent-to-treat: missing/discontinuation = failure analysis showed similar responses to FPV/r100 and ATV/r100 (HIV-1 RNA 3, p = 0.398 [Wilcoxon rank sum test]. Fasting total/LDL/HDL-cholesterol changes-from-baseline were also similar, although week 48 median fasting triglycerides were higher with FPV/r100 (150 vs 131 mg/dL. FPV/r100-treated patients experienced fewer treatment-related grade 2–4 adverse events (15% vs 57%, with differences driven by ATV-related hyperbilirubinemia. Three patients discontinued TDF/FTC because their GFR decreased to Conclusion The all-QD regimens of FPV/r100 and ATV/r100, plus TDF/FTC, provided similar virologic, CD4+ response, and fasting total/LDL/HDL-cholesterol changes through 48 weeks. Fewer FPV/r100-treated patients experienced treatment-related grade 2–4 adverse events.

Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate

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Seo JH

2015-07-01

Full Text Available Jae Hong Seo, Jung Bae Park, Woong-Kee Choi, Sunhwa Park, Yun Jin Sung, Euichaul Oh, Soo Kyung Bae College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, South Korea Objective: Cilostazol is a Biopharmaceutical Classification System class II drug with low solubility and high permeability, so its oral absorption is variable and incomplete. The aim of this study was to prepare two sulfonate salts of cilostazol to increase the dissolution and hence the oral bioavailability of cilostazol.Methods: Cilostazol mesylate and cilostazol besylate were synthesized from cilostazol by acid addition reaction with methane sulfonic acid and benzene sulfonic acid, respectively. The salt preparations were characterized by nuclear magnetic resonance spectroscopy. The water contents, hygroscopicity, stress stability, and photostability of the two cilostazol salts were also determined. The dissolution profiles in various pH conditions and pharmacokinetic studies in rats were compared with those of cilostazol-free base.Results: The two cilostazol salts exhibited good physicochemical properties, such as nonhygroscopicity, stress stability, and photostability, which make it suitable for the preparation of pharmaceutical formulations. Both cilostazol mesylate and cilostazol besylate showed significantly improved dissolution rate and extent of drug release in the pH range 1.2–6.8 compared to the cilostazol-free base. In addition, after oral administration to rats, cilostazol mesylate and cilostazol besylate showed increases in Cmax and AUCt of approximately 3.65- and 2.87-fold and 3.88- and 2.94-fold, respectively, compared to cilostazol-free base.Conclusion: This study showed that two novel salts of cilostazol, such as cilostazol mesylate and cilostazol besylate, could be used to enhance its oral absorption. The findings warrant further preclinical and clinical studies on cilostazol mesylate and

Effects of co-dergocrine mesylate (Hydergine) in multi-infarct dementia as evaluated by positron emission tomography

International Nuclear Information System (INIS)

Nagasawa, Haruo; Kogure, Kyuya; Kawashima, Koichiro; Ido, Tatsuo; Itoh, Masatoshi; Hatazawa, Jun.

1990-01-01

Three female patients aged from 74 to 79 with multi-infarct dementia were studied using positron emission tomography (PET) to assess the effect of co-dergocrine mesylate (Hydergine) on cerebral glucose metabolism. The cerebral glucose utilization (CMRGlc) of each patient was evaluated by PET scan using 2-deoxy-[ 18 F]-2-fluoro-D-glucose (FDG). Following the first PET study, 0.04 mg/kg of co-dergocrine mesylate was injected intravenously with 250 ml saline solution, and then the second PET study was performed. The CMRGlc was determined from the images of the PET scan and the radioactivity of 18 F in the plasma. After the administration of co-dergocrine mesylate, the value of CMRGlc increased significantly in the cerebral cortex (p<0.01 and p<0.05) and basal ganglia (p<0.05) compared with values before the administration, but no significant increase was found in the centrum semiovale. These results suggest that co-dergocrine mesylate stimulates glucose metabolism of neurons in the human brain. (author)

Current Efavirenz (EFV or ritonavir-boosted lopinavir (LPV/r use correlates with elevate markers of atherosclerosis in HIV-infected subjects in Addis Ababa, Ethiopia.

Directory of Open Access Journals (Sweden)

Rudolph L Gleason

Full Text Available HIV patients on antiretroviral therapy have shown elevated incidence of dyslipidemia, lipodystrophy, and cardiovascular disease (CVD. Most studies, however, focus on cohorts from developed countries, with less data available for these co-morbidities in Ethiopia and sub-Saharan Africa.Adult HIV-negative (n = 36, treatment naïve (n = 51, efavirenz (EFV-treated (n = 91, nevirapine (NVP-treated (n = 95, or ritonavir-boosted lopinavir (LPV/r-treated (n=44 subjects were recruited from Black Lion Hospital in Addis Ababa, Ethiopia. Aortic pressure, augmentation pressure, and pulse wave velocity (PWV were measured via applanation tonometry and carotid intima-media thickness (cIMT and carotid arterial stiffness, and brachial artery flow-mediated dilation (FMD were measured via non-invasive ultrasound. Body mass index, waist-to-hip circumference ratio (WHR, skinfold thickness, and self-reported fat redistribution were used to quantify lipodystrophy. CD4+ cell count, plasma HIV RNA levels, fasting glucose, total-, HDL-, and LDL-cholesterol, triglycerides, hsCRP, sVCAM-1, sICAM-1, leptin and complete blood count were measured.PWV and normalized cIMT were elevate and FMD impaired in EFV- and LPV/r-treated subjects compared to NVP-treated subjects; normalized cIMT was also elevated and FMD impaired in the EFV- and LPV/r-treated subjects compared to treatment-naïve subjects. cIMT was not statistically different across groups. Treated subjects exhibited elevated markers of dyslipidemia, inflammation, and lipodystrophy. PWV was associated with age, current EFV and LPV/r used, heart rate, blood pressure, triglycerides, LDL, and hsCRP, FMD with age, HIV duration, WHR, and glucose, and cIMT with age, current EFV use, skinfold thickness, and blood pressure.Current EFV- or LPV/r-treatment, but not NVP-treatment, correlated with elevated markers of atherosclerosis, which may involve mechanisms distinct from traditional risk factors.

Interaction of dipeptide prodrugs of saquinavir with multidrug resistance protein-2 (MRP-2): evasion of MRP-2 mediated efflux.

Science.gov (United States)

Jain, Ritesh; Agarwal, Sheetal; Mandava, Nanda Kishore; Sheng, Ye; Mitra, Ashim K

2008-10-01

Saquinavir (SQV), the first protease inhibitor approved by FDA to treat HIV-1 infection. This drug is a well-known substrate for multidrug resistance protein-2 (MRP-2). The objective of this study was to investigate whether derivatization of SQV to dipeptide prodrugs, valine-valine-saquinavir (Val-Val-SQV) and glycine-valine-saquinavir (Gly-Val-SQV), targeting peptide transporter can circumvent MRP-2 mediated efflux. Uptake and transport studies were carried out across MDCKII-MRP2 cell monolayers to investigate the interaction of SQV and its prodrugs with MRP-2. In situ single pass intestinal perfusion experiments in rat jejunum were performed to calculate intestinal absorption rate constants and permeabilities of SQV, Val-Val-SQV and Gly-Val-SQV. Uptake studies demonstrated that the prodrugs have significantly lower interaction with MRP-2 relative to SQV. Transepithelial transport of Val-Val-SQV and Gly-Val-SQV across MDCKII-MRP2 cells exhibited an enhanced absorptive flux and reduced secretory flux as compared to SQV. Intestinal perfusion studies revealed that synthesized prodrugs have higher intestinal permeabilities relative to SQV. Enhanced absorption of Val-Val-SQV and Gly-Val-SQV relative to SQV can be attributed to their translocation by the peptide transporter in the jejunum. In the presence of MK-571, a MRP family inhibitor, there was a significant increase in the permeabilities of SQV and Gly-Val-SQV indicating that these compounds are probably substrates for MRP-2. However, there was no change in the permeability of Val-Val-SQV with MK-571 indicating lack of any interaction of Val-Val-SQV with MRP-2. In conclusion, peptide transporter targeted prodrug modification of MRP-2 substrates may lead to shielding of these drug molecules from MRP-2 efflux pumps.

Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy.

LENUS (Irish Health Repository)

Lambert, J S

2011-03-01

The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir\\/ritonavir (LPV\\/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum.

Imatinib mesylate induces responses in patients with liver metastases from gastrointestinal stromal tumor failing intra-arterial hepatic chemotherapy

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Fiorentini Giammaria

2006-01-01

Full Text Available Background: Imatinib mesylate represents a real major paradigm shift in cancer therapy, targeting the specific molecular abnormalities, crucial in the etiology of tumor. Intra-arterial hepatic chemotherapy (IAHC followed by embolization, has been considered an interesting palliative option for patients with liver metastases from gastrointestinal stromal tumor (GIST, due to the typically hypervascular pattern of the tumor. Aims: We report our experience with IAHC followed by Imatinib mesylate, in order to show the superiority of the specific molecular approach in liver metastases from GIST. Materials and Methods: Three patients (pts with pretreated massive liver metastases from GIST, received IAHC with Epirubicin 50 mg/mq, every 3 weeks for 6 cycles. At the evidence of progression, they received Imatinib mesylate. Results: We observed progressive diseases in all cases. In 1998, one patient underwent Thalidomide at 150 mg orally, every day for 4 months, with evidence of stable disease and clinical improvement. In 2001, two patients received Imatinib mesylate at 400 mg orally, every day, with evidence of partial response lasting 18+ months and 16 months. One of them had grade 3 neutropenia, with suspension of therapy for 3 weeks. Conclusion: No patient treated with IAHC, reported objective responses, but two of them obtained partial response after the assumption of Imatinib mesylate and one showed temporary stabilization with thalidomide. Imatinib mesylate represents a new opportunity in GIST therapy, targeting the specific molecular alteration. It seems to be superior to conventional intra arterial hepatic chemotherapy.

Identification and Structural Characterization of I84C and I84A Mutations That Are Associated with High-Level Resistance to Human Immunodeficiency Virus Protease Inhibitors and Impair Viral Replication▿

Science.gov (United States)

Mo, Hongmei; Parkin, Neil; Stewart, Kent D.; Lu, Liangjun; Dekhtyar, Tatyana; Kempf, Dale J.; Molla, Akhteruzzaman

2007-01-01

Two novel human immunodeficiency virus protease mutations, I84C and I84A, were identified in patient isolates. The mutants with I84C displayed high-level resistance (median, at least 56-fold) to nelfinavir and saquinavir, but the majority remained susceptible to lopinavir. In contrast, isolates with the I84A mutation exhibited ≥33-fold median increased levels of resistance to nelfinavir, indinavir, amprenavir, ritonavir, lopinavir, saquinavir, and atazanavir. Isolates with the I84A or I84C mutation tended to be more resistant than the isolates with the I84V mutation. Modeling of the structure of the mutant proteases indicated that the I84V, I84C, and I84A mutations all create unoccupied volume in the active site, with I84A introducing the greatest change in the accessible surface area from that of the wild-type structure. PMID:17101675

Identification of cysteine-644 as the covalent site of attachment of dexamethasone 21-mesylate to murine glucocorticoid receptors in WEHI-7 cells

International Nuclear Information System (INIS)

Smith, L.I.; Bodwell, J.E.; Mendel, D.B.; Ciardelli, T.; North, W.G.; Munck, A.

1988-01-01

Dexamethasone 21-mesylate is a highly specific synthetic glucocorticoid derivative that binds covalently to glucocorticoid receptors via sulfhydryl groups. The authors have identified the amino acid that reacts with the dexamethasone 21-mesylate by using enzymatic digestion and microsequencing for radiolabel. Nonactivated glucocorticoid receptors obtained from labeling intact WEHI-7 mouse thymoma cells with [ 3 H]dexamethasone 21-mesylate were immunopurified and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Trypsin digestion followed by reversed-phase high-performance liquid chromatography (reversed-phase HPLC) produced a single [ 3 H]dexamethasone 21-mesylate labeled peptide. Automated Edman degradation of this peptide revealed that the [ 3 H]dexamethasone 21-mesylate was located at position 5 from the amino terminus. Dual-isotope labeling studies with [ 3 H]dexamethasone 21-mesylate and [ 35 S]methionine demonstrated that this peptide contained methionine. Staphylococcus aureus V8 protease digestion of [ 3 H]dexamethasone 21-mesylate labeled steroid-binding subunits generated a different radiolabeled peptide containing label at position 7 from the amino terminus. On the basis of the published amino acid sequence of the murine glucocorticoid receptor, their data clearly identify cysteine-644 as the single residue in the steroid-binding domain that covalently binds dexamethasone 21-mesylate. They have confirmed this finding by demonstrating that a synthetic peptide representing the amino acid sequence 640-650 of the murine glucocorticoid receptor behaves in an identical manner on reversed-phase HPLC as the trypsin-generated peptide from intact cells

Management of CML in the Pediatric Age Group: Imatinib Mesylate or SCT.

Science.gov (United States)

El-Alfy, Mohsen S; Al-Haddad, Alaa M; Hamed, Ahmed A

2010-12-01

Management of CML has changed markedly since the introduction of tyrosine kinase inhibitors (TKIs). However stem cell transplantation (SCT) remains a valid therapeutic modality especially in developing countries due to its relatively lower cost. We aim to compare between imatinib mesylate and SCT as regard outcome in CML in the pediatric age group. Forty-eight patients with newly diagnosed CML in the chronic phase, aged 3 to 18 years were enrolled in this prospective study. Patients without a matched donor (Group I; N=30) were assigned to receive imatinib mesylate at a dose of 340mg÷m2÷day, while patients with a fully matched related donor (Group II; N=18), were offered SCT. Response (hematologic, cytogenetic and molecular), side effects and survival were analyzed. Complete hematologic response was obtained in 97% of the patients in group I and 94% in group II. Major cytogenetic response (CyR) was obtained in 80% of patients in group I and 100% in group II. Complete CyR was 57% in group I and 64% in group II. Major molecular response (MMR) was 36% in group I and 50% in group II with no significant difference between both groups. Six years overall survival (OS) was 87% in the 1st group and 61% in the 2nd group (pSCT group (55% had GVHD and 78% had infection). Imatinib mesylate has a superior OS and EFS than SCT in children. It is generally safe and well tolerated. Imatinib mesylate should be the 1st line treatment of pediatric patients with CML in the chronic phase. CML- Imatinib- SCT- Pediatrics.

Early neuropsychological adverse events after switching from PI/r to dolutegravir could be related to hyperthyroidism in patients under levothyroxine.

Science.gov (United States)

Berger, Jean-Luc; Nguyen, Yohan; Lebrun, Delphine; Migault, Caroline; Hentzien, Maxime; Marty, Hélène; Bani-Sadr, Firouzé

2017-01-01

We report two patients who had taken levothyroxine at the same dose for several years and who had stable thyroid stimulating hormone (TSH) levels, and who developed clinical and biological hyperthyroidism following switch from ritonavir-boosted protease inhibitors (PIs) to dolutegravir-based HAART. Levothyroxine is metabolized by deiodination and glucuronidation and the induction of glucuronidation by ritonavir leads to an increased elimination of levothyroxine and a necessity of higher daily doses. Patients who switch from ritonavir-boosted PIs to antiretroviral drugs-based HAART with minimal drug-interaction such as dolutegravir, may require an adjustment in their dose of levothyroxine in order to prevent hyperthyroidism due to impaired elimination of levothyroxine without ritonavir.

Efficacy and Safety of Lopinavir/ritonavir- versus Efavirenz-based Antiretroviral Therapy in HIV-Infected Pregnant Ugandan Women

Science.gov (United States)

COHAN, Deborah; NATUREEBA, Paul; KOSS, Catherine A.; PLENTY, Albert; LUWEDDE, Flavia; MWESIGWA, Julia; ADES, Veronica; CHARLEBOIS, Edwin D.; GANDHI, Monica; CLARK, Tamara D.; NZARUBARA, Bridget; ACHAN, Jane; RUEL, Theodore; KAMYA, Moses R.; HAVLIR, Diane V.

2015-01-01

Objective Combination antiretroviral therapy (ART) is now the global standard for HIV-infected pregnant and breastfeeding women at all CD4 cell counts. We compared the efficacy and safety of an efavirenz versus lopinavir/ritonavir regimen for HIV-infected pregnant women initiating ART in rural Uganda. Design Randomized clinical trial. Methods We performed a planned secondary analysis comparing viral load suppression (HIV-1 RNA ≤400 copies/ml), safety, and HIV transmission to infants in a trial designed to test the hypothesis that lopinavir/ritonavir- versus efavirenz-based ART would reduce placental malaria (PROMOTE, ClinicalTrials.gov, NCT00993031). HIV-infected, ART-naïve pregnant women at 12–28 weeks gestation and any CD4 cell count were randomized. ART was provided and participants were counseled to breastfeed for one year postpartum. Results The median age of the 389 study participants was 29 years; median CD4 cell count was 370 cells/mm3. At delivery, virologic suppression was 97.6% in the efavirenz arm and 86.0% in the lopinavir/ritonavir arm, p HIV (both in the lopinavir/ritonavir arm) and HIV-free infant survival was similar between study arms: 92.9% (lopinavir/ritonavir) versus 97.2% (efavirenz), p = 0.10. Conclusions Virologic suppression at delivery was higher with an efavirenz- versus lopinavir/ritonavir-based regimen. However, women in both arms achieved high levels of virologic suppression through one year postpartum and the risk of transmission to infants was low. PMID:25426808

Efficacy and safety of lopinavir/ritonavir versus efavirenz-based antiretroviral therapy in HIV-infected pregnant Ugandan women.

Science.gov (United States)

Cohan, Deborah; Natureeba, Paul; Koss, Catherine A; Plenty, Albert; Luwedde, Flavia; Mwesigwa, Julia; Ades, Veronica; Charlebois, Edwin D; Gandhi, Monica; Clark, Tamara D; Nzarubara, Bridget; Achan, Jane; Ruel, Theodore; Kamya, Moses R; Havlir, Diane V

2015-01-14

Combination antiretroviral therapy (ART) is now the global standard for HIV-infected pregnant and breastfeeding women at all CD4⁺ cell counts. We compared the efficacy and safety of an efavirenz versus lopinavir/ritonavir regimen for HIV-infected pregnant women initiating ART in rural Uganda. Randomized clinical trial. We performed a planned secondary analysis comparing viral load suppression (HIV-1 RNA ≤400 copies/ml), safety, and HIV transmission to infants in a trial designed to test the hypothesis that lopinavir/ritonavir versus efavirenz-based ART would reduce placental malaria (PROMOTE, ClinicalTrials.gov, NCT00993031). HIV-infected, ART-naive pregnant women at 12-28 weeks gestation and any CD4⁺ cell count were randomized. ART was provided and participants were counseled to breastfeed for 1 year postpartum. The median age of the 389 study participants was 29 years; median CD4⁺ cell count was 370 cells/μl. At delivery, virologic suppression was 97.6% in the efavirenz arm and 86.0% in the lopinavir/ritonavir arm (P HIV (both in the lopinavir/ritonavir arm), and HIV-free infant survival was similar between study arms: 92.9% (lopinavir/ritonavir) versus 97.2% (efavirenz) (P = 0.10). Virologic suppression at delivery was higher with an efavirenz versus lopinavir/ritonavir-based regimen. However, women in both arms achieved high levels of virologic suppression through 1 year postpartum and the risk of transmission to infants was low.

Evaluation of different substrates for inkjet printing of rasagiline mesylate

DEFF Research Database (Denmark)

Genina, Natalja; Janßen, Eva Maria; Breitenbach, Armin

2013-01-01

The main goal of the present study was to evaluate applicability of the different model substrates, namely orodispersible films (ODFs), porous copy paper sheets, and water impermeable transparency films (TFs) in preparation of the inkjet-printed drug-delivery systems. Rasagiline mesylate (RM...

Atazanavir is not associated with an increased risk of cardio- or cerebrovascular disease events

DEFF Research Database (Denmark)

Monforte, Antonella d'Arminio; Reiss, Peter; Nielsen, Lene Ryom

2013-01-01

To investigate whether there is any association between exposure to atazanavir (ATV), either when boosted or unboosted by ritonavir, and myocardial infarction (MI) or stroke within the D:A:D: Study.......To investigate whether there is any association between exposure to atazanavir (ATV), either when boosted or unboosted by ritonavir, and myocardial infarction (MI) or stroke within the D:A:D: Study....

Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium

DEFF Research Database (Denmark)

Xia, Dengning; He, Yuan; Li, Qiuxia

2018-01-01

are transported. To improve cellular uptake and transport of pure nanodrug in cells, here, a lipid covered saquinavir (SQV) pure drug NP (Lipo@nanodrug) was designed by modifying a pure SQV NP (nanodrug) with a phospholipid bilayer. We studied their endocytosis, intracellular trafficking mechanism using Caco-2...... their intracellular processing, helping to improve drug transport across intestinal epithelium. To our knowledge, this is the first presentation of the novel phospholipid bilayer covered SQV pure drug NP design, and a mechanistic study on intracellular trafficking in in vitro cell models has been described......Pure drug nanoparticles (NPs) represent a promising formulation for improved drug solubility and controlled dissolution velocity. However, limited absorption by the intestinal epithelium remains challenge to their clinical application, and little is known about how these NPs within the cells...

Validated UV-Spectrophotometric Methods for Determination of Gemifloxacin Mesylate in Pharmaceutical Tablet Dosage Forms

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R. Rote Ambadas

2010-01-01

Full Text Available Two simple, economic and accurate UV spectrophotometric methods have been developed for determination of gemifloxacin mesylate in pharmaceutical tablet formulation. The first UV-spectrophotometric method depends upon the measurement of absorption at the wavelength 263.8 nm. In second area under curve method the wavelength range for detection was selected from 268.5-258.5 nm. Beer’s law was obeyed in the range of 2 to 12 μgmL-1 for both the methods. The proposed methods was validated statistically and applied successfully to determination of gemifloxacin mesylate in pharmaceutical formulation.

The role of interleukin-18 in glioblastoma pathology implies therapeutic potential of two old drugs-disulfiram and ritonavir.

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Kast, Richard E

2015-04-09

Based on reporting in the last several years, an impressive but dismal list of cytotoxic chemotherapies that fail to prolong the median overall survival of patients with glioblastoma has prompted the development of treatment protocols designed to interfere with growth-facilitating signaling systems by using non-cytotoxic, non-oncology drugs. Recent recognition of the pro-mobility stimulus, interleukin-18, as a driver of centrifugal glioblastoma cell migration allows potential treatment adjuncts with disulfiram and ritonavir. Disulfiram and ritonavir are well-tolerated, non-cytotoxic, non-oncology chemotherapeutic drugs that are marketed for the treatment of alcoholism and human immunodeficiency virus (HIV) infection, respectively. Both drugs exhibit an interleukin-18-inhibiting function. Given the favorable tolerability profile of disulfiram and ritonavir, the unlikely drug-drug interaction with temozolomide, and the poor prognosis of glioblastoma, trials of addition of disulfiram and ritonavir to current standard initial treatment of glioblastoma would be warranted.

Platelet Dysfunction in Patients with Chronic Myeloid Leukemia: Does Imatinib Mesylate Improve It?

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Olga Meltem Akay

2016-05-01

Full Text Available Objective: The aim of this study was to investigate the effects of imatinib mesylate on platelet aggregation and adenosine triphosphate (ATP release in chronic myeloid leukemia patients. Materials and Methods: Platelet aggregation and ATP release induced by 5.0 mM adenosine diphosphate, 0.5 mM arachidonic acid, 1.0 mg/ mL ristocetin, and 2 µg/mL collagen were studied by whole blood platelet lumi-aggregometer in 20 newly diagnosed chronic myeloid leukemia patients before and after imatinib mesylate treatment. Results: At the time of diagnosis, 17/20 patients had abnormal platelet aggregation results; 8 (40% had hypoactivity, 6 (30% had hyperactivity, and 3 (15% had mixed hypo- and hyperactivity. Repeat platelet aggregation studies were performed after a mean of 19 months (min: 5 months-max: 35 months in all patients who received imatinib mesylate during this period. After therapy, 18/20 (90% patients had abnormal laboratory results; 12 (60% had hypoactive platelets, 4 (20% had mixed hypo- and hyperactive platelets, and 2 (10% had hyperactive platelets. Three of the 8 patients with initial hypoactivity remained hypoactive, while 2 developed a mixed picture, 2 became hyperactive, and 1 normalized. Of the 6 patients with initial hyperactivity, 4 became hypoactive and 2 developed a mixed pattern. All of the 3 patients with initial hypo- and hyperactivity became hypoactive. Finally, 2 of the 3 patients with initial normal platelets became hypoactive while 1 remained normal. There was a significant decrease in ristocetin-induced platelet aggregation after therapy (p0.05. Conclusion: These findings indicate that a significant proportion of chronic myeloid leukemia patients have different patterns of platelet function abnormalities and imatinib mesylate has no effect on these abnormalities, with a significant impairment in ristocetin-induced platelet aggregation.

The bile acid sensor FXR protects against dyslipidemia and aortic plaques development induced by the HIV protease inhibitor ritonavir in mice.

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Andrea Mencarelli

Full Text Available BACKGROUND: Although human immunodeficiency virus (HIV-related morbidity and mortality rates in patients treated with a combination of high active antiretroviral therapy (HAART have declined, significant metabolic/vascular adverse effects associated with the long term use of HIV protease inhibitors (PIs have emerged as a significant side effect. Here we illustrate that targeting the bile acid sensor farnesoid X receptor (FXR protects against dyslipidemia and vascular injury induced HIV-PIs in rodents. METHODOLOGY/PRINCIPAL FINDINGS: Administration of the HIV PI ritonavir to wild type mice increased plasma triacylglycerols and cholesterol levels and this effect was exacerbated by dosing ritonavir to mice harbouring a disrupted FXR. Dyslipidemia induced by ritonavir associated with a shift in the liver expression of signature genes, Sterol Regulatory Element-Binding Protein (SREBP-1 and fatty acid synthase. Treating wild type mice with the FXR agonist (chenodeoxycholic acid, CDCA protected against development of dyslipidemia induced by ritonavir. Administration of ritonavir to ApoE(-/- mice, a strain that develop spontaneously atherosclerosis, increased the extent of aortic plaques without worsening the dyslipidemia. Treating these mice with CDCA reduced the extent of aortic plaques by 70% without changing plasma lipoproteins or the liver expression of signature genes. A beneficial effect on aortic plaques was also obtained by treating ApoE(-/- mice with gemfibrozil, a PPARα agonist. FXR activation counter-regulated induction of expression/activity of CD36 caused by HIV-PIs in circulating monocytes and aortic plaques. In macrophages cell lines, CDCA attenuated CD36 induction and uptake of acetylated LDL caused by ritonavir. Natural and synthetic FXR ligands reduced the nuclear translocation of SREBP1c caused by ritonavir. CONCLUSIONS/SIGNIFICANCE: Activation of the bile acid sensor FXR protects against dyslipidemia and atherosclerotic caused by

Therapeutic drug monitoring of atazanavir/ritonavir in pregnancy.

LENUS (Irish Health Repository)

Else, L J

2014-11-01

Pregnant women experience physiological changes during pregnancy that can have a significant impact on antiretroviral pharmacokinetics. Ensuring optimal plasma concentrations of antiretrovirals is essential for maternal health and to minimize the risk of vertical transmission. Here we describe atazanavir\\/ritonavir (ATV\\/r) plasma concentrations in a cohort of pregnant women undergoing routine therapeutic drug monitoring (TDM).

Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas.

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Desjardins, Annick; Quinn, Jennifer A; Vredenburgh, James J; Sathornsumetee, Sith; Friedman, Allan H; Herndon, James E; McLendon, Roger E; Provenzale, James M; Rich, Jeremy N; Sampson, John H; Gururangan, Sridharan; Dowell, Jeannette M; Salvado, August; Friedman, Henry S; Reardon, David A

2007-05-01

Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG). Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate. Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1-7) and the median number of prior treatment regimens was 3 (range, 1-8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses. Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.

Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the male and female genital tract.

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Else, Laura J; Taylor, Stephen; Back, David J; Khoo, Saye H

2011-01-01

HIV resides within anatomical 'sanctuary sites', where local drug exposure and viral dynamics may differ significantly from the systemic compartment. Suboptimal antiretroviral concentrations in the genital tract may result in compartmentalized viral replication, selection of resistant mutations and possible re-entry of wild-type/resistant virus into the systemic circulation. Therefore, achieving adequate antiretroviral exposure in the genital tract has implications for the prevention of sexual and vertical transmission of HIV. Penetration of antiretrovirals in the genital tract is expressed by accumulation ratios derived from the measurement of drug concentrations in time-matched seminal plasma/cervicovaginal fluid and plasma samples. Penetration varies by gender and may be drug (as opposed to class) specific with high interindividual variability. Concentrations in seminal plasma are highest for nucleoside analogues and lowest for protease inhibitors and efavirenz. Seminal accumulation of newer agents, raltegravir and maraviroc, is moderate (rank order of accumulation is nucleoside/nucleotide reverse transcriptase inhibitors [lamivudine/zidovudine/tenofovir/didanosine > stavudine/abacavir] > raltegravir > indinavir/maraviroc/nevirapine > efavirenz/protease inhibitors [amprenavir/atazanavir/darunavir > lopinavir/ritonavir > saquinavir] > enfuvirtide). In the female genital tract, the nucleoside analogues exhibit high accumulation ratios, whereas protease inhibitors have limited penetration; however, substantial variability exists between individuals and study centres. Second generation non-nucleoside reverse transcriptase inhibitor etravirine, and maraviroc and raltegravir, demonstrate effective accumulation in cervicovaginal secretions (rank order of accumulation is nucleoside/nucleotide reverse transcriptase inhibitor [zidovudine/lamivudine/didanosine > emtricitabine/tenofovir] > indinavir > maraviroc/raltegravir/darunavir/etravirine > nevirapine

Development of a Tumour Growth Inhibition Model to Elucidate the Effects of Ritonavir on Intratumoural Metabolism and Anti-tumour Effect of Docetaxel in a Mouse Model for Hereditary Breast Cancer.

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Yu, Huixin; Hendrikx, Jeroen J M A; Rottenberg, Sven; Schellens, Jan H M; Beijnen, Jos H; Huitema, Alwin D R

2016-03-01

In a mouse tumour model for hereditary breast cancer, we previously explored the anti-cancer effects of docetaxel, ritonavir and the combination of both and studied the effect of ritonavir on the intratumoural concentration of docetaxel. The objective of the current study was to apply pharmacokinetic (PK)-pharmacodynamic (PD) modelling on this previous study to further elucidate and quantify the effects of docetaxel when co-administered with ritonavir. PK models of docetaxel and ritonavir in plasma and in tumour were developed. The effect of ritonavir on docetaxel concentration in the systemic circulation of Cyp3a knock-out mice and in the implanted tumour (with inherent Cyp3a expression) was studied, respectively. Subsequently, we designed a tumour growth inhibition model that included the inhibitory effects of both docetaxel and ritonavir. Ritonavir decreased docetaxel systemic clearance with 8% (relative standard error 0.4%) in the co-treated group compared to that in the docetaxel only-treated group. The docetaxel concentration in tumour tissues was significantly increased by ritonavir with mean area under the concentration-time curve 2.5-fold higher when combined with ritonavir. Observed tumour volume profiles in mice could be properly described by the PK/PD model. In the co-treated group, the enhanced anti-tumour effect was mainly due to increased docetaxel tumour concentration; however, we demonstrated a small but significant anti-tumour effect of ritonavir addition (p value effect observed when docetaxel is combined with ritonavir is mainly caused by enhanced docetaxel tumour concentration and to a minor extent by a direct anti-tumour effect of ritonavir.

Profile of paritaprevir/ritonavir/ombitasvir plus dasabuvir in the treatment of chronic hepatitis C virus genotype 1 infection

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Smith MA

2015-11-01

Full Text Available Michael A Smith, Alice LimDepartment of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USAAbstract: Over the last several years, many advances have been made in the treatment of chronic hepatitis C virus (HCV infection with the development of direct-acting antivirals. Paritaprevir/ritonavir/ombitasvir with dasabuvir (PrOD is a novel combination of a nonstructural (NS 3/4A protein inhibitor boosted by ritonavir, an NS5A protein inhibitor, and an NS5B nonnucleoside polymerase inhibitor. This review aims to discuss the pharmacology, efficacy, safety, drug interactions, and viral drug resistance of PrOD in the treatment of HCV genotype 1 infections. Phase I, II, and III human and animal studies that describe the pharmacology, pharmacokinetics, efficacy, and safety of PrOD for HCV were identified and included. Studies that evaluated patients without cirrhosis (n=2,249 and with cirrhosis (n=422 demonstrated that PrOD for 12 or 24 weeks was effective at achieving sustained virologic response rates (>90% in patients with genotype 1a or 1b HCV infection. Although indicated for the treatment of HCV genotype 1 infection, PrOD is also recommended for the treatment of HCV in patients coinfected with HIV. Additionally, promising data exist for the use of PrOD in liver-transplant recipients. The most common adverse drug events associated with PrOD included nausea, pruritus, insomnia, diarrhea, asthenia, dry skin, vomiting, and anemia. The high efficacy rates seen coupled with a favorable side effect profile seen with PrOD with or without ribavirin have led to its addition as a recommended treatment regimen for HCV genotype 1 infection.Keywords: direct-acting antiviral, interferon-free, ribavirin-free

A cross-sectional study to evaluate second line virological failure and elevated bilirubin as a surrogate for adherence to atazanavir/ritonavir in two urban HIV clinics in Lilongwe, Malawi.

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Ongubo, Dennis Miyoge; Lim, Robertino; Tweya, Hannock; Stanley, Christopher Chikhosi; Tembo, Petros; Broadhurst, Richard; Gugsa, Salem; Ngongondo, McNeil; Speight, Colin; Heller, Tom; Phiri, Sam; Hosseinipour, Mina C

2017-07-03

Malawi's national antiretroviral therapy program provides atazanavir/ritonavir-based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi. We conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi. Antiretroviral therapy history and adherence data were extracted from the electronic medical records and blood was drawn for viral load, complete blood count, total bilirubin, and CD4 cell count at a clinic visit. Factors associated with virological failure were assessed using multivariate logistic regression model. Out of 376 patients on second line antiretroviral therapy evaluated, 372 (98.9%) were on atazanavir/ritonavir-based therapy and 142 (37.8%) were male. Mean age was 40.9 years (SD ± 10.1), mean duration on second line antiretroviral therapy was 41.9 months (SD ± 27.6) and 256 patients (68.1%) had elevated bilirubin >1.3 mg/dL. Overall, 35 (9.3%) patients had viral load >1000 copies/ml (virological failure). Among the virologically failing vs. non-failing patients, bilirubin was elevated in 34.3% vs. 72.0% respectively (p bilirubin levels (aOR 5.4, p bilirubin levels better predicted virological failure than pill count adherence. Therefore, strategic use of bilirubin and viral load testing to target adherence counseling and support may be cost-effective in monitoring second line antiretroviral therapy adherence and virological failure. Drug resistance testing targeted for patients with virological failure despite elevated bilirubin levels would facilitate timely switch to third line antiretroviral regimens whenever available.

Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells

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Yang S

2013-08-01

Full Text Available Sidi Yang,1,2 Yufei Chen,1,2 Kaien Gu,1,2 Alicia Dash,1,2 Casey L Sayre,1 Neal M Davies,1 Emmanuel A Ho1,2 1Faculty of Pharmacy, 2Laboratory for Drug Delivery and Biomaterials, University of Manitoba, Winnipeg, MB, Canada Abstract: The goal of this study was to develop and characterize an intravaginal nanomedicine for the active targeted delivery of saquinavir (SQV to CD4+ immune cells as a potential strategy to prevent or reduce HIV infection. The nanomedicine was formulated into a vaginal gel to provide ease in self-administration and to enhance retention within the vaginal tract. SQV-encapsulated nanoparticles (SQV-NPs were prepared from poly(lactic-co-glycolic acid(PLGA and conjugated to antihuman anti-CD4 antibody. Antibody-conjugated SQV-NPs (Ab-SQV-NPs had an encapsulation efficiency (EE% of 74.4% ± 3.7% and an antibody conjugation efficiency (ACE% of 80.95% ± 1.10%. Over 50% of total loaded SQV was released from NPs over 3 days. NPs were rapidly taken up by Sup-T1 cells, with more than a twofold increase in the intracellular levels of SQV when delivered by Ab-SQV-NPs in comparison to controls 1 hour post-treatment. No cytotoxicity was observed when vaginal epithelial cells were treated for 24 hours with drug-free Ab-NPs (1,000 µg/mL, 1% HEC placebo gel (200 mg/mL, or 1% HEC gel loaded with drug-free Ab-NPs (5 mg NPs/g gel, 200 mg/mL of gel mixture. Overall, we described an intravaginal nanomedicine that is nontoxic and can specifically deliver SQV into CD4+ immune cells. This platform may demonstrate potential utility in its application as postexposure prophylaxis for the treatment or reduction of HIV infection, but further studies are required. Keywords: nanoparticles, saquinavir, antibody conjugation, intravaginal gel, HIV/AIDS, microbicide

Raltegravir versus lopinavir/ritonavir for treatment of HIV-infected late-presenting pregnant women.

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Brites, Carlos; Nóbrega, Isabella; Luz, Estela; Travassos, Ana Gabriela; Lorenzo, Cynthia; Netto, Eduardo M

2018-06-01

Background Late-presenting pregnant women pose a challenge in the prevention of HIV-1 mother-to-child-transmission. We compared the safety and efficacy of raltegravir and lopinavir/ritonavir for this population. Methods We did a single-center, pilot, open-label, randomized trial in Brazil (N = 44). We randomly allocated late-presenting HIV-infected pregnant women (older than 18 years with a plasma HIV-1 RNA >1000 copies/mL) to receive raltegravir 400 mg twice a day or lopinavir/ritonavir 400/100 mg twice a day plus zidovudine and lamivudine (1:1). The primary endpoint was virological suppression at delivery (HIV-1 RNA HIV-infected late-presenting pregnant women.

Long-term remission in BCR/ABL-positive AML-M6 patient treated with Imatinib Mesylate.

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Pompetti, Franca; Spadano, Antonio; Sau, Antonella; Mennucci, Antonio; Russo, Rosa; Catinella, Virginia; Franchi, Paolo Guanciali; Calabrese, Giuseppe; Palka, Giandomenico; Fioritoni, Giuseppe; Iacone, Antonio

2007-04-01

BCR/ABL-positive acute myeloid leukemia (AML) is a rare disease, characterized by a poor prognosis, with resistance to induction chemotherapy and frequent relapses in responsive patients. Here we report a case of BCR/ABL-positive AML-M6 who, after relapse, was treated with Imatinib Mesylate (600 mg/die) and within 4 months achieved a cytogenetic and molecular complete response. After more than 4 years of continuous Imatinib therapy, nested RT-PCR for BCR/ABL is persistently negative. The case reported shows that the response obtained with Imatinib Mesylate in BCR/ABL-positive AML may be long lasting, offering a chance of successful treatment for this poor prognosis group of patients.

Successful Treatment For Chronic Eosinophilic Leukemia (CEL With Imatinib Mesylate

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Rayane da Silva Souza

2017-12-01

Full Text Available We report a case of a patient with Chronic Eosinophilic Leukemia (CEL with mutation in alfa PDGFR gene exhibiting a satisfactory response to treatment with imatinib mesylate. A 25-year-old man presented in a hematology service with a persistent cough and hemogram alterations. His blood count showed a hemoglobin level of 12.5 g/dL and a white blood cell count of 94,030/mm3, eosinophils were 68% of all cells. Bone marrow aspiration and biopsy showed hypercellularity with marked eosinophilia (77% and erythroid differentiation series was hypocellular with normoblast maturation. The immunohistochemically of the bone biopsy was positive for myeloperoxidase and negative for CD34/CD99, consistent with CEL. Fluorescence in situ hybridization (FISH for the beta-fraction of platelet-derived growth factor (PDGFRβ and Philadelphia chromosome (Ph 1 were negative and the alfa PDGFR (Platelet-Derived Growth Factor was positive and showed heterozygosis in c.2531T>C on 18 Exon and homozygous in C.2562+1G>A at the region of the splicing site at the 18 intron. Treatment was initiated and maintained by administering 400mg/day imatinib mesylate. Laboratory findings returned to normal ranges, with clinical improvement and a hematological response observed after the second month of therapy. Currently, the patient’s blood count shows the white blood cell count (5,400 total leukocytes, eosinophils (8.6/mm3, hemoglobin (15.5 g/dl, hematocrit (45.4% and platelets (298,000/mm3 within normal ranges. The mutation search was negative in in peripheral blood one year after the initial treatment. Our work corroborates other studies on the efficacy of imatinib mesylate in the treatment of patients with CSF PDGFR alpha positive. We emphasize the importance of molecular studies, considering its relevance for the correct staging of the disease. Since CEL is a rare disease, it is important to define its etiology and anticipate its treatment, thus minimizing the damage induced by

Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial.

Science.gov (United States)

Ciaffi, Laura; Koulla-Shiro, Sinata; Sawadogo, Adrien Bruno; Ndour, Cheik Tidiane; Eymard-Duvernay, Sabrina; Mbouyap, Pretty Rosereine; Ayangma, Liliane; Zoungrana, Jacques; Gueye, Ndeye Fatou Ngom; Diallo, Mohamadou; Izard, Suzanne; Bado, Guillaume; Kane, Coumba Toure; Aghokeng, Avelin Fobang; Peeters, Martine; Girard, Pierre Marie; Le Moing, Vincent; Reynes, Jacques; Delaporte, Eric

2017-09-01

Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART). We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per μL, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1:1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI

Up regulation of K A I 1 gene expression and apoptosis effect of imatinib mesylate in gastric adenocarcinoma (AGS cell line

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eyed Ataollah Sadat Shandiz

2016-02-01

Full Text Available Objective: To evaluate the effect of imatinib mesylate on KAI1 gene expression and apoptosis properties in human gastric carcinoma AGS cell line. Methods: Cell viability was assessed by MTT assay and quantitative real time PCR method was applied for investigation of Bax, Bcl-2, and KAI1 gene expression in AGS cells. The quantity of KAI1, Bax, and Bcl-2 compared to GAPDH gene expressions were examined using the formula 2-∆∆Ct. Furthermore, cell apoptosis/necrosis was carried out by annexin V/PI staining and quantified with flow cytometry after treatment with imatinib. Results: Imatinib mesylate was showed to have a dose-dependent toxicity effect against AGS cells. KAI1/GAPDH gene expression ratios were 1.07 ± 0.02 (P > 0.05, 1.68 ± 0.19 (P > 0.05, 3.60 ± 0.55 (P < 0.05, 6.54 ± 0.27 (P < 0.001 for 20, 50, 80 and 100 μmol/L of imatinib concentrations. The mRNA levels of Bax detected by real-time PCR after treatment with imatinib mesylate were significantly increased. Also, the number of apoptotic cells was increased from 3.72% (statistically significant; P < 0.05 in untreated AGS cells to 21.72%, 83.04% and 85.80%, respectively, following treatment with 20, 40, and 60 μmol/L imatinib mesylate. Conclusions: The results suggest that imatinib mesylate can induce apoptosis pathway in a dose-dependent mode and might modulate metastasis by up regulating KAI1 gene expression in human gastric carcinoma AGS cell line.

Cost-effectiveness analysis of lopinavir/ritonavir and atazanavir+ritonavir regimens in the CASTLE study.

Science.gov (United States)

Simpson, Kit N; Rajagopalan, Rukmini; Dietz, Birgitta

2009-02-01

The purpose of the study was to conduct a cost-effectiveness analysis and budget impact analysis comparing lopinavir with ritonavir (LPV/r) and atazanavir plus ritonavir (ATV+RTV) for antiretroviral-naïve patients with a baseline CD4+ T-cell distribution and total cholesterol (TC) profile as reported in the CASTLE study. This decision analysis study used a previously published Markov model of HIV disease, incorporating coronary heart disease (CHD) events to compare the short- and long-term budget impacts and CHD consequences expected for the two regimens. Patients were assumed to have a baseline CHD risk of 4.6% (based on demographic data) and it was also assumed that 50% of the population in the CASTLE study were smokers. The CHD risk differences (based on percent of patients with TC >240 mg/dL) in favor of ATV+RTV resulted in an average improvement in life expectancy of 0.031 quality-adjusted life years (QALYs) (11 days), and an incremental cost-effectiveness ratio of $1,409,734/QALY. Use of the LPV/r regimen saved $24,518 and $36,651 at 5 and 10 years, respectively, with lifetime cost savings estimated at $38,490. A sensitivity analysis using a cohort of all smokers on antihypertensive medication estimated an average improvement in life expectancy of 31 quality-adjusted days in favor of ATV+RTV, and a cost-effectiveness ratio of $520,861/QALY: a ratio that is still above the acceptable limit within the US. The use of an LPV/r-based regimen in antiretroviral-naïve patients with a baseline CHD risk similar to patients in the CASTLE study appears to be a more cost-effective use of resources compared with an ATV+RTV-based regimen. The very small added CHD risk predicted by LPV/r treatment is more than offset by the substantial short- and long-term cost savings expected with the use of LPV/r in antiretroviral-naïve individuals with average to moderately elevated CHD risk.

Comparison of single and boosted protease inhibitor versus nonnucleoside reverse transcriptase inhibitor-containing cART regimens in antiretroviral-naïve patients starting cART after January 1, 2000

DEFF Research Database (Denmark)

Mocroft, A; Horban, A; Clumeck, N

2006-01-01

increase) response in antiretroviral-naïve patients starting either a single protease inhibitor (PI; n = 183), a ritonavir-boosted PI regimen (n = 197), or a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based cART regimen (n = 447) after January 1, 2000, and the odds of lack of virologic...... or immunologic response at 3 years after starting cART. METHOD: Cox proportional hazards models and logistic regression. RESULTS: After adjustment, compared to patients taking an NNRTI-regimen, patients taking a single-PI regimen were significantly less likely to achieve a viral load (VL)

Homologous recombination induced by doxazosin mesylate and saw palmetto in the Drosophila wing-spot test.

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Gabriel, Katiane Cella; Dihl, Rafael Rodrigues; Lehmann, Mauricio; Reguly, Maria Luiza; Richter, Marc François; Andrade, Heloisa Helena Rodrigues de

2013-03-01

Benign prostatic hyperplasia (BPH) is the most common tumor in men over 40 years of age. Acute urinary retention (AUR) is regarded as the most serious hazard of untreated BPH. α-Blockers, such as doxazosin mesylate, and 5-α reductase inhibitors, such as finasteride, are frequently used because they decrease both AUR and the need for BPH-related surgery. An extract of the fruit from American saw palmetto plant has also been used as an alternative treatment for BPH. The paucity of information available concerning the genotoxic action of these compounds led us to assess their activity as inducers of different types of DNA lesions using the somatic mutation and recombination test in Drosophila melanogaster. Finasteride did not induce gene mutation, chromosomal mutation or mitotic recombination, which means it was nongenotoxic in our experimental conditions. On the other hand, doxazosin mesylate and saw palmetto induced significant increases in spot frequencies in trans-heterozygous flies. In order to establish the actual role played by mitotic recombination and by mutation in the genotoxicity observed, the balancer-heterozygous flies were also analyzed, showing no increment in the total spot frequencies in relation to the negative control, for both drugs. Doxazosin mesylate and saw palmetto were classified as specific inducers of homologous recombination in Drosophila proliferative cells, an event linked to the loss of heterozygosity. Copyright © 2011 John Wiley & Sons, Ltd.

[Challenges of lopinavir/ritonavir in the chronicity of human immunodeficiency virus infection].

Science.gov (United States)

Aguirrebengoa, Koldo

2014-11-01

Combination antiretroviral therapy (ART) has increased patient survival, which is currently similar to that of the general population in western countries. However, ART is unable to completely restore normal health, given the persistence of chronic immune activation. Human immunodeficiency virus (HIV) infection has become a chronic disease and 50% of patients will soon be older than 50 years. Currently, there is a debate on the possibility of accelerated aging in the HIV-infected population. An overlap has been observed between chronic inflammation, age-related comorbidities, lifestyle, and the long-term toxicity of ART. ART-related toxicity can encourage the development of comorbidities, especially cardiovascular and renal complications, while toxicity-especially that of thymidine analogs-can also contribute to inflammation and aging. Evidence is available on simplification strategies with boosted protease inhibitor monotherapy aiming to avoid or reduce potential or demonstrated toxicity. Currently, studies are underway of dual therapy strategies with lopinavir/ritonavir (LPV/r) with distinct antiretroviral agents. The studies with the largest samples are those with raltegravir and lamivudine. The GARDEL trial has demonstrated that dual therapy with LPV/r plus a generic drug such as lamivudine is non-inferior to triple therapy in treatment- naïve patients. All of the above indicates the response to the challenge posed to LPV/r by the chronic phase of the disease and by the need to reduce costs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Clinical Course and Management of Iatrogenic Cushing’s Syndrome after Co-Administration of Injected-Triamcinolone and Ritonavir: a Systematic Review

OpenAIRE

John, Gregor Raphaël; Ollo, Diana; Meyer, Patrick; Herold, Markus; Samer, Caroline Flora; Calmy, Alexandra

2013-01-01

Iatrogenic Cushing Syndrome (ICS) has been reported after co-administration of injectedtriamcinolone and ritonavir. Clinical evolution is however poorly described and recommendations on how to manage this drug-drug interaction are lacking. Methods: We performed a systematic review of all reported cases of ICS exploring Pubmed, Embase, Cochrane library, and articles references. Time to Hypothalamic-Pituitary-Adrenal (HPA) axis recovery for patients with or without ritonavir interruption, was c...

To boost or not boost in radiotherapy

International Nuclear Information System (INIS)

Maciejewski, B.; Suwinski, R.; Withers, H.R.; Fowler, J.; Fijuth, J.

2004-01-01

The aim of this paper it to analyse and discuss standard definition of the 'boost' procedure in relation to clinical results and new forms of the boost designed on physical and radiobiological bases. Seventeen sets of clinical data including over 5000 cases cancer with different tumour stages and locations and treated with various forms of 'boost' method have been subtracted from literature. Effectiveness of boost is analyzed regarding its place in combined treatment, timing and subvolume involved. Radiobiological parameter of D10 and normalization method for biologically equivalent doses and dose intensity are used to simulated cold and not subvolumes (hills and dales) and its influence of effectiveness on the boost delivery. Sequential and concomitant boost using external irradiation, although commonly used, offers LTC benefit lower than expected. Brachytherapy, intraoperative irradiation and concurrent chemotherapy boost methods appear more effective. Conformal radiotherapy, with or without dose-intensity modulation, allows heterogeneous increase in dose intensity within the target volume and can be used to integrate the 'boost dose' into baseline treatment (Simultaneous Integrated Boost and SIB). Analysis of interrelationships between boost-dose; boost volume and its timing shows that a TCP benefit from boosting can be expected when a relatively large part of the target volume is involved. Increase in boost dose above 1.2-1.3 of baseline dose using 'standard' methods does not substantially further increase the achieved TCP benefit unless hypoxic cells are a problem. Any small uncertainties in treatment planning can ruin all potential beneficial effect of the boost. For example, a 50% dose deficit in a very small (e.g. 1%) volume of target can decrease TCP to zero. Therefore boost benefits should be carefully weighed against any risk of cold spots in the target volume. Pros and cons in discussion of the role of boost in radiotherapy lead to the important

Gynecomastia during imatinib mesylate treatment for gastrointestinal stromal tumor: a rare adverse event

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Yan ZhongShu

2011-11-01

Full Text Available Abstract Background Imatinib mesylate has been the standard therapeutic treatment for chronic myeloid leukemia, advanced and metastatic gastrointestinal stromal tumor (GIST. It is well tolerated with mild adverse effects. Gynecomastia development during the course of treatment has been rarely reported. Methods Ninety-eight patients with advanced or recurrent GIST were treated with imatinib mesylate. Among the fifty-seven male patients six developed gynecomastia during the treatment. The lesions were confirmed by sonography. Sex hormone levels were determined in six patients with and without the presence of gynecomastia respectively. The patients with gynecomatia were treated with tamoxifene and the sex hormones were assayed before and after tamoxifene treatment. Results In patients with gynecomastia the lump underneath the bilateral nipples was 2.5 to 5 centimeters in diameter. Their serum free testosterone levels ranged between 356.61 and 574.60 ng/dl with a mean ± SD of 408.64 ± 82.06 ng/dl (95% CI 343.03~474.25 ng/dl, which is within the normal range. The level of serum estradiol was 42.89 ± 16.54 pg/ml (95% CI 29.66~56.12 pg/ml. Three patients had higher levels (43.79~71.21 pg/ml and the others' were within normal range of 27.00~34.91 pg/ml. Six patients without the development of gynecomastia had normal free testosterone. One patient died because of large tumor burden. The sex hormones had no significant changes before and after tamoxifene treatment.(P > 0.05 Conclusions Testosterone levels were not decreased in the six GIST patients with gynecomastia. Three patients had increased serum estradiol level which suggests that imbalance of sex hormones may be the cause of gynecomastia during treatment with imatinib mesylate.

Combined derivatization and high-performance liquid chromatography with fluorescence and ultraviolet detection for simultaneous analysis of octreotide and gabexate mesylate metabolite in human pancreatic juice samples.

Science.gov (United States)

Carlucci, Giuseppe; Selvaggi, Federico; Sulpizio, Sara; Bassi, Claudio; Carlucci, Maura; Cotellese, Roberto; Ferrone, Vincenzo; Innocenti, Paolo; Locatelli, Marcello

2015-06-01

A simple and sensitive method based on the combination of derivatization and high-performance liquid chromatography with ultraviolet and fluorimetric detection was developed for the simultaneous determination of octreotide and gabexate mesylate metabolite in human pancreatic juice samples. Parameters of the derivatization procedure affecting extraction efficiency were optimized. The developed method was validated according to the International Conference on Harmonization guidelines. The calibration curves were linear over a range of 0.1-15 µg/mL for octreotide and 0.20-15 µg/mL for gabexate mesylate metabolite. Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The limits of detection were 0.025 and 0.05, respectively, for octreotide and gabexate mesylate metabolite. This paper reports the validation of a quantitative high performance liquid chromatography-photodiode array-fluorescence (HPLC-PDA-FL) method for the simultaneous analysis of octreotide and gabexate mesylate metabolite in pancreatic juice by protein precipitation using zinc sulfate-methanol-acetonitrile containing the derivatizing reagent, 4-fluoro-7-nitro-[2,1,3]-benzoxadiazole (NBD-F). Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The method was validated over the concentration ranges 0.1-15 and 0.2-15 µg/mL for octreotide and gabexate mesylate metabolite, respectively, in human pancreatic juice. Biphalin and methyl-p-hydroxybenzoate were used as the internal standards. This method was successfully utilized to support clinical studies in humans. The results from assay validations show that the method is selective, sensitive and robust. The limit

Formulation and In Vitro, In Vivo Evaluation of Effervescent Floating Sustained-Release Imatinib Mesylate Tablet

Science.gov (United States)

Kadivar, Ali; Kamalidehghan, Behnam; Javar, Hamid Akbari; Davoudi, Ehsan Taghizadeh; Zaharuddin, Nurul Dhania; Sabeti, Bahareh; Chung, Lip Yong; Noordin, Mohamed Ibrahim

2015-01-01

Introduction Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets. Methodology Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted. Results and Discussion Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent

Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet.

Directory of Open Access Journals (Sweden)

Ali Kadivar

Full Text Available Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT. Conventional imatinib mesylate (Gleevec tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M, with Sodium alginate (SA and Carbomer 934P (CP as release-retarding polymers, sodium bicarbonate (NaHCO3 as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec in 0.1 N HCl (pH 1.2 at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted.Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec. Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours

Analysis of Hepatitis C Virus Genotype 1b Resistance Variants in Japanese Patients Treated with Paritaprevir-Ritonavir and Ombitasvir.

Science.gov (United States)

Krishnan, Preethi; Schnell, Gretja; Tripathi, Rakesh; Beyer, Jill; Reisch, Thomas; Zhang, Xinyan; Setze, Carolyn; Rodrigues, Lino; Burroughs, Margaret; Redman, Rebecca; Chayama, Kazuaki; Kumada, Hiromitsu; Collins, Christine; Pilot-Matias, Tami

2016-02-01

Treatment of HCV genotype 1b (GT1b)-infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) in studies M12-536 and GIFT-I demonstrated high sustained virologic response (SVR) rates. The virologic failure rate was 3% (13/436) across the two studies. Analyses were conducted to evaluate the impact of baseline resistance-associated variants (RAVs) on treatment outcome and the emergence and persistence of RAVs in patients experiencing virologic failure. Baseline paritaprevir resistance-conferring variants in NS3 were infrequent, while Y93H in NS5A was the most prevalent ombitasvir resistance-conferring variant at baseline. A comparison of baseline prevalence of polymorphisms in Japanese and western patients showed that Q80L and S122G in NS3 and L28M, R30Q, and Y93H in NS5A were significantly more prevalent in Japanese patients. In the GIFT-I study, the prevalence of Y93H in NS5A varied between 13% and 21% depending on the deep-sequencing detection threshold. Among patients with Y93H comprising 40% of their preexisting viral population, the 24-week SVR (SVR24) rates were >99% (276/277), 93% (38/41), and 76% (25/33), respectively, indicating that the prevalence of Y93H within a patient's viral population is a good predictor of treatment response. The predominant RAVs at the time of virologic failure were D168A/V in NS3 and Y93H alone or in combination with other variants in NS5A. While levels of NS3 RAVs declined over time, NS5A RAVs persisted through posttreatment week 48. Results from these analyses are informative in understanding the resistance profile of an ombitasvir- plus paritaprevir/ritonavir-based regimen in Japanese GT1b-infected patients. Copyright © 2016 Krishnan et al.

Cholelithiasis and Nephrolithiasis in HIV-Positive Patients in the Era of Combination Antiretroviral Therapy.

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Kuan-Yin Lin

Full Text Available This study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy.We retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT 1A1*28 and multidrug resistance gene 1 (MDR1 G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed.During the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9% with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%, unboosted atazanavir (34.4%, ritonavir-boosted lopinavir (20.4%, and ritonavir-boosted atazanavir (5.5%. The overall prevalence of cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12-35.16 and older age (AOR, 1.04; 95% CI, 1.00-1.09. The positive association between duration of exposure to ritonavir-boosted atazanavir and incident

The Safety, Effectiveness and Concentrations of Adjusted Lopinavir/Ritonavir in HIV-Infected Adults on Rifampicin-Based Antitubercular Therapy

Science.gov (United States)

Decloedt, Eric H.; Maartens, Gary; Smith, Peter; Merry, Concepta; Bango, Funeka; McIlleron, Helen

2012-01-01

Objective Rifampicin co-administration dramatically reduces plasma lopinavir concentrations. Studies in healthy volunteers and HIV-infected patients showed that doubling the dose of lopinavir/ritonavir (LPV/r) or adding additional ritonavir offsets this interaction. However, high rates of hepatotoxicity were observed in healthy volunteers. We evaluated the safety, effectiveness and pre-dose concentrations of adjusted doses of LPV/r in HIV infected adults treated with rifampicin-based tuberculosis treatment. Methods Adult patients on a LPV/r-based antiretroviral regimen and rifampicin-based tuberculosis therapy were enrolled. Doubled doses of LPV/r or an additional 300 mg of ritonavir were used to overcome the inducing effect of rifampicin. Steady-state lopinavir pre-dose concentrations were evaluated every second month. Results 18 patients were enrolled with a total of 79 patient months of observation. 11/18 patients were followed up until tuberculosis treatment completion. During tuberculosis treatment, the median (IQR) pre-dose lopinavir concentration was 6.8 (1.1–9.2) mg/L and 36/47 (77%) were above the recommended trough concentration of 1 mg/L. Treatment was generally well tolerated with no grade 3 or 4 toxicity: 8 patients developed grade 1 or 2 transaminase elevation, 1 patient defaulted additional ritonavir due to nausea and 1 patient developed diarrhea requiring dose reduction. Viral loads after tuberculosis treatment were available for 11 patients and 10 were undetectable. Conclusion Once established on treatment, adjusted doses of LPV/r co-administered with rifampicin-based tuberculosis treatment were tolerated and LPV pre-dose concentrations were adequate. PMID:22412856

Characterization of HIV-1 from patients with virological failure to a boosted protease inhibitor regimen

DEFF Research Database (Denmark)

Lillemark, Marie Rathcke; Gerstoft, Jan; Obel, Niels

2011-01-01

The use of highly active antiretroviral treatment (HAART) regimens with unboosted protease inhibitors (PIs) has resulted in a high level of virological failure primarily due to the development of resistant virus. Current boosted PI regimens combine successfully low-dose ritonavir (r) with a second.......3%) experienced virological failure, of whom 19 (83%) started PI/r treatment before 2001. Patients from Copenhagen (n=19) were selected to study the development of protease (PR) and gag cleavage site (CS) mutations during PI/r treatment and PI plasma levels at the time of virological failure. Three patients (16......%) developed major PI resistance mutations. Mutations in the p7/p1 and p1/p6 gag CS only developed in patients with major or minor mutations in PR. Drug concentrations were low or undetectable in 10 out of the 19 patients. In total PR resistance mutations and low drug levels could account for 12 (63...

"Antifibrotic effect after low-dose imatinib mesylate treatment in patients with nephrogenic systemic fibrosis: An open-label non-randomized, uncontrolled clinical trial"

DEFF Research Database (Denmark)

Elmholdt, Tina Rask; Olesen, Anne Braae

2011-01-01

Background Nephrogenic systemic fibrosis is a disease affecting the connective tissue of the skin and internal organs in patients with renal failure. No effective treatments are available. Objectives To investigate if the tyrosine kinase inhibitor, imatinib mesylate was effective in patients...... Imatinib mesylate may be an effective drug in the treatment of skin fibrosis in moderate to severe NSF cases, even at reduced doses. We found a positive clinical effect on the skin, but no convincing improvement of the joint mobility. Only few patients could be recruited limiting the interpretation...

Effectiveness of dasabuvir/ombitasvir/paritaprevir/ritonavir for hepatitis C virus in clinical practice: A population-based observational study.

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Maya Leventer-Roberts

Full Text Available Direct acting antivirals for hepatitis C virus have shown dramatic results in clinical trials. However, their effectiveness has yet to be demonstrated within observational cohorts which lack exclusion criteria found in randomized control trials.To determine the effectiveness of dasabuvir/ombitasvir/paritaprevir/ritonavir in achieving sustained virological response.Retrospective observational cohort study of all Clalit Health Services members with hepatitis C virus genotype 1 who were dispensed dasabuvir/ombitasvir/paritaprevir/ritonavir from January 1, 2015 to-November 31, 2015.There were 564 participants during the study period. The average age was 61.9 years, 52.0% were male, and 61.5% were born Eastern/Central Europe or Central Asia. The prevalence of diabetes was 31.7% and 70.3% were overweight/obese. Cirrhosis was present in 41.0% of participants, of whom 52.8% had stage 4 fibrosis. Of the cohort, 416 (74.8% had follow-up viral load testing at 10 or more weeks after the end of treatment. We report a sustained virological response of 98.8% among those tested.Treatment with dasabuvir/ombitasvir/paritaprevir/ritonavir demonstrated a near universal effectiveness in achieving a sustained virological response among HCV patients in a large cohort.

Iatrogenic Cushing syndrome in patients receiving inhaled budesonide and itraconazole or ritonavir: two cases and literature review.

Science.gov (United States)

Blondin, Marie-Christine; Beauregard, Hugues; Serri, Omar

2013-01-01

To present two cases of iatrogenic Cushing syndrome caused by the interaction of budesonide, an inhaled glucocorticoid, with ritonavir and itraconazole. We present the clinical and biochemical data of two patients in whom diagnosis of Cushing syndrome was caused by this interaction. We also reviewed the pertinent literature and management options. A 71-year-old man was treated with inhaled budesonide for a chronic obstructive pulmonary disease and itraconazole for a pulmonary aspergillosis. The patient rapidly developed a typical Cushing syndrome complicated by bilateral avascular necrosis of the femoral heads. Serum 8:00 AM cortisol concentrations were suppressed at 0.76 and 0.83 μg/dL on two occasions. The patient died 4 days later of a massive myocardial infarction. The second case is a 46-year-old woman who was treated for several years with inhaled budesonide for asthma. She was put on ritonavir, a retroviral protease inhibitor, for the treatment of human immunodeficiency virus (HIV). In the following months, she developed typical signs of Cushing syndrome. Her morning serum cortisol concentration was 1.92 μg/dL. A cosyntropin stimulation test showed values of serum cortisol of Cushing syndrome and secondary adrenal insufficiency due to the association of inhaled corticosteroids with itraconazole or ritonavir.

The clinical effect of deferoxamine mesylate on edema after intracerebral hemorrhage.

Science.gov (United States)

Yu, Yao; Zhao, Wei; Zhu, Chunpeng; Kong, Zhiping; Xu, Yan; Liu, Guangzhi; Gao, Xuguang

2015-01-01

It has been shown that 3 days of 62 mg/kg/day deferoxamine infusion (maximum dose not to exceed 6000 mg/day) is safe and tolerated by intracerebral hemorrhage (ICH) patients. The aim of this study was to investigate the efficacy of deferoxamine mesylate for edema resolution and hematoma absorption after ICH. From February 2013 to May 2014, spontaneous ICH patients diagnosed by computed tomography (CT) within 18 hours of onset were evaluated. Patients were randomly divided into two groups: an experimental group and a control group. The treatment of the two groups was similar except that the experimental group received deferoxamine mesylate. Patients were evaluated by CT and neurology scale at the time of admission, and on the fourth, eighth, and fifteenth day (or at discharge) after admission. Patients were followed up for the first 30 days and clinical data of the two groups were compared. Forty-two patients completed 30 days of follow-up by May 2014; 21 cases in the experimental group and 21 cases in the control group. The control group's relative edema volume on the fifteenth day (or discharge) was 10.26 ± 17.54, which was higher than the experimental group (1.91 ± 1.94; P edema volume on the fourth, eighth, and fifteenth day (or discharge) was higher than the experimental group (P edema after ICH, although further investigation is required to form definitive conclusions. Chinese Clinical Trial Registry ChiCTR-TRC-14004979.

Drug Interactions Between Hepatoprotective Agents Ursodeoxycholic Acid or Glycyrrhizin and Ombitasvir/Paritaprevir/Ritonavir in Healthy Japanese Subjects.

Science.gov (United States)

Zha, Jiuhong; Badri, Prajakta S; Ding, Bifeng; Uchiyama, Naotaka; Alves, Katia; Rodrigues, Lino; Redman, Rebecca; Dutta, Sandeep; Menon, Rajeev M

2015-11-01

The 2 direct-acting antiviral combination (2D) of ombitasvir and paritaprevir (coadministered with ritonavir) is being evaluated for the treatment of chronic hepatitis C virus infection in Japan. Ursodeoxycholic acid (UDCA) and glycyrrhizin (GCR) are hepatoprotective agents widely used in Japan. A drug-drug interaction (DDI) study was conducted to guide dosing recommendations for UDCA and GCR when coadministered with the 2D regimen. DDIs between the 2D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg orally once daily) and UDCA (50 mg orally 3 times daily) or GCR (80 mg intravenously once daily) were evaluated in a 2-arm, multiple-dose study in 24 Japanese healthy subjects under fed conditions. Pharmacokinetic and safety evaluations were performed when UDCA or GCR and the 2D regimen were administered alone and during coadministration. Exposures from coadministration of the 2D regimen plus UDCA or GCR versus the 2D regimen, UDCA, or GCR alone were compared using repeated-measures analyses of natural logarithms of the maximum plasma concentration (Cmax) and area under the curve (AUC). After coadministration of the 2D regimen and UDCA, steady-state exposures (Cmax and AUC) of ombitasvir, paritaprevir, and ritonavir showed a ≤9% change, and UDCA exposures showed a ≤20% change compared with administration alone. When the 2D regimen and GCR were coadministered, steady-state exposures of ombitasvir, paritaprevir, and ritonavir were not affected (≤9% change), GCR AUC increased by 49%, and GCR Cmax was unaffected (<1% change). No dose adjustment is needed for UDCA, GCR, or the 2D regimen when UDCA or GCR is coadministered with the 2D regimen in hepatitis C virus-infected patients under fed conditions. Clinical monitoring of patients using GCR is recommended due to an approximately 50% increase in GCR AUC when coadministered with the 2D regimen. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Contribution of different antiretroviral regimens containing zidovudine, lamivudine and ritonavir-boosted lopinavir on HIV viral load reduction during pregnancy.

Science.gov (United States)

Sripan, Patumrat; Le Coeur, Sophie; Ingsrisawang, Lily; Cressey, Tim R; Bouazza, Naïm; Foissac, Frantz; Ngo-Giang-Huong, Nicole; Traisathit, Patrinee; Srirompotong, Ussanee; Ayudhaya, Orada Patamasingh Na; Puangsombat, Achara; Jungpipun, Jantana; Jittayanun, Kanokwan; Tréluyer, Jean-Marc; Jourdain, Gonzague; Lallemant, Marc; Urien, Saïk

2016-01-01

Antiretroviral (ARV) regimens used for the prevention of mother-to-child transmission of HIV have evolved over time. We evaluated the contribution of different ARV regimens on the reduction of the plasma HIV RNA viral load (VL) during pregnancy. A total of 1,833 VL measurements from ARV-naive pregnant women participating in perinatal prevention trials in Thailand were included. Women received either zidovudine (ZDV) monotherapy, ZDV plus lopinavir/ritonavir (LPV/r), or ZDV plus lamivudine (3TC) plus LPV/r. VL time-course during pregnancy was described as a function of pretreatment VL and treatment duration using an Emax non-linear mixed-effect model. VL reduction and median time to achieve a VL<50 copies/ml were estimated for each regimen. Among 745 women, 279 (37%), 145 (20%) and 321 (43%) received ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. The predicted VL reduction from baseline to delivery after a median of 10 weeks of treatment were 0.5, 2.7 and 2.9 log10 copies/ml with ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. At delivery, 1%, 57% and 63% of women receiving ZDV monotherapy, ZDV+LPV/r or ZDV+3TC+LPV/r had a VL<50 copies/ml. The addition of 3TC to ZDV+LPV/r reduced the time to achieve a VL<50 copies/ml and the higher the pretreatment VL, the larger the effect 3TC had on reducing the time to VL<50 copies/ml. The addition of 3TC to ZDV+LPV/r was associated with a slight further VL reduction but the time to reach a VL<50 copies/ml was shorter. This beneficial effect of 3TC is crucial for prevention of mother-to-child transmission in women who receive ARVs late and with high pretreatment VL.

Continued indinavir versus switching to indinavir/ritonavir in HIV-infected patients with suppressed viral load.

NARCIS (Netherlands)

Arnaiz, J.A.; Mallolas, J.; Podzamczer, D.; Gerstoft, J.; Lundgren, J.D.; Cahn, P.; Fatkenheuer, G.; D'Arminio-Monforte, A.; Casiro, A.; Reiss, P.; Burger, D.M.; Stek Jr, M.; Gatell, J.M.

2003-01-01

OBJECTIVE: To compare continued indinavir (IDV) 8-hourly (q8h) with switching to indinavir/ritonavir (IDV/RTV) 12-hourly (q12h) in HIV-positive patients having suppressed viral load with IDV q8h plus two nucleoside reverse transcriptase inhibitors (NRTI). DESIGN: Multicentre, international,

Continued indinavir versus switching to indinavir/ritonavir in HIV-infected patients with suppressed viral load

NARCIS (Netherlands)

Arnaiz, Juan A.; Mallolas, Josep; Podzamczer, Daniel; Gerstoft, Jan; Lundgren, Jens D.; Cahn, Pedro; Fätkenheuer, Gerd; D'Arminio-Monforte, Antonella; Casiró, Arnaldo; Reiss, Peter; Burger, David M.; Stek, Michael; Gatell, José M.

2003-01-01

Objective: To compare continued indinavir (IDV) 8-hourly (q8h) with switching to indinavir/ritonavir (IDV/RTV) 12-hourly (q12h) in HIV-positive patients having suppressed viral load with IDV q8h plus two nucleoside reverse transcriptase inhibitors (NRTI). Design: Multicentre, international,

Pharmacokinetics and 48-week safety and efficacy of generic lopinavir/ritonavir in Thai HIV-infected patients

NARCIS (Netherlands)

Ramautarsing, Reshmie A.; van der Lugt, Jasper; Gorowara, Meena; Sophonphan, Jiratchaya; Ananworanich, Jintanat; Lange, Joep M. A.; Burger, David M.; Phanuphak, Praphan; Ruxthungtham, Kiat; Avihingsanon, Anchalee

2013-01-01

Background: Generic products reduce the costs of HIV treatment. Few generic second-line antiretroviral products are available. We assessed pharmacokinetics, safety and efficacy of generic lopinavir/ritonavir (LPV/r) produced by the Government Pharmaceutical Organization (GPO) of Thailand in Thai

[Lopinavir/ritonavir in patients with human immunodeficiency virus infection in special situations].

Science.gov (United States)

Tasias, María; Aldeguer, José López

2014-11-01

Ritonavir-boosted lopinavir (LPV/r) is a protease inhibitor used for the treatment of human immunodeficiency virus (HIV) infection in both normal patients and in certain situations. In patients with renal failure, LPV/r does not require dosage adjustment because it is metabolized in the liver. Cohort studies have shown that the incidence of varying degrees of renal disease and/or crystalluria related to combination antiretroviral therapy with tenofovir and some protease inhibitors (PI) does not appear with LPV/r or that the incidence is much lower with this combination. Neurocognitive impairments are described in a high proportion of patients with HIV infection and viral replication or related inflammatory activity in the subarachnoid space. In these patients, LPV/r is one of the therapeutic options. A score has been published that rates antiretroviral drugs according to the concentration attained in the cerebrospinal fluid (CSF). LPV/r levels reached in CSF exceed the IC50 of wild-type HIV and has a valuable score (score 3) of the drugs currently used. The most important comorbid condition is chronic hepatitis, due to its frequency and because the biotransformation of LPV/r occurs in the liver. In these circumstances, it is important to evaluate the influence of liver failure on blood drug levels and how these values may cause liver toxicity. LPV/r dose modification has not been established in the presence of liver failure. LPV/r-induced liver toxicity has only been reported with a certain frequency when liver enzymes were elevated at baseline or in patients with chronic hepatitis C, although most cases of liver toxicity were mild. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

In vitro profiling of the vaginal permeation potential of anti-HIV microbicides and the influence of formulation excipients.

Science.gov (United States)

Grammen, Carolien; Augustijns, Patrick; Brouwers, Joachim

2012-11-01

In the search for an effective anti-HIV microbicidal gel, limited drug penetration into the vaginal submucosa is a possible reason for failed protection against HIV transmission. To address this issue in early development, we here describe a simple in vitro strategy to predict the tissue permeation potential of vaginally applied drugs, based on solubility, permeability and flux assessment. We demonstrated this approach for four model microbicides (tenofovir, darunavir, saquinavir mesylate and dapivirine) and additionally examined the influence of formulation excipients on the permeation potential. When formulated in an aqueous-based HEC gel, high flux values across an HEC-1A cell layer were reached by tenofovir, as a result of its high aqueous solubility. In contrast, saquinavir and dapivirine fluxes remained low due to poor permeability and solubility, respectively. These low fluxes suggest limited in vivo tissue penetration, possibly leading to lack of efficacy. Dapivirine fluxes, however, could be enhanced up to 30-fold, by including formulation excipients such as polyethylene glycol 1000 (20%) or cyclodextrins (5%) in the HEC gels. Alternative formulations, i.e. emulsions or silicone elastomer gels, were less effective in flux enhancement compared to cyclodextrin-HEC gels. In conclusion, implementing the proposed solubility and permeability profiling in early microbicide development may contribute to the successful selection of promising microbicide candidates and appropriate formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

Resistance profiles and adherence at primary virological failure in three different highly active antiretroviral therapy regimens: analysis of failure rates in a randomized study

DEFF Research Database (Denmark)

Røge, B T; Barfod, T S; Kirk, O

2004-01-01

OBJECTIVES: To investigate the interplay between resistance and adherence in the virological failure of three fundamentally different highly active antiretroviral therapy (HAART) regimens. METHODS: We retrospectively identified 56 verified primary virological failures (viral load >400 HIV-1 RNA...... copies/mL) among 293 patients randomized to two nucleoside reverse transcriptase inhibitors (NRTIs)+ritonavir+saquinavir (RS-arm) (n=115), two NRTIs+nevirapine+nelfinavir (NN-arm) (n=118), or abacavir+stavudine+didanosine (ASD-arm) (n=60) followed up for a median of 90 weeks. Data on adherence were...... collected from patient files, and genotyping was performed on plasma samples collected at time of failure. RESULTS: Treatment interruption or poor adherence was mainly caused by side effects and accounted for 74% of failures, and was associated with absence of resistance mutations. In the 30 failing...

Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretrovirals.

Science.gov (United States)

McCormack, Shelley A; Best, Brookie M

2014-11-01

Maternal-to-fetal transfer of antiretroviral drugs contributes to prevention of vertical transmission of HIV. This systematic review discusses published studies containing data pertaining to the pharmacokinetics of placental transfer of antiretrovirals in humans, including paired cord and maternal plasma samples collected at the time of delivery as well as ex vivo placental perfusion models. Articles pertaining to placental transfer of antiretrovirals were identified from PubMed, from references of included articles, and from US Department of Health and Human Services Panel on Treatment of HIV-infected Pregnant Women and Prevention of Perinatal Transmission guidelines. Articles from non-human animal models or that had no original maternal-to-fetal transfer data were excluded. PRISMA guidelines were followed. A total of 103 published studies were identified. Data across studies appeared relatively consistent for the nucleoside reverse transcriptase inhibitors (NRTIs) and the non-nucleotide reverse transcriptase inhibitors (NNRTIs), with cord to maternal ratios approaching 1 for many of these agents. The protease inhibitors atazanavir and lopinavir exhibited consistent maternal-to-fetal transfer across studies, although the transfer may be influenced by variations in drug-binding proteins. The protease inhibitors indinavir, nelfinavir, and saquinavir exhibited unreliable placental transport, with cord blood concentrations that were frequently undetectable. Limited data, primarily from case reports, indicate that darunavir and raltegravir provide detectable placental transfer. These findings appear consistent with current guidelines of using two NRTIs plus an NNRTI, atazanavir/ritonavir, or lopinavir/ritonavir to maximize placental transfer as well as to optimally suppress maternal viral load. Darunavir/ritonavir and raltegravir may reasonably serve as second-line agents.

A Hepatitis C Virus-Associated Cirrhotic Patient Developing Interstitial Pneumonia during the Course of Antiviral Therapy with Ombitasvir/Paritaprevir/Ritonavir

Directory of Open Access Journals (Sweden)

Kazuo Tarao

2017-06-01

Full Text Available Oral direct-acting antivirals (DAAs are the main therapy for hepatitis C virus (HCV-associated liver disease in Japan. Daclatasvir/asunaprevir is the first agent and sofosbuvir/ledipasvir is the secondary agent for HCV genotype 1b. More recently, ombitasvir/paritaprevir/ritonavir is also recommended as a potent therapy for HCV genotype 1b. Among the adverse events associated with these oral DAAs, interstitial pneumonia is one of the most severe ones. Regarding treatment with daclatasvir plus asunaprevir or sofosbuvir plus ledipasvir, a few cases have already been reported in a postmarketing surveillance. Recently, we have encountered a HCV-associated genotype 1b cirrhosis patient who developed interstitial pneumonia during treatment with ombitasvir/paritaprevir/ritonavir and who recovered after drug discontinuation without corticosteroid therapy. Interstitial pneumonia was confirmed by chest x-ray and chest computed tomography. The serum KL-6 level was elevated to 1,180 U/mL. The total duration of the drug administration was 7 weeks, and she achieved SVR24. This is the first detailed report in the literature on the development of interstitial pneumonia during treatment with ombitasvir/paritaprevir/ritonavir. When dry cough appeared in the treatment with DAAs, chest computed tomography and the evaluation of serum KL-6 level were recommended.

Exposure-Response Relationship for Ombitasvir and Paritaprevir/Ritonavir in Hepatitis C Virus Subgenotype 1b-Infected Japanese Patients in the Phase 3 Randomized GIFT-I Study.

Science.gov (United States)

Gopalakrishnan, Sathej; Khatri, Amit; Mensing, Sven; Redman, Rebecca; Menon, Rajeev; Zha, Jiuhong

2016-04-01

The all-oral 2 direct-acting antiviral (DAA) regimen of ombitasvir/paritaprevir/ritonavir 25/150/100 mg once a day has been evaluated in hepatitis C virus subgenotype 1b-infected Japanese adults in the GIFT-I study. The aim of this analysis was to evaluate potential relationships between DAA exposures and laboratory abnormalities/adverse events of peripheral edema in patients in GIFT-I. The GIFT-I study consisted of a randomized, double-blind, placebo-controlled substudy in patients without cirrhosis and an open-label substudy in patients with compensated cirrhosis. Patients received ombitasvir/paritaprevir/ritonavir for 12 weeks. Exposure-response relationships between individual components of the ombitasvir/paritaprevir/ritonavir regimen and clinical parameters of interest were explored using pharmacokinetic and clinical data from patients in the study. Graphical analyses were performed. For events that occurred in at least 10 patients (total bilirubin elevation ≥grade 2 and peripheral edema ≥grade 1), multivariate logistic regression analyses were used to identify significant relationships between predictor variables (drug exposures) and response variables (probability of adverse events or laboratory abnormalities), with consideration for the effect of potential covariates and baseline status of response variables. Data from 321 noncirrhotic and 42 compensated cirrhotic patients were analyzed. There were 14 events of peripheral edema (10 at grade 1 and 4 at grade 2) in patients who received concomitant administration of calcium channel blockers and ombitasvir/paritaprevir/ritonavir. There was no apparent relationship between the incidences of peripheral edema and exposures of paritaprevir, ombitasvir, or ritonavir. There was a shallow relationship between total bilirubin elevation and exposures of paritaprevir which is an inhibitor of bilirubin transporter organic anion-transporting polypeptide 1B. Based on graphical analyses, exposures of paritaprevir

Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial.

Science.gov (United States)

Pulido, Federico; Ribera, Esteban; Lagarde, María; Pérez-Valero, Ignacio; Palacios, Rosario; Iribarren, José A; Payeras, Antoni; Domingo, Pere; Sanz, José; Cervero, Miguel; Curran, Adrián; Rodríguez-Gómez, Francisco J; Téllez, María J; Ryan, Pablo; Barrufet, Pilar; Knobel, Hernando; Rivero, Antonio; Alejos, Belén; Yllescas, María; Arribas, José R

2017-11-29

Our objective was to assess the therapeutic noninferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus 2 nucleos(t)ides for maintenance of human immunodeficiency virus type 1 (HIV-1) suppression. This was a multicenter, open-label, noninferiority trial (margin 12%). Patients with HIV-1 RNA dual- and triple-therapy arms was 88.9% (112/126) and 92.7% (114/123; difference, -3.8%; 95% confidence interval, -11.0 to 3.4), respectively. Four participants in the dual-therapy arm and 2 in the triple-therapy arm developed protocol-defined virological failure. Switching to dual therapy was associated with a significant increase in total, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol, but not in the total-to-HDL cholesterol ratio. Serious adverse events and study drug discontinuations due to adverse events occurred in 4.8% vs 4.9%P = .97) and in 0.8% (1/126) vs 1.6% P = .55) in dual therapy vs triple therapy, respectively. Dual therapy with darunavir/ritonavir and lamivudine demonstrated noninferior therapeutic efficacy and similar tolerability compared to triple therapy. NCT02159599. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial

DEFF Research Database (Denmark)

Grunberg, Steven M; Rolski, Janusz; Strausz, Janos

2009-01-01

in the control group. The most common serious adverse events were neutropenia (n=5 [3%] in the control group, n=3 [1%] in the single-dose oral casopitant mesylate group, and n=11 [4%] in the 3-day intravenous plus oral casopitant mesylate group), febrile neutropenia (n=1 [

Pharmacokinetics of pediatric lopinavir/ritonavir tablets in children when administered twice daily according to FDA weight bands

NARCIS (Netherlands)

Bastiaans, D.E.T.; Forcat, S.; Lyall, H.; Cressey, T.R.; Hansudewechakul, R.; Kanjanavanit, S.; Noguera-Julian, A.; Konigs, C.; Inshaw, J.R.; Chalermpantmetagul, S.; Saidi, Y.; Compagnucci, A.; Harper, L.M.; Giaquinto, C.; Colbers, A.P.; Burger, D.M.

2014-01-01

BACKGROUND: Lopinavir/ritonavir (LPV/r) pediatric tablets (100/25 mg) are approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) as part of combination antiretroviral therapy. Dosing is based on body weight bands or body surface area under FDA approval

Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein

International Nuclear Information System (INIS)

Sohn, Eun Jeong; Kim, Dae Won; Kim, Young Nam; Kim, So Mi; Lim, Soon Sung; Kang, Tae-Cheon; Kwon, Hyeok Yil; Kim, Duk-Soo; Cho, Sung-Woo; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Hwang, Hyun Sook; Choi, Soo Young

2011-01-01

Research highlights: → We studied effects of pergolide mesylate (PM) on in vitro and in vivo transduction of PEP-1-catalase. → PEP-1-catatase inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. → PM enhanced the transduction of PEP-1-catalase into HaCaT cells and skin tissue. → PM increased anti-inflammatory activity of PEP-1-catalase. → PM stimulated therapeutic action of anti-oxidant enzyme catalase in oxidative-related diseases. -- Abstract: The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1β, and tumor necrosis factor-α induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.

Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein

Energy Technology Data Exchange (ETDEWEB)

Sohn, Eun Jeong; Kim, Dae Won; Kim, Young Nam; Kim, So Mi [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Lim, Soon Sung [Department of Food Science and Nutrition and RIC Center, Hallym University, Chunchon 200-702 (Korea, Republic of); Kang, Tae-Cheon [Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Kwon, Hyeok Yil [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Kim, Duk-Soo [Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Hwang, Hyun Sook, E-mail: wazzup@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

2011-03-18

Research highlights: {yields} We studied effects of pergolide mesylate (PM) on in vitro and in vivo transduction of PEP-1-catalase. {yields} PEP-1-catatase inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. {yields} PM enhanced the transduction of PEP-1-catalase into HaCaT cells and skin tissue. {yields} PM increased anti-inflammatory activity of PEP-1-catalase. {yields} PM stimulated therapeutic action of anti-oxidant enzyme catalase in oxidative-related diseases. -- Abstract: The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1{beta}, and tumor necrosis factor-{alpha} induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.

Ritonavir and Topical Ocular Corticosteroid Induced Cushing's Syndrome in an Adolescent With HIV-1 Infection.

Science.gov (United States)

Rainsbury, Paul G; Sharp, Jessica; Tappin, Alison; Hussey, Martin; Lenko, Alexandra; Foster, Caroline

2017-05-01

Cushing's syndrome after topical ocular corticosteroid use is extremely rare. We describe a case of symptomatic Cushing's syndrome in an adolescent male with sight-threatening vernal keratoconjunctivitis on antiretroviral therapy for HIV-1 infection that included ritonavir, a potent cytochrome p450 CYP3A4 inhibitor. CYP3A4 inhibition reduces the metabolism of exogenous corticosteroids leading to suppression of endogenous steroid production and Cushing's syndrome.

The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs

Directory of Open Access Journals (Sweden)

Russell Barrett Van Dyke

2016-05-01

Full Text Available The Surveillance Monitoring for ART Toxicities (SMARTT cohort of the Pediatric HIV/AIDS Cohort Study (PHACS includes over 3500 HIV-exposed but uninfected (HEU infants and children at 22 sites in the U.S. including Puerto Rico. The goal of the study is to determine the safety of in utero exposure to antiretrovirals (ARV and to estimate the incidence of adverse events. Domains being assessed include metabolic, growth and development, cardiac, neurological, neurodevelopmental, behavior, language, and hearing. SMARTT employs an innovative trigger-based design as an efficient means to identify and evaluate adverse events. Participants who met a predefined clinical or laboratory threshold (trigger undergo additional evaluations to define their case status. After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain with exposure to combination ARVs (cARV, any ARV class, or any specific ARV. However, several individual ARVs were significantly associated with case status in individual domains, including zidovudine for a metabolic case, first trimester stavudine for a language case, and didanosine plus stavudine for a neurodevelopmental case. We found an increased rate of preterm birth with first trimester exposure to protease inhibitor-based cARV. Although there was no overall increase in congenital anomalies with first trimester cARV, a significant increase was seen with exposure to atazanavir, ritonavir, and didanosine plus stavudine. Tenofovir exposure was associated with significantly lower mean whole-body bone mineral content in the newborn period and a lower length and head circumference at 1 year of age. With neurodevelopmental testing at 1 year of age, specific ARVs (atazanavir, ritonavir-boosted lopinavir, nelfinavir, and tenofovir were associated with lower performance, although all groups were within the normal range. No ARVs or classes were

Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function

DEFF Research Database (Denmark)

Nielsen, Lene Ryom; Mocroft, A.; Kirk, O.

2013-01-01

Background. Several antiretroviral agents (ARVs) are associated with chronic renal impairment, but the extent of such adverse events among human immunodeficiency virus (HIV)-positive persons with initially normal renal function is unknown.Methods. D:A:D study participants with an estimated...... glomerular filtration rate (eGFR) of ≥90 mL/min after 1 January 2004 were followed until they had a confirmed eGFR of ≤70 mL/min (the threshold below which we hypothesized that renal interventions may begin to occur) or ≤60 mL/min (a value indicative of moderately severe chronic kidney disease [CKD...... [95% CI, 1.16-1.28], respectively). Associations were unaffected by censoring for concomitant ARV use but diminished after discontinuation of these ARVs.Conclusions. Tenofovir, ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir use were independent predictors of chronic renal impairment...

Cardiovascular disease and use of contemporary protease inhibitors

DEFF Research Database (Denmark)

Ryom, Lene; Lundgren, Jens D; El-Sadr, Wafaa

2018-01-01

BACKGROUND: Although earlier protease inhibitors have been associated with increased risk of cardiovascular disease, whether this increased risk also applies to more contemporary protease inhibitors is unknown. We aimed to assess whether cumulative use of ritonavir-boosted atazanavir and ritonavir......-boosted darunavir were associated with increased incidence of cardiovascular disease in people living with HIV. METHODS: The prospective Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study consists of people living with HIV-1 from 11 cohorts in Australia, Europe, and the USA. Participants were...... monitored from Jan 1, 2009, until the earliest of a cardiovascular event, 6 months after the last visit, or until Feb 1, 2016. The outcome of interest was the incidence of cardiovascular disease in adults (aged ≥16 years) living with HIV who were being treated with contemporary treatments. We defined...

The influence of the boost in breast-conserving therapy on cosmetic outcome in the EORTC 'boost versus no boost' trial

International Nuclear Information System (INIS)

Vrieling, Conny; Collette, Laurence; Fourquet, Alain; Hoogenraad, Willem J.; Horiot, Jean-Claude; Jager, Jos J.; Pierart, Marianne; Poortmans, Philip M.; Struikmans, Henk; Hulst, Marleen van der; Schueren, Emmanuel van der; Bartelink, Harry

1999-01-01

Purpose: To evaluate the influence of a radiotherapy boost on the cosmetic outcome after 3 years of follow-up in patients treated with breast-conserving therapy (BCT). Methods and Materials: In EORTC trial 22881/10882, 5569 Stage I and II breast cancer patients were treated with tumorectomy and axillary dissection, followed by tangential irradiation of the breast to a dose of 50 Gy in 5 weeks, at 2 Gy per fraction. Patients having a microscopically complete tumor excision were randomized between no boost and a boost of 16 Gy. The cosmetic outcome was evaluated by a panel, scoring photographs of 731 patients taken soon after surgery and 3 years later, and by digitizer measurements, measuring the displacement of the nipple of 3000 patients postoperatively and of 1141 patients 3 years later. Results: There was no difference in the cosmetic outcome between the two treatment arms after surgery, before the start of radiotherapy. At 3-year follow-up, both the panel evaluation and the digitizer measurements showed that the boost had a significant adverse effect on the cosmetic result. The panel evaluation at 3 years showed that 86% of patients in the no-boost group had an excellent or good global result, compared to 71% of patients in the boost group (p = 0.0001). The digitizer measurements at 3 years showed a relative breast retraction assessment (pBRA) of 7.6 pBRA in the no-boost group, compared to 8.3 pBRA in the boost group, indicating a worse cosmetic result in the boost group at follow-up (p = 0.04). Conclusions: These results showed that a boost dose of 16 Gy had a negative, but limited, impact on the cosmetic outcome after 3 years

Chronic Kidney Disease and Antiretroviral Therapy in HIV-Positive Individuals

DEFF Research Database (Denmark)

Achhra, Amit C; Nugent, Melinda; Mocroft, Amanda

2016-01-01

Chronic kidney disease (CKD) has emerged as an important health concern in HIV-positive individuals. Preventing long-term kidney toxicity from an antiretroviral therapy is therefore critical. Selected antiretroviral agents, especially tenofovir disoproxil fumarate (TDF) and some ritonavir-boosted...

Managing Drug-Drug Interaction Between Ombitasvir, Paritaprevir/Ritonavir, Dasabuvir, and Mycophenolate Mofetil.

Science.gov (United States)

Lemaitre, Florian; Ben Ali, Zeineb; Tron, Camille; Jezequel, Caroline; Boglione-Kerrien, Christelle; Verdier, Marie-Clémence; Guyader, Dominique; Bellissant, Eric

2017-08-01

No drug-drug interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of drug-drug interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D.

Efficacy and safety of atazanavir/ritonavir-based antiretroviral therapy for HIV-1 infected subjects: a systematic review and meta-analysis.

Science.gov (United States)

Menshawy, Amr; Ismail, Ammar; Abushouk, Abdelrahman Ibrahim; Ahmed, Hussien; Menshawy, Esraa; Elmaraezy, Ahmed; Gadelkarim, Mohamed; Abdel-Maboud, Mohamed; Attia, Attia; Negida, Ahmed

2017-08-01

Atazanavir (ATZ) is a well-tolerated protease inhibitor that can be boosted with ritonavir (r) to treat infection with resistant strains of human immunodeficiency virus 1 (HIV-1). The aim of this meta-analysis was to compare the efficacy, safety, and metabolic effects of ATZ/r regimen versus commonly used antiretroviral drugs such as lopinavir (LPV) and darunavir (DRV) in HIV-1-infected patients. We searched PubMed, Scopus, Embase and Cochrane CENTRAL, using relevant keywords. Data were extracted from eligible randomized trials and pooled as risk ratios (RR) or standardized mean differences (SMD) in a meta-analysis model using RevMan software. Nine randomized controlled trials (RCTs) (3292 patients) were eligible for the final analysis. After 96 weeks of treatment, the pooled effect estimate did not favor either ATZ/r or LPV/r in terms of virological failure rate (RR 1.11, 95% CI [0.74, 1.66]). However, ATZ/r was marginally superior to LPV/r in terms of increasing the proportion of patients with HIV RNA SMD -0.06, 95%CI [-0.33, 0.21]) or subcutaneous adipose tissue (SMD 0.12, 95% CI [-0.15, 0.39]). The ATZ/r regimen was generally as effective and well-tolerated as the LPV/r regimen for the treatment of HIV-1 patients. Compared to the DRV/r regimen, ATZ/r has no favorable effect on the plasma lipid profile or adipose tissue distribution.

LDA boost classification: boosting by topics

Science.gov (United States)

Lei, La; Qiao, Guo; Qimin, Cao; Qitao, Li

2012-12-01

AdaBoost is an efficacious classification algorithm especially in text categorization (TC) tasks. The methodology of setting up a classifier committee and voting on the documents for classification can achieve high categorization precision. However, traditional Vector Space Model can easily lead to the curse of dimensionality and feature sparsity problems; so it affects classification performance seriously. This article proposed a novel classification algorithm called LDABoost based on boosting ideology which uses Latent Dirichlet Allocation (LDA) to modeling the feature space. Instead of using words or phrase, LDABoost use latent topics as the features. In this way, the feature dimension is significantly reduced. Improved Naïve Bayes (NB) is designed as the weaker classifier which keeps the efficiency advantage of classic NB algorithm and has higher precision. Moreover, a two-stage iterative weighted method called Cute Integration in this article is proposed for improving the accuracy by integrating weak classifiers into strong classifier in a more rational way. Mutual Information is used as metrics of weights allocation. The voting information and the categorization decision made by basis classifiers are fully utilized for generating the strong classifier. Experimental results reveals LDABoost making categorization in a low-dimensional space, it has higher accuracy than traditional AdaBoost algorithms and many other classic classification algorithms. Moreover, its runtime consumption is lower than different versions of AdaBoost, TC algorithms based on support vector machine and Neural Networks.

Boost.Unicode

OpenAIRE

Wien, Erik; Gigstad, Lars Erik

2005-01-01

The project has resulted in a Unicode string library for C++ that abstracts away the complexity of working with Unicode text. The idea behind the project originated from the Boost community's developer mailings lists, and is developed with inclusion into the Boost library collection in mind.

What to Start: Selecting a First HIV Regimen

Science.gov (United States)

... CCR5 antagonists Integrase strand transfer inhibitors (INSTIs) Post-attachment inhibitors In general, a person's first HIV regimen includes two NRTIs plus an INSTI, an NNRTI, or a PI boosted with cobicistat (brand name: Tybost) or ritonavir (brand name: Norvir). Cobicistat ...

A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection

NARCIS (Netherlands)

Dybul, M; Nies-Kraske, E; Dewar, R; Maldarelli, F; Hallahan, CW; Daucher, M; Piscitelli, SC; Ehler, L; Weigand, A; Palmer, S; Metcalf, JA; Davey, RT; Kress, DMR; Powers, A; Beck, [No Value; Frenkel, L; Baseler, M; Coffin, J; Fauci, AS

2004-01-01

Background. We previously demonstrated that short-cycle structured intermittent therapy ( SIT; 7 days without therapy followed by 7 days with antiretroviral therapy [ART]) with a ritonavir-boosted, indinavir-based, twice-daily regimen maintained suppression of plasma HIV viremia while reducing serum

The simultaneous boost technique

International Nuclear Information System (INIS)

Lebesque, J.V.; Keus, R.B.

1991-01-01

Simultaneous boost technique in radiotherapy consists of delivering the boost treatment (additional doses to reduced volumes) simultaneously with the basic (large-field) treatment for all treatment sessions. Both the dose per fraction delivered by basic-treatment fields and by boost-treatment fields have to be reduced to end up with the same total dose in boost volume as in the original schedule, where basic treatment preceded boost treatment. These dose reductions and corresponding weighting factors have been calculated using the linear-quadratic (LQ) model and the concept of Normalized Total Dose (NTD). Relative NTD distributions were computed to evaluate the dose distributions resulting for the simultaneous boost technique with respect to acute and late normal tissue damage and tumor control. For the example of treatment of prostate cancer the weighting factors were calculated on basis of NTD for late normal tissue damage. For treatment of oropharyngeal cancer NTD for acute and normal tissue damage was used to determine the weighting factors. In this last example a theoretical sparing of late normal tissue damage can be demonstrated. Another advantage of simultaneous boost technique is that megavoltage images of the large basic-treatment fields facilitates the determination of the position of the patient with respect to the small boost-treatment fields. (author). 42 refs., 8 figs

Effects of resveratrol on P-glycoprotein and cytochrome P450 3A in vitro and on pharmacokinetics of oral saquinavir in rats

Directory of Open Access Journals (Sweden)

Li JP

2016-11-01

Full Text Available Jiapeng Li,1,2 Yang Liu,2 Jingru Zhang,1,2 Xiaotong Yu,1,2 Xiaoling Wang,1 Libo Zhao11Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, 2Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China Background: The intestinal cytochrome P450 3A (CYP 3A and P-glycoprotein (P-gp present a barrier to the oral absorption of saquinavir (SQV. Resveratrol (RESV has been indicated to have modulatory effects on P-gp and CYP 3A. Therefore, this study was to investigate the effects of RESV on P-gp and CYP 3A activities in vitro and in vivo on oral SQV pharmacokinetics in rats.Methods: In vitro, intestinal microsomes were used to evaluate RESV effect on CYP 3A-mediated metabolism of SQV; MDR1-expressing Madin–Darby canine kidney (MDCKII-MDR1 cells were employed to assess the impact of RESV on P-gp-mediated efflux of SQV. In vivo effects were studied using 10 rats randomly assigned to receive oral SQV (30 mg/kg with or without RESV (20 mg/kg. Serial blood samples were obtained over the following 24 h. Concentrations of SQV in samples were ascertained using high-performance liquid chromatography-tandem mass spectrometry analysis.Results: RESV (1–100 µM enhanced residual SQV (% of control in a dose-dependent manner after incubation with intestinal microsomes. RESV (1–100 µM reduced the accumulation of SQV in MDCKII-MDR1 cells in a concentration-dependent manner. A double peaking phenomenon was observed in the plasma SQV profiles in rats. The first peak of plasma SQV concentration was increased, but the second peak was reduced by coadministration with RESV. The mean AUC0–∞ of SQV was slightly decreased, with no statistical significance probably due to the high individual variation.Conclusion: RESV can alter the plasma SQV concentration profiles, shorten the Tmax of SQV. RESV might also cause a slight decrease tendency in the

Boost.Asio C++ network programming

CERN Document Server

Torjo, John

2013-01-01

What you want is an easy level of abstraction, which is just what this book provides in conjunction with Boost.Asio. Switching to Boost.Asio is just a few extra #include directives away, with the help of this practical and engaging guide.This book is great for developers that need to do network programming, who don't want to delve into the complicated issues of a raw networking API. You should be familiar with core Boost concepts, such as smart pointers and shared_from_this, resource classes (noncopyable), functors and boost::bind, boost mutexes, and the boost date/time library. Readers should

Tenofovir alafenamide versus tenofovir disoproxil fumarate: is there a true difference in efficacy and safety?

Science.gov (United States)

Hill, Andrew; Hughes, Sophie L; Gotham, Dzintars; Pozniak, Anton L

2018-04-01

Higher plasma tenofovir concentrations are associated with higher risks of renal and bone adverse events. The pharmacokinetic boosters ritonavir (RTV) and cobicistat (COBI) significantly increase plasma area under the curve (AUC) concentrations of tenofovir disoproxil fumarate (TDF), by 25-37%. When combined with RTV or COBI, the dose of tenofovir alafenamide (TAF) is lowered from 25 mg to 10 mg daily, but the TDF dose is maintained at 300 mg daily. To assess the differences in safety and efficacy between tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) in regimens with and without the pharmacokinetic boosters RTV and COBI. A PubMed/Embase search inclusive of dates up to 17 July 2017 identified 11 randomised head-to-head trials (8111 patients) of TDF versus TAF. The Mantel-Haenszel method was used to calculate pooled risk differences and 95% confidence intervals using random-effects models. A pre-defined sub-group analysis compared TAF with TDF, either when boosted with RTV or COBI, or when unboosted. Nine clinical trials compared TAF and TDF for treatment of HIV-1 and two were for hepatitis B treatment. The eleven clinical trials documented 4574 patients with boosting RTV or COBI in both arms, covering 7198 patient-years of follow-up. Some 3537 patients received unboosted regimens, totalling 3595 patient-years of follow-up. Boosted TDF-treated patients showed borderline lower HIV RNA suppression TAF and unboosted TDF. TDF boosted with RTV or COBI was associated with higher risks of bone and renal adverse events, and lower HIV RNA suppression rates, compared with TAF. By contrast, when ritonavir and cobicistat were not used, there were no efficacy differences between TAF and TDF, and marginal differences in safety. The health economic value of TAF versus low-cost generic TDF may be limited when these drugs are used without cobicistat or ritonavir.

Boosting foundations and algorithms

CERN Document Server

Schapire, Robert E

2012-01-01

Boosting is an approach to machine learning based on the idea of creating a highly accurate predictor by combining many weak and inaccurate "rules of thumb." A remarkably rich theory has evolved around boosting, with connections to a range of topics, including statistics, game theory, convex optimization, and information geometry. Boosting algorithms have also enjoyed practical success in such fields as biology, vision, and speech processing. At various times in its history, boosting has been perceived as mysterious, controversial, even paradoxical.

The history of antiretrovirals: key discoveries over the past 25 years.

Science.gov (United States)

De Clercq, Erik

2009-09-01

Within 25 years after zidovudine (3'-azido-2',3'-dideoxythymidine, AZT) was first described as an inhibitor of HIV replication, 25 anti-HIV drugs have been formally approved for clinical use in the treatment of HIV infections: seven nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine; one nucleotide reverse transcriptase inhibitor (NtRTI): tenofovir [in its oral prodrug form: tenofovir disoproxil fumarate (TDF)]; four non-nucleoside reverse transcriptase inhibitors (NNRTIs): nevirapine, delavirdine, efavirenz and etravirine; ten protease inhibitors (PIs): saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and darunavir; one fusion inhibitor (FI): enfuvirtide; one co-receptor inhibitor (CRI): maraviroc and one integrase inhibitor (INI): raltegravir. These compounds are used in various drug combination (some at fixed dose) regimens so as to achieve the highest possible benefit and tolerability, and to diminish the risk of virus-drug resistance development. (c) 2009 John Wiley & Sons, Ltd.

Diet-boosting foods

Science.gov (United States)

Obesity - diet-boosting foods; Overweight - diet-boosting foods ... Low-fat and nonfat milk, yogurt, and cottage cheese are healthy sources of calcium, vitamin D , and potassium. Unlike sweetened drinks with extra calories, milk ...

Clinical outcome among HIV-infected patients starting saquinavir hard gel compared to ritonavir or indinavir

DEFF Research Database (Denmark)

Kirk, O; Mocroft, A; Pradier, C

2001-01-01

-up within the EuroSIDA study. METHODS: Changes in plasma viral load (pVL) and CD4 cell count from baseline were compared between treatment groups. Time to new AIDS-defining events and death were compared in Kaplan--Meier models, and Cox models were established to further assess differences in clinical...

SemiBoost: boosting for semi-supervised learning.

Science.gov (United States)

Mallapragada, Pavan Kumar; Jin, Rong; Jain, Anil K; Liu, Yi

2009-11-01

Semi-supervised learning has attracted a significant amount of attention in pattern recognition and machine learning. Most previous studies have focused on designing special algorithms to effectively exploit the unlabeled data in conjunction with labeled data. Our goal is to improve the classification accuracy of any given supervised learning algorithm by using the available unlabeled examples. We call this as the Semi-supervised improvement problem, to distinguish the proposed approach from the existing approaches. We design a metasemi-supervised learning algorithm that wraps around the underlying supervised algorithm and improves its performance using unlabeled data. This problem is particularly important when we need to train a supervised learning algorithm with a limited number of labeled examples and a multitude of unlabeled examples. We present a boosting framework for semi-supervised learning, termed as SemiBoost. The key advantages of the proposed semi-supervised learning approach are: 1) performance improvement of any supervised learning algorithm with a multitude of unlabeled data, 2) efficient computation by the iterative boosting algorithm, and 3) exploiting both manifold and cluster assumption in training classification models. An empirical study on 16 different data sets and text categorization demonstrates that the proposed framework improves the performance of several commonly used supervised learning algorithms, given a large number of unlabeled examples. We also show that the performance of the proposed algorithm, SemiBoost, is comparable to the state-of-the-art semi-supervised learning algorithms.

[Comparative cost-effectiveness analysis between darunavir/ritonavir and other protease inhibitors in treatment-naive human immunodeficiency syndrome type 1-infected patients in Spain].

Science.gov (United States)

Smets, Erik; Brogan, Anita J; Hill, Andrew; Adriaenssen, Ines; Sawyer, Anthony W; Domingo-Pedrol, Pere; Gostkorzewicz, Joana; Ledesma, Francisco

2013-01-01

GESIDA (AIDS Study Group) has proposed preferred regimens of antiretroviral treatment as initial therapy in HIV infected patients. The objective of this analysis is to compare the costs and effectiveness of darunavir/r QD and other ritonavir-boosted (/r) protease inhibitors (PIs) currently recommended in GESIDA guidelines for treatment-naïve patients. A cost-efficacy model compared the boosted PIs recommended as preferred or alternative treatment choices, each used with a nucleoside reverse transcriptase inhibitor backbone. Efficacy was measured by 48-week virological response (viral load < 50 copies/mL) adjusted by baseline viral load and CD4 cell count. To generate efficiency frontiers and cost-efficacy ratios, one-year antiretroviral therapy costs in Spain, and 48-week efficacy values were used. The model estimated that starting treatment with darunavir/r QD was the most cost-effective choice compared with the other preferred PI/r based therapies. The average cost per patient with a virological response was lower for darunavir/r QD (13,420€) than for atazanavir/r QD (14,000€), or lopinavir/r BID (13,815€). Among the preferred PI/r-based therapies, darunavir/r QD also was estimated to be the most efficient option for treatment-naïve patients. Atazanavir/r QD and lopinavir/r BID were found to be «dominated» by darunavir/r) and, consequently, were outside the efficiency frontier of PI/r-based first-line treatment. Given a fixed budget of 10 million euros for PI/r-based first-line therapy, the model estimated that darunavir/r QD would yield more responders (745) than atazanavir/r QD (714), or lopinavir/r BID (724). At the same time, darunavir/r QD would reduce the number of individuals failing treatment (150) compared with atazanavir/r QD (172) and lopinavir/r BID (286). In this model, darunavir/r QD was found to be the most cost-effective choice, among the preferred PI/r-based therapies recommended in the Spanish guidelines for treatment-naïve patients

Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting

NARCIS (Netherlands)

van Zyl, Gert Uves; van Mens, Thijs E.; McIlleron, Helen; Zeier, Michele; Nachega, Jean B.; Decloedt, Eric; Malavazzi, Carolina; Smith, Peter; Huang, Yong; van der Merwe, Lize; Gandhi, Monica; Maartens, Gary

2011-01-01

In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure. We conducted a cross-sectional survey to investigate the aetiology of virologic failure in 2 public

Robust boosting via convex optimization

Science.gov (United States)

Rätsch, Gunnar

2001-12-01

In this work we consider statistical learning problems. A learning machine aims to extract information from a set of training examples such that it is able to predict the associated label on unseen examples. We consider the case where the resulting classification or regression rule is a combination of simple rules - also called base hypotheses. The so-called boosting algorithms iteratively find a weighted linear combination of base hypotheses that predict well on unseen data. We address the following issues: o The statistical learning theory framework for analyzing boosting methods. We study learning theoretic guarantees on the prediction performance on unseen examples. Recently, large margin classification techniques emerged as a practical result of the theory of generalization, in particular Boosting and Support Vector Machines. A large margin implies a good generalization performance. Hence, we analyze how large the margins in boosting are and find an improved algorithm that is able to generate the maximum margin solution. o How can boosting methods be related to mathematical optimization techniques? To analyze the properties of the resulting classification or regression rule, it is of high importance to understand whether and under which conditions boosting converges. We show that boosting can be used to solve large scale constrained optimization problems, whose solutions are well characterizable. To show this, we relate boosting methods to methods known from mathematical optimization, and derive convergence guarantees for a quite general family of boosting algorithms. o How to make Boosting noise robust? One of the problems of current boosting techniques is that they are sensitive to noise in the training sample. In order to make boosting robust, we transfer the soft margin idea from support vector learning to boosting. We develop theoretically motivated regularized algorithms that exhibit a high noise robustness. o How to adapt boosting to regression problems

Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes.

Science.gov (United States)

Stagno, Fabio; Stella, Stefania; Spitaleri, Antonio; Pennisi, Maria Stella; Di Raimondo, Francesco; Vigneri, Paolo

2016-01-01

The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment.

Effect of fosamprenavir-ritonavir on the pharmacokinetics of dolutegravir in healthy subjects.

Science.gov (United States)

Song, Ivy; Borland, Julie; Chen, Shuguang; Peppercorn, Amanda; Wajima, Toshihiro; Piscitelli, Stephen C

2014-11-01

Dolutegravir (DTG) is an HIV integrase inhibitor (INI) with demonstrated activity in INI-naive and INI-resistant patients. The objective of this open-label, 2-period, single-sequence study was to evaluate the effect of fosamprenavir-ritonavir (FPV-RTV) on the steady-state plasma pharmacokinetics of DTG. Twelve healthy subjects received 50 mg DTG once daily for 5 days (period 1), followed by 10 days of 50 mg DTG once daily in combination with 700/100 mg FPV-RTV every 12 h (period 2). All doses were administered in the fasting state. Serial pharmacokinetic samples for DTG and amprenavir and safety assessments were obtained throughout the study. Noncompartmental pharmacokinetic analysis was performed, and geometric least-squares mean ratios and 90% confidence intervals were generated for within-subject treatment comparison. Fosamprenavir-ritonavir decreased the DTG area under the concentration-time curve, maximum concentration in plasma, and concentration in plasma at the end of the dosing interval by 35%, 24%, and 49%, respectively. Both DTG and DTG with FPV-RTV were well tolerated; no subject withdrew because of adverse events. The most frequently reported drug-related adverse events were rash, abnormal dreams, and nasopharyngitis. The modest decrease in DTG exposure when it was coadministered with FPV-RTV is not considered clinically significant, and DTG dose adjustment is not required with coadministration of FPV-RTV in INI-naive patient populations on the basis of established "no-effect" boundaries of DTG. In the INI-resistant population, as a cautionary measure, alternative combinations that do not include FPV-RTV should be considered. (This study has been registered at ClinicalTrials.gov under identifier NCT01209065.). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Imatinib mesylate is effective in children with chronic myelogenous leukemia in late chronic and advanced phase and in relapse after stem cell transplantation

NARCIS (Netherlands)

Millot, F; Guilhot, J; Nelken, B; Leblanc, T; De Bont, ES; Bekassy, AN; Gadner, H; Sufliarska, S; Stary, J; Gschaidmeier, H; Guilhot, F; Suttorp, M

A multicentric phase 2 study was conducted to determine the efficiency and the tolerance of imatinib mesylate in children with chronic myelogenous leukemia (CML) in advanced phase of the disease, in relapse after stem cell transplantation, or in case of failure to an interferon a-based regimen. In

Falla cardiaca asociada con el uso de imatinib mesilato: Reporte de un caso Heart failure associated to imatinib mesylate use: Case report

Directory of Open Access Journals (Sweden)

Clara Saldarriaga

2008-12-01

Full Text Available La cardiotoxicidad por medicamentos es un evento cada vez más frecuente en la práctica clínica diaria. Inhibidores de la proteína de fusión Brc/Abl como el imatinib mesilato, son una nueva herramienta para el tratamiento de algunas neoplasias hematológicas, en especial de la leucemia mieloide crónica. Sin embargo, en la literatura se reporta desarrollo de cardiotoxicidad a causa de este medicamento. Se presenta el caso de una mujer joven con corazón de estructura sana quien desarrolla cardiotoxicidad por imatinib pocas semanas después de iniciarlo.Cardiotoxicity due to drugs has become a frequent event in the daily clinical practice. Fusion protein Brc/Abl inhibitors such as imatinib mesylate constitute a new tool for the treatment of some hematogical neoplasias, especially chronic myeloid leukemia. Nevertheless, there have been reports in the literature regarding imatinib mesylate toxicity. We present the case of a young woman with a structurally healthy heart who developed cardiotoxicity with imatinib few weeks after its initiation.

Marrow signal changes observed in follow-up whole-body MRI studies in children and young adults with neurofibromatosis type 1 treated with imatinib mesylate (Gleevec) for plexiform neurofibromas

Energy Technology Data Exchange (ETDEWEB)

Karmazyn, Boaz; Cohen, Mervyn D. [Riley Hospital for Children, Indiana University Health, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN (United States); Jennings, Samuel Gregory [Indiana University School of Medicine, Department of Radiology and Imaging Sciences, Indianapolis, IN (United States); Robertson, Kent A. [Riley Hospital for Children, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN (United States)

2012-10-15

We observed bone marrow signal changes (BMSC) in patients with plexiform neurofibromas after treatment with imatinib mesylate (Gleevec). To evaluate the pattern and natural history of BMSC. The data were obtained from a pilot study of imatinib mesylate in patients with plexiform neurofibromas. All patients underwent baseline and sequential whole-body STIR 1.5-T MRI after treatment. The bone marrow signal on MRI was evaluated for abnormalities, location and pattern, and any change on follow-up studies. The study group included 16 patients (8 males) with a median age of 14 years (range 4 to 25 years). The mean whole-body MRI follow-up duration was 1.9 years. Of the 16 patients, 14 (88%) developed BMSC. The signal change was asymmetrical in 9 of the 14 patients (64%). The appendicular skeleton was involved in all 14 patients and the axial skeleton in 3 patients (21%). BMSC was followed in 13 patients and decreased signal was seen in 9 patients (69%) after a mean duration of 1.3 years of treatment (range 0.6 to 2.9 years); no complications were observed. BMSC appeared in most patients with neurofibromatosis type 1 following treatment with imatinib mesylate. BMSC was unusually asymmetrical and involved the lower extremities. On follow-up, BMSC often showed a decrease without complications. (orig.)

Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study.

Science.gov (United States)

Teófilo, Eugénio; Rocha-Pereira, Nuno; Kuhlmann, Birger; Antela, Antonio; Knechten, Heribert; Santos, Jesús; Jiménez-Expósito, Maria Jesús

2016-02-01

Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited. We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study. This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen. Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years. In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function.

Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers

NARCIS (Netherlands)

Aarnoutse, Rob E; Kleinnijenhuis, Johanneke; Koopmans, Peter P; Touw, Daan J; Wieling, Jaap; Hekster, Yechiel A; Burger, David M

2005-01-01

OBJECTIVE: In the treatment of human immunodeficiency virus infection, the protease inhibitor ritonavir is used in a low dose (100 mg twice daily) to inhibit cytochrome P450 (CYP) 3A4 and thereby increase plasma concentrations of coadministered protease inhibitors. When applied in a therapeutic dose

Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers.

NARCIS (Netherlands)

Aarnoutse, R.E.; Kleinnijenhuis, J.; Koopmans †, P.P.; Touw, D.J.; Wieling, J.; Hekster, Y.A.; Burger, D.M.

2005-01-01

OBJECTIVE: In the treatment of human immunodeficiency virus infection, the protease inhibitor ritonavir is used in a low dose (100 mg twice daily) to inhibit cytochrome P450 (CYP) 3A4 and thereby increase plasma concentrations of coadministered protease inhibitors. When applied in a therapeutic dose

Quantitative determination of pefloxacin mesylate by residual-base neutralisation method

Directory of Open Access Journals (Sweden)

HULIKALCHANDRA SHEKAR PRAMEELA

2004-05-01

Full Text Available This work describes two procedures based on residual base determination for the quantification of pefloxacin mesylate (PFM in bulk drug and in pharmaceutical products. In the first method involving titrimetry, the drug solution is treated with a measured excess of sodium hydroxide followed by back titration of the residual base with hydrochloric acid using a phenol red-bromothymol blue mixed indicator. The second spectrophotometrie method involves treatment of a fixed amount of sodium hydroxide – phenol red mixture with varying amounts of the drug, and measuring the decrease in the absorbance of the dye at 560 nm. In the titrimetric method, a reaction stoichiometry of 1:1 was found in the quantification range of 4–20 mg of drug. The spectrophotometric method allows the determination of PFM in the 5–40 mg ml-1 range. The molar absorptivity is 5.91¤103 l mol-1 cm-1 and the Sandell sensitivity is 56.37 ng cm-2. The methods were applied successfully to the determination of PFM in pharmaceutical preparations.

Distribution-Specific Agnostic Boosting

OpenAIRE

Feldman, Vitaly

2009-01-01

We consider the problem of boosting the accuracy of weak learning algorithms in the agnostic learning framework of Haussler (1992) and Kearns et al. (1992). Known algorithms for this problem (Ben-David et al., 2001; Gavinsky, 2002; Kalai et al., 2008) follow the same strategy as boosting algorithms in the PAC model: the weak learner is executed on the same target function but over different distributions on the domain. We demonstrate boosting algorithms for the agnostic learning framework tha...

Noncanonical Wnt signaling promotes osteoclast differentiation and is facilitated by the human immunodeficiency virus protease inhibitor ritonavir

International Nuclear Information System (INIS)

Santiago, Francisco; Oguma, Junya; Brown, Anthony M.C.; Laurence, Jeffrey

2012-01-01

Highlights: ► First demonstration of direct role for noncanonical Wnt in osteoclast differentiation. ► Demonstration of Ryk as a Wnt5a/b receptor in inhibition of canonical Wnt signaling. ► Modulation of noncanonical Wnt signaling by a clinically important drug, ritonavir. ► Establishes a mechanism for an important clinical problem: HIV-associated bone loss. -- Abstract: Wnt proteins that signal via the canonical Wnt/β-catenin pathway directly regulate osteoblast differentiation. In contrast, most studies of Wnt-related effects on osteoclasts involve indirect changes. While investigating bone mineral density loss in the setting of human immunodeficiency virus (HIV) infection and its treatment with the protease inhibitor ritonavir (RTV), we observed that RTV decreased nuclear localization of β-catenin, critical to canonical Wnt signaling, in primary human and murine osteoclast precursors. This occurred in parallel with upregulation of Wnt5a and Wnt5b transcripts. These Wnts typically stimulate noncanonical Wnt signaling, and this can antagonize the canonical Wnt pathway in many cell types, dependent upon Wnt receptor usage. We now document RTV-mediated upregulation of Wnt5a/b protein in osteoclast precursors. Recombinant Wnt5b and retrovirus-mediated expression of Wnt5a enhanced osteoclast differentiation from human and murine monocytic precursors, processes facilitated by RTV. In contrast, canonical Wnt signaling mediated by Wnt3a suppressed osteoclastogenesis. Both RTV and Wnt5b inhibited canonical, β-catenin/T cell factor-based Wnt reporter activation in osteoclast precursors. RTV- and Wnt5-induced osteoclast differentiation were dependent upon the receptor-like tyrosine kinase Ryk, suggesting that Ryk may act as a Wnt5a/b receptor in this context. This is the first demonstration of a direct role for Wnt signaling pathways and Ryk in regulation of osteoclast differentiation, and its modulation by a clinically important drug, ritonavir. These studies

Ritonavir binds to and downregulates estrogen receptors: Molecular mechanism of promoting early atherosclerosis

Energy Technology Data Exchange (ETDEWEB)

Xiang, Jin [Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071 (China); Wang, Ying [Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Su, Ke [Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Liu, Min [Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071 (China); Hu, Peng-Chao [Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Ma, Tian; Li, Jia-Xi [Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071 (China); Wei, Lei [Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zheng, Zhongliang, E-mail: biochem@whu.edu.cn [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072 (China); Yang, Fang, E-mail: fang-yang@whu.edu.cn [Department of Physiology, School of Medicine, Wuhan University, Wuhan 430071 (China)

2014-10-01

Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor α (ERα) and ERβ expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17β-estradiol (E2), suggesting RTV acts as an antagonist for E2. Computational modeling shows a similar interaction with ERα between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ERα. We also found that RTV directly bound to ERα and selectively inhibited the nuclear localization of ERα, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ERα-LBD like E2, which explained how ERα lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17β-estradiol in regulating α subtype estrogen receptor function and early events of atherosclerosis. - Graphical abstract: RTV directly binds to ERα and Leu536 in the hydrophobic core of ligand binding domain is essential for the interaction. - Highlights: • RTV increases the thickness of rat coronary artery wall and foam cell formation. • RTV downregulates the expression of ERα and ERβ. • RTV inhibits ERα promoter activity. • RTV directly binds to ERα and the key amino acid is Leu536. • RTV inhibits the nuclear translocation of ERα and GPER.

Ritonavir binds to and downregulates estrogen receptors: Molecular mechanism of promoting early atherosclerosis

International Nuclear Information System (INIS)

Xiang, Jin; Wang, Ying; Su, Ke; Liu, Min; Hu, Peng-Chao; Ma, Tian; Li, Jia-Xi; Wei, Lei; Zheng, Zhongliang; Yang, Fang

2014-01-01

Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor α (ERα) and ERβ expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17β-estradiol (E2), suggesting RTV acts as an antagonist for E2. Computational modeling shows a similar interaction with ERα between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ERα. We also found that RTV directly bound to ERα and selectively inhibited the nuclear localization of ERα, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ERα-LBD like E2, which explained how ERα lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17β-estradiol in regulating α subtype estrogen receptor function and early events of atherosclerosis. - Graphical abstract: RTV directly binds to ERα and Leu536 in the hydrophobic core of ligand binding domain is essential for the interaction. - Highlights: • RTV increases the thickness of rat coronary artery wall and foam cell formation. • RTV downregulates the expression of ERα and ERβ. • RTV inhibits ERα promoter activity. • RTV directly binds to ERα and the key amino acid is Leu536. • RTV inhibits the nuclear translocation of ERα and GPER

Gradient Boosting Machines, A Tutorial

Directory of Open Access Journals (Sweden)

Alexey eNatekin

2013-12-01

Full Text Available Gradient boosting machines are a family of powerful machine-learning techniques that have shown considerable success in a wide range of practical applications. They are highly customizable to the particular needs of the application, like being learned with respect to different loss functions. This article gives a tutorial introduction into the methodology of gradient boosting methods. A theoretical information is complemented with many descriptive examples and illustrations which cover all the stages of the gradient boosting model design. Considerations on handling the model complexity are discussed. A set of practical examples of gradient boosting applications are presented and comprehensively analyzed.

Atazanavir intracellular concentrations remain stable during pregnancy in HIV-infected patients.

Science.gov (United States)

Focà, Emanuele; Calcagno, Andrea; Bonito, Andrea; Simiele, Marco; Domenighini, Elisabetta; D'Avolio, Antonio; Quiros Roldan, Eugenia; Trentini, Laura; Casari, Salvatore; Di Perri, Giovanni; Castelli, Francesco; Bonora, Stefano

2017-11-01

Atazanavir (300 mg) boosted by ritonavir (100 mg) is the preferred third drug in pregnancy. However, there is still discordance on atazanavir dose increase during the third trimester. To evaluate plasma and intracellular atazanavir and ritonavir concentrations in HIV-infected women during pregnancy and after delivery. This was an observational study. HIV-infected pregnant patients treated with atazanavir/ritonavir plus either tenofovir/emtricitabine or abacavir/lamivudine had been prospectively enrolled after having signed a written informed consent form. Plasma and intracellular atazanavir and ritonavir Ctrough (24 ± 3 h after drug intake) were measured at each visit during the first, second and third trimesters and post-partum using validated HPLC-MS and HPLC-photodiode array methods (with direct evaluation of cellular volume). Data are described as median (IQR) and compared through non-parametric tests. Twenty-five patients were enrolled; at baseline, the median age was 32 years (27-35). All patients had plasma HIV RNA  0.05). This is the first demonstration that intracellular atazanavir exposure remains unchanged during pregnancy supporting the standard 300/100 mg atazanavir/ritonavir dosing throughout pregnancy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Imatinib mesylate--gold standards and silver linings.

Science.gov (United States)

Peggs, K

2004-09-01

Imatinib mesylate represents the first of a new generation of molecularly targeted therapies engineered to disrupt signal transduction pathways. It is a tyrosine kinase inhibitor with relatively selective activity against the Abelson (ABL) proto-oncogene, platelet-derived growth factor receptor, and c-KIT receptor. Deregulated tyrosine kinase activity has been implicated as a central pathogenic event in a number of human malignancies, most notably chronic myeloid leukemia. In this myeloproliferative disorder the t(9;22) reciprocal translocation results in the generation of a novel fusion oncoprotein, BCR-ABL, with constitutive tyrosine kinase activity. Imatinib inhibits this activity, inducing remarkable rates of hematological and cytogenetic remission in excess of those seen with alternative medical therapies. Following a large phase III study comparing its efficacy with the combination of interferon alpha and low-dose cytarabine, it has emerged as the current gold standard therapy for patients with chronic-phase disease without a potential bone marrow donor and those considered unsuitable for bone marrow transplantation. Its integration into the management of those patients who might be considered for transplantation, which has historically been considered the only potentially curative approach, remains a major challenge. The increasing recognition and subsequent molecular characterization of resistance mechanisms has reinforced the need to exercise caution against deferring a proven curative therapy in favor of a treatment approach that is still investigational, with the spectre of increased numbers of patients progressing to sudden-onset blast crisis remaining the potential dark cloud in the silver lining for imatinib.

Robust loss functions for boosting.

Science.gov (United States)

Kanamori, Takafumi; Takenouchi, Takashi; Eguchi, Shinto; Murata, Noboru

2007-08-01

Boosting is known as a gradient descent algorithm over loss functions. It is often pointed out that the typical boosting algorithm, Adaboost, is highly affected by outliers. In this letter, loss functions for robust boosting are studied. Based on the concept of robust statistics, we propose a transformation of loss functions that makes boosting algorithms robust against extreme outliers. Next, the truncation of loss functions is applied to contamination models that describe the occurrence of mislabels near decision boundaries. Numerical experiments illustrate that the proposed loss functions derived from the contamination models are useful for handling highly noisy data in comparison with other loss functions.

Validation and application of a high-performance liquid chromatography-tandem mass spectrometric method for simultaneous quantification of lopinavir and ritonavir in human plasma using semi-automated 96-well liquid-liquid extraction.

Science.gov (United States)

Wang, Perry G; Wei, Jack S; Kim, Grace; Chang, Min; El-Shourbagy, Tawakol

2006-10-20

Kaletra is an important antiretroviral drug, which has been developed by Abbott Laboratories. It is composed of lopinavir (low-pin-a-veer) and ritonavir (ri-toe-na-veer). Both have been proved to be human immunodeficiency virus (HIV) protease inhibitors and have substantially reduced the morbidity and mortality associated with HIV-1 infection. We have developed and validated an assay, using liquid chromatography coupled with atmospheric pressure chemical ionization tandem mass spectrometry (LC/MS/MS), for the routine quantification of lopinavir and ritonavir in human plasma, in which lopinavir and ritonavir can be simultaneously analyzed with high throughput. The sample preparation consisted of liquid-liquid extraction with a mixture of hexane: ethyl acetate (1:1, v/v), using 100 microL of plasma. Chromatographic separation was performed on a Waters Symmetry C(18) column (150 mm x 3.9 mm, particle size 5 microm) with reverse-phase isocratic using mobile phase of 70:30 (v/v) acetonitrile: 2 mM ammonium acetate aqueous solution containing 0.01% formic acid (v/v) at a flow rate of 1.0 mL/min. A Waters symmetry C(18) guard column (20 mm x 3.9 mm, particle size 5 microm) was connected prior to the analytical column, and a guard column back wash was performed to reduce the analytical column contamination using a mixture of tetrahydrofuran (THF), methanol and water (45:45:10, v/v/v). The analytical run was 4 min. The use of a 96-well plate autosampler allowed a batch size up to 73 study samples. A triple-quadrupole mass spectrometer was operated in a positive ion mode and multiple reaction monitoring (MRM) was used for drug quantification. The method was validated over the concentration ranges of 19-5,300 ng/mL for lopinavir and 11-3,100 ng/mL for ritonavir. A-86093 was used as an internal standard (I.S.). The relative standard deviation (RSD) were <6% for both lopinavir and ritonavir. Mean accuracies were between the designed limits (+/-15%). The robust and rapid LC

Chronic myeloid leukemia: an overview of the determinants of effectiveness and therapeutic response in the first decade of treatment with imatinib mesylate in a Brazilian hospital

Directory of Open Access Journals (Sweden)

Danielle Maria Camelo Cid

2013-01-01

Full Text Available Background: In the last decade, there has been a revolution in chronic myeloid leukemia treatment with the introduction of tyrosine kinase inhibitors with imatinib mesylate becoming the frontline therapy. Objective: To evaluate the therapeutic efficacy of imatinib mesylate in treating chronic myeloid leukemia patients and to identify factors related to therapeutic efficacy. Methods: This retrospective study was based on information obtained from patients'records in the Hematology Service of Hospital Universitário Walter Cantídio of the Universidade Federal do Ceará (HUWC / UFC. All patients diagnosed with chronic myeloid leukemia that took imatinib mesylate for a minimum of 12 months in the period from January 2001 to January 2011 were included. From a population of 160 patients, 100 were eligible for analysis. Results: The study population consisted of 100 patients who were mostly male (51% with ages rangingbetween 21 and 40 years (42%, from the countryside (59%, in the chronic phase (95%, with high-riskprognostic factors (40%; the prognosis of high risk was not associated with complete hematologic responseor complete cytogenetic response, but correlated to complete molecular response or major molecularresponse. Reticulin condensation was associated with complete hematologic response and completecytogenetic response. It was found that 53% of patients had greater than 90% adherence to treatment. Thehigh adherence was correlated to attaining complete cytogenetic response in less than 12 months. Moreover,20% of patients had good response. Conclusion: Significant changes are indispensable in the monitoring of patients with chronic myeloid leukemia. Thus, the multidisciplinary team is important as it provides access to the full treatment and not just to medications.

Deep Incremental Boosting

OpenAIRE

Mosca, Alan; Magoulas, George D

2017-01-01

This paper introduces Deep Incremental Boosting, a new technique derived from AdaBoost, specifically adapted to work with Deep Learning methods, that reduces the required training time and improves generalisation. We draw inspiration from Transfer of Learning approaches to reduce the start-up time to training each incremental Ensemble member. We show a set of experiments that outlines some preliminary results on some common Deep Learning datasets and discuss the potential improvements Deep In...

High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil

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José Ernesto Vidal

Full Text Available OBJECTIVES: To assess the virologic and immunological response of darunavir/ritonavir plus optimized background therapy in highly antiretroviral-experienced HIV-infected patients in Brazil. METHODS: Prospective cohort study carried out in a tertiary center in Sao Paulo, Brazil. Three-class antiretroviral-experienced patients with confirmed virologic failure began darunavir/ritonavir plus optimized background therapy (nucleoside/tide reverse transcriptase inhibitors ± raltegravir ± enfuvirtide ± maraviroc after performing a genotypic resistance assay. Clinical evaluation and laboratory tests were collected at baseline and at weeks 12, 24, and 48. Multivariate analysis was performed to identify predictors of virologic response at 48 weeks. RESULTS: Ninety-two patients were included. The median of darunavir resistant mutation was 1 (range 0-6. The median genotypic sensitivity score in the optimized background therapy was 2 (interquartile range 1-2. At week 48, 83% (95% CI: 75-90% had an HIV RNA level 100 000 copies/mL was inversely associated with virologic success at week 48 (HR: 0.22, 95% CI: 0.06-0.85, p = 0.028. CONCLUSIONS: Darunavir/ritonavir plus optimized background therapy was a highly effective salvage regimen under clinical routine conditions in a referral center in Brazil, which is similar to the reported in high-income countries.

High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil

Directory of Open Access Journals (Sweden)

José Ernesto Vidal

2013-02-01

Full Text Available OBJECTIVES: To assess the virologic and immunological response of darunavir/ritonavir plus optimized background therapy in highly antiretroviral-experienced HIV-infected patients in Brazil. METHODS: Prospective cohort study carried out in a tertiary center in Sao Paulo, Brazil. Three-class antiretroviral-experienced patients with confirmed virologic failure began darunavir/ritonavir plus optimized background therapy (nucleoside/tide reverse transcriptase inhibitors ± raltegravir ± enfuvirtide ± maraviroc after performing a genotypic resistance assay. Clinical evaluation and laboratory tests were collected at baseline and at weeks 12, 24, and 48. Multivariate analysis was performed to identify predictors of virologic response at 48 weeks. RESULTS: Ninety-two patients were included. The median of darunavir resistant mutation was 1 (range 0-6. The median genotypic sensitivity score in the optimized background therapy was 2 (interquartile range 1-2. At week 48, 83% (95% CI: 75-90% had an HIV RNA level 100 000 copies/mL was inversely associated with virologic success at week 48 (HR: 0.22, 95% CI: 0.06-0.85, p = 0.028. CONCLUSIONS: Darunavir/ritonavir plus optimized background therapy was a highly effective salvage regimen under clinical routine conditions in a referral center in Brazil, which is similar to the reported in high-income countries.

Component-Minimized Buck-Boost Voltage Source Inverters

DEFF Research Database (Denmark)

Gao, F.; Loh, P.C.; Blaabjerg, Frede

2007-01-01

This paper presents the design of buck-boost B4 inverters that can be derived from either Ćuk- or SEPIC-derived buck-boost B6 inverters. Unlike traditional inverters, the integration of front-end voltage boost circuitry and inverter circuitry allows it to perform buck-boost voltage inversion...... between capacitors. Modulation wise, the proposed buck-boost B4 inverters can be controlled using a carefully designed carrier-based pulse-width modulation (PWM) scheme that will always ensure balanced threephase outputs as desired, while simultaneously achieving minimal voltage stress across...

Can you boost your metabolism?

Science.gov (United States)

... this page: //medlineplus.gov/ency/patientinstructions/000893.htm Can you boost your metabolism? To use the sharing ... boosting metabolism than tactics that work. Some myths can backfire. If you think you are burning more ...

Learning Boost C++ libraries

CERN Document Server

Mukherjee, Arindam

2015-01-01

If you are a C++ programmer who has never used Boost libraries before, this book will get you up-to-speed with using them. Whether you are developing new C++ software or maintaining existing code written using Boost libraries, this hands-on introduction will help you decide on the right library and techniques to solve your practical programming problems.

Detection of Illegitimate Emails using Boosting Algorithm

DEFF Research Database (Denmark)

Nizamani, Sarwat; Memon, Nasrullah; Wiil, Uffe Kock

2011-01-01

and spam email detection. For our desired task, we have applied a boosting technique. With the use of boosting we can achieve high accuracy of traditional classification algorithms. When using boosting one has to choose a suitable weak learner as well as the number of boosting iterations. In this paper, we......In this paper, we report on experiments to detect illegitimate emails using boosting algorithm. We call an email illegitimate if it is not useful for the receiver or for the society. We have divided the problem into two major areas of illegitimate email detection: suspicious email detection...

Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201.

Directory of Open Access Journals (Sweden)

John E McKinnon

Full Text Available Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI for future use and decreased toxicity. We hypothesized that the level of immune activation (IA and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification.Thirty-four participants with virologic suppression ≥ 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8, natural killer (NK (CD3+CD56+CD16+ cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279.Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL >50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL >50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023, with an odds ratio of 10.3 (95% CI: 1.92-55.3. Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels.Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring.ClinicalTrials.gov NCT00084019.

Boosted tops at ATLAS

CERN Document Server

Villaplana, M; The ATLAS collaboration

2011-01-01

A sample of candidate events for highly boosted top quarks is selected following the standard ATLAS selection for semi-leptonic ttbar events plus a requirement that the invariant mass of the reconstructed ttbar pair is greater than 700 GeV. Event displays are presented for the most promising candidates, as well as quantitative results for observables designed to isolate a boosted top quark signal.

Synthesis of chitosan-PEO hydrogels via mesylation and regioselective Cu(I)-catalyzed cycloaddition.

Science.gov (United States)

Tirino, Pasquale; Laurino, Rosaria; Maglio, Giovanni; Malinconico, Mario; d'Ayala, Giovanna Gomez; Laurienzo, Paola

2014-11-04

In this work, a well-defined hydrogel was developed by coupling chitosan with PEO through "click chemistry". Azide functionalities were introduced onto chitosan, through mesylation of C-6 hydroxyl groups, and reacted with a di-alkyne PEO by a regioselective Cu(I)-catalyzed cycloaddition. This synthetic approach allowed us to obtain a hydrogel with a controlled crosslinking degree. In fact, the extent of coupling is strictly dependent on the amount of azido groups on chitosan, which in turn can be easily modulated. The obtained hydrogel, with a crosslinking degree of around 90%, showed interesting swelling properties. With respect to chitosan hydrogels reported in literature, a considerably higher equilibrium uptake was reached (940%). The possibility to control the crosslinking degree of hydrogel and its capability to rapidly absorb high amounts of water make this material suitable for several applications, such as controlled drug release and wound healing. Copyright © 2014. Published by Elsevier Ltd.

Lack of immunotoxicity of saquinavir (Ro 31-8959) used alone or in double or triple combination with AZT and ddC.

Science.gov (United States)

Viora, M; Di Genova, G; Quaranta, M G; Boirivant, M; Camponeschi, B

1998-09-01

Saquinavir (Ro 31-8959; SQV) has been demonstrated to be a potent inhibitor of human immunodeficiency virus (HIV) proteinases and acts synergistically with dideoxynucleoside analogues. The aim of this study was to investigate the in vitro immunomodulatory effects of SQV on normal human peripheral blood mononuclear cells (PBMC) and on lamina propria mononuclear cells (LPMC). We used the drug either alone or in double and triple combination with AZT and ddC to assess whether SQV enhances the immunomodulatory effects induced by AZT and ddC that we previously observed. We demonstrated that SQV did not induce any modulation of the proliferative response either in PBMC or in LPMC. Similarly, NK cell-mediated cytotoxic activity and cytokine production were not modified by SQV. More importantly, SQV/AZT, SQV/ddC, and SQV/AZT/ddC combinations did not strengthen neither the inhibition of PBMC and LPMC proliferative response or the modulation of cytokine production induced by AZT, ddC, and AZT/ddC. On the other hand, the increased IL-2 production induced by AZT and ddC was not observed adding SQV to the dideoxynucleoside analogues. In conclusion, we demonstrated that SQV used in combination with AZT and ddC did not add any further immunotoxicity.

BoostEMM : Transparent boosting using exceptional model mining

NARCIS (Netherlands)

van der Zon, S.B.; Zeev Ben Mordehay, O.; Vrijdag, T.S.; van Ipenburg, W.; Veldsink, J.; Duivesteijn, W.; Pechenizkiy, M.; Bordino, I.; Caldarelli, G.; Fumarola, F.; Gullo, F.; Squartini, T.

2017-01-01

Boosting is an iterative ensemble-learning paradigm. Every iteration, a weak predictor learns a classification task, taking into account performance achieved in previous iterations. This is done by assigning weights to individual records of the dataset, which are increased if the record is

Buck-Boost Current-Source Inverters With Diode-Inductor Network

DEFF Research Database (Denmark)

Gao, Feng; Liang, Chao; Loh, Poh Chiang

2009-01-01

This paper presents a number of novel currentsource inverters (CSIs) with enhanced current buck-boost capability. By adding a unique diode-inductor network between the inverter circuitry and current-boost elements, the proposed buck-boost CSIs demonstrate a doubling of current-boost capability......, as compared with other recently reported buck-boost CSIs. For controlling the proposed CSIs, two modulation schemes are designed for achieving either optimized harmonic performance or minimized commutation count without influencing the inverter current buck-boost gain. These theoretical findings were...

Gateways to clinical trials.

Science.gov (United States)

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

AlignerBoost: A Generalized Software Toolkit for Boosting Next-Gen Sequencing Mapping Accuracy Using a Bayesian-Based Mapping Quality Framework.

Directory of Open Access Journals (Sweden)

Qi Zheng

2016-10-01

Full Text Available Accurate mapping of next-generation sequencing (NGS reads to reference genomes is crucial for almost all NGS applications and downstream analyses. Various repetitive elements in human and other higher eukaryotic genomes contribute in large part to ambiguously (non-uniquely mapped reads. Most available NGS aligners attempt to address this by either removing all non-uniquely mapping reads, or reporting one random or "best" hit based on simple heuristics. Accurate estimation of the mapping quality of NGS reads is therefore critical albeit completely lacking at present. Here we developed a generalized software toolkit "AlignerBoost", which utilizes a Bayesian-based framework to accurately estimate mapping quality of ambiguously mapped NGS reads. We tested AlignerBoost with both simulated and real DNA-seq and RNA-seq datasets at various thresholds. In most cases, but especially for reads falling within repetitive regions, AlignerBoost dramatically increases the mapping precision of modern NGS aligners without significantly compromising the sensitivity even without mapping quality filters. When using higher mapping quality cutoffs, AlignerBoost achieves a much lower false mapping rate while exhibiting comparable or higher sensitivity compared to the aligner default modes, therefore significantly boosting the detection power of NGS aligners even using extreme thresholds. AlignerBoost is also SNP-aware, and higher quality alignments can be achieved if provided with known SNPs. AlignerBoost's algorithm is computationally efficient, and can process one million alignments within 30 seconds on a typical desktop computer. AlignerBoost is implemented as a uniform Java application and is freely available at https://github.com/Grice-Lab/AlignerBoost.

AlignerBoost: A Generalized Software Toolkit for Boosting Next-Gen Sequencing Mapping Accuracy Using a Bayesian-Based Mapping Quality Framework.

Science.gov (United States)

Zheng, Qi; Grice, Elizabeth A

2016-10-01

Accurate mapping of next-generation sequencing (NGS) reads to reference genomes is crucial for almost all NGS applications and downstream analyses. Various repetitive elements in human and other higher eukaryotic genomes contribute in large part to ambiguously (non-uniquely) mapped reads. Most available NGS aligners attempt to address this by either removing all non-uniquely mapping reads, or reporting one random or "best" hit based on simple heuristics. Accurate estimation of the mapping quality of NGS reads is therefore critical albeit completely lacking at present. Here we developed a generalized software toolkit "AlignerBoost", which utilizes a Bayesian-based framework to accurately estimate mapping quality of ambiguously mapped NGS reads. We tested AlignerBoost with both simulated and real DNA-seq and RNA-seq datasets at various thresholds. In most cases, but especially for reads falling within repetitive regions, AlignerBoost dramatically increases the mapping precision of modern NGS aligners without significantly compromising the sensitivity even without mapping quality filters. When using higher mapping quality cutoffs, AlignerBoost achieves a much lower false mapping rate while exhibiting comparable or higher sensitivity compared to the aligner default modes, therefore significantly boosting the detection power of NGS aligners even using extreme thresholds. AlignerBoost is also SNP-aware, and higher quality alignments can be achieved if provided with known SNPs. AlignerBoost's algorithm is computationally efficient, and can process one million alignments within 30 seconds on a typical desktop computer. AlignerBoost is implemented as a uniform Java application and is freely available at https://github.com/Grice-Lab/AlignerBoost.

Acute development of Cushing syndrome in an HIV-infected child on atazanavir/ritonavir based antiretroviral therapy

Directory of Open Access Journals (Sweden)

Gueorgui Dubrocq

2017-10-01

Full Text Available An 11-year-old male with perinatally acquired human immune deficiency virus (HIV infection on antiretroviral regimen, which included abacavir plus lamivudine (Epzicom, didanosine, ritonavir and atazanavir presented with bilateral axillary striae, increased appetite, fatigue, facial swelling and acute weight gain. Two months prior to presentation, the patient had received a diagnostic and therapeutic intra-articular triamcinolone injection in the knee for pain relief and subsequently became progressively swollen in the face, developed striae bilaterally at the axillae, experienced increased appetite, fatigue and an 8 pound weight gain. During the endocrine workup, suspicion for adrenal insufficiency prompted 24-h urine collection for free cortisol, which was found to be undetectable (below LLQ of 1.0 μg/L. This prompted further evaluation of the hypothalamic–pituitary axis (HPA by standard dose adrenocorticotropic hormone (ACTH stimulation test. A 250 μg cosyntropin stimulation test was performed and confirmed HPA axis suppression. Baseline cortisol level was <1 μg/dL and stimulated cortisol level at 30 min was 3.8 μg/dL. The patient was diagnosed with iatrogenic Cushing syndrome and suppression of HPA axis secondary to the drug interaction between ritonavir (RTV and intra-articular triamcinolone injection. Following endocrine evaluation and workup, the patient was admitted for planned orthopaedic procedure including elective left hamstring lengthening, distal femoral osteotomy and patellar tendon advancement. Taking into consideration the diagnosis of iatrogenic Cushing syndrome, at the start of the surgical procedure, 100 mg IV stress dose of hydrocortisone followed by 50 mg hydrocortisone every 8 h for 24 h was administered. Stress dosing was discontinued 24 h after the procedure. Throughout the hospitalization and upon discharge, the patient continued his ART. From initial presentation, patient has remained clinically stable throughout

Extending statistical boosting. An overview of recent methodological developments.

Science.gov (United States)

Mayr, A; Binder, H; Gefeller, O; Schmid, M

2014-01-01

Boosting algorithms to simultaneously estimate and select predictor effects in statistical models have gained substantial interest during the last decade. This review highlights recent methodological developments regarding boosting algorithms for statistical modelling especially focusing on topics relevant for biomedical research. We suggest a unified framework for gradient boosting and likelihood-based boosting (statistical boosting) which have been addressed separately in the literature up to now. The methodological developments on statistical boosting during the last ten years can be grouped into three different lines of research: i) efforts to ensure variable selection leading to sparser models, ii) developments regarding different types of predictor effects and how to choose them, iii) approaches to extend the statistical boosting framework to new regression settings. Statistical boosting algorithms have been adapted to carry out unbiased variable selection and automated model choice during the fitting process and can nowadays be applied in almost any regression setting in combination with a large amount of different types of predictor effects.

Effect of gamma-irradiation on biodegradable microspheres loaded with rasagiline mesylate

International Nuclear Information System (INIS)

Fernandez, Marcos; Barcia, Emilia; Negro, Sofia

2016-01-01

In the present study, the influence of gamma-irradiation was evaluated on the physicochemical characteristics and in vitro release of rasagiline mesylate (RM), a selective MAO-B inhibitor used in Parkinson's disease, from poly(D,L-lactide-co-glycolide) (PLGA) microspheres. Microspheres were prepared using PLGA 50:50 by the solvent evaporation technique (O/W emulsion). Microspheres were sterilized by gamma-irradiation and their influence was assessed by scanning electron microscopy (SEM), laser light diffraction, differential scanning calorimetry (DSC), X-ray diffraction (XRD), gel permeation chromatography (GPC), encapsulation efficiency (EE) and in vitro drug release. Gamma-irradiation of RM-loaded microspheres did not affect EE, DSC and XRD patterns. After gamma-irradiation, changes on the surface were observed by SEM, but no significant difference in mean particle size was observed. GPC measurements showed a decrease in molecular weight of the polymer after five days of in vitro release. The similarity factor value between irradiated and non-irradiates microspheres was <50, indicating the non-similarity of the release profiles. The sterilization technique had an effect on the integrity of polymeric system, significantly affecting in vitro release of RM from PLGA microspheres. Therefore, from our results we conclude that gamma-irradiation is not a suitable sterilization procedure for this formulation

OKVAR-Boost: a novel boosting algorithm to infer nonlinear dynamics and interactions in gene regulatory networks.

Science.gov (United States)

Lim, Néhémy; Senbabaoglu, Yasin; Michailidis, George; d'Alché-Buc, Florence

2013-06-01

Reverse engineering of gene regulatory networks remains a central challenge in computational systems biology, despite recent advances facilitated by benchmark in silico challenges that have aided in calibrating their performance. A number of approaches using either perturbation (knock-out) or wild-type time-series data have appeared in the literature addressing this problem, with the latter using linear temporal models. Nonlinear dynamical models are particularly appropriate for this inference task, given the generation mechanism of the time-series data. In this study, we introduce a novel nonlinear autoregressive model based on operator-valued kernels that simultaneously learns the model parameters, as well as the network structure. A flexible boosting algorithm (OKVAR-Boost) that shares features from L2-boosting and randomization-based algorithms is developed to perform the tasks of parameter learning and network inference for the proposed model. Specifically, at each boosting iteration, a regularized Operator-valued Kernel-based Vector AutoRegressive model (OKVAR) is trained on a random subnetwork. The final model consists of an ensemble of such models. The empirical estimation of the ensemble model's Jacobian matrix provides an estimation of the network structure. The performance of the proposed algorithm is first evaluated on a number of benchmark datasets from the DREAM3 challenge and then on real datasets related to the In vivo Reverse-Engineering and Modeling Assessment (IRMA) and T-cell networks. The high-quality results obtained strongly indicate that it outperforms existing approaches. The OKVAR-Boost Matlab code is available as the archive: http://amis-group.fr/sourcecode-okvar-boost/OKVARBoost-v1.0.zip. Supplementary data are available at Bioinformatics online.

Simultaneous regression of Philadelphia chromosome and multiple nonrecurrent clonal chromosomal abnormalities with imatinib mesylate in a patient autografted 22 years before for chronic myelogenous leukemia.

Science.gov (United States)

Van Den Akker, J; Coppo, P; Portnoï, M F; Barbu, V; Bories, D; Gorin, N C

2007-09-01

A 31-year-old patient developed chronic myelogenous leukemia (CML) in November, 1983. In November 1984, following a diagnosis of acceleration, he received an autologous hemopoietic transplant after conditioning with cyclophosphamide and total body irradiation. The autologous marrow was purged with mafosfamide. Over 20 years, the patient remained in chronic phase of CML. Multiple nonrecurrent clonal chromosomal abnormalities appeared leading to a very complex karyotype, including among others involvement of chromosomes 1, 7, 9, 13, 19, and X. Fluorescent in situ hybridization showed that the two chromosomes 9 were involved. Acute myeloid crisis was diagnosed in February, 2004. Treatment with imatinib mesylate resulted within 6 months in a total disappearance of all chromosomal abnormalities with a complete cytogenetic and molecular response, which persists 3 years later. We question whether the ex vivo purging procedure with mafosfamide has favored the occurrence of these particular cytogenetic abnormalities (with no independent oncogenic potential) within the original leukemic stem cell pool. It remains unclear whether the autologous transplantation has indeed resulted into some prolongation of the duration of the chronic phase, which lasted for 20 years. At time of acute crisis, the dramatic response to imatinib mesylate leading to a complete cytogenetic and molecular response is noteworthy.

Boosting Learning Algorithm for Stock Price Forecasting

Science.gov (United States)

Wang, Chengzhang; Bai, Xiaoming

2018-03-01

To tackle complexity and uncertainty of stock market behavior, more studies have introduced machine learning algorithms to forecast stock price. ANN (artificial neural network) is one of the most successful and promising applications. We propose a boosting-ANN model in this paper to predict the stock close price. On the basis of boosting theory, multiple weak predicting machines, i.e. ANNs, are assembled to build a stronger predictor, i.e. boosting-ANN model. New error criteria of the weak studying machine and rules of weights updating are adopted in this study. We select technical factors from financial markets as forecasting input variables. Final results demonstrate the boosting-ANN model works better than other ones for stock price forecasting.

Validation of Simultaneous Quantitative Method of HIV Protease Inhibitors Atazanavir, Darunavir and Ritonavir in Human Plasma by UPLC-MS/MS

Directory of Open Access Journals (Sweden)

Tulsidas Mishra

2014-01-01

Full Text Available Objectives. HIV protease inhibitors are used in the treatment of patients suffering from AIDS and they act at the final stage of viral replication by interfering with the HIV protease enzyme. The paper describes a selective, sensitive, and robust method for simultaneous determination of three protease inhibitors atazanavir, darunavir and ritonavir in human plasma by ultra performance liquid chromatography-tandem mass spectrometry. Materials and Methods. The sample pretreatment consisted of solid phase extraction of analytes and their deuterated analogs as internal standards from 50 μL human plasma. Chromatographic separation of analytes was performed on Waters Acquity UPLC C18 (50 × 2.1 mm, 1.7 μm column under gradient conditions using 10 mM ammonium formate, pH 4.0, and acetonitrile as the mobile phase. Results. The method was established over a concentration range of 5.0–6000 ng/mL for atazanavir, 5.0–5000 ng/mL for darunavir and 1.0–500 ng/mL for ritonavir. Accuracy, precision, matrix effect, recovery, and stability of the analytes were evaluated as per US FDA guidelines. Conclusions. The efficiency of sample preparation, short analysis time, and high selectivity permit simultaneous estimation of these inhibitors. The validated method can be useful in determining plasma concentration of these protease inhibitors for therapeutic drug monitoring and in high throughput clinical studies.

HIV Therapies and the Kidney: Some Good, Some Not So Good?

DEFF Research Database (Denmark)

Ryom, Lene; Mocroft, Amanda; Lundgren, Jens

2012-01-01

declining eGFR in persons without clinical symptoms of urolithiasis, especially when the plasma drug concentration is boosted by concomitant ritonavir use. In 2012, only a minority of HIV-positive individuals are affected by drug-induced nephrotoxicity. However, in the future, the clinical impact and hence...... the requirement for more research in this area will likely increase due to ageing and continued cART exposure of the HIV-positive population....

Cytoprotective effect of imatinib mesylate in non-BCR-ABL-expressing cells along with autophagosome formation

International Nuclear Information System (INIS)

Ohtomo, Tadashi; Miyazawa, Keisuke; Naito, Munekazu; Moriya, Shota; Kuroda, Masahiko; Itoh, Masahiro; Tomoda, Akio

2010-01-01

Treatment with imatinib mesylate (IM) results in an increased viable cell number of non-BCR-ABL-expressing cell lines by inhibiting spontaneous apoptosis. Electron microscopy revealed an increase of autophagosomes in response to IM. IM attenuated the cytotoxic effect of cytosine arabinoside, as well as inhibiting cell death with serum-deprived culture. Cytoprotection with autophagosome formation by IM was observed in various leukemia and cancer cell lines as well as normal murine embryonic fibroblasts (MEFs). Complete inhibition of autophagy by knockdown of atg5 in the Tet-off atg5 -/- MEF system attenuated the cytoprotective effect of IM, indicating that the effect is partially dependent on autophagy. However, cytoprotection by IM was not mediated through suppression of ROS production via mitophagy, ER stress via ribophagy, or proapoptotic function of ABL kinase. Although the target tyrosine kinase(s) of IM remains unclear, our data provide novel therapeutic possibilities of using IM for cytoprotection.

Spectrophotometric Determination of Gemifloxacin Mesylate in Pharmaceutical Formulations Through Ion-Pair Complex Formation

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Marothu Vamsi Krishna

2008-01-01

Full Text Available Four simple and sensitive ion-pairing spectrophotometric methods have been described for the assay of gemifloxacin mesylate (GFX either in pure form or in pharmaceutical formulations. The developed methods involve formation of colored chloroform extractable ion-pair complexes of the drug with safranin O (SFN O and methylene blue (MB in basic medium; Napthol blue 12BR (NB 12BR and azocaramine G (AG in acidic medium. The extracted complexes showed absorbance maxima at 525, 650, 620 and 540 nm for SFN O, MB, NB 12BR and AG, respectively.Beer's law is obeyed in the concentration ranges 3-15, 4-20, 2-10 and 2-10 μg/mL with molar absorptivity of 2.81 × 104, 2.20 x 104, 4.02 × 104 and 4.15 × 104 L mole−1 cm−1 and relative standard deviation of 0.077, 0.104, 0.080 and 0.103% for SFN O, MB, NB 12BR and AG, respectively. These methods have been successfully applied for the assay of drug in pharmaceutical formulations. No interference was observed from common pharmaceutical adjuvants. Results of analysis were validated statistically and through recovery studies.

Face Alignment Using Boosting and Evolutionary Search

NARCIS (Netherlands)

Zhang, Hua; Liu, Duanduan; Poel, Mannes; Nijholt, Antinus; Zha, H.; Taniguchi, R.-I.; Maybank, S.

2010-01-01

In this paper, we present a face alignment approach using granular features, boosting, and an evolutionary search algorithm. Active Appearance Models (AAM) integrate a shape-texture-combined morphable face model into an efficient fitting strategy, then Boosting Appearance Models (BAM) consider the

Inelastic Boosted Dark Matter at direct detection experiments

Science.gov (United States)

Giudice, Gian F.; Kim, Doojin; Park, Jong-Chul; Shin, Seodong

2018-05-01

We explore a novel class of multi-particle dark sectors, called Inelastic Boosted Dark Matter (iBDM). These models are constructed by combining properties of particles that scatter off matter by making transitions to heavier states (Inelastic Dark Matter) with properties of particles that are produced with a large Lorentz boost in annihilation processes in the galactic halo (Boosted Dark Matter). This combination leads to new signals that can be observed at ordinary direct detection experiments, but require unconventional searches for energetic recoil electrons in coincidence with displaced multi-track events. Related experimental strategies can also be used to probe MeV-range boosted dark matter via their interactions with electrons inside the target material.

Effect of six antiretroviral drugs (delavirdine, stavudine, lamivudine, nelfinavir, amprenavir and lopinavir/ritonavir in association) on albino pregnant rats (Rattus norvegicus Albinus, Rodentia, Mammalia): biological assay.

Science.gov (United States)

Nakamura, M U; Araujo Júnior, E; Simões, J M; Oliveria, R M Filho; Kulay, L Júnior

2014-08-01

To compare the chronic effects of antiretrovirals (lamivudine, stavudine, delavirdine, nelfinavir, amprenavir and an association of lopinavir/ritonavir) on albino pregnant rats. Review. Department of Obstetrics, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. This was a comparative retrospective study formed by 18 groups of 10 pregnant rats each, which were nearly three months of age and weighed 200 g. All of them were medicated every day using a stomach probe, while the control group was given 1 mL of distilled water. The study groups received lamivudine (at 5, 15 and 45 mg/kg/day); stavudine (at 1, 3 and 9 mg/kg/day); nelfinavir (at 40, 120 and 360 mg/kg/day); amprenavir (at 46, 138 and 414 mg/kg/day); lopinavir/ritonavir (at 12.8/3.2, 38.4/9.6 and 115/28.8 mg/kg/day) and delavirdine (at 20 and 60 mg/kg/day). These represented 1, 3 and 9 times the human therapeutic dose, except for the last drug, for which the 9-times dose was not used. Maternal, litter and placental weights, implantation and reabsorption numbers, major external fetal malformations and fetal and maternal deaths were evaluated. The Kruskal-Wallis test was used to compare quantitative variables and the chi-square test was used to compare qualitative variables. At all three doses, stavudine increased the maternal weight (p=0.001), while lamivudine at 3- and 9-times doses reduced it (p0.05). Stavudine at all doses reduced the litter weights (p<0.001); however, lamivudine at the usual and 3-times doses, delavirdine at 3-times dose, and amprenavir at 3-times dose increased the litter weight (p<0.001). In the maternal compartment, we observed lethal toxicity in the pregnant rats that received amprenavir and ritonavir/lopinavir; and maternal weight change with lamivudine and stavudine. In the fetal compartment, adverse effects were observed in relation to litter weight from stavudine, lamivudine, delavirdine and amprenavir.

Fast neutron boost for the treatment of grade IV astrocytomas

International Nuclear Information System (INIS)

Breteau, N.; Destembert, B.; Favre, A.; Pheline, C.; Schlienger, M.

1989-01-01

A previous study, on grade IV astrocytomas, compared a combination of photons and fast neutron boost to photons only, both treatments being delivered following a concentrated irradiation schedule. A slight improvement in survival was observed after neutron boost for non operated patients, but not for operated patients. Since death was always related to local recurrence and since no complication occurred after neutron boost, the neutron dose was increased from 6 to 7 Gy in January 1985. No improvement in survival was observed for patients treated with neutron boost after complete resection. After subtotal resection, the group that was treated with the higher neutron boost (7 Gy) showed a significant benefit in survival at twelve months. When patients had only a biopsy before irradiation, there was a benefit in survival after neutron boost, but no additional benefit was gained when the size of the neutron boost was increased from 6 to 7 Gy. (orig.) [de

Orthodontics Align Crooked Teeth and Boost Self-Esteem

Science.gov (United States)

... desktop! more... Orthodontics Align Crooked Teeth and Boost Self- esteem Article Chapters Orthodontics Align Crooked Teeth and Boost Self- esteem print full article print this chapter email this ...

Experiencia del tratamiento con lopinavirritonavir en pacientes del programa de infección por VIH en un hospital universitario, Bogotá, Colombia Experience with lopinavir/ritonavir for patients with HIV infection at an university hospital in Bogotá, Colombia

Directory of Open Access Journals (Sweden)

JORGE ALBERTO CORTÉS

2006-12-01

Full Text Available Resumen La terapia antirretroviral con varios medicamentos de diferentes familias es altamente efectiva para controlar la replicación viral y mejorar la respuesta inmunológica y las posibilidades de supervivencia en los pacientes infectados por el VIH. Objetivos. Evaluar la eficacia del tratamiento de rescate con lopinavir/ritonavir en una cohorte de pacientes en un país subdesarrollado. Materiales y métodos. Se hizo una revisión retrospectiva de los pacientes que recibieron tratamiento antirretroviral con la combinación de lopinavir/ritonavir en el Hospital Universitario de San Ignacio. Se seleccionaron los pacientes del programa integral de atención a pacientes con infección por VIH y se evaluaron la respuesta virológica e inmunológica, la tolerancia y el cumplimiento de la terapia. Resultados. Veinticinco pacientes con tratamiento anitrretroviral previo y un paciente con tratamiento por primera vez tuvieron un seguimiento promedio de 13 meses, con medición de la carga viral y recuento de CD4. El promedio de esquemas antirretrovirales utilizados fue de 2,28. El recuento de CD4 se elevó significativamente y ninguno de los pacientes con seguimiento de 36 meses tuvo recuentos de CD4 menores a 50 por mililitro. El porcentaje de pacientes con carga viral indetectable (Objective. To evaluate the efficacy of rescue treatment with lopinavir/ritonavir in a cohort of patients infected with HIV in a developing country. Methods. Retrospective evaluation of patients who received combined antiretroviral treatment (cART using lopinavir/ritonavir at an universitary hospital in Bogotá, Colombia. The virological and immunological follow up was evaluated, together with the tolerance and adherence. Results. 25 patients with previous cART and a patient naïve had a mean follow up of 13 months. The mean of previously used cART schemes was 2.28. The CD4 count increased over time and none of the individuals with a follow up of 36 months had CD4 counts

Pharmacokinetics and Pharmacodynamics of Atazanavir in HIV-1-Infected Children Treated With Atazanavir Powder and Ritonavir: Combined Analysis of the PRINCE-1 and -2 Studies.

Science.gov (United States)

Sevinsky, Heather; Zaru, Luna; Wang, Reena; Xu, Xiaohui; Pikora, Cheryl; Correll, Todd A; Eley, Timothy

2018-06-01

Two clinical studies (PRINCE-1 and -2) in HIV-1-infected children assessed the safety, efficacy and pharmacokinetics of dual nucleos(t)ide reverse transcriptase inhibitor background therapy plus once-daily atazanavir (ATV) powder formulation boosted with ritonavir (ATV + RTV). Here, we present a combined analysis of ATV pharmacokinetics and pharmacodynamics across these studies. Intensive 24-hour pharmacokinetic profiles at steady state compared ATV exposures (area under the concentration-time curve in one dosing interval) in 5 ATV + RTV baseline weight-band dosing categories, with historic data in adults receiving ATV + RTV 300/100 mg capsules. Repeated ATV Ctrough measurements over 48 weeks explored relationships between ATV composite Ctrough quartiles (CCQs) with virologic efficacy and key safety parameters. Of 146 children included in this combined analysis, 49.3% were male, 56.8% were Black/African American and 62.3% were antiretroviral experienced. Proportions with HIV-1 RNA <50 copies/mL at week 48 were 13/32, 24/32, 19/32 and 13/28 in the lowest through highest ATV CCQs, respectively. Mean changes from baseline in total bilirubin at week 48 were +0.3, +0.5, +0.6 and +1.0 mg/dL in the lowest through highest ATV CCQs, respectively. Corresponding proportions with adverse events of hyperbilirubinemia by week 48 were 1/36, 4/36, 5/36 and 13/35, respectively. Changes from baseline in total amylase or electrocardiogram parameters and adverse events of diarrhea did not vary by ATV CCQs. Weight-band dosing of ATV + RTV plus optimized dual nucleos(t)ide reverse transcriptase inhibitors in young HIV-1-infected children achieved similar ATV exposure to that in adults; no unexpected safety findings occurred, and with the exception of lower virologic suppression in the lowest ATV CCQ, there was no apparent trend in virologic suppression across ATV CCQs.

Boost.Unicode : a Unicode library for C++

OpenAIRE

Wien, Erik; Gigstad, Lars Erik

2005-01-01

The project has resulted in a Unicode string library for C++ that abstracts away the complexity of working with Unicode text. The idea behind the project originated from the Boost community's developer mailings lists, and is developed with inclusion into the Boost library collection in mind.

Preparation of 14C-labeled 8,9-didehydro-6,8-dimethyl-2-methylthioergoline mesylate, a dopamine antagonist potentially useful in the treatment of schizophrenia

International Nuclear Information System (INIS)

Wheeler, W.J.

1988-01-01

We have prepared 14 C-labeled 8,9-didehydro-6,8-dimethyl-2-methyl-thioergoline mesylate (LY 170542), a dopamine antagonist potentially useful as an anti-psychotic. The 14 C-label was introduced via a novel application of the Wittig reaction on 1-(4'-toluene-sulfonyl)-8,9-didehydro-6-methyl-ergolin-8-one and subsequent reduction of 1-(4'-toluenesulfonyl)-17-[ 14 C]-lysergene by lithium/ammonia at -33 0 C. The 17-[ 14 C]-agroclavine thus prepared was converted into 17-[ 14 C]-LY 170542 by reaction with methanesulfenyl chloride/methanesulfonic acid. (author)

Inelastic Boosted Dark Matter at direct detection experiments

OpenAIRE

Giudice, Gian F.; Kim, Doojin; Park, Jong-Chul; Shin, Seodong

2018-01-01

We explore a novel class of multi-particle dark sectors, called Inelastic Boosted Dark Matter (iBDM). These models are constructed by combining properties of particles that scatter off matter by making transitions to heavier states (Inelastic Dark Matter) with properties of particles that are produced with a large Lorentz boost in annihilation processes in the galactic halo (Boosted Dark Matter). This combination leads to new signals that can be observed at ordinary direct detection experimen...

Boosted top: experimental tools overview

CERN Document Server

Usai, Emanuele

2015-01-01

An overview of tools and methods for the reconstruction of high-boost top quark decays at the LHC is given in this report. The focus is on hadronic decays, in particular an overview of the current status of top quark taggers in physics analyses is presented. The most widely used jet substructure techniques, normally used in combination with top quark taggers, are reviewed. Special techniques to treat pileup in large cone jets are described, along with a comparison of the performance of several boosted top quark reconstruction techniques.

A PIPO Boost Converter with Low Ripple and Medium Current Application

Science.gov (United States)

Bandri, S.; Sofian, A.; Ismail, F.

2018-04-01

This paper presents a Parallel Input Parallel Output (PIPO) boost converter is proposed to gain power ability of converter, and reduce current inductors. The proposed technique will distribute current for n-parallel inductor and switching component. Four parallel boost converters implement on input voltage 20.5Vdc to generate output voltage 28.8Vdc. The PIPO boost converter applied phase shift pulse width modulation which will compare with conventional PIPO boost converters by using a similar pulse for every switching component. The current ripple reduction shows an advantage PIPO boost converter then conventional boost converter. Varies loads and duty cycle will be simulated and analyzed to verify the performance of PIPO boost converter. Finally, the unbalance of current inductor is able to be verified on four area of duty cycle in less than 0.6.

Concomitant boost radiotherapy for muscle invasive bladder cancer

Energy Technology Data Exchange (ETDEWEB)

Pos, Floris J; Tienhoven, Geertjan van; Hulshof, Maarten C.C.M.; Koedooder, Kees; Gonzalez Gonzalez, Dionisio

2003-07-01

Purpose: To evaluate the feasibility and efficacy of a concomitant partial bladder boost schedule in radiotherapy for invasive bladder cancer, coupling a limited boost volume with shortening of the overall treatment time. Methods and materials: Between 1994 and 1999, 50 patients with a T2-T4 N0M0 transitional cell carcinoma of the bladder received radiotherapy delivered in a short overall treatment time with a concomitant boost technique. With this technique a dose of 40 Gy in 2-Gy fractions was administered to the small pelvis with a concomitant boost limited to the bladder tumor area plus margin of 15 Gy in fractions of 0.75 Gy. The total tumor dose was 55 Gy in 20 fractions in 4 weeks. Toxicity was scored according to EORTC/RTOG toxicity criteria. Results: The feasibility of the treatment was good. Severe acute toxicity {>=}G3 was observed in seven patients (14%). Severe late toxicity {>=}G3 was observed in six patients (13%). Thirty-seven patients (74%) showed a complete and five (10 %) a partial remission after treatment. The actuarial 3-year freedom of local progression was 55%. Conclusion: In external radiotherapy for muscle invasive bladder cancer a concomitant boost technique coupling a partial bladder boost with shortening of the overall treatment time provides a high probability of local control with acceptable toxicity.

Concomitant boost radiotherapy for muscle invasive bladder cancer

International Nuclear Information System (INIS)

Pos, Floris J.; Tienhoven, Geertjan van; Hulshof, Maarten C.C.M.; Koedooder, Kees; Gonzalez Gonzalez, Dionisio

2003-01-01

Purpose: To evaluate the feasibility and efficacy of a concomitant partial bladder boost schedule in radiotherapy for invasive bladder cancer, coupling a limited boost volume with shortening of the overall treatment time. Methods and materials: Between 1994 and 1999, 50 patients with a T2-T4 N0M0 transitional cell carcinoma of the bladder received radiotherapy delivered in a short overall treatment time with a concomitant boost technique. With this technique a dose of 40 Gy in 2-Gy fractions was administered to the small pelvis with a concomitant boost limited to the bladder tumor area plus margin of 15 Gy in fractions of 0.75 Gy. The total tumor dose was 55 Gy in 20 fractions in 4 weeks. Toxicity was scored according to EORTC/RTOG toxicity criteria. Results: The feasibility of the treatment was good. Severe acute toxicity ≥G3 was observed in seven patients (14%). Severe late toxicity ≥G3 was observed in six patients (13%). Thirty-seven patients (74%) showed a complete and five (10 %) a partial remission after treatment. The actuarial 3-year freedom of local progression was 55%. Conclusion: In external radiotherapy for muscle invasive bladder cancer a concomitant boost technique coupling a partial bladder boost with shortening of the overall treatment time provides a high probability of local control with acceptable toxicity

Measurement and prediction of dabigatran etexilate mesylate Form II solubility in mono-solvents and mixed solvents

International Nuclear Information System (INIS)

Xiao, Yan; Wang, Jingkang; Wang, Ting; Ouyang, Jinbo; Huang, Xin; Hao, Hongxun; Bao, Ying; Fang, Wen; Yin, Qiuxiang

2016-01-01

Highlights: • Solubility of DEM Form II in mono-solvents and binary solvent mixtures was measured. • Regressed UNIFAC model was used to predict the solubility in solvent mixtures. • The experimental solubility data were correlated by different models. - Abstract: UV spectrometer method was used to measure the solubility data of dabigatran etexilate mesylate (DEM) Form II in five mono-solvents (methanol, ethanol, ethane-1,2-diol, DMF, DMAC) and binary solvent mixtures of methanol and ethanol in the temperature range from 287.37 K to 323.39 K. The experimental solubility data in mono-solvents were correlated with modified Apelblat equation, van’t Hoff equation and λh equation. GSM model and Modified Jouyban-Acree model were employed to correlate the solubility data in mixed solvent systems. And Regressed UNIFAC model was used to predict the solubility of DEM Form II in the binary solvent mixtures. Results showed that the predicted data were consistent with the experimental data.

Introducing state-trajectory control for the synchronous interleaved boost converter

DEFF Research Database (Denmark)

Peña-Alzola, Rafael; Ksiazek, Peter; Ordonez, Martin

2015-01-01

Synchronous interleaved boost converters (SIBCs) result in lower ripple currents and bidirectional power flow. The boost topology has a non-minimum phase characteristic, producing instability problems when a large bandwidth is required. Linear controllers inherently limit the boost controller...

4 Types of Foods that Boost Your Memory

Science.gov (United States)

... 4 Types of Foods to Help Boost Your Memory By Marisa Moore, MBA, RDN, LD Published November ... in brain health. The best menu for boosting memory and brain function encourages good blood flow to ...

Drug-Drug Interactions Between the Anti-Hepatitis C Virus 3D Regimen of Ombitasvir, Paritaprevir/Ritonavir, and Dasabuvir and Eight Commonly Used Medications in Healthy Volunteers.

Science.gov (United States)

Polepally, Akshanth R; King, Jennifer R; Ding, Bifeng; Shuster, Diana L; Dumas, Emily O; Khatri, Amit; Chiu, Yi-Lin; Podsadecki, Thomas J; Menon, Rajeev M

2016-08-01

The three direct-acting antiviral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D regimen) is approved for treatment of hepatitis C virus (HCV) genotype 1 infection. Drug-drug interaction (DDI) studies of the 3D regimen and commonly used medications were conducted in healthy volunteers to provide information on coadministering these medications with or without dose adjustments. Three phase I studies evaluated DDIs between the 3D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily + dasabuvir 250 mg twice daily) and hydrocodone bitartrate/acetaminophen (5/300 mg), metformin hydrochloride (500 mg), diazepam (2 mg), cyclobenzaprine hydrochloride (5 mg), carisoprodol (250 mg), or sulfamethoxazole/trimethoprim (SMZ/TMP) (800/160 mg twice daily), all administered orally. DDI magnitude was determined using geometric mean ratios and 90 % confidence intervals for the maximum plasma concentration (C max) and area under the plasma concentration-time curve (AUC). Changes in exposures (C max and AUC geometric mean ratios) of acetaminophen, metformin, sulfamethoxazole, trimethoprim, and diazepam were ≤25 % upon coadministration with the 3D regimen. The C max and AUC of nordiazepam, an active metabolite of diazepam, increased by 10 % and decreased by 44 %, respectively. Exposures of cyclobenzaprine and carisoprodol decreased by ≤40 and ≤46 %, respectively, whereas exposures of hydrocodone increased up to 90 %. Ombitasvir, paritaprevir, ritonavir, and dasabuvir exposures changed by ≤25 %, except for a 37 % decrease in paritaprevir C max with metformin and a 33 % increase in dasabuvir AUC with SMZ/TMP. Acetaminophen, metformin, sulfamethoxazole, and trimethoprim can be coadministered with the 3D regimen without dose adjustment. Higher doses may be needed for diazepam, cyclobenzaprine, and carisoprodol based on clinical monitoring. A 50 % lower dose and/or clinical monitoring should be considered for hydrocodone. No dose

Diode-Assisted Buck-Boost Current Source Inverters

DEFF Research Database (Denmark)

Gao, F.; Cai, Liang; Loh, P.C.

2007-01-01

This paper presents a couple of novel current source inverters (CSIs) with the enhanced current buckboost capability. With the unique diode-inductor network added between current source inverter circuitry and current boost elements, the proposed buck-boost current source inverters demonstrate...... uninfluenced. Lastly, all theoretical findings were verified experimentally using constructed laboratory prototypes....

Primary Paralleled Isolated Boost Converter with Extended Operating Voltage Range

DEFF Research Database (Denmark)

Hernandez Botella, Juan Carlos; Sen, Gökhan; Mira Albert, Maria del Carmen

2012-01-01

Applications requiring wide input and output voltage range cannot often be satisfied by using buck or boost derived topologies. Primary paralleled isolated boost converter (PPIBC) [1]-[2] is a high efficiency boost derived topology. This paper proposes a new operation mode for extending the input...

Symmetry boost of the fidelity of Shor factoring

Science.gov (United States)

Nam, Y. S.; Blümel, R.

2018-05-01

In Shor's algorithm quantum subroutines occur with the structure F U F-1 , where F is a unitary transform and U is performing a quantum computation. Examples are quantum adders and subunits of quantum modulo adders. In this paper we show, both analytically and numerically, that if, in analogy to spin echoes, F and F-1 can be implemented symmetrically when executing Shor's algorithm on actual, imperfect quantum hardware, such that F and F-1 have the same hardware errors, a symmetry boost in the fidelity of the combined F U F-1 quantum operation results when compared to the case in which the errors in F and F-1 are independently random. Running the complete gate-by-gate implemented Shor algorithm, we show that the symmetry-induced fidelity boost can be as large as a factor 4. While most of our analytical and numerical results concern the case of over- and under-rotation of controlled rotation gates, in the numerically accessible case of Shor's algorithm with a small number of qubits, we show explicitly that the symmetry boost is robust with respect to more general types of errors. While, expectedly, additional error types reduce the symmetry boost, we show explicitly, by implementing general off-diagonal SU (N ) errors (N =2 ,4 ,8 ), that the boost factor scales like a Lorentzian in δ /σ , where σ and δ are the error strengths of the diagonal over- and underrotation errors and the off-diagonal SU (N ) errors, respectively. The Lorentzian shape also shows that, while the boost factor may become small with increasing δ , it declines slowly (essentially like a power law) and is never completely erased. We also investigate the effect of diagonal nonunitary errors, which, in analogy to unitary errors, reduce but never erase the symmetry boost. Going beyond the case of small quantum processors, we present analytical scaling results that show that the symmetry boost persists in the practically interesting case of a large number of qubits. We illustrate this result

An Update on Statistical Boosting in Biomedicine.

Science.gov (United States)

Mayr, Andreas; Hofner, Benjamin; Waldmann, Elisabeth; Hepp, Tobias; Meyer, Sebastian; Gefeller, Olaf

2017-01-01

Statistical boosting algorithms have triggered a lot of research during the last decade. They combine a powerful machine learning approach with classical statistical modelling, offering various practical advantages like automated variable selection and implicit regularization of effect estimates. They are extremely flexible, as the underlying base-learners (regression functions defining the type of effect for the explanatory variables) can be combined with any kind of loss function (target function to be optimized, defining the type of regression setting). In this review article, we highlight the most recent methodological developments on statistical boosting regarding variable selection, functional regression, and advanced time-to-event modelling. Additionally, we provide a short overview on relevant applications of statistical boosting in biomedicine.

Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial

Directory of Open Access Journals (Sweden)

Eduardo Arathoon

2017-01-01

Full Text Available Objective: VIOLIN (TMC125IFD3002; NCT01422330 evaluated the safety, tolerability, and pharmacokinetics of etravirine with antiretrovirals other than darunavir/ritonavir in HIV-1-infected patients. Methods: In a 48-week, phase IV, single-arm, multicenter study, patients on prior antiretroviral therapy (⩾8 weeks who needed to change regimen for virologic failure (viral load ⩾ 500 copies/mL or simplification/adverse events (viral load < 50 copies/mL received etravirine 200 mg bid with ⩾1 other active antiretroviral, excluding darunavir/ritonavir or only nucleoside/tide reverse transcriptase inhibitors. Results: Of 211 treated patients, 73% (n = 155 had baseline viral load ⩾ 50 copies/mL and 27% (n = 56 had baseline viral load < 50 copies/mL. Protease inhibitors were the most common background antiretrovirals (83%. Diarrhea was the most frequent adverse event (17%. Serious adverse events (no rash occurred in 5% of patients; none were etravirine related. Overall, median etravirine AUC12h was 5390 ng h/mL and C0h was 353 ng/mL (N = 199. Week 48 virologic response rates (viral load < 50 copies/mL; Food and Drug Administration Snapshot algorithm were 48% (74/155 (baseline viral load ⩾ 50 copies/mL and 75% (42/56 (baseline viral load < 50 copies/mL. Virologic failure rates were 42% and 13%, respectively. The most frequently emerging etravirine resistance-associated mutations in virologic failures were Y181C, E138A, and M230L. Virologic response rates for patients with baseline viral load ⩾ 50 copies/mL were 38% (30/79 (non-adherent versus 64% (44/69 (adherent subset. Conclusion: Etravirine 200 mg bid in combination with antiretrovirals other than darunavir/ritonavir was well tolerated in the studied treatment-experienced HIV-1-infected population. The overall etravirine safety and tolerability profile and pharmacokinetics (specifically in those patients who were adherent

Internationalization of Boost Juice to Malaysia

OpenAIRE

Jane L. Menzies; Stuart C. Orr

2014-01-01

This case describes the process that the Australian juice retail chain, Boost Juice, has used to internationalize to Malaysia. The main objective of this case is to demonstrate good practice in regard to internationalization. The case provides the background of the juice bar industry in Malaysia and determines that it is an attractive market for new start-up juice bars. An analysis of Boost Juice's capability determined that the company utilized the skills of its staff, product innovations, b...

Radiographer-led breast boost localisation – A service evaluation study

International Nuclear Information System (INIS)

Smith, S.; Comins, C.

2015-01-01

A radiation boost to the tumour bed as part of breast conserving therapy reduces the rate of local recurrence. Radiographer-led planning for tangential field radiotherapy has been the practice at our centre since 2007. The transition from conventional simulation to computed tomography (CT) and virtual simulation enhanced the radiographer's role in the breast planning process. Electron boost mark ups continued to be marked up freehand by doctors using available imaging to determine tumour bed. The paper reports on a service evaluation undertaken to establish a change in practice for electron breast boosts to be simulated using the virtual simulator by suitably trained radiographers. The retrospective simulation of ten patients confirmed the consistency of radiographer tumour bed localisation, followed by the prospective simulation of ten patients' boost fields. The introduction of a radiographer-led planning breast boost service has given greater autonomy and job satisfaction to individuals as well as resulting in a cost effective use of available resources. - Highlights: • A service evaluation study was undertaken to train a radiographer to perform breast boost planning. • Retrospective breast boost planning established proposed technique was workable. • Prospective planning by radiographer proved their competence. • Introduction of new technique provided job satisfaction and service improvement

An Update on Statistical Boosting in Biomedicine

Directory of Open Access Journals (Sweden)

Andreas Mayr

2017-01-01

Full Text Available Statistical boosting algorithms have triggered a lot of research during the last decade. They combine a powerful machine learning approach with classical statistical modelling, offering various practical advantages like automated variable selection and implicit regularization of effect estimates. They are extremely flexible, as the underlying base-learners (regression functions defining the type of effect for the explanatory variables can be combined with any kind of loss function (target function to be optimized, defining the type of regression setting. In this review article, we highlight the most recent methodological developments on statistical boosting regarding variable selection, functional regression, and advanced time-to-event modelling. Additionally, we provide a short overview on relevant applications of statistical boosting in biomedicine.

Boosted jets

International Nuclear Information System (INIS)

Juknevich, J.

2014-01-01

We present a study of the substructure of jets high transverse momentum at hadron colliders. A template method is introduced to distinguish heavy jets by comparing their energy distributions to the distributions of a set of templates which describe the kinematical information from signal or background. As an application, a search for a boosted Higgs boson decaying into bottom quarks in association with a leptonically decaying W boson is presented as well. (author)

Three-level boost converter with zero voltage transition

Directory of Open Access Journals (Sweden)

Kuo-Ing Hwu

2017-06-01

Full Text Available As compared with the traditional boost converter, the three-level boost converter possesses several advantages, such as lower switch voltage stresses and lower inductor current ripple. To improve the efficiency, this paper proposes a zero voltage transition (ZVT three-level boost converter. With the proposed ZVT circuit, the switches can achieve soft switching. Moreover, by using the voltage balance control, the output voltage can be equally across the output capacitors. In this study, the effectiveness of the proposed topology is verified by the experimental results based on the field-programmable gate array control.

The protease inhibitors ritonavir and saquinavir influence lipid metabolism: a pig model for the rapid evaluation of new drugs

DEFF Research Database (Denmark)

Petersen, E.; Mu, Huiling; Porsgaard, Trine

2010-01-01

a general decrease in polyunsaturated fatty acids; changes in both saturated and monounsaturated fatty acids were also apparent after antiretroviral treatment. The changes were observed after 4 weeks of treatment. At 4 weeks post-treatment, the levels of all fatty acids were lower compared with pretreatment...

Improved Stereo Matching With Boosting Method

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Shiny B

2015-06-01

Full Text Available Abstract This paper presents an approach based on classification for improving the accuracy of stereo matching methods. We propose this method for occlusion handling. This work employs classification of pixels for finding the erroneous disparity values. Due to the wide applications of disparity map in 3D television medical imaging etc the accuracy of disparity map has high significance. An initial disparity map is obtained using local or global stereo matching methods from the input stereo image pair. The various features for classification are computed from the input stereo image pair and the obtained disparity map. Then the computed feature vector is used for classification of pixels by using GentleBoost as the classification method. The erroneous disparity values in the disparity map found by classification are corrected through a completion stage or filling stage. A performance evaluation of stereo matching using AdaBoostM1 RUSBoost Neural networks and GentleBoost is performed.

Safety and Efficacy of Atazanavir Powder and Ritonavir in HIV-1-Infected Infants and Children From 3 Months to The PRINCE-2 Study.

Science.gov (United States)

Cotton, Mark F; Liberty, Afaaf; Torres-Escobar, Indiana; Gonzalez-Tome, Maria Isabel; Lissens, Jurgen; Zaru, Luna; Klauck, Isabelle; Cambilargiu, Daniela; Pikora, Cheryl; Correll, Todd A

2018-06-01

Novel antiretroviral formulations that are palatable, safe, and effective are needed for infants and children. PRINCE-2 is an ongoing clinical trial assessing safety, efficacy, and palatability of once-daily atazanavir powder formulation boosted with ritonavir (ATV + RTV) plus optimized dual nucleos(t)ide reverse transcriptase inhibitors therapy in antiretroviral-naïve/experienced children with screening HIV-1 RNA ≥1000 copies/mL. Children 3 months to <11 years received ATV + RTV by 5 baseline weight bands: 5 to <10 kg = 150/80 mg; 5 to <10 kg = 200/80 mg; 10 to <15 kg = 200/80 mg; 15 to <25 kg = 250/80 mg; and 25 to <35 kg = 300/100 mg. Of 99 treated children, 83.8% and 59.6% remained on ATV powder until 24 and 48 weeks, respectively. Through 48 weeks, the most common adverse events were upper respiratory tract infections (33.3%), gastroenteritis (28.3%), vomiting (21.2%) and hyperbilirubinemia (18.2%; none leading to treatment discontinuation). Serious adverse events occurred in 20.2% of patients. Laboratory grade 3-4 hyperbilirubinemia occurred in 9.2% and elevated total/pancreatic amylase in 33.7%/3.1%. At week 24, proportions with virologic suppression (HIV-1 RNA <50 copies/mL; intention-to-treat analysis) across weight bands were 10/23 (43.5%), 2/12 (16.5%), 10/21 (47.6%), 19/35 (54.3%) and 5/8 (62.5%), respectively. Virologic suppression was similar in antiretroviral-naïve/experienced patients and lowest in the 5 to <10 kg = 200/80 mg group, likely because of higher baseline HIV-1 RNA and discontinuation (66.7%). Overall, virologic suppression at weeks 24 (46.5%) and 48 (43.0%) was comparable. At week 48, 83.3% and 74.1% of caregivers reported no trouble giving ATV powder and RTV, respectively. ATV powder palatability, efficacy and lack of unexpected safety findings support its use for HIV-1-infected children ≥3 months to <11 years.

Topological Design and Modulation Strategy for Buck-Boost Three-Level Inverters

DEFF Research Database (Denmark)

Gao, Feng; Loh, Poh Chiang; Teodorescu, Remus

2009-01-01

To date, designed topologies for dc-ac inversion with both voltage buck and boost capabilities are mainly focused on two-level circuitries with extensions to three-level possibilities left nearly unexplored. Contributing to this area of research, this paper presents the design of a number of viable...... can perform distinct five-level line voltage and three-level phase voltage switching by simply controlling the active switches located in the designed voltage boost section of the circuits. As a cost saving option, one active switch can further be removed from the voltage boost section of the circuits...... buck-boost threelevel inverters that can also support bidirectional power conversion. The proposed front-end circuitry is developed from the C´ ukderived buck-boost two-level inverter, and by using the "alternative phase opposition disposition" modulation scheme, the buck-boost three-level inverters...

Boosted beta regression.

Directory of Open Access Journals (Sweden)

Matthias Schmid

Full Text Available Regression analysis with a bounded outcome is a common problem in applied statistics. Typical examples include regression models for percentage outcomes and the analysis of ratings that are measured on a bounded scale. In this paper, we consider beta regression, which is a generalization of logit models to situations where the response is continuous on the interval (0,1. Consequently, beta regression is a convenient tool for analyzing percentage responses. The classical approach to fit a beta regression model is to use maximum likelihood estimation with subsequent AIC-based variable selection. As an alternative to this established - yet unstable - approach, we propose a new estimation technique called boosted beta regression. With boosted beta regression estimation and variable selection can be carried out simultaneously in a highly efficient way. Additionally, both the mean and the variance of a percentage response can be modeled using flexible nonlinear covariate effects. As a consequence, the new method accounts for common problems such as overdispersion and non-binomial variance structures.

[Disappearance of a Philadelphia chromosome-positive clone and appearance of a -negative clone following treatment with imatinib mesylate in acute myelomonocytic leukemia].

Science.gov (United States)

Takahashi, Wataru; Arai, Yukihiro; Tadokoro, Jiro; Takeuchi, Kengo; Yamagata, Tetsuya; Mitani, Kinuko

2006-02-01

A 63-year-old female was diagnosed as having Philadelphia chromosome-positive acute myelomonocytic leukemia in June 2002. The patient received monotherapy with imatinib mesylate or combination therapy with DCM and idarubicin/cytarabine, both of which failed in attaining disease remission. However, the second imatinib administration plus CAG therapy resulted in disappearance of the Philadelphia chromosome-positive clone and increase of Philadelphia chromosome-negative cells. During a therapy-withholding period due to fungal infection, the Philadelphia chromosome-positive clone expanded and the patient died of cerebral hemorrhage in February 2003. The transient suppression of the Philadelphia chromosome-positive clone may have brought about amplification of the Philadelphia chromosome-negative cells after the secondary imatinib treatment.

CyberKnife Boost for Patients with Cervical Cancer Unable to Undergo Brachytherapy

International Nuclear Information System (INIS)

Haas, Jonathan Andrew; Witten, Matthew R.; Clancey, Owen; Episcopia, Karen; Accordino, Diane; Chalas, Eva

2012-01-01

Standard radiation therapy for patients undergoing primary chemosensitized radiation for carcinomas of the cervix usually consists of external beam radiation followed by an intracavitary brachytherapy boost. On occasion, the brachytherapy boost cannot be performed due to unfavorable anatomy or because of coexisting medical conditions. We examined the safety and efficacy of using CyberKnife stereotactic body radiotherapy (SBRT) as a boost to the cervix after external beam radiation in those patients unable to have brachytherapy to give a more effective dose to the cervix than with conventional external beam radiation alone. Six consecutive patients with anatomic or medical conditions precluding a tandem and ovoid boost were treated with combined external beam radiation and CyberKnife boost to the cervix. Five patients received 45 Gy to the pelvis with serial intensity-modulated radiation therapy boost to the uterus and cervix to a dose of 61.2 Gy. These five patients received an SBRT boost to the cervix to a dose of 20 Gy in five fractions of 4 Gy each. One patient was treated to the pelvis to a dose of 45 Gy with an external beam boost to the uterus and cervix to a dose of 50.4 Gy. This patient received an SBRT boost to the cervix to a dose of 19.5 Gy in three fractions of 6.5 Gy. Five percent volumes of the bladder and rectum were kept to ≤75 Gy in all patients (i.e., V75 Gy ≤ 5%). All of the patients remain locally controlled with no evidence of disease following treatment. Grade 1 diarrhea occurred in 4/6 patients during the conventional external beam radiation. There has been no grade 3 or 4 rectal or bladder toxicity. There were no toxicities observed following SBRT boost. At a median follow-up of 14 months, CyberKnife radiosurgical boost is well tolerated and efficacious in providing a boost to patients with cervix cancer who are unable to undergo brachytherapy boost. Further follow-up is required to see if these results remain durable.

Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment-naïve HIV-1-infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort.

Science.gov (United States)

Rokx, C; Gras, L; van de Vijver, Damc; Verbon, A; Rijnders, Bja

2016-09-01

Lamivudine (3TC) and emtricitabine (FTC) are considered interchangeable in recommended tenofovir disoproxil-fumarate (TDF)-containing combination antiretroviral therapies (cARTs). This statement of equivalence has not been systematically studied. We compared the treatment responses to 3TC and FTC combined with TDF in boosted protease inhibitor (PI)-based cART for HIV-1-infected patients. An observational study in the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort was carried out between 2002 and 2013. Virological failure rates, time to HIV RNA suppression treatment failure were analysed using multivariable logistic regression and Cox proportional hazard models. Sensitivity analyses included propensity score-adjusted models. A total of 1582 ART-naïve HIV-1-infected patients initiated 3TC or FTC with TDF and ritonavir-boosted darunavir (29.6%), atazanavir (41.5%), lopinavir (27.1%) or another PI (1.8%). Week 48 virological failure rates on 3TC and FTC were comparable (8.9% and 5.6%, respectively; P = 0.208). The multivariable adjusted odds ratio of virological failure when using 3TC instead of FTC with TDF in PI-based cART was 0.75 [95% confidence interval (CI) 0.32-1.79; P = 0.51]. Propensity score-adjusted models showed comparable results. The adjusted hazard ratio (HR) for treatment failure of 3TC compared with FTC was 1.15 (95% CI 0.58-2.27) within 240 weeks after cART initiation. The time to two consecutive HIV RNA measurements treatment failure after suppression treatment-naïve HIV-1-infected patients starting either 3TC/TDF or FTC/TDF and a ritonavir-boosted PI. © 2016 British HIV Association.

Sequentially delivered boost plans are superior to simultaneously delivered plans in head and neck cancer when the boost volume is located further away from the parotid glands

International Nuclear Information System (INIS)

Lamers-Kuijper, Emmy; Heemsbergen, Wilma; Mourik, Anke van; Rasch, Coen

2011-01-01

Purpose: To find parameters that predict which head and neck patients benefit from a sequentially delivered boost treatment plan compared to a simultaneously delivered plan, with the aim to spare the salivary glands. Methods and materials: We evaluated 50 recently treated head and neck cancer patients. Apart from the clinical plan with a sequentially (SEQ) given boost using an Intensity Modulated Radiotherapy Technique (IMRT), a simultaneous integrated boost (SIB) technique plan was constructed with the same beam set-up. The mean dose to the parotid glands was calculated and compared. The elective nodal areas were bilateral in all cases, with a boost on either one side or both sides of the neck. Results: When the parotid gland volume and the Planning Target Volume (PTV) for the boost overlap there is on average a lower dose to the parotid gland with a SIB technique (-1.2 Gy), which is, however, not significant (p = 0.08). For all parotid glands with no boost PTV overlap, there is a benefit from a SEQ technique compared to a SIB technique for the gland evaluated (on average a 2.5 Gy lower dose to the parotid gland, p < 0.001). When the distance between gland and PTV is 0-1 cm, this difference is on average 0.8 Gy, for 1-2 cm distance 2.9 Gy and for glands with a distance greater than 2 cm, 3.3 Gy. When the lymph nodes on the evaluated side are also included in the boost PTV, however, this relationship between the distance and the gain of a SEQ seems less clear. Conclusions: A sequentially delivered boost technique results in a better treatment plan for most cases, compared to a simultaneous integrated boost IMRT technique, if the boost PTV is more than 1 cm away from at least one parotid gland.

Clustering Using Boosted Constrained k-Means Algorithm

Directory of Open Access Journals (Sweden)

Masayuki Okabe

2018-03-01

Full Text Available This article proposes a constrained clustering algorithm with competitive performance and less computation time to the state-of-the-art methods, which consists of a constrained k-means algorithm enhanced by the boosting principle. Constrained k-means clustering using constraints as background knowledge, although easy to implement and quick, has insufficient performance compared with metric learning-based methods. Since it simply adds a function into the data assignment process of the k-means algorithm to check for constraint violations, it often exploits only a small number of constraints. Metric learning-based methods, which exploit constraints to create a new metric for data similarity, have shown promising results although the methods proposed so far are often slow depending on the amount of data or number of feature dimensions. We present a method that exploits the advantages of the constrained k-means and metric learning approaches. It incorporates a mechanism for accepting constraint priorities and a metric learning framework based on the boosting principle into a constrained k-means algorithm. In the framework, a metric is learned in the form of a kernel matrix that integrates weak cluster hypotheses produced by the constrained k-means algorithm, which works as a weak learner under the boosting principle. Experimental results for 12 data sets from 3 data sources demonstrated that our method has performance competitive to those of state-of-the-art constrained clustering methods for most data sets and that it takes much less computation time. Experimental evaluation demonstrated the effectiveness of controlling the constraint priorities by using the boosting principle and that our constrained k-means algorithm functions correctly as a weak learner of boosting.

Boosted black holes on Kaluza-Klein bubbles

International Nuclear Information System (INIS)

Iguchi, Hideo; Mishima, Takashi; Tomizawa, Shinya

2007-01-01

We construct an exact stationary solution of black-hole-bubble sequence in the five-dimensional Kaluza-Klein theory by using solitonic solution-generating techniques. The solution describes two stationary black holes with topology S 3 on a Kaluza-Klein bubble and has a linear momentum component in the compactified direction. We call the solution boosted black holes on Kaluza-Klein bubble because it has the linear momentum. The Arnowitt-Deser-Misner mass and the linear momentum depend on the two boosted velocity parameters of black holes. In the effective four-dimensional theory, the solution has an electric charge which is proportional to the linear momentum. The solution includes the static solution found by Elvang and Horowitz. The small and the big black holes limits are investigated. The relation between the solution and the single boosted black string are considered

Centrifugal compressor design for electrically assisted boost

International Nuclear Information System (INIS)

Yang, M Y; Martinez-Botas, R F; Zhuge, W L; Qureshi, U; Richards, B

2013-01-01

Electrically assisted boost is a prominent method to solve the issues of transient lag in turbocharger and remains an optimized operation condition for a compressor due to decoupling from turbine. Usually a centrifugal compressor for gasoline engine boosting is operated at high rotational speed which is beyond the ability of an electric motor in market. In this paper a centrifugal compressor with rotational speed as 120k RPM and pressure ratio as 2.0 is specially developed for electrically assisted boost. A centrifugal compressor including the impeller, vaneless diffuser and the volute is designed by meanline method followed by 3D detailed design. Then CFD method is employed to predict as well as analyse the performance of the design compressor. The results show that the pressure ratio and efficiency at design point is 2.07 and 78% specifically

Solar-Based Boost Differential Single Phase Inverter | Eya | Nigerian ...

African Journals Online (AJOL)

Solar-Based Boost Differential Single Phase Inverter. ... Solar-based boost differential inverter is reduced down to 22.37% in closed loop system with the aid of Proportional –integral-Differential (PID) ... The dc power source is photovoltaic cell.

Substructure boosts to dark matter annihilation from Sommerfeld enhancement

International Nuclear Information System (INIS)

Bovy, Jo

2009-01-01

The recently introduced Sommerfeld enhancement of the dark matter annihilation cross section has important implications for the detection of dark matter annihilation in subhalos in the Galactic halo. In addition to the boost to the dark matter annihilation cross section from the high densities of these subhalos with respect to the main halo, an additional boost caused by the Sommerfeld enhancement results from the fact that they are kinematically colder than the Galactic halo. If we further believe the generic prediction of the cold dark matter paradigm that in each subhalo there is an abundance of substructure which is approximately self-similar to that of the Galactic halo, then I show that additional boosts coming from the density enhancements of these small substructures and their small velocity dispersions enhance the dark matter annihilation cross section even further. I find that very large boost factors (10 5 to 10 9 ) are obtained in a large class of models. The implications of these boost factors for the detection of dark matter annihilation from dwarf spheroidal galaxies in the Galactic halo are such that, generically, they outshine the background gamma-ray flux and are detectable by the Fermi Gamma-ray Space Telescope.

TOPOLOGICAL REVIEW AND ANALYSIS OF DC-DC BOOST CONVERTERS

Directory of Open Access Journals (Sweden)

V. INDRA GANDHI

2017-06-01

Full Text Available DC voltage boost up is essential in numerous applications; especially considering Photovoltaic (PV based renewable power generation system. The conventional DC-DC boost converter is the most admired configuration for this scheme, even if the converter efficiency is restricted at duty cycle near to maximum value. In order to find solution to the problem and improve its conversion capability, many converter configurations have been implemented so far. With this circumstance, this research work proposes to give overview of a few most imperative research works related to DC-DC boost converters. Some configurations are covered and classified basically based on the application. The major benefits and disadvantages related to the available techniques are also briefly conveyed. At last, a proper evaluation is recognized among the important types of DC-DC boost converters in terms of efficiency, number of components, and stability.

Boosted Multivariate Trees for Longitudinal Data

Science.gov (United States)

Pande, Amol; Li, Liang; Rajeswaran, Jeevanantham; Ehrlinger, John; Kogalur, Udaya B.; Blackstone, Eugene H.; Ishwaran, Hemant

2017-01-01

Machine learning methods provide a powerful approach for analyzing longitudinal data in which repeated measurements are observed for a subject over time. We boost multivariate trees to fit a novel flexible semi-nonparametric marginal model for longitudinal data. In this model, features are assumed to be nonparametric, while feature-time interactions are modeled semi-nonparametrically utilizing P-splines with estimated smoothing parameter. In order to avoid overfitting, we describe a relatively simple in sample cross-validation method which can be used to estimate the optimal boosting iteration and which has the surprising added benefit of stabilizing certain parameter estimates. Our new multivariate tree boosting method is shown to be highly flexible, robust to covariance misspecification and unbalanced designs, and resistant to overfitting in high dimensions. Feature selection can be used to identify important features and feature-time interactions. An application to longitudinal data of forced 1-second lung expiratory volume (FEV1) for lung transplant patients identifies an important feature-time interaction and illustrates the ease with which our method can find complex relationships in longitudinal data. PMID:29249866

Top reconstruction and boosted top experimental overview

CERN Document Server

Skinnari, Louise

2015-01-01

An overview of techniques used to reconstruct resolved and boosted top quarks is presented. Techniques for resolved top quark reconstruction include kinematic likelihood fitters and pseudo- top reconstruction. Many tools and methods are available for the reconstruction of boosted top quarks, such as jet grooming techniques, jet substructure variables, and dedicated top taggers. Different techniques as used by ATLAS and CMS analyses are described and the performance of different variables and top taggers are shown.

Concurrent Male Gynecomastia and Testicular Hydrocele after Imatinib Mesylate Treatment of a Gastrointestinal Stromal Tumor

Science.gov (United States)

Kim, Hawk; Chang, Heung-Moon; Ryu, Min-Hee; Kim, Tae-Won; Sohn, Hee-Jung; Kim, So-Eun; Kang, Hye-Jin; Park, Sarah; Lee, Jung-Shin

2005-01-01

We report a gastrointestinal stromal tumor (GIST) patient with male gynecomastia and testicular hydrocele after treatment with imatinib mesylate. A 42 yr-old male patient presented for management of hepatic masses. Two years earlier, he had undergone a small bowel resection to remove an intraabdominal mass later shown to be a GIST, followed by adjuvant radiation therapy. At presentation, CT scan revealed multiple hepatic masses, which were compatible with metastatic GIST, and he was prescribed imatinib 400 mg/day. During treatment, he experienced painful enlargement of the left breast and scrotal swelling. Three months after cessation of imatinib treatment, the tumors recurred, and, upon recommencing imatinib, he experienced painful enlargement of the right breast and scrotal swelling. He was diagnosed with male gynecomastia caused by decreased testosterone and non-communicative testicular hydrocele. He was given androgen support and a hydrocelectomy, which improved his gynecomastia. The mechanism by which imatinib induces gynecomastia and hydrocele is thought to be associated with an inhibition of c-KIT and platelet-derive growth factor. This is the first report, to our knowledge, describing concurrent male gynecomastia and testicular hydrocele after imatinib treatment of a patient with GIST. PMID:15953881

Brachytherapy Boost Utilization and Survival in Unfavorable-risk Prostate Cancer.

Science.gov (United States)

Johnson, Skyler B; Lester-Coll, Nataniel H; Kelly, Jacqueline R; Kann, Benjamin H; Yu, James B; Nath, Sameer K

2017-11-01

There are limited comparative survival data for prostate cancer (PCa) patients managed with a low-dose rate brachytherapy (LDR-B) boost and dose-escalated external-beam radiotherapy (DE-EBRT) alone. To compare overall survival (OS) for men with unfavorable PCa between LDR-B and DE-EBRT groups. Using the National Cancer Data Base, we identified men with unfavorable PCa treated between 2004 and 2012 with androgen suppression (AS) and either EBRT followed by LDR-B or DE-EBRT (75.6-86.4Gy). Treatment selection was evaluated using logistic regression and annual percentage proportions. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards, and propensity score matching. We identified 25038 men between 2004 and 2012, during which LDR-B boost utilization decreased from 29% to 14%. LDR-B was associated with better OS on univariate (7-yr OS: 82% vs 73%; pLDR-B boost (HR 0.74, 95% CI 0.66-0.89). The OS benefit of LDR-B boost persisted when limited to men aged LDR-B boost utilization declined and was associated with better OS compared to DE-EBRT alone. LDR-B boost is probably the ideal treatment option for men with unfavorable PCa, pending long-term results of randomized trials. We compared radiotherapy utilization and survival for prostate cancer (PCa) patients using a national database. We found that low-dose rate brachytherapy (LDR-B) boost, a method being used less frequently, was associated with better overall survival when compared to dose-escalated external-beam radiotherapy alone for men with unfavorable PCa. Randomized trials are needed to confirm that LDR-B boost is the ideal treatment. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

arXiv Inelastic Boosted Dark Matter at Direct Detection Experiments

CERN Document Server

Giudice, Gian F.; Park, Jong-Chul; Shin, Seodong

2018-05-10

We explore a novel class of multi-particle dark sectors, called Inelastic Boosted Dark Matter (iBDM). These models are constructed by combining properties of particles that scatter off matter by making transitions to heavier states (Inelastic Dark Matter) with properties of particles that are produced with a large Lorentz boost in annihilation processes in the galactic halo (Boosted Dark Matter). This combination leads to new signals that can be observed at ordinary direct detection experiments, but require unconventional searches for energetic recoil electrons in coincidence with displaced multi-track events. Related experimental strategies can also be used to probe MeV-range boosted dark matter via their interactions with electrons inside the target material.

adabag: An R Package for Classification with Boosting and Bagging

Directory of Open Access Journals (Sweden)

Esteban Alfaro

2013-09-01

Full Text Available Boosting and bagging are two widely used ensemble methods for classification. Their common goal is to improve the accuracy of a classifier combining single classifiers which are slightly better than random guessing. Among the family of boosting algorithms, AdaBoost (adaptive boosting is the best known, although it is suitable only for dichotomous tasks. AdaBoost.M1 and SAMME (stagewise additive modeling using a multi-class exponential loss function are two easy and natural extensions to the general case of two or more classes. In this paper, the adabag R package is introduced. This version implements AdaBoost.M1, SAMME and bagging algorithms with classification trees as base classifiers. Once the ensembles have been trained, they can be used to predict the class of new samples. The accuracy of these classifiers can be estimated in a separated data set or through cross validation. Moreover, the evolution of the error as the ensemble grows can be analysed and the ensemble can be pruned. In addition, the margin in the class prediction and the probability of each class for the observations can be calculated. Finally, several classic examples in classification literature are shown to illustrate the use of this package.

Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy.

LENUS (Irish Health Repository)

Lambert, J S

2012-02-01

OBJECTIVES: The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir\\/ritonavir (LPV\\/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum. METHODS: Women were enrolled in the study who were receiving the LPV\\/r tablet as part of their routine prenatal care. Demographic and clinical data were collected and LPV plasma (total) and ultrafiltrate (unbound) concentrations were determined in the first, second and third trimesters using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS\\/MS). Postpartum sampling was performed where applicable. Antepartum and postpartum trough concentrations (C(trough) ) were compared independently [using analysis of variance (anova)] and on a longitudinal basis (using a paired t-test). RESULTS: Forty-six women were enrolled in the study (38 Black African). Forty women initiated LPV\\/r treatment in pregnancy. Median (range) gestation at initiation was 25 (15-36) weeks and median (range) baseline CD4 count and viral load were 346 (14-836) cells\\/muL and 8724 (<50-267408) HIV-1 RNA copies\\/mL, respectively. Forty women (87%) had LPV concentrations above the accepted minimum effective concentration for wild-type virus (MEC; 1000 ng\\/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first\\/second [3525 (2823-4227) ng\\/mL; n=16] and third [3346 (2813-3880) ng\\/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693-6579) ng\\/mL; n=12] (P=0.006). In a paired analysis (n=12), LPV concentrations were reduced in the third trimester [3657 (2851-4463) ng\\/mL] vs. postpartum (P=0.021). No significant differences were observed in the LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV\\/r tablet is appropriate during pregnancy

Tumour bed boost radiotherapy for women after breast-conserving surgery.

Science.gov (United States)

Kindts, Isabelle; Laenen, Annouschka; Depuydt, Tom; Weltens, Caroline

2017-11-06

Breast-conserving therapy, involving breast-conserving surgery followed by whole-breast irradiation and optionally a boost to the tumour bed, is a standard therapeutic option for women with early-stage breast cancer. A boost to the tumour bed means that an extra dose of radiation is applied that covers the initial tumour site. The rationale for a boost of radiotherapy to the tumour bed is that (i) local recurrence occurs mostly at the site of the primary tumour because remaining microscopic tumour cells are most likely situated there; and (ii) radiation can eliminate these causative microscopic tumour cells. The boost continues to be used in women at high risk of local recurrence, but is less widely accepted for women at lower risk. Reasons for questioning the boost are twofold. Firstly, the boost brings higher treatment costs. Secondly, the potential adverse events are not negligible. In this Cochrane Review, we investigated the effect of the tumour bed boost on local control and side effects. To assess the effects of tumour bed boost radiotherapy after breast-conserving surgery and whole-breast irradiation for the treatment of breast cancer. We searched the Cochrane Breast Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to 1 March 2017), Embase (1980 to 1 March 2017), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov on 1 March 2017. We also searched the European Society of Radiotherapy and Oncology Annual Meeting, the St Gallen Oncology Conferences, and the American Society for Radiation Oncology Annual Meeting for abstracts. Randomised controlled trials comparing the addition and the omission of breast cancer tumour bed boost radiotherapy. Two review authors (IK and CW) performed data extraction and assessed risk of bias using Cochrane's 'Risk of bias' tool, resolving any disagreements through discussion. We entered data into Review Manager 5 for

The Synergy Between PAV and AdaBoost

OpenAIRE

WILBUR, W. JOHN; YEGANOVA, LANA; KIM, WON

2005-01-01

Schapire and Singer’s improved version of AdaBoost for handling weak hypotheses with confidence rated predictions represents an important advance in the theory and practice of boosting. Its success results from a more efficient use of information in weak hypotheses during updating. Instead of simple binary voting a weak hypothesis is allowed to vote for or against a classification with a variable strength or confidence. The Pool Adjacent Violators (PAV) algorithm is a method for converting a ...

14 CFR 27.695 - Power boost and power-operated control system.

Science.gov (United States)

2010-01-01

... Systems § 27.695 Power boost and power-operated control system. (a) If a power boost or power-operated... failure of all engines. (b) Each alternate system may be a duplicate power portion or a manually operated... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Power boost and power-operated control...

14 CFR 29.695 - Power boost and power-operated control system.

Science.gov (United States)

2010-01-01

... Systems § 29.695 Power boost and power-operated control system. (a) If a power boost or power-operated... failure of all engines. (b) Each alternate system may be a duplicate power portion or a manually operated... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Power boost and power-operated control...

Non-Inverting Buck-Boost Converter for Fuel Cell Applications

DEFF Research Database (Denmark)

Schaltz, Erik; Rasmussen, Peter Omand; Khaligh, Alireza

2008-01-01

Fuel cell DC/DC converters often have to be able to both step-up and step-down the input voltage, and provide a high efficiency in the whole range of output power. Conventional negative output buck-boost and non-inverting buck-boost converters provide both step-up and step-down characteristics....... In this paper the non-inverting buck-boost with either diodes or synchronous rectifiers is investigated for fuel cell applications. Most of previous research does not consider  the parasitic in the evaluation of the converters. In this study, detailed analytical expressions of the efficiencies for the system...

DESAIN DAN IMPLEMENTSI SOFT SWITCHING BOOST KONVERTER DENGAN SIMPLE AUXILLARY RESONANT SWITCH (SARC

Directory of Open Access Journals (Sweden)

Dimas Bagus Saputra

2017-01-01

Full Text Available Boost konverter merupakan penaik tegangan DC ke tegangan DC yang mempunyai tegangan output yang lebih tinggi dibanding inputnya. Penggunaan boost konverter diera modern semakin meningkat dan dibuat dengan dimensi yang lebih kecil, berat yang lebih ringan dan efisiensi yang lebih tinggi dibanding dengan boost konverter generasi terdahulu. Tetapi rugi-rugi periodik saat on/off meningkat. Untuk meraih kriteria tersebut, teknik hard switching boost konverter berevolusi menjadi teknik soft switching dengan menambah rangkaian simple auxiliary resonant circuit (SARC. Karena penambahan rangkaian SARC tersebut konverter bekerja pada kondisi zero-voltage switching switch (ZVS dan zero current switch (ZCS, sehingga saklar semikonduktor tidak bekerja secara hard switching lagi. Pada penelitian ini akan di desain dan diimplementaskan soft switching boost konverter dengan SARC. Kelebihan dari soft switching boost konverter dengan SARC adalah mempunyai efisiensi yang lebih tinggi dibanding dengan boost konverter konventional. Dari hasil implementasi menunjukkan konverter yang diajukan telah meraih zero voltage switch (ZVS. Sehingga boost konverter zero voltage switch (ZVS bisa diaplikasikan pada sistem power suplay yang membutuhkan efisiensi energi yang tinggi terutama pada daya yang tinggi.

Y-Source Boost DC/DC Converter for Distributed Generation

DEFF Research Database (Denmark)

Siwakoti, Yam P.; Loh, Poh Chiang; Blaabjerg, Frede

2015-01-01

This paper introduces a versatile Y-source boost dc/dc converter intended for distributed power generation, where high gain is often demanded. The proposed converter uses a Y-source impedance network realized with a tightly coupled three-winding inductor for high voltage boosting that is presently...

Nudging and Boosting: Steering or Empowering Good Decisions.

Science.gov (United States)

Hertwig, Ralph; Grüne-Yanoff, Till

2017-11-01

In recent years, policy makers worldwide have begun to acknowledge the potential value of insights from psychology and behavioral economics into how people make decisions. These insights can inform the design of nonregulatory and nonmonetary policy interventions-as well as more traditional fiscal and coercive measures. To date, much of the discussion of behaviorally informed approaches has emphasized "nudges," that is, interventions designed to steer people in a particular direction while preserving their freedom of choice. Yet behavioral science also provides support for a distinct kind of nonfiscal and noncoercive intervention, namely, "boosts." The objective of boosts is to foster people's competence to make their own choices-that is, to exercise their own agency. Building on this distinction, we further elaborate on how boosts are conceptually distinct from nudges: The two kinds of interventions differ with respect to (a) their immediate intervention targets, (b) their roots in different research programs, (c) the causal pathways through which they affect behavior, (d) their assumptions about human cognitive architecture, (e) the reversibility of their effects, (f) their programmatic ambitions, and (g) their normative implications. We discuss each of these dimensions, provide an initial taxonomy of boosts, and address some possible misconceptions.

Boost breaking in the EFT of inflation

Energy Technology Data Exchange (ETDEWEB)

Delacrétaz, Luca V.; Senatore, Leonardo [Stanford Institute for Theoretical Physics, Stanford University, Stanford, CA 94305 (United States); Noumi, Toshifumi, E-mail: lvd@stanford.edu, E-mail: tnoumi@phys.sci.kobe-u.ac.jp, E-mail: senatore@stanford.edu [Jockey Club Institute for Advanced Study, Hong Kong University of Science and Technology (Hong Kong)

2017-02-01

If time-translations are spontaneously broken, so are boosts. This symmetry breaking pattern can be non-linearly realized by either just the Goldstone boson of time translations, or by four Goldstone bosons associated with time translations and boosts. In this paper we extend the Effective Field Theory of Multifield Inflation to consider the case in which the additional Goldstone bosons associated with boosts are light and coupled to the Goldstone boson of time translations. The symmetry breaking pattern forces a coupling to curvature so that the mass of the additional Goldstone bosons is predicted to be equal to √2 H in the vast majority of the parameter space where they are light. This pattern therefore offers a natural way of generating self-interacting particles with Hubble mass during inflation. After constructing the general effective Lagrangian, we study how these particles mix and interact with the curvature fluctuations, generating potentially detectable non-Gaussian signals.

Three-Dimensional Conformal Simultaneously Integrated Boost Technique for Breast-Conserving Radiotherapy

International Nuclear Information System (INIS)

Laan, Hans Paul van der; Dolsma, Wil V.; Maduro, John H.; Korevaar, Erik W.; Hollander, Miranda; Langendijk, Johannes A.

2007-01-01

Purpose: To compare the target coverage and normal tissue dose with the simultaneously integrated boost (SIB) and the sequential boost technique in breast cancer, and to evaluate the incidence of acute skin toxicity in patients treated with the SIB technique. Methods and Materials: Thirty patients with early-stage left-sided breast cancer underwent breast-conserving radiotherapy using the SIB technique. The breast and boost planning target volumes (PTVs) were treated simultaneously (i.e., for each fraction, the breast and boost PTVs received 1.81 Gy and 2.3 Gy, respectively). Three-dimensional conformal beams with wedges were shaped and weighted using forward planning. Dose-volume histograms of the PTVs and organs at risk with the SIB technique, 28 x (1.81 + 0.49 Gy), were compared with those for the sequential boost technique, 25 x 2 Gy + 8 x 2 Gy. Acute skin toxicity was evaluated for 90 patients treated with the SIB technique according to Common Terminology Criteria for Adverse Events, version 3.0. Results: PTV coverage was adequate with both techniques. With SIB, more efficiently shaped boost beams resulted in smaller irradiated volumes. The mean volume receiving ≥107% of the breast dose was reduced by 20%, the mean volume outside the boost PTV receiving ≥95% of the boost dose was reduced by 54%, and the mean heart and lung dose were reduced by 10%. Of the evaluated patients, 32.2% had Grade 2 or worse toxicity. Conclusion: The SIB technique is proposed for standard use in breast-conserving radiotherapy because of its dose-limiting capabilities, easy implementation, reduced number of treatment fractions, and relatively low incidence of acute skin toxicity

Measuring performance in health care: case-mix adjustment by boosted decision trees.

Science.gov (United States)

Neumann, Anke; Holstein, Josiane; Le Gall, Jean-Roger; Lepage, Eric

2004-10-01

The purpose of this paper is to investigate the suitability of boosted decision trees for the case-mix adjustment involved in comparing the performance of various health care entities. First, we present logistic regression, decision trees, and boosted decision trees in a unified framework. Second, we study in detail their application for two common performance indicators, the mortality rate in intensive care and the rate of potentially avoidable hospital readmissions. For both examples the technique of boosting decision trees outperformed standard prognostic models, in particular linear logistic regression models, with regard to predictive power. On the other hand, boosting decision trees was computationally demanding and the resulting models were rather complex and needed additional tools for interpretation. Boosting decision trees represents a powerful tool for case-mix adjustment in health care performance measurement. Depending on the specific priorities set in each context, the gain in predictive power might compensate for the inconvenience in the use of boosted decision trees.

Concomitant GRID boost for Gamma Knife radiosurgery

International Nuclear Information System (INIS)

Ma Lijun; Kwok, Young; Chin, Lawrence S.; Simard, J. Marc; Regine, William F.

2005-01-01

We developed an integrated GRID boost technique for Gamma Knife radiosurgery. The technique generates an array of high dose spots within the target volume via a grid of 4-mm shots. These high dose areas were placed over a conventional Gamma Knife plan where a peripheral dose covers the full target volume. The beam weights of the 4-mm shots were optimized iteratively to maximize the integral dose inside the target volume. To investigate the target volume coverage and the dose to the adjacent normal brain tissue for the technique, we compared the GRID boosted treatment plans with conventional Gamma Knife treatment plans using physical and biological indices such as dose-volume histogram (DVH), DVH-derived indices, equivalent uniform dose (EUD), tumor control probabilities (TCP), and normal tissue complication probabilities (NTCP). We found significant increase in the target volume indices such as mean dose (5%-34%; average 14%), TCP (4%-45%; average 21%), and EUD (2%-22%; average 11%) for the GRID boost technique. No significant change in the peripheral dose coverage for the target volume was found per RTOG protocol. In addition, the EUD and the NTCP for the normal brain adjacent to the target (i.e., the near region) were decreased for the GRID boost technique. In conclusion, we demonstrated a new technique for Gamma Knife radiosurgery that can escalate the dose to the target while sparing the adjacent normal brain tissue

Boosting aquaculture production systems in Osun state: Role of ...

African Journals Online (AJOL)

This scenario leaves a high percentage of the population who depend on fish and fish products food insecure, and thus, the need to boost aquaculture production to argument the supply from the wild. The study therefore looks into the possibility of boosting the production systems through the use of micro-credit and ...

Radiotherapy Breast Boost With Reduced Whole-Breast Dose Is Associated With Improved Cosmesis: The Results of a Comprehensive Assessment From the St. George and Wollongong Randomized Breast Boost Trial

International Nuclear Information System (INIS)

Hau, Eric; Browne, Lois H.; Khanna, Sam; Cail, Stacy; Cert, Grad; Chin, Yaw; Clark, Catherine; Inder, Stephanie; Szwajcer, Alison; Graham, Peter H.

2012-01-01

Purpose: To evaluate comprehensively the effect of a radiotherapy boost on breast cosmetic outcomes after 5 years in patients treated with breast-conserving surgery. Methods: The St. George and Wollongong trial (NCT00138814) randomized 688 patients with histologically proven Tis-2, N 0–1, M0 carcinoma to the control arm of 50 Gy in 25 fractions (342 patients) and the boost arm of 45 Gy in 25 fractions to the whole breast followed by a 16 Gy in 8 fraction electron boost (346 patients). Five-year cosmetic outcomes were assessed by a panel subjectively in 385 patients and objectively using pBRA (relative breast retraction assessment). A subset of patients also had absolute BRA measurements. Clinician assessment and patient self-assessment of overall cosmetic and specific items as well as computer BCCT.core analysis were also performed. Results: The boost arm had improved cosmetic overall outcomes as scored by the panel and BCCT.core software with 79% (p = 0.016) and 81% (p = 0.004) excellent/good cosmesis respectively compared with 68% in no-boost arm. The boost arm also had lower pBRA and BRA values with a mean difference of 0.60 and 1.82 mm, respectively, but was not statistically significant. There was a very high proportion of overall excellent/good cosmetic outcome in 95% and 93% in the boost and no–boost arms using patient self-assessment. However, no difference in overall and specific items scored by clinician assessment and patient self-assessment was found. Conclusion: The results show the negative cosmetic effect of a 16-Gy boost is offset by a lower whole-breast dose of 45 Gy.

Boosted top production in ATLAS and CMS

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00237277; The ATLAS collaboration

2017-01-01

An overview of the boosted top production analyses using data collected by the ATLAS and CMS experiments at $\\sqrt{s}=$' 8 TeV and 13 TeV of proton-proton collisions at the LHC is presented. These analyses use techniques for the reconstruction of boosted objects to measure the production of top quarks at high transverse momenta. The measurements are optimized for the different final states and for different ranges of the transverse momenta of the particles involved, improving on measurements with traditional objects reconstruction based on the combination of resolved objects.

The boosts in the noncommutative special relativity

International Nuclear Information System (INIS)

Lagraa, M.

2001-01-01

From the quantum analogue of the Iwasawa decomposition of SL(2, C) group and the correspondence between quantum SL(2, C) and Lorentz groups we deduce the different properties of the Hopf algebra representing the boost of particles in noncommutative special relativity. The representation of the boost in the Hilbert space states is investigated and the addition rules of the velocities are established from the coaction. The q-deformed Clebsch-Gordon coefficients describing the transformed states of the evolution of particles in noncommutative special relativity are introduced and their explicit calculation are given. (author)

Response by gender of HIV-1-infected subjects treated with abacavir/lamivudine plus atazanavir, with or without ritonavir, for 144 weeks

Directory of Open Access Journals (Sweden)

Squires KE

2017-03-01

Full Text Available Kathleen E Squires,1 Benjamin Young,2,3 Lizette Santiago,4 Robin H Dretler,5 Sharon L Walmsley,6 Henry H Zhao,7 Gary E Pakes,8 Lisa L Ross,8 Mark S Shaefer8 On behalf of the ARIES Study Team 1Thomas Jefferson University, Philadelphia, PA, 2Apex Family Medicine and Research, Denver, CO, 3International Association of Physicians in AIDS Care, Washington DC, USA; 4HOPE Clinic and Wellness Center, San Juan, Puerto Rico; 5ID Specialists of Atlanta, Decatur, GA, USA; 6University Health Network, Toronto, ON, Canada; 7GlaxoSmithKline, 8ViiV Healthcare, Research Triangle Park, NC, USA Purpose: The 144-week results of the open-label, multicenter Atazanavir/Ritonavir Induction with Epzicom Study (ARIES were stratified by gender to compare treatment responses.Methods: A total of 369 HIV-infected, antiretroviral-naïve subjects receiving once-daily abacavir/lamivudine + atazanavir/ritonavir (ATV/r whose HIV-1 RNA was <50 copies/mL by week 30 were randomized 1:1 at week 36 to maintain or discontinue ritonavir for 108 subsequent weeks. Between- and within-treatment gender-related efficacy and safety differences were analyzed.Results: Subjects were 85% male; 64% white; and had a mean age of 39 years, baseline median HIV-1 RNA of 114,815 copies/mL, and median CD4+ cell count of 198 cells/mm3. Gender (ATV [n=189]: 29 females/160 males; ATV/r [n=180]: 25 females/155 males and most other demographics were similar between groups; more females than males were black (65% vs 25% and fewer females had baseline HIV-1 RNA ≥100,000 copies/mL (41% vs 58%. At week 144, no significant differences between genders were observed in proportion maintaining HIV-1 RNA <50 copies/mL (ATV, 79% vs 77%; ATV/r, 60% vs 75% or <400 copies/mL (ATV, 83% vs 84%; ATV/r, 68% vs 82% (intent-to-treat-exposed: time to loss of virologic response analysis; median CD4+ change from baseline (ATV, +365 vs +300 cells/mm3; ATV/r, +344 vs +301 cells/mm3; proportion with treatment-related grade 2–4

Studies on the toxic effects of periodontal sustained release drug containing ornidazole and pefloxacin mesylate on early embryonic development of SD rat

Directory of Open Access Journals (Sweden)

Zheng-mou DONG

2011-01-01

Full Text Available Objective To evaluate the toxic effects of periodontal sustained release drug containing ornidazole and pefloxacin mesylate on early embryonic development of SD rats.Methods A total of 100female SD rats were randomly divided into negative control,low-,medium-,high-dose group and intervention group(20each.Rats in low-,medium-and high-dose group were fed daily with the sustained release drug at 1,4,and 8g/kg respectively;those in negative control group were fed daily with distilled water from the 14th day before mating to the 7th day of pregnancy continuously,and those in intervention group received cyclophosphamide(40mg/kgby intraperitoneal injection for 5successive days.During this period,the general status,mating,pregnancy,coefficient of ovary and uterus,the numbers of corpus luteum,nidation,live births,stillbirths,absorbed embryo,prenidatory and postnidatory mortality,serum testosterone(Tand estradiol(E2were determined respectively.Histopathologic examination of the ovary and uterus,immunohistochemical observation of ovaries for proliferating cell nuclear antigen(PCNAand Bcl-2associated X protein(Baxwere also performed respectively.Results The general status of those rats was good except one in the low-dose group and one in the intervention group died on the 14th day of administration,and one in negative control and one in high dose group died on the 5th day of pregnancy,respectively.The body weight of animals decreased significantly(P 0.05.The serum T level in medium-and high-dose group and the E2level in high-dose group declined compared to that in negative control group(P < 0.05.Conclusions Although the periodontal sustained release drug containing ornidazole and pefloxacin mesylate shows no toxicity to the early embryonic development of SD rats,the high dose drug has certain toxicity to ovary.Declined serum concentrations of T and E2,reduced expression of PCNA,and increased Bax may be the causes of the toxicity.

Evaluation of the Safety of Imatinib Mesylate in 200 Iraqi Patients with Chronic Myeloid Leukemia in the Chronic Phase: Single-Center Study

Directory of Open Access Journals (Sweden)

Bassam Francis Matti

2013-12-01

Full Text Available OBJECTIVE: Imatinib mesylate, a tyrosine kinase inhibitor, is presently the drug of choice for chronic myeloid leukemia (CML. During therapy, a few patients may develop hematological and non-hematological adverse effects. METHODS: The aim of this study was to evaluate the safety of imatinib therapy in patients with CML. Between December 2007 and October 2009 two hundred patients with CML in chronic phase were included in the study. Written informed consent was obtained from all patients prior to the start of the study. Imatinib was started at 400 mg orally daily. Patients were monitored carefully for any adverse effects. Complete blood count, liver, and renal function tests were done once in 2 weeks during the first month and on a monthly basis during follow-up. Toxicities that encountered were graded as per the National Cancer Institute common toxicity criteria version 2. Both hematologic and non-hematologic toxicities were managed with short interruptions of treatment and supportive measures, but the daily dose of imatinib was not reduced below 300 mg/day. RESULTS: Two hundred CML patients in chronic phase were included in this study; the male: female ratio was 0.7: 1 with mean age 39.06±13.21 years (ranged from 15-81 years. The study showed that the commonest hematological side effects were grade 2 anemia (12.5% followed by leukopenia (8% and thrombocytopenia (4%, while the most common non-hematological adverse effects were superficial edema and weight gain (51.5%, followed by musculoskeletal pain (35.5%, then gastro-intestinal symptoms (vomiting, diarrhea (19%. Fluid retention was the commonest side effect, which responded to low-dose diuretics. The drug was safe and well tolerated. There were no deaths due to toxicity. CONCLUSION: Imatinib mesylate a well-tolerated drug, and all undesirable effects could be ameliorated easily. The most common hematological and non-hematological side effects were anemia and fluid retention, respectively.

Desain dan Implementsi Soft Switching Boost Konverter dengan Simple Auxillary Resonant Switch (Sarc)

OpenAIRE

Saputra, Dimas Bagus; Suryoatmojo, Heri; Musthofa, Arif

2016-01-01

Boost konverter merupakan penaik tegangan DC ke tegangan DC yang mempunyai tegangan output yang lebih tinggi dibanding inputnya. Penggunaan boost konverter diera modern semakin meningkat dan dibuat dengan dimensi yang lebih kecil, berat yang lebih ringan dan efisiensi yang lebih tinggi dibanding dengan boost konverter generasi terdahulu. Tetapi rugi-rugi periodik saat on/off meningkat. Untuk meraih kriteria tersebut, teknik hard switching boost konverter berevolusi menjadi teknik soft switchi...

Modeling and Simulation of Buck-Boost Converter with Voltage Feedback Control

Directory of Open Access Journals (Sweden)

Zhou Xuelian

2015-01-01

Full Text Available In order to design the control system, it is necessary to have an exact model of buck-boost converter. This paper put forward the transfer function model of buck-boost converter by the state-space average method. The open-loop transfer function model of uncompensated system is deduced according to the mathematic model of the buck-boost converter, the controller is designed according to frequency domain. The phase and magnitude margin of the open-loop system of the buck-boost converter with compensator have both been increased. After compensating, this control system has the advantages of small overshoot and short settling time. It can also improve control system’s real time property and anti-interference ability.

Spectrofluorimetric determination of gemifloxacin mesylate and linezolid in pharmaceutical formulations: Application of quinone-based fluorophores and enhanced native fluorescence

Directory of Open Access Journals (Sweden)

Moussa Bahia Abbas

2014-03-01

Full Text Available Quinone-based fluorophores and enhanced native fluorescence techniques were applied for a fast quantitative analysis of gemifloxacin mesylate (GEM and linezolid (LIN in pharmaceutical formulations. For this purpose, three sensitive, accurate and precise spectrofluorimetric methods were developed. GEM, as an n-electron donor, reacts with 7,7,8,8-tetracyanoquinodimethane (method A and 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (method B as п-electron acceptors, forming charge transfer complexes that exhibit high fluorescence intensity at 441 and 390 nm upon excitation at 260 and 339 nm, respectively. Method C depends on measurement of enhanced native fluorescence of LIN in phosphate buffer (pH 5 at 380 nm upon excitation at 260 nm. Experimental factors affecting fluorescence intensity were optimized. Linearity was obtained over concentration ranges 50-500, 10-60 and 20-400 ng mL-1 for methods A, B and C, respectively. The developed methods were validated and successfully applied for determination of the cited drugs in tablets.

Active pre-filters for dc/dc Boost regulators

Directory of Open Access Journals (Sweden)

Carlos Andrés Ramos-Paja

2014-05-01

Full Text Available This paper proposes an active pre-filter to mitigate the current harmonics generated by classical dc/dc Boost regulators, which generate current ripples proportional to the duty cycle. Therefore, high output voltage conditions, i.e., high voltage conversion ratios, produce high current harmonics that must be filtered to avoid damage or source losses. Traditionally, these current components are filtered using electrolytic capacitors, which introduce reliability problems because of their high failure rate. The solution introduced in this paper instead uses a dc/dc converter based on the parallel connection of the Boost canonical cells to filter the current ripples generated by the Boost regulator, improving the system reliability. This solution provides the additional benefits of improving the overall efficiency and the voltage conversion ratio. Finally, the solution is validated with simulations and experimental results.

Comparison of three concomitant boost techniques for early-stage breast cancer

International Nuclear Information System (INIS)

Horton, Janet K.; Halle, Jan S.; Chang, Sha X.; Sartor, Carolyn I.

2006-01-01

Purpose: Whole breast radiotherapy (RT) followed by a tumor bed boost typically spans 5-6 weeks of treatment. Interest is growing in RT regimens, such as concomitant boost, that decrease overall treatment time, lessening the time/cost burden to patients and facilities. Methods and Materials: Computed tomography (CT) scans from 20 cases were selected for this retrospective, dosimetric study to compare three different techniques of concomitant boost delivery: (1) standard tangents plus an electron boost (2) intensity-modulated RT (IMRT) tangents using custom compensators plus an electron boost, and (3) IMRT tangents plus a conformal photon boost. The equivalent uniform dose model was used to compare the plans. Results: The average breast equivalent uniform dose value for the three techniques (standard, IMRT plus electrons, and IMRT plus photons) was 48.6, 47.9, and 48.3, respectively. The plans using IMRT more closely approximated the prescribed dose of 46 Gy to the whole breast. The breast volume receiving >110% of the dose was less with the IMRT tangents than with standard RT (p 0.037), but no significant difference in the maximal dose or other evaluated parameters was noted. Conclusion: Although the IMRT techniques delivered the prescribed dose with better dose uniformity, the small improvement seen did not support a goal of improved resource use

Spectrophotometric Determination of Gemifloxacin Mesylate, Moxifloxacin Hydrochloride, and Enrofloxacin in Pharmaceutical Formulations Using Acid Dyes

Directory of Open Access Journals (Sweden)

Ayman A. Gouda

2014-01-01

Full Text Available Simple, rapid, and extractive spectrophotometric methods were developed for the determination of some fluoroquinolones antibiotics: gemifloxacin mesylate (GMF, moxifloxacin hydrochloride (MXF, and enrofloxacin (ENF in pure forms and pharmaceutical formulations. These methods are based on the formation of ion-pair complexes between the basic drugs and acid dyes, namely, bromocresol green (BCG, bromocresol purple (BCP, bromophenol blue (BPB, bromothymol blue (BTB, and methyl orange (MO in acidic buffer solutions. The formed complexes were extracted with chloroform and measured at 420, 408, 416, 415, and 422 nm for BCG, BCP, BPB, BTB, and MO, respectively, for GMF; at 410, 415, 416, and 420 nm for BCP, BTB, BPB, and MO, respectively, for MXF; and at 419 and 414 nm for BCG and BTB, respectively, in case of ENF. The analytical parameters and their effects are investigated. Beer’s law was obeyed in the ranges 1.0–30, 1.0–20, and 2.0–24 μg mL−1 for GMF, MXF, and ENF, respectively. The proposed methods have been applied successfully for the analysis of the studied drugs in pure forms and pharmaceutical formulations. Statistical comparison of the results with the reference methods showed excellent agreement and indicated no significant difference in accuracy and precision.

Enhanced Silver Nanoparticle Chemiluminescence Method for the Determination of Gemifloxacin Mesylate using Sequential Injection Analysis

International Nuclear Information System (INIS)

Alarfaj, N.A.; Aly, F.A.; Tamimi, A.A.

2013-01-01

A sequential injection analysis (SIA) with chemiluminescence detection has been proposed for the determination of the antibiotic gemifloxacin mesylate (GFX). The developed method is based on the enhancement effect of silver nanoparticles (Ag NPs) on the chemiluminescence (CL) signal of luminol-potassium ferricyanide reaction in alkaline medium. The introduction of gemifloxacin in this system produced a significant decrease in the CL intensity in presence of (Ag NPs). The optimum conditions for CL emission were investigated. Linear relationship between the decrease in CL intensity and concentration was obtained in the range 0.01-1000 ng mL-1, (r = 0.9997) with detection limit of 2.0 pg mL-1 and quantification limit of 0.01 pg mL-1. The relative standard deviation was 1.3 %. The proposed method was employed for the determination of gemifloxacin in bulk drug, in its pharmaceutical dosage forms and biological fluids such as human serum and urine. The interference of some common additive compounds such as glucose, lactose, starch, talc and magnesium stearate was investigated, and no interference was found from these excipients. The obtained SIA results were statistically compared with those obtained from a reported method and did not show any significant difference at confidence level 95%. (author)

Solid state light source driver establishing buck or boost operation

Science.gov (United States)

Palmer, Fred

2017-08-29

A solid state light source driver circuit that operates in either a buck convertor or a boost convertor configuration is provided. The driver circuit includes a controller, a boost switch circuit and a buck switch circuit, each coupled to the controller, and a feedback circuit, coupled to the light source. The feedback circuit provides feedback to the controller, representing a DC output of the driver circuit. The controller controls the boost switch circuit and the buck switch circuit in response to the feedback signal, to regulate current to the light source. The controller places the driver circuit in its boost converter configuration when the DC output is less than a rectified AC voltage coupled to the driver circuit at an input node. The controller places the driver circuit in its buck converter configuration when the DC output is greater than the rectified AC voltage at the input node.

High-dose simultaneously integrated breast boost using intensity-modulated radiotherapy and inverse optimization

International Nuclear Information System (INIS)

Hurkmans, Coen W.; Meijer, Gert J.; Vliet-Vroegindeweij, Corine van; Sangen, Maurice J. van der; Cassee, Jorien

2006-01-01

Purpose: Recently a Phase III randomized trial has started comparing a boost of 16 Gy as part of whole-breast irradiation to a high boost of 26 Gy in young women. Our main aim was to develop an efficient simultaneously integrated boost (SIB) technique for the high-dose arm of the trial. Methods and Materials: Treatment planning was performed for 5 left-sided and 5 right-sided tumors. A tangential field intensity-modulated radiotherapy technique added to a sequentially planned 3-field boost (SEQ) was compared with a simultaneously planned technique (SIB) using inverse optimization. Normalized total dose (NTD)-corrected dose volume histogram parameters were calculated and compared. Results: The intended NTD was produced by 31 fractions of 1.66 Gy to the whole breast and 2.38 Gy to the boost volume. The average volume of the PTV-breast and PTV-boost receiving more than 95% of the prescribed dose was 97% or more for both techniques. Also, the mean lung dose and mean heart dose did not differ much between the techniques, with on average 3.5 Gy and 2.6 Gy for the SEQ and 3.8 Gy and 2.6 Gy for the SIB, respectively. However, the SIB resulted in a significantly more conformal irradiation of the PTV-boost. The volume of the PTV-breast, excluding the PTV-boost, receiving a dose higher than 95% of the boost dose could be reduced considerably using the SIB as compared with the SEQ from 129 cc (range, 48-262 cc) to 58 cc (range, 30-102 cc). Conclusions: A high-dose simultaneously integrated breast boost technique has been developed. The unwanted excessive dose to the breast was significantly reduced

Natural working fluids for solar-boosted heat pumps

Energy Technology Data Exchange (ETDEWEB)

Chaichana, C.; Lu Aye [University of Melbourne, Victoria (Australia). International Technologies Centre, Department of Civil and Environmental Engineering; Charters, W.W.S. [University of Melbourne, Victoria (Australia). Department of Mechanical and Manufacturing Engineering

2003-09-01

The option of using natural working fluids as a substitute of R-22 for solar-boosted heat pumps depends not only upon thermal performance and hazardous rating but also on potential impacts on the environment. This paper presents the comparative assessment of natural working fluids with R-22 in terms of their characteristics and thermophysical properties, and thermal performance. Some justification is given for using natural working fluids in a solar boosted heat pump water heater. The results show that R-744 is not suitable for solar-boosted heat pumps because of its low critical temperature and high operational pressures. On the other hand, R-717 seems to be a more appropriate substitute in terms of operational parameters and overall performance. However, major changes in the heat pumps are required. R-290 and R-1270 are identified as candidates for direct drop-in substitutes for R-22. (author)

The gradient boosting algorithm and random boosting for genome-assisted evaluation in large data sets.

Science.gov (United States)

González-Recio, O; Jiménez-Montero, J A; Alenda, R

2013-01-01

In the next few years, with the advent of high-density single nucleotide polymorphism (SNP) arrays and genome sequencing, genomic evaluation methods will need to deal with a large number of genetic variants and an increasing sample size. The boosting algorithm is a machine-learning technique that may alleviate the drawbacks of dealing with such large data sets. This algorithm combines different predictors in a sequential manner with some shrinkage on them; each predictor is applied consecutively to the residuals from the committee formed by the previous ones to form a final prediction based on a subset of covariates. Here, a detailed description is provided and examples using a toy data set are included. A modification of the algorithm called "random boosting" was proposed to increase predictive ability and decrease computation time of genome-assisted evaluation in large data sets. Random boosting uses a random selection of markers to add a subsequent weak learner to the predictive model. These modifications were applied to a real data set composed of 1,797 bulls genotyped for 39,714 SNP. Deregressed proofs of 4 yield traits and 1 type trait from January 2009 routine evaluations were used as dependent variables. A 2-fold cross-validation scenario was implemented. Sires born before 2005 were used as a training sample (1,576 and 1,562 for production and type traits, respectively), whereas younger sires were used as a testing sample to evaluate predictive ability of the algorithm on yet-to-be-observed phenotypes. Comparison with the original algorithm was provided. The predictive ability of the algorithm was measured as Pearson correlations between observed and predicted responses. Further, estimated bias was computed as the average difference between observed and predicted phenotypes. The results showed that the modification of the original boosting algorithm could be run in 1% of the time used with the original algorithm and with negligible differences in accuracy

Intensity modulated radiotherapy with simultaneous integrated boost vs. conventional radiotherapy with sequential boost for breast cancer - A preliminary result.

Science.gov (United States)

Lee, Hsin-Hua; Hou, Ming-Feng; Chuang, Hung-Yi; Huang, Ming-Yii; Tsuei, Le-Ping; Chen, Fang-Ming; Ou-Yang, Fu; Huang, Chih-Jen

2015-10-01

This study was aimed to assess the acute dermatological adverse effect from two distinct RT techniques for breast cancer patients. We compared intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and conventional radiotherapy followed by sequential boost (CRT-SB). The study population was composed of 126 consecutive female breast cancer patients treated with breast conserving surgery. Sixty-six patients received IMRT-SIB to 2 dose levels simultaneously. They received 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Sixty patients in the CRT-SB group received 50 Gy in 25 fractions to the whole breast followed by a boost irradiation to tumor bed in 5-7 fractions to a total dose of 60-64 Gy. Acute skin toxicities were documented in agreement with the Common Terminology Criteria for Adverse Events version 3 (CTCAE v.3.0). Ninety-eight patients had grade 1 radiation dermatitis while 14 patients had grade 2. Among those with grade 2, there were 3 patients in IMRT-SIB group (4.5%) while 11 in CRT-SB group (18.3%). (P = 0.048) There was no patient with higher than grade 2 toxicity. Three year local control was 99.2%, 3-year disease free survival was 97.5% and 3-year overall survival was 99.2%. A significant reduction in the severity of acute radiation dermatitis from IMRT-SIB comparing with CRT-SB is demonstrated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improvement of lipoatrophy by switching from efavirenz to lopinavir/ritonavir.

Science.gov (United States)

Rojas, J; Lonca, M; Imaz, A; Estrada, V; Asensi, V; Miralles, C; Domingo, P; Montero, M; del Rio, L; Fontdevila, J; Perez, I; Cruceta, A; Gatell, J M; Arnedo, M; Martínez, E

2016-05-01

To assess whether changes in antiretroviral drugs other than thymidine nucleoside reverse transcriptase inhibitors (NRTI) may have a body fat impact in HIV-infected patients with lipoatrophy. Ninety-six-week phase IV, open-label, multicentre, pilot randomized trial. HIV-infected patients with moderate/severe lipoatrophy at one or more body sites despite long-term thymidine NRTI-free therapy were randomized to continue their efavirenz (EFV)-based antiretroviral regimen or to switch from EFV to lopinavir/ritonavir (LPV/r). The primary endpoint was the absolute change in limb fat mass measured by dual X-ray absorptiometry from baseline to 96 weeks. Changes in other body fat measurements, subjective perception of lipoatrophy, subcutaneous fat gene expression and plasma lipids were also assessed. Thirty-three patients (73% men, median age 52 years) were recruited. At 96 weeks, absolute limb fat mass increased in the LPV/r arm vs. the EFV arm (estimated difference +1082.1 g; 95% CI +63.7 to +2103.5; P = 0.04); this difference remained significant after adjustment by gender, age, fat mass, body mass index and CD4 cell count at baseline. Subjective lipoatrophy perception scores also improved in the LPV/r arm relative to the EFV arm. Adipogenesis, glucose and lipid metabolism, and mitochondrial gene expression increased in the LPV/r arm compared with the EFV arm at 96 weeks. HDL cholesterol decreased in the LPV/r arm relative to the EFV arm. Switching from EFV to LPV/r in HIV-infected patients with lipoatrophy may offer further limb fat gain beyond thymidine NRTI discontinuation, although this strategy decreased plasma HDL cholesterol and caused changes in subcutaneous fat gene expression that may be associated with increased insulin resistance. © 2015 British HIV Association.

Boosted dark matter signals uplifted with self-interaction

OpenAIRE

Kong, Kyoungchul; Mohlabeng, Gopolang; Park, Jong-Chul

2018-01-01

We explore detection prospects of a non-standard dark sector in the context of boosted dark matter. We focus on a scenario with two dark matter particles of a large mass difference, where the heavier candidate is secluded and interacts with the standard model particles only at loops, escaping existing direct and indirect detection bounds. Yet its pair annihilation in the galactic center or in the Sun may produce boosted stable particles, which could be detected as visible Cherenkov light in l...

Searches with Boosted Objects at ATLAS and CMS

CERN Document Server

Behr, K; The ATLAS collaboration

2014-01-01

This talk presents an overview of searches for new physics in boosted final states conducted by the ATLAS and CMS experiments during Run-I of the LHC. An emphasis is put on techniques for the reconstruction and identification of both hadronic and leptonic decays of objects with large transverse momenta: Various substructure and grooming techniques as well as modified lepton isolation criteria are reviewed and their use in the most common algorithms for boosted top and boson tagging is discussed.

Impact of the Radiation Boost on Outcomes After Breast-Conserving Surgery and Radiation

International Nuclear Information System (INIS)

Murphy, Colin; Anderson, Penny R.; Li Tianyu; Bleicher, Richard J.; Sigurdson, Elin R.; Goldstein, Lori J.; Swaby, Ramona; Denlinger, Crystal; Dushkin, Holly; Nicolaou, Nicos; Freedman, Gary M.

2011-01-01

Purpose: We examined the impact of radiation tumor bed boost parameters in early-stage breast cancer on local control and cosmetic outcomes. Methods and Materials: A total of 3,186 women underwent postlumpectomy whole-breast radiation with a tumor bed boost for Tis to T2 breast cancer from 1970 to 2008. Boost parameters analyzed included size, energy, dose, and technique. Endpoints were local control, cosmesis, and fibrosis. The Kaplan-Meier method was used to estimate actuarial incidence, and a Cox proportional hazard model was used to determine independent predictors of outcomes on multivariate analysis (MVA). The median follow-up was 78 months (range, 1-305 months). Results: The crude cosmetic results were excellent in 54%, good in 41%, and fair/poor in 5% of patients. The 10-year estimate of an excellent cosmesis was 66%. On MVA, independent predictors for excellent cosmesis were use of electron boost, lower electron energy, adjuvant systemic therapy, and whole-breast IMRT. Fibrosis was reported in 8.4% of patients. The actuarial incidence of fibrosis was 11% at 5 years and 17% at 10 years. On MVA, independent predictors of fibrosis were larger cup size and higher boost energy. The 10-year actuarial local failure was 6.3%. There was no significant difference in local control by boost method, cut-out size, dose, or energy. Conclusions: Likelihood of excellent cosmesis or fibrosis are associated with boost technique, electron energy, and cup size. However, because of high local control and rare incidence of fair/poor cosmesis with a boost, the anatomy of the patient and tumor cavity should ultimately determine the necessary boost parameters.

Boosting instance prototypes to detect local dermoscopic features.

Science.gov (United States)

Situ, Ning; Yuan, Xiaojing; Zouridakis, George

2010-01-01

Local dermoscopic features are useful in many dermoscopic criteria for skin cancer detection. We address the problem of detecting local dermoscopic features from epiluminescence (ELM) microscopy skin lesion images. We formulate the recognition of local dermoscopic features as a multi-instance learning (MIL) problem. We employ the method of diverse density (DD) and evidence confidence (EC) function to convert MIL to a single-instance learning (SIL) problem. We apply Adaboost to improve the classification performance with support vector machines (SVMs) as the base classifier. We also propose to boost the selection of instance prototypes through changing the data weights in the DD function. We validate the methods on detecting ten local dermoscopic features from a dataset with 360 images. We compare the performance of the MIL approach, its boosting version, and a baseline method without using MIL. Our results show that boosting can provide performance improvement compared to the other two methods.

StentBoost Visualization for the Evaluation of Coronary Stent Expansion During Percutaneous Coronary Interventions

OpenAIRE

Cura, Fernando; Albertal, Mariano; Candiello, Alfonsina; Nau, Gerardo; Bonvini, Victor; Tricherri, Hernan; Padilla, Lucio T.; Belardi, Jorge A.

2013-01-01

Introduction Inadequate stent implantation is associated with stent thrombosis and restenosis. StentBoost can enhance stent visualization and evaluate stent expansion. Currently, there are limited comparison studies between StentBoost and intravascular ultrasound (IVUS). We aimed to test the correlation and agreement between IVUS and StentBoost measurements. Methods From December 2010 to December 2011, 38 patients (54 stents) were analyzed using IVUS and StentBoost. Minimal stent diameter and...

FULL ELECTROMAGNETIC FEL SIMULATION VIA THE LORENTZ-BOOSTED FRAME TRANSFORMATION

International Nuclear Information System (INIS)

Fawley, William; Vay, Jean-Luc

2010-01-01

Numerical electromagnetic simulation of some systems containing charged particles with highly relativistic directed motion can by speeded up by orders of magnitude by choice of the proper Lorentz-boosted frame. A particularly good application for calculation in a boosted frame isthat of short wavelength free-electron lasers (FELs) where a high energy electron beam with small fractional energy spread interacts with a static magnetic undulator. In the optimal boost frame (i.e., the ponderomotive rest frame), the red-shifted FEL radiation and blue-shifted undulator field have identical wavelengths and the number of required longitudinal grid cells and time-steps for fully electromagnetic simulation (relative to the laboratory frame) decrease by factors of gamma 2 each. In theory, boosted frame EM codes permit direct study of FEL problems for which the eikonal approximation for propagation of the radiation field and wiggler-period-averaging for the particle-field interaction may be suspect. We have adapted the WARP code to apply this method to several electromagnetic FEL problems including spontaneous emission, strong exponential gain in a seeded, single pass amplifier configuration, and emission from e-beams in undulators with multiple harmonic components. WARP has a standard relativistic macroparticle mover and a fully 3-D electromagnetic field solver. We discuss our boosted frame results and compare with those obtained using the 'standard' eikonal FEL simulation approach.

Higgs boson creation in laser-boosted lepton collisions

International Nuclear Information System (INIS)

Müller, Sarah J.; Keitel, Christoph H.; Müller, Carsten

2014-01-01

Electroweak processes in high-energy lepton collisions are considered in a situation where the incident center-of-mass energy lies below the reaction threshold, but is boosted to the required level by subsequent laser acceleration. Within the framework of laser-dressed quantum field theory, we study the laser-boosted process ℓ + ℓ − →HZ 0 in detail and specify the technical demands needed for its experimental realization. Further, we outline possible qualitative differences to field-free processes regarding the detection of the produced Higgs bosons.

Multiclass Boosting with Adaptive Group-Based kNN and Its Application in Text Categorization

Directory of Open Access Journals (Sweden)

Lei La

2012-01-01

Full Text Available AdaBoost is an excellent committee-based tool for classification. However, its effectiveness and efficiency in multiclass categorization face the challenges from methods based on support vector machine (SVM, neural networks (NN, naïve Bayes, and k-nearest neighbor (kNN. This paper uses a novel multi-class AdaBoost algorithm to avoid reducing the multi-class classification problem to multiple two-class classification problems. This novel method is more effective. In addition, it keeps the accuracy advantage of existing AdaBoost. An adaptive group-based kNN method is proposed in this paper to build more accurate weak classifiers and in this way control the number of basis classifiers in an acceptable range. To further enhance the performance, weak classifiers are combined into a strong classifier through a double iterative weighted way and construct an adaptive group-based kNN boosting algorithm (AGkNN-AdaBoost. We implement AGkNN-AdaBoost in a Chinese text categorization system. Experimental results showed that the classification algorithm proposed in this paper has better performance both in precision and recall than many other text categorization methods including traditional AdaBoost. In addition, the processing speed is significantly enhanced than original AdaBoost and many other classic categorization algorithms.

Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults.

Science.gov (United States)

Hersh, Elliot V; Moore, Paul A; Papas, Athena S; Goodson, J Max; Navalta, Laura A; Rogy, Siegfried; Rutherford, Bruce; Yagiela, John A

2008-08-01

The authors conducted two multicenter, randomized, double-blinded, controlled Phase III clinical trials to study the efficacy and safety of phentolamine mesylate (PM) in shortening the duration and burden of soft-tissue anesthesia. The study involved 484 subjects who received one of four commercially available local anesthetic solutions containing vasoconstrictors for restorative or scaling procedures. On completion of the dental procedure, subjects randomly received a PM or a sham injection (an injection in which a needle does not penetrate the soft tissue) in the same site as the local anesthetic injection. The investigators measured the duration of soft-tissue anesthesia by using standardized lip- and tongue-tapping procedures every five minutes for five hours. They also evaluated functional measures and subject-perceived altered function, sensation, appearance and safety. Median recovery times in the lower lip and tongue for subjects in the PM group were 70 minutes and 60 minutes, respectively. Median recovery times in the lower lip and tongue for subjects in the sham group were 155 minutes and 125 minutes, respectively. Upper lip median recovery times were 50 minutes for subjects in the PM group and 133 minutes for subjects in the sham group. These differences were significant (P < .0001). Recovery from actual functional deficits and subject-perceived altered function, sensation and appearance also showed significant differences between the PM and the sham groups. PM was efficacious and safe in reducing the duration of local anesthetic- induced soft-tissue numbness and its associated functional deficits. Clinicians can use PM to accelerate reversal of soft-tissue anesthesia and the associated functional deficits.

A Reconfigurable Buck, Boost, and Buck-Boost Converter: Unified Model and Robust Controller

Directory of Open Access Journals (Sweden)

Martín Antonio Rodríguez Licea

2018-01-01

Full Text Available The need for reconfigurable, high power density, and low-cost configurations of DC-DC power electronic converters (PEC in areas such as the transport electrification and the use of renewable energy has spread out the requirement to incorporate in a single circuit several topologies, which generally result in an increment of complexity about the modeling, control, and stability analyses. In this paper, a reconfigurable topology is presented which can be applied in alterative/changing power conversion scenarios and consists of a reconfigurable Buck, Boost, and Buck-Boost DC-DC converter (RBBC. A unified averaged model of the RBBC is obtained, a robust controller is designed through a polytopic representation, and a Lyapunov based switched stability analysis of the closed-loop system is presented. The reported RBBC provides a wide range of voltage operation, theoretically from -∞ to ∞ volts with a single power source. Robust stability, even under arbitrarily fast (bounded parameter variations and reconfiguration changes, is reported including numerical and experimental results. The main advantages of the converter and the robust controller proposed are simple design, robustness against abrupt changes in the parameters, and low cost.

Effect of Methamphetamine on Spectral Binding, Ligand Docking and Metabolism of Anti-HIV Drugs with CYP3A4

Science.gov (United States)

Ande, Anusha; Wang, Lei; Vaidya, Naveen K.; Li, Weihua; Kumar, Santosh; Kumar, Anil

2016-01-01

Cytochrome P450 3A4 (CYP3A4) is the major drug metabolic enzyme, and is involved in the metabolism of antiretroviral drugs, especially protease inhibitors (PIs). This study was undertaken to examine the effect of methamphetamine on the binding and metabolism of PIs with CYP3A4. We showed that methamphetamine exhibits a type I spectral change upon binding to CYP3A4 with δAmax and KD of 0.016±0.001 and 204±18 μM, respectively. Methamphetamine-CYP3A4 docking showed that methamphetamine binds to the heme of CYP3A4 in two modes, both leading to N-demethylation. We then studied the effect of methamphetamine binding on PIs with CYP3A4. Our results showed that methamphetamine alters spectral binding of nelfinavir but not the other type I PIs (lopinavir, atazanavir, tipranavir). The change in spectral binding for nelfinavir was observed at both δAmax (0.004±0.0003 vs. 0.0068±0.0001) and KD (1.42±0.36 vs.2.93±0.08 μM) levels. We further tested effect of methamphetamine on binding of 2 type II PIs; ritonavir and indinavir. Our results showed that methamphetamine alters the ritonavir binding to CYP3A4 by decreasing both the δAmax (0.0038±0.0003 vs. 0.0055±0.0003) and KD (0.043±0.0001 vs. 0.065±0.001 nM), while indinavir showed only reduced KD in presence of methamphetamine (0.086±0.01 vs. 0.174±0.03 nM). Furthermore, LC-MS/MS studies in high CYP3A4 human liver microsomes showed a decrease in the formation of hydroxy ritonavir in the presence of methamphetamine. Finally, CYP3A4 docking with lopinavir and ritonavir in the absence and presence of methamphetamine showed that methamphetamine alters the docking of ritonavir, which is consistent with the results obtained from spectral binding and metabolism studies. Overall, our results demonstrated differential effects of methamphetamine on the binding and metabolism of PIs with CYP3A4. These findings have clinical implication in terms of drug dose adjustment of antiretroviral medication, especially with ritonavir-boosted

In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of breast cancer cells

International Nuclear Information System (INIS)

Weigel, Marion T; Maass, Nicolai; Mundhenke, Christoph; Dahmke, Linda; Schem, Christian; Bauerschlag, Dirk O; Weber, Katrin; Niehoff, Peter; Bauer, Maret; Strauss, Alexander; Jonat, Walter

2010-01-01

Breast cancer treatment is based on a combination of adjuvant chemotherapy followed by radiotherapy effecting intracellular signal transduction. With the tyrosine kinase inhibitors new targeted drugs are available. Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha, beta and c-kit. The purpose of this study was to determine whether Imatinib has an influence on the effectiveness of radiotherapy in breast cancer cell lines and if a combination of imatinib with standard chemotherapy could lead to increased cytoreduction. Colony-forming tests of MCF 7 and MDA MB 231 were used to study differences in cell proliferation under incubation with imatinib and radiation. Changes in expression and phosphorylation of target receptors were detected using western blot. Cell proliferation, migration and apoptosis assays were performed combining imatinib with doxorubicin. The combination of imatinib and radiotherapy showed a significantly stronger inhibition of cell proliferation compared to single radiotherapy. Differences in PDGFR expression could not be detected, but receptor phosphorylation was significantly inhibited when treated with imatinib. Combination of imatinib with standard chemotherapy lead to an additive effect on cell growth inhibition compared to single treatment. Imatinib treatment combined with radiotherapy leads in breast cancer cell lines to a significant benefit which might be influenced through inhibition of PDGFR phosphorylation. Combining imatinib with chemotherapy enhances cytoreductive effects. Further in vivo studies are needed to evaluate the benefit of Imatinib in combination with radiotherapy and chemotherapy on the treatment of breast cancer

Terapia antiviral para VIH-SIDA

Directory of Open Access Journals (Sweden)

Alicia Tarinas Reyes

2000-12-01

Full Text Available En los últimos años, muchos agentes antivirales nuevos han sido incorporados a la quimioterapéutica. En esta revisión se resumen tanto los fármacos establecidos de años atrás como los nuevos medicamentos desarrollados para el tratamiento de individuos infectados por VIH. El AZT fue el primero aprobado en marzo de 1987, le siguió el ddl (1991, ddC (1992, d4T (1994, 3TC (1995. Luego fue aprobado el primer inhibidor de proteasa, saquinavir en diciembre de 1995, seguido de ritonavir (1996, indinavir (1996, nelfinavir (1997; además de otros inhibidores de la reverso transcriptasa como nevirapine (1996, delavirdine (1997, efavirenz (1998, entre otros. En estos momentos se siguen buscando y desarrollando nuevas terapias alternativas para esta afección. En este trabajo se exponen algunas de las características de dichos medicamentos, como son: mecanismos de acción (sobre qué enzima actúa cada uno y cómo lo hacen, el ciclo viral, dosificación, incompatibilidades y reacciones adversas.During the last years many new antiviral agents have been incorporated to the chemotherapeutics. The pharmaceuticals established years ago as well as the new ones developed to treat HIV infected individuals are included in this review. The AZT was the first approved in March, 1987, followed by ddl (1991, ddc (1992, d4t (1994, and 3TC (1995. Later, the first protease inhibitor, saquinovir, was approved in December, 1995, followed by ritonavir (1996, indinavir (1996, and nelfinavir (1997; in addition to other inhibitors of the reverse transcriptase as neviparine (1996, delavirdine (1997, and efavirenz (1998, among others. At present new alternative therapies for this affection are being searched and developed. Some of the characteristics of these dugs, such as: action mechanisms (on which enzime each of them act and how they do it, viral cycle, dosage, incompatibilites and adverse reactions are dealt with in this paper.

Is it beneficial to selectively boost high-risk tumor subvolumes? A comparison of selectively boosting high-risk tumor subvolumes versus homogeneous dose escalation of the entire tumor based on equivalent EUD plans

International Nuclear Information System (INIS)

Kim, Yusung; To me, Wolfgang A.

2008-01-01

Purpose. To quantify and compare expected local tumor control and expected normal tissue toxicities between selective boosting IMRT and homogeneous dose escalation IMRT for the case of prostate cancer. Methods. Four different selective boosting scenarios and three different high-risk tumor subvolume geometries were designed to compare selective boosting and homogeneous dose escalation IMRT plans delivering the same equivalent uniform dose (EUD) to the entire PTV. For each scenario, differences in tumor control probability between both boosting strategies were calculated for the high-risk tumor subvolume and remaining low-risk PTV, and were visualized using voxel based iso-TCP maps. Differences in expected rectal and bladder complications were quantified using radiobiological indices (generalized EUD (gEUD) and normal tissue complication probability (NTCP)) as well as %-volumes. Results. For all investigated scenarios and high-risk tumor subvolume geometries, selective boosting IMRT improves expected TCP compared to homogeneous dose escalation IMRT, especially when lack of control of the high-risk tumor subvolume could be the cause for tumor recurrence. Employing, selective boosting IMRT significant increases in expected TCP can be achieved for the high-risk tumor subvolumes. The three conventional selective boosting IMRT strategies, employing physical dose objectives, did not show significant improvement in rectal and bladder sparing as compared to their counterpart homogeneous dose escalation plans. However, risk-adaptive optimization, utilizing radiobiological objective functions, resulted in reduction in NTCP for the rectum when compared to its corresponding homogeneous dose escalation plan. Conclusions. Selective boosting is a more effective method than homogeneous dose escalation for achieving optimal treatment outcomes. Furthermore, risk-adaptive optimization increases the therapeutic ratio as compared to conventional selective boosting IMRT

Two-inductor boost and buck converters

Science.gov (United States)

White, J. L.; Muldoon, W. J.

The derivation, analysis and design of a coupled inductor boost converter is presented. Aspects of the qualitative ac behavior of coupled inductor converters are discussed. Considerations for the design of the magnetics for such converters are addressed.

Prolonged treatment with imatinib mesylate in patients with advanced chronic myeloid leukemia causes a reduction of bcr/abl mRNA levels independent of cytogenetic response.

Science.gov (United States)

Cariani, E; Capucci, M; Micheletti, M; Spalenza, F; Zanella, I; Albertini, A; Rossi, G

2003-06-01

Bcr/abl mRNA levels were monitored in 13 patients with chronic myeloid leukemia receiving imatinib mesylate over a period of 78 weeks. During treatment median bcr/abl mRNA levels progressively declined from 77.2 normalized dose (nD) at baseline to 11.28 nD after 13 weeks ( P<0.05) and to 1.28 nD after 78 weeks ( P<0.05). After 13 weeks, bcr/abl mRNA levels were significantly lower in cytogenetic responders compared to nonresponders ( P<0.05), but subsequent decrease in the transcript levels caused the loss of any correlation to the cytogenetic status. These results suggest that bcr/abl mRNA levels may reflect cytogenetic response only during the early phases of imatinib therapy.

Experimental Treatment for Duchenne Muscular Dystrophy Gets Boost from Existing Medication

Science.gov (United States)

... Boost from Existing Medication Spotlight on Research Experimental Treatment for Duchenne Muscular Dystrophy Gets Boost from Existing Medication By Colleen Labbe, M.S. | March 1, 2013 A mouse hanging on a wire during a test of muscle strength. Mice with a mutant dystrophin gene, which ...

Single Phase Transformer-less Buck-Boost Inverter with Zero Leakage Current for PV Systems

DEFF Research Database (Denmark)

Mostaan, Ali; Abdelhakim, Ahmed; N. Soltani, Mohsen

2017-01-01

In this paper, a novel single-stage single-phase transformer-less buck-boost inverter is proposed, in which a reduced number of passive components is used. The proposed inverter combines the conventional buck, boost, and buck-boost converters in one converter in order to obtain a sinusoidal output...

Balanced G-band Gm-boosted frequency doublers in transferred substrate InP HBT technology

DEFF Research Database (Denmark)

Johansen, Tom Keinicke; Thualfiqar, Al-Sawaf; Weimann, Nils

2016-01-01

In this paper, balanced G-band Gm-boosted frequency doublers in transferred substrate (TS) InP HBT technology are reported for the first time. The Gm-boosted frequency doublers consist of a phase compensated Marchand balun, Gm-boosted doubler stage, and an optional cascode gain stage at the outpu...

Generalized Switched-Inductor Based Buck-Boost Z-H Converter

Directory of Open Access Journals (Sweden)

E. Babaei

2017-12-01

Full Text Available In this paper, a generalized buck-boost Z-H converter based on switched inductors is proposed. This structure consists of a set of series connected switched-inductor cells. The voltage conversion ratio of the proposed structure is adjusted by changing the number of cells and the duty cycle. Like the conventional Z-H converter, the shoot-through switching state and the diode before LC network are eliminated. The proposed converter can provide high voltage gain in low duty cycles. Considering different values for duty cycle, the proposed structure works in two operating zones. In the first operating zone, it works as a buck-boost converter and in the second operating zone, it works as a boost converter. In this paper, a complete analysis of the proposed converter is presented. In order to confirm the accuracy of mathematic calculations, the simulations results by using PSCAD/EMTDC software are given.

Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial.

Science.gov (United States)

Arabi, Yaseen M; Alothman, Adel; Balkhy, Hanan H; Al-Dawood, Abdulaziz; AlJohani, Sameera; Al Harbi, Shmeylan; Kojan, Suleiman; Al Jeraisy, Majed; Deeb, Ahmad M; Assiri, Abdullah M; Al-Hameed, Fahad; AlSaedi, Asim; Mandourah, Yasser; Almekhlafi, Ghaleb A; Sherbeeni, Nisreen Murad; Elzein, Fatehi Elnour; Memon, Javed; Taha, Yusri; Almotairi, Abdullah; Maghrabi, Khalid A; Qushmaq, Ismael; Al Bshabshe, Ali; Kharaba, Ayman; Shalhoub, Sarah; Jose, Jesna; Fowler, Robert A; Hayden, Frederick G; Hussein, Mohamed A

2018-01-30

It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

Brachytherapy boost for breast cancer: what do we know? where do we go?

International Nuclear Information System (INIS)

Hannoun-Levi, J.M.; Marsiglia, H.

2004-01-01

Since many years, Brachytherapy (BT) appears to play an important role in the treatment of many solid tumors. For breast cancer, BT is usually used as boost after postoperative external beam radiation therapy. In certain circumstances. BT can be used as sole radiation technique focalized on the tumor bed or more rarely, as second conservative treatment in case of local recurrence for woman refusing salvage mastectomy. Boost BT is most often applied via an interstitial technique while the dose rate can vary from low to high close rate through pulse dose rate. All of those boost techniques were published and some of them compared the results obtained with BT and external beam electron therapy. The analysis of the published phase II and III trials was not able to show significant differences between the two boost techniques in term of local control as well as late skin side effects. However, we noted that the patients who received BT boost presented a higher risk of local recurrence compare to those treated with electron therapy, due to age, margin status or presence of extensive intraductal component. Only a phase III trial randomizing BT boost vs electron therapy boost could show a possible improvement of local control rate in the BT arm; however, this trial should enroll patients with a real high risk of local recurrence in order to take benefit from the dosimetric advantages of BT. (author)

Estimation of age-specific rates of reactivation and immune boosting of the varicella zoster virus

Directory of Open Access Journals (Sweden)

Isabella Marinelli

2017-06-01

Full Text Available Studies into the impact of vaccination against the varicella zoster virus (VZV have increasingly focused on herpes zoster (HZ, which is believed to be increasing in vaccinated populations with decreasing infection pressure. This idea can be traced back to Hope-Simpson's hypothesis, in which a person's immune status determines the likelihood that he/she will develop HZ. Immunity decreases over time, and can be boosted by contact with a person experiencing varicella (exogenous boosting or by a reactivation attempt of the virus (endogenous boosting. Here we use transmission models to estimate age-specific rates of reactivation and immune boosting, exogenous as well as endogenous, using zoster incidence data from the Netherlands (2002–2011, n = 7026. The boosting and reactivation rates are estimated with splines, enabling these quantities to be optimally informed by the data. The analyses show that models with high levels of exogenous boosting and estimated or zero endogenous boosting, constant rate of loss of immunity, and reactivation rate increasing with age (to more than 5% per year in the elderly give the best fit to the data. Estimates of the rates of immune boosting and reactivation are strongly correlated. This has important implications as these parameters determine the fraction of the population with waned immunity. We conclude that independent evidence on rates of immune boosting and reactivation in persons with waned immunity are needed to robustly predict the impact of varicella vaccination on the incidence of HZ.

Breast conserving treatment for breast cancer: dosimetric comparison of sequential versus simultaneous integrated photon boost.

Science.gov (United States)

Van Parijs, Hilde; Reynders, Truus; Heuninckx, Karina; Verellen, Dirk; Storme, Guy; De Ridder, Mark

2014-01-01

Breast conserving surgery followed by whole breast irradiation is widely accepted as standard of care for early breast cancer. Addition of a boost dose to the initial tumor area further reduces local recurrences. We investigated the dosimetric benefits of a simultaneously integrated boost (SIB) compared to a sequential boost to hypofractionate the boost volume, while maintaining normofractionation on the breast. For 10 patients 4 treatment plans were deployed, 1 with a sequential photon boost, and 3 with different SIB techniques: on a conventional linear accelerator, helical TomoTherapy, and static TomoDirect. Dosimetric comparison was performed. PTV-coverage was good in all techniques. Conformity was better with all SIB techniques compared to sequential boost (P = 0.0001). There was less dose spilling to the ipsilateral breast outside the PTVboost (P = 0.04). The dose to the organs at risk (OAR) was not influenced by SIB compared to sequential boost. Helical TomoTherapy showed a higher mean dose to the contralateral breast, but less than 5 Gy for each patient. SIB showed less dose spilling within the breast and equal dose to OAR compared to sequential boost. Both helical TomoTherapy and the conventional technique delivered acceptable dosimetry. SIB seems a safe alternative and can be implemented in clinical routine.

Spectrophotometric method for simultaneous estimation of atazanavir sulfate and ritonavir in tablet dosage form

Directory of Open Access Journals (Sweden)

Disha A Patel

2015-01-01

Full Text Available Background: Ritonavir (RTV and atazanavir sulfate (ATV are protease inhibitor and RTV mostly used as a booster for increasing the bioavailability of other protease inhibitors like ATV. Aims: Quality assessment of the new dosage form of RTV and ATV i.e., tablets is very essential and hence this work deals with to develop sensitive, simple and precise method for simultaneous estimation of ATV and RTV in tablet dosage form by absorbance correction method. Materials and Methods: The present work was carried out on Shimadzu Ultraviolate(UV-1700 double beam spectrophotometer with 1 cm path length supported by S Shimadzu, model-1700(Japan, UV-Probe software, version 2.31 was used for spectral measurements with 10 mm matched quartz cells. Standard ATV and RTV were supplied by Cipla Pharmaceutical Ltd. Methanol was purchased from Finar Chemicals Pvt. Ltd. Results and Conclusion: The λmax or the absorption maxima for ATV and RTV were found to be 279 and 240 nm, respectively in methanol as solvent. The drugs follow Beer-Lambert′s law in the concentration range 30-90 and 10-30 μg/mL for ATV and RTV, respectively. The percentage recovery was found to be 100-100.33% and 100-101.5% for ATV and RTV, respectively. The method was validated for different parameters as per the International Conference for Harmonization Guidelines.

Thermodynamic solution properties of pefloxacin mesylate and its interactions with organized assemblies of anionic surfactant, sodium dodecyl sulphate

International Nuclear Information System (INIS)

Usman, Muhammad; Rashid, Muhammad Abid; Mansha, Asim; Siddiq, Mohammad

2013-01-01

Graphical abstract: - Highlights: • Free energy of adsorption is more negative than free energy of micellization. • Micellization becomes more spontaneous at high temperature. • There is strong interaction between PFM and SDS. - Abstract: This manuscript reports the physicochemical behavior of antibiotic amphiphilic drug pefloxacin mesylate (PFM) and its interaction with anionic surfactant, sodium dodecyl sulfate (SDS). The data of surface tension and electrical conductivity are helpful to detect the CMC as well as to calculate surface parameters, i.e. surface pressure, π, surface excess concentration, Γ, area per molecule of drug and standard Gibbs free energy of adsorption, ΔG ads and thermodynamic parameters like standard free energy of micellization, ΔG m , standard enthalpy of micellization, ΔH m and standard entropy of micellization, ΔS m . The interaction of this drug with anionic surfactant, sodium dodecyl sulfate (SDS) was studied by electrical conductivity and UV/visible spectroscopy. This enabled us to compute the values of partition coefficient (K x ), free energy of partition, ΔG p , binding constant, K b , free energy of binding, ΔG b , number of drug molecules per micelle, n, and thermodynamic parameters of drug–surfactant interaction

Electroanalytical Determination of Gemifloxacin Mesylate in Bulk, Tablets and Human Urine Using Gold Nanoparticles Modified Carbon Paste Electrode

Directory of Open Access Journals (Sweden)

Ali Attia

2014-12-01

Full Text Available A simple, precise, inexpensive and sensitive voltammetric method has been developed for the determination of gemifloxacin mesylate (GEM in the presence of tween 80 in the bulk, farmaceutical dosage forms and human urine at gold nanoparticles modified carbon paste electrode (GNCPE. The electrochemical behavior of GEM has been investigated by using cyclic voltammetry (CV and differential pulse voltammetry (DPV techniques. The electrochemical oxidation of GEM was an irreversible process which exhibited adsorption-diffusion controlled process behavior in Britton-Robinson (BR buffer over the entire pH range of values from 2 to 9. The adsorptive stripping response was evaluated as a function of some variables such as pH, type of surfactant, scan rate and accumulation time. The anodic peak current varied linearly over the range from 8.0 × 10-7 to 2.8 × 10-5 M. The limits of detection and quantification were 7.32 × 10-8 M and 2.44 × 10-7 M, respectively. The relative standard deviations and the percentage recoveries were found in the following ranges: 0.58-1.35% and 99.37-101.76%, respectively.

Targeted intraoperative radiotherapy tumour bed boost during breast-conserving surgery after neoadjuvant chemotherapy

Energy Technology Data Exchange (ETDEWEB)

Kolberg, Hans-Christian; Akpolat-Basci, Leyla; Stephanou, Miltiades [Marienhospital Bottrop gGmbH, Department of Gynecology and Obstetrics, Bottrop (Germany); Loevey, Gyoergy [BORAD, Bottrop (Germany); Fasching, Peter A. [University of Erlangen, Erlangen (Germany); Untch, Michael [Helios Klinikum Berlin-Buch, Berlin (Germany); Liedtke, Cornelia [University Hospital Schleswig-Holstein/Campus Luebeck, Luebeck (Germany); Bulsara, Max [University of Notre Dame, Fremantle (Australia); University College, London (United Kingdom); Vaidya, Jayant S. [University College, London (United Kingdom)

2017-01-15

The use of targeted intraoperative radiotherapy (TARGIT-IORT) as a tumour bed boost during breast-conserving surgery (BCS) for breast cancer has been reported since 1998. We present its use in patients undergoing breast conservation following neoadjuvant therapy (NACT). In this retrospective study involving 116 patients after NACT we compared outcomes of 61 patients who received a tumour bed boost with IORT during lumpectomy versus 55 patients treated in the previous 13 months with external (EBRT) boost. All patients received whole breast radiotherapy. Local recurrence-free survival (LRFS), disease-free survival (DFS), distant disease-free survival (DDFS), breast cancer mortality (BCM), non-breast cancer mortality (NBCM) and overall mortality (OS) were compared. Median follow up was 49 months. The differences in LRFS, DFS and BCM were not statistically significant. The 5-year Kaplan-Meier estimate of OS was significantly better by 15% with IORT: IORT 2 events (96.7%, 95%CI 87.5-99.2), EBRT 9 events (81.7%, 95%CI 67.6-90.1), hazard ratio (HR) 0.19 (0.04-0.87), log rank p = 0.016, mainly due to a reduction of 10.1% in NBCM: IORT 100%, EBRT 89.9% (77.3-95.7), HR (not calculable), log rank p = 0.015. The DDFS was as follows: IORT 3 events (95.1%, 85.5-98.4), EBRT 12 events (69.0%, 49.1-82.4), HR 0.23 (0.06-0.80), log rank p = 0.012. IORT during lumpectomy after neoadjuvant chemotherapy as a tumour bed boost appears to give results that are not worse than external beam radiotherapy boost. These data give further support to the inclusion of such patients in the TARGIT-B (boost) randomised trial that is testing whether IORT boost is superior to EBRT boost. (orig.) [German] Die intraoperative Radiotherapie (TARGIT-IORT) als vorgezogener Boost im Rahmen der brusterhaltenden Therapie (BET) ist seit 1998 Gegenstand der wissenschaftlichen Diskussion. Wir praesentieren Daten zum Einsatz der IORT bei der BET nach neoadjuvanter Therapie (NACT). In diese retrospektive Analyse

A Novel Single Switch Transformerless Quadratic DC/DC Buck-Boost Converter

DEFF Research Database (Denmark)

Mostaan, Ali; A. Gorji, Saman; N. Soltani, Mohsen

2017-01-01

A novel quadratic buck-boost DC/DC converter is presented in this study. The proposed converter utilizes only one active switch and can step-up/down the input voltage, while the existing single switch quadratic buck/boost converters can only work in step-up or step-down mode. First, the proposed ...

Estimation of reliability of a interleaving PFC boost converter

Directory of Open Access Journals (Sweden)

Gulam Amer Sandepudi

2010-01-01

Full Text Available Reliability plays an important role in power supplies. For other electronic equipment, a certain failure mode, at least for a part of the total system, can often be employed without serious (critical effects. However, for power supply no such condition can be accepted, since very high demands on its reliability must be achieved. At higher power levels, the continuous conduction mode (CCM boost converter is preferred topology for implementation a front end with PFC. As a result, significant efforts have been made to improve the performance of high boost converter. This paper is one of the efforts for improving the performance of the converter from the reliability point of view. In this paper, interleaving boost power factor correction converter is simulated with single switch in continuous conduction mode (CCM, discontinuous conduction mode (DCM and critical conduction mode (CRM under different output power ratings. Results of the converter are explored from reliability point of view.

Pulse width modulated buck-boost five-level current source inverters

DEFF Research Database (Denmark)

Blaabjerg, Frede; Gao, F.; Loh, P.C.

2008-01-01

, resulting in the natural balance of input current. For maintaining the normalized volt-sec average unchanged, the alternative phase opposition disposition (APOD) modulation scheme with typical gating signal mapping technique from voltage source inverter (VSI) to CSI can be assumed to control the five......This paper presents new five-level current source inverters (CSIs) with voltage/current buck-boost capability. Being different from the existing multilevel CSI, the proposed CSIs were first designed to regulate the flowing path of dc input current by controlling two additional active switches......-level buck-boost CSIs. Next by observing the hidden current charging path during inductive charging interval under APOD modulation, it is noted that the buck-boost five-level CSI can then be further modified with lesser active component without degrading output performance. To verify the theoretical findings...

Application of a synchronous generator with a boost converter in wind turbines: an experimental overview

DEFF Research Database (Denmark)

Sharma, Ranjan; Rasmussen, Tonny Wederberg; Jensen, Bogi Bech

2012-01-01

An electrical structure of a variable-speed wind turbine based on an externally excited synchronous generator; a passive diode rectifier; and a boost converter is discussed in this study. The clear advantage of such a system is its lower-semi-conductor devices count. A brief theoretical explanation...... of such a system is included. A boost converter normally utilies an inductor (energy storage) to boost the voltage level from its input to a higher output value. This study analyses the possibility of using the generator inductance as a boost inductor. It is discussed and verified in the study that for the given...... switching frequency of the boost converter (fs=1= kHz), the generator sub-transient inductance (not the synchronous inductance) appears as an equivalent inductance seen by the boost converter. The parasitic capacitors present in the generator terminals are often neglected from design issues. It is presented...

Heterologous Prime-Boost Immunizations with a Virosomal and an Alphavirus Replicon Vaccine

NARCIS (Netherlands)

Walczak, Mateusz; de Mare, Arjan; Riezebos-Brilman, Annelies; Regts, Joke; Hoogeboom, Baukje-Nynke; Visser, Jeroen T.; Fiedler, Marc; Jansen-Duerr, Pidder; van der Zee, Ate G. J.; Nijman, Hans W.; Wilschut, Jan; Daemen, Toos

2011-01-01

Heterologous prime-boost immunization strategies in general establish higher frequencies of antigen-specific T lymphocytes than homologous prime-boost protocols or single immunizations. We developed virosomes and recombinant Semliki Forest virus (rSFV) as antigen delivery systems, each capable of

Early boost and slow consolidation in motor skill learning.

Science.gov (United States)

Hotermans, Christophe; Peigneux, Philippe; Maertens de Noordhout, Alain; Moonen, Gustave; Maquet, Pierre

2006-01-01

Motorskill learning is a dynamic process that continues covertly after training has ended and eventually leads to delayed increments in performance. Current theories suggest that this off-line improvement takes time and appears only after several hours. Here we show an early transient and short-lived boost in performance, emerging as early as 5-30 min after training but no longer observed 4 h later. This early boost is predictive of the performance achieved 48 h later, suggesting its functional relevance for memory processes.

Breast Conserving Treatment for Breast Cancer: Dosimetric Comparison of Sequential versus Simultaneous Integrated Photon Boost

Directory of Open Access Journals (Sweden)

Hilde Van Parijs

2014-01-01

Full Text Available Background. Breast conserving surgery followed by whole breast irradiation is widely accepted as standard of care for early breast cancer. Addition of a boost dose to the initial tumor area further reduces local recurrences. We investigated the dosimetric benefits of a simultaneously integrated boost (SIB compared to a sequential boost to hypofractionate the boost volume, while maintaining normofractionation on the breast. Methods. For 10 patients 4 treatment plans were deployed, 1 with a sequential photon boost, and 3 with different SIB techniques: on a conventional linear accelerator, helical TomoTherapy, and static TomoDirect. Dosimetric comparison was performed. Results. PTV-coverage was good in all techniques. Conformity was better with all SIB techniques compared to sequential boost (P = 0.0001. There was less dose spilling to the ipsilateral breast outside the PTVboost (P = 0.04. The dose to the organs at risk (OAR was not influenced by SIB compared to sequential boost. Helical TomoTherapy showed a higher mean dose to the contralateral breast, but less than 5 Gy for each patient. Conclusions. SIB showed less dose spilling within the breast and equal dose to OAR compared to sequential boost. Both helical TomoTherapy and the conventional technique delivered acceptable dosimetry. SIB seems a safe alternative and can be implemented in clinical routine.

Boosted dark matter signals uplifted with self-interaction

Energy Technology Data Exchange (ETDEWEB)

Kong, Kyoungchul, E-mail: kckong@ku.edu [Department of Physics and Astronomy, University of Kansas, Lawrence, KS 66045 (United States); Mohlabeng, Gopolang, E-mail: mohlabeng319@gmail.com [Department of Physics and Astronomy, University of Kansas, Lawrence, KS 66045 (United States); Park, Jong-Chul, E-mail: log1079@gmail.com [Department of Physics and Astronomy, University of Kansas, Lawrence, KS 66045 (United States); Department of Physics, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

2015-04-09

We explore detection prospects of a non-standard dark sector in the context of boosted dark matter. We focus on a scenario with two dark matter particles of a large mass difference, where the heavier candidate is secluded and interacts with the standard model particles only at loops, escaping existing direct and indirect detection bounds. Yet its pair annihilation in the galactic center or in the Sun may produce boosted stable particles, which could be detected as visible Cherenkov light in large volume neutrino detectors. In such models with multiple candidates, self-interaction of dark matter particles is naturally utilized in the assisted freeze-out mechanism and is corroborated by various cosmological studies such as N-body simulations of structure formation, observations of dwarf galaxies, and the small scale problem. We show that self-interaction of the secluded (heavier) dark matter greatly enhances the capture rate in the Sun and results in promising signals at current and future experiments. We perform a detailed analysis of the boosted dark matter events for Super-Kamiokande, Hyper-Kamiokande and PINGU, including notable effects such as evaporation due to self-interaction and energy loss in the Sun.

Influence of the timing of a concomitant boost during fractionated irradiation of rat rhabdomyosarcoma R1H

International Nuclear Information System (INIS)

Dubben, H.H.; Beck-Bornholdt, H.P.

1993-01-01

Rhabdomyosarcomas R1H of the rat (WAG/Rij) were treated using fractionation schedules including a boost. The total dose was 60 Gy. Overall treatment time was 6 weeks. Four different boost schedules were applied: A single dose boost (12.15 Gy) at the last day of treatment, a single dose boost (12.15 Gy) at the first day of treatment, a schedule including the boost in 7 fractions during the first week, and a schedule including the boost in 10 fractions during the first week of treatment. A standard schedule with 30 fractions of 2 Gy without a boost was used for comparison. Initially accelerated schedules, i.e. those with a boost at start of treatment, revealed higher effect on tumour parenchyma as monitored by local control rate and net growth delay. This could be due to a decrease of radio-sensitivity, that is, an increase of the hypoxic fraction of clonogenic tumour cells during fractionated irradiation. (orig.)

Nelfinavir augments proteasome inhibition by bortezomib in myeloma cells and overcomes bortezomib and carfilzomib resistance

International Nuclear Information System (INIS)

Kraus, M; Bader, J; Overkleeft, H; Driessen, C

2013-01-01

HIV protease inhibitors (HIV-PI) are oral drugs for HIV treatment. HIV-PI have antitumor activity via induction of ER-stress, inhibition of phospho-AKT (p-AKT) and the proteasome, suggesting antimyeloma activity. We characterize the effects of all approved HIV-PI on myeloma cells. HIV-PI were compared regarding cytotoxicity, proteasome activity, ER-stress induction and AKT phosphorylation using myeloma cells in vitro. Nelfinavir is the HIV-PI with highest cytotoxic activity against primary myeloma cells and with an IC 50 near therapeutic drug blood levels (8–14 μM), irrespective of bortezomib sensitivity. Only nelfinavir inhibited intracellular proteasome activity in situ at drug concentrations <40 μℳ. Ritonavir, saquinavir and lopinavir inhibited p-AKT comparable to nelfinavir, and showed similar synergistic cytotoxicity with bortezomib against bortezomib-sensitive cells. Nelfinavir had superior synergistic activity with bortezomib/carfilzomib in particular against bortezomib/carfilzomib-resistant myeloma cells. It inhibited not only the proteasomal β1/β5 active sites, similar to bortezomib/carfilzomib, but in addition the β2 proteasome activity not targeted by bortezomib/carfilzomib. Additional inhibition of β2 proteasome activity is known to sensitize cells for bortezomib and carfilzomib. Nelfinavir has unique proteasome inhibiting activity in particular on the bortezomib/carfilzomib-insensitive tryptic (β2) proteasome activity in intact myeloma cells, and is active against bortezomib/carfilzomib-resistant myeloma cells in vitro

Quadratic Boost A-Source Impedance Network

DEFF Research Database (Denmark)

Siwakoti, Yam Prasad; Blaabjerg, Frede; Chub, Andrii

2016-01-01

A novel quadratic boost A-source impedance network is proposed to realize converters that demand very high voltage gain. To satisfy the requirement, the network uses an autotransformer where the obtained gain is quadratically dependent on the duty ratio and is unmatched by any existing impedance...

Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity.

Science.gov (United States)

Basciani, Sabrina; Brama, Marina; Mariani, Stefania; De Luca, Gabriele; Arizzi, Mario; Vesci, Loredana; Pisano, Claudio; Dolci, Susanna; Spera, Giovanni; Gnessi, Lucio

2005-03-01

Leydig cell tumors are usually benign tumors of the male gonad. However, if the tumor is malignant, no effective treatments are currently available. Leydig cell tumors express platelet-derived growth factor (PDGF), kit ligand and their respective receptors, PDGFR and c-kit. We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the c-kit and PDGFR tyrosine kinases, on the growth of rodent Leydig tumor cell lines in vivo and in vitro, and examined, in human Leydig cell tumor samples, the expression of activated PDGFR and c-kit and the mutations in exons of the c-kit gene commonly associated with solid tumors. Imatinib caused concentration-dependent decreases in the viability of Leydig tumor cell lines, which coincided with apoptosis and inhibition of proliferation and ligand-stimulated phosphorylation of c-kit and PDGFRs. Mice bearing s.c. allografts of a Leydig tumor cell line treated with imatinib p.o., had an almost complete inhibition of tumor growth, less tumor cell proliferation, increased apoptosis, and a lesser amount of tumor-associated mean vessel density compared with controls. No drug-resistant tumors appeared during imatinib treatment but tumors regrew after drug withdrawal. Human Leydig cell tumors showed an intense expression of the phosphorylated form of c-kit and a less intense expression of phosphorylated PDGFRs. No activating mutations in common regions of mutation of the c-kit gene were found. Our studies suggest that Leydig cell tumors might be a potential target for imatinib therapy.

Substructure of Highly Boosted Massive Jets

Energy Technology Data Exchange (ETDEWEB)

Alon, Raz [Weizmann Inst. of Science, Rehovot (Israel)

2012-10-01

Modern particle accelerators enable researchers to study new high energy frontiers which have never been explored before. This realm opens possibilities to further examine known fields such as Quantum Chromodynamics. In addition, it allows searching for new physics and setting new limits on the existence of such. This study examined the substructure of highly boosted massive jets measured by the CDF II detector. Events from 1.96 TeV proton-antiproton collisions at the Fermilab Tevatron Collider were collected out of a total integrated luminosity of 5.95 fb$^{-1}$. They were selected to have at least one jet with transverse momentum above 400 GeV/c. The jet mass, angularity, and planar flow were measured and compared with predictions of perturbative Quantum Chromodynamics, and were found to be consistent with the theory. A search for boosted top quarks was conducted and resulted in an upper limit on the production cross section of such top quarks.

Lopinavir/ritonavir dosing during pregnancy in Brazil and maternal/infant laboratory abnormalities

Directory of Open Access Journals (Sweden)

Mario Ferreira Peixoto

Full Text Available OBJECTIVES: To describe laboratory abnormalities among HIV-infected women and their infants with standard and increased lopinavir/ritonavir (LPV/r dosing during the third trimester of pregnancy. METHODS: We evaluated data on pregnant women from NISDI cohorts (2002-2009 enrolled in Brazil, who received at least 28 days of LPV/r during the third pregnancy trimester and gave birth to singleton infants. RESULTS: 164 women received LPV/r standard dosing [(798/198 or 800/200 mg/day (Group 1] and 70 increased dosing [(> 800/200 mg/day (Group 2]. Group 1 was more likely to have advanced clinical disease and to use ARVs for treatment, and less likely to have CD4 counts > 500 cells/mm³. Mean plasma viral load was higher in Group 2. There were statistically significant, but not clinically meaningful, differences between groups in mean AST, ALT, cholesterol, and triglycerides. The proportion of women with Grade 3 or 4 adverse events was very low, with no statistically significant differences between groups in severe adverse events related to ALT, AST, total bilirubin, cholesterol, or triglycerides. There were statistically significant, but not clinically meaningful, differences between infant groups in ALT and creatinine. The proportion of infants with Grade 3 or 4 adverse events was very low, and there were no statistically significant differences in severe adverse events related to ALT, AST, BUN, or creatinine. CONCLUSION: The proportions of women and infants with severe laboratory adverse events were very low. Increased LPV/r dosing during the third trimester of pregnancy appears to be safe for HIV-infected women and their infants.

Diode-Assisted Buck-Boost Voltage-Source Inverters

DEFF Research Database (Denmark)

Gao, Feng; Loh, Poh Chiang; Teodorescu, Remus

2009-01-01

, a number of diode-assisted inverter variants can be designed with each having its own operational principle and voltage gain expression. For controlling them, a generic modulation scheme that can be used for controlling all diode-assisted variants with minimized harmonic distortion and component stress......This paper proposes a number of diode-assisted buck-boost voltage-source inverters with a unique X-shaped diode-capacitor network inserted between the inverter circuitry and dc source for producing a voltage gain that is comparatively higher than those of other buck-boost conversion techniques....... Using the diode-assisted network, the proposed inverters can naturally configure themselves to perform capacitive charging in parallel and discharging in series to give a higher voltage multiplication factor without compromising waveform quality. In addition, by adopting different front-end circuitries...

Effect of pole zero location on system dynamics of boost converter for micro grid

Science.gov (United States)

Lavanya, A.; Vijayakumar, K.; Navamani, J. D.; Jayaseelan, N.

2018-04-01

Green clean energy like photo voltaic, wind energy, fuel cell can be brought together by microgrid.For low voltage sources like photovoltaic cell boost converter is very much essential. This paper explores the dynamic analysis of boost converter in a continuous conduction mode (CCM). The transient performance and stability analysis is carried out in this paper using time domain analysis and frequency domain analysis techniques. Boost converter is simulated using both PSIM and MATLAB software. Furthermore, state space model obtained and the transfer function is derived. The converter behaviour when a step input is applied is analyzed and stability of the converter is analyzed from bode plot frequency for open loop. Effect of the locations of poles and zeros in the transfer function of boost converter and how the performance parameters are affected is discussed in this paper. Closed loop performance with PI controller is also analyzed for boost converter.

CT planning of boost irradiation in radiotherapy of breast cancer after conservative surgery

International Nuclear Information System (INIS)

Messer, Peter M.; Kirikuta, Ion C.; Bratengeier, Klaus; Flentje, Michael

1997-01-01

Background and purpose: A study was performed to compare the accuracy of clinical treatment set-up and CT planning of boost irradiation in radiotherapy of breast cancer. Material and methods: Between September 1993 and October 1994, 45 women who underwent breast conserving surgery and irradiation containing a boost to the tumour bed were investigated. Prospective evaluation of CT planning of the boost was carried out. The target volume/boost field, electron energy and treatment set-up had been defined on the basis of clinical examination, initial and postsurgical mammograms by one radiotherapist. Next, a planning CT was performed in treatment position and a CT-based treatment plan was calculated according to a target volume defined by another radiotherapist. The clinical treatment set-up was imported into our computer planning system and the resulting isodose plots were compared with those from CT planning and reviewed critically. Results: The clinically defined treatment set-up had to be modified in 80% of the patients. Most discrepancies observed were related to the size of the boost field itself and the chosen electron energy. Minor changes had to be made with respect to angle of table and gantry. Conclusions: Critical review of the isodose plots from both methods showed clear advantages for CT planning. Guidelines for target definition in CT planning of boost irradiation and subgroups of patients benefiting from this technique are described

Maximum power point tracking techniques for wind energy systems using three levels boost converter

Science.gov (United States)

Tran, Cuong Hung; Nollet, Frédéric; Essounbouli, Najib; Hamzaoui, Abdelaziz

2018-05-01

This paper presents modeling and simulation of three level Boost DC-DC converter in Wind Energy Conversion System (WECS). Three-level Boost converter has significant advantage compared to conventional Boost. A maximum power point tracking (MPPT) method for a variable speed wind turbine using permanent magnet synchronous generator (PMSG) is also presented. Simulation of three-level Boost converter topology with Perturb and Observe algorithm and Fuzzy Logic Control is implemented in MATLAB/SIMULINK. Results of this simulation show that the system with MPPT using fuzzy logic controller has better performance to the Perturb and Observe algorithm: fast response under changing conditions and small oscillation.

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies

Science.gov (United States)

Manitz, Juliane; Burger, Patricia; Amos, Christopher I.; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike

2017-01-01

The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility. PMID:28785300

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies.

Science.gov (United States)

Friedrichs, Stefanie; Manitz, Juliane; Burger, Patricia; Amos, Christopher I; Risch, Angela; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike; Hofner, Benjamin

2017-01-01

The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.

A THREE-PHASE BOOST DC-AC CONVERTER

African Journals Online (AJOL)

dc-ac converter (inverter) based on the dc-dc boost converters. ... Sliding mode controllers are designed to perform a robust control for the ... Computer simulations and spectral analysis demon- ... the conventional three-phase buck inverter,.

Avoiding Anemia: Boost Your Red Blood Cells

Science.gov (United States)

... Issues Subscribe January 2014 Print this issue Avoiding Anemia Boost Your Red Blood Cells En español Send ... Disease When Blood Cells Bend Wise Choices Preventing Anemia To prevent or treat iron-deficiency anemia: Eat ...

A Survey on Voltage Boosting Techniques for Step-Up DC-DC Converters

DEFF Research Database (Denmark)

Forouzesh, Mojtaba; Siwakoti, Yam Prasad; Gorji, Saman Asghari

2016-01-01

boosting techniques and topologies are large, which at times may be confusing and difficult to follow/adapt for different applications. Considering these aspects and in order to make a clear sketch of the general law and framework of various voltage boosting techniques, this paper comprehensively reviews...

Semi-supervised learning via regularized boosting working on multiple semi-supervised assumptions.

Science.gov (United States)

Chen, Ke; Wang, Shihai

2011-01-01

Semi-supervised learning concerns the problem of learning in the presence of labeled and unlabeled data. Several boosting algorithms have been extended to semi-supervised learning with various strategies. To our knowledge, however, none of them takes all three semi-supervised assumptions, i.e., smoothness, cluster, and manifold assumptions, together into account during boosting learning. In this paper, we propose a novel cost functional consisting of the margin cost on labeled data and the regularization penalty on unlabeled data based on three fundamental semi-supervised assumptions. Thus, minimizing our proposed cost functional with a greedy yet stagewise functional optimization procedure leads to a generic boosting framework for semi-supervised learning. Extensive experiments demonstrate that our algorithm yields favorite results for benchmark and real-world classification tasks in comparison to state-of-the-art semi-supervised learning algorithms, including newly developed boosting algorithms. Finally, we discuss relevant issues and relate our algorithm to the previous work.

Chagas Parasite Detection in Blood Images Using AdaBoost

Directory of Open Access Journals (Sweden)

Víctor Uc-Cetina

2015-01-01

Full Text Available The Chagas disease is a potentially life-threatening illness caused by the protozoan parasite, Trypanosoma cruzi. Visual detection of such parasite through microscopic inspection is a tedious and time-consuming task. In this paper, we provide an AdaBoost learning solution to the task of Chagas parasite detection in blood images. We give details of the algorithm and our experimental setup. With this method, we get 100% and 93.25% of sensitivity and specificity, respectively. A ROC comparison with the method most commonly used for the detection of malaria parasites based on support vector machines (SVM is also provided. Our experimental work shows mainly two things: (1 Chagas parasites can be detected automatically using machine learning methods with high accuracy and (2 AdaBoost + SVM provides better overall detection performance than AdaBoost or SVMs alone. Such results are the best ones known so far for the problem of automatic detection of Chagas parasites through the use of machine learning, computer vision, and image processing methods.

Boosted decision trees as an alternative to artificial neural networks for particle identification

International Nuclear Information System (INIS)

Roe, Byron P.; Yang Haijun; Zhu Ji; Liu Yong; Stancu, Ion; McGregor, Gordon

2005-01-01

The efficacy of particle identification is compared using artificial neutral networks and boosted decision trees. The comparison is performed in the context of the MiniBooNE, an experiment at Fermilab searching for neutrino oscillations. Based on studies of Monte Carlo samples of simulated data, particle identification with boosting algorithms has better performance than that with artificial neural networks for the MiniBooNE experiment. Although the tests in this paper were for one experiment, it is expected that boosting algorithms will find wide application in physics

Boosting bonsai trees for handwritten/printed text discrimination

Science.gov (United States)

Ricquebourg, Yann; Raymond, Christian; Poirriez, Baptiste; Lemaitre, Aurélie; Coüasnon, Bertrand

2013-12-01

Boosting over decision-stumps proved its efficiency in Natural Language Processing essentially with symbolic features, and its good properties (fast, few and not critical parameters, not sensitive to over-fitting) could be of great interest in the numeric world of pixel images. In this article we investigated the use of boosting over small decision trees, in image classification processing, for the discrimination of handwritten/printed text. Then, we conducted experiments to compare it to usual SVM-based classification revealing convincing results with very close performance, but with faster predictions and behaving far less as a black-box. Those promising results tend to make use of this classifier in more complex recognition tasks like multiclass problems.

Y-source impedance-network-based isolated boost DC/DC converter

DEFF Research Database (Denmark)

Siwakoti, Yam P.; Town, Graham; Loh, Poh Chiang

2014-01-01

A dc-dc converter with very high voltage gain is proposed in this paper for any medium-power application requiring a high voltage boost with galvanic isolation. The proposed converter topology can be realized using only two switches. With this topology a very high voltage boost can be achieved even...... with a relatively low duty cycle of the switches, and the gain obtainable is presently not matched by any existing impedance network based converter operated at the same duty ratio. The proposed converter has a Y-source impedance network to boost the voltage at the intermediate dc-link side and a push......-pull transformer for square-wave AC inversion and isolation. The voltage-doubler rectifier provides a constant dc voltage at the output stage. A theoretical analysis of the converter is presented, supported by simulation and experimental results. A 250 W down-scaled prototype was implemented in the laboratory...

Performance of Boosted W Boson Identification with the ATLAS Detector

CERN Document Server

The ATLAS collaboration

2014-01-01

This note presents the performance of a variety of techniques used to identify highly- boosted hadronically-decaying $W$ bosons. The studies presented here are divided into two parts: the first is based on Monte Carlo simulation, and the second compares the simulations to 20.3$\\pm$0.6 fb$^{-1}$ of proton-–proton collisions data collected by the ATLAS detector in 2012 at $\\sqrt{s} = 8$ TeV. Various tagging approaches and different grooming algorithms are compared in simulation, using a signal of large-$R$ jets containing a highly boosted $W$ boson and a background of large-$R$ jets originating from high-momentum light quarks or gluons. These techniques could also be utilised to identify hadronic decays of boosted $Z$ and Higgs bosons. A sample enriched in $t\\bar{t}\\to (W^+b)(W^-\\bar{b}) \\to (q\\bar{q}b)(\\mu \\bar{\

Demonstration of brachytherapy boost dose-response relationships in glioblastoma multiforme

International Nuclear Information System (INIS)

Sneed, Penny K.; Lamborn, Kathleen R.; Larson, David A.; Prados, Michael D.; Malec, Mary K.; McDermott, Michael W.; Weaver, Keith A.; Phillips, Theodore L.; Wara, William M.; Gutin, Philip H.

1996-01-01

Purpose: To evaluate brachytherapy dose-response relationships in adults with glioblastoma undergoing temporary 125 I implant boost after external beam radiotherapy. Methods and Materials: Since June 1987, orthogonal radiographs using a fiducial marker box have been used to verify brain implant source positions and generate dose-volume histograms at the University of California, San Francisco. For adults who underwent brachytherapy boost for glioblastoma from June 1987 through December 1992, tumor volumes were reoutlined to ensure consistency and dose-volume histograms were recalculated. Univariate and multivariate analyses of various patient and treatment parameters were performed evaluating for influence of dose on freedom from local failure (FFLF) and actuarial survival. Results: Of 102 implant boosts, 5 were excluded because computer plans were unavailable. For the remaining 97 patients, analyses with adjustment for known prognostic factors (age, KPS, extent of initial surgical resection) and prognostic factors identified on univariate testing (adjuvant chemotherapy) showed that higher minimum brachytherapy tumor dose was strongly associated with improved FFLF (p = 0.001). A quadratic relationship was found between total biological effective dose and survival, with a trend toward optimal survival probability at 47 Gy minimum brachytherapy tumor dose (corresponding to about 65 Gy to 95% of the tumor volume); survival decreased with lower or higher doses. Two patients expired and one requires hospice care because of brain necrosis after brachytherapy doses > 63 Gy to 95% of the tumor volume with 60 Gy to > 18 cm 3 of normal brain. Conclusion: Although higher minimum brachytherapy tumor dose was strongly associated with better local control, a brachytherapy boost dose > 50-60 Gy may result in life-threatening necrosis. We recommend careful conformation of the prescription isodose line to the contrast enhancing tumor volume, delivery of a minimum brachytherapy

Related factors to atazanavir plasma levels in a cohort of HIV positive individuals with undetectable viral load

Directory of Open Access Journals (Sweden)

Ana Júlia Luz

Full Text Available OBJECTIVE: To evaluate the factors associated with plasma concentrations of atazanavir (ATV in a cohort of well-controlled HIV infected subjects (undetectable viremia. Design: Cross-sectional study where 69 subjects were consecutively enrolled between April and November, 2011. METHODS: Patients had to be on atazanavir for at least six months, undetectable viral load for a period equal to or longer than 12 months, T CD4+ lymphocyte count higher than 200 cells/mm³, and aged between 18 years and 70 years old. Exclusion criteria were pregnancy, any neurologic disease, active opportunistic disease, hepatitis or cancer. Atazanavir plasma levels were measured by ultra-performance liquid chromatography. RESULTS AND DISCUSSION: Overall, 54 patients (mean age of 47 years and 50% women were included in the analysis. Those without ritonavir (unboosted atazanavir had statistically lower plasma concentrations than those with ritonavir boosted atazanavir (p = 0.001 and total and indirect bilirubin were statistically associated with plasma concentration of atazanavir (r = 0.32 and r = 0.33 respectively; p < 0.05 in both cases. no statistical association was found among gender, ethnicity, age, weight, body mass index (BMI, lipid profile, and the plasma concentration of atazanavir. CONCLUSION: in summary, as expected, concomitant ritonavir use was the only factor associated with atazanavir plasma levels. prospective studies with a larger sample size might help to observe an association of atazanavir concentrations to other characteristics such as body weight, since the p-value showed to be close to significance (p = 0.068.

Boosted H­->bb Tagger In Run II

CERN Document Server

Sahinsoy, Merve; The ATLAS collaboration

2016-01-01

Several searches for Higgs bosons decaying to b­quark pairs benefit from the increased Run II centre­of­mass energy by exploiting the large transvers­momentum (boosted) Higgs boson regime, where the two b­jets are merged into one large­radius jet. ATLAS uses a boosted H­>bb tagger algorithm to separate the Higgs signal from the background processes (QCD, W and Z bosons, top quarks). The tagger takes as input a large­R=1.0 jet calibrating the pseudorapidity, energy and mass scale. The tagger employs b­tagging, Higgs candidate mass, and substructure information. The performance of several operating points in Higgs boson signal and QCD and ttbar all­hadronic backgrounds are presented. Systematic uncertainties are evaluated so that this tagger can be used in analyses.

Application of Boosting Regression Trees to Preliminary Cost Estimation in Building Construction Projects

Directory of Open Access Journals (Sweden)

Yoonseok Shin

2015-01-01

Full Text Available Among the recent data mining techniques available, the boosting approach has attracted a great deal of attention because of its effective learning algorithm and strong boundaries in terms of its generalization performance. However, the boosting approach has yet to be used in regression problems within the construction domain, including cost estimations, but has been actively utilized in other domains. Therefore, a boosting regression tree (BRT is applied to cost estimations at the early stage of a construction project to examine the applicability of the boosting approach to a regression problem within the construction domain. To evaluate the performance of the BRT model, its performance was compared with that of a neural network (NN model, which has been proven to have a high performance in cost estimation domains. The BRT model has shown results similar to those of NN model using 234 actual cost datasets of a building construction project. In addition, the BRT model can provide additional information such as the importance plot and structure model, which can support estimators in comprehending the decision making process. Consequently, the boosting approach has potential applicability in preliminary cost estimations in a building construction project.

Traditional grains boost nutrition in rural India

International Development Research Centre (IDRC) Digital Library (Canada)

India, particularly among vulnerable women and children. The research ... This approach will improve the quality of life for farmers, and is part of a long-term solution to rural poverty in India. ... Traditional grains boost nutrition in rural India.

An imaging evaluation of the simultaneously integrated boost breast radiotherapy technique

Energy Technology Data Exchange (ETDEWEB)

Turley, Jessica; Claridge Mackonis, Elizabeth [Department of Radiation Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales (Australia)

2015-09-15

To evaluate in-field megavoltage (MV) imaging of simultaneously integrated boost (SIB) breast fields to determine its feasibility in treatment verification for the SIB breast radiotherapy technique, and to assess whether the current-imaging protocol and treatment margins are sufficient. For nine patients undergoing SIB breast radiotherapy, in-field MV images of the SIB fields were acquired on days that regular treatment verification imaging was performed. The in-field images were matched offline according to the scar wire on digitally reconstructed radiographs. The offline image correction results were then applied to a margin recipe formula to calculate safe margins that account for random and systematic uncertainties in the position of the boost volume when an offline correction protocol has been applied. After offline assessment of the acquired images, 96% were within the tolerance set in the current department-imaging protocol. Retrospectively performing the maximum position deviations on the Eclipse™ treatment planning system demonstrated that the clinical target volume (CTV) boost received a minimum dose difference of 0.4% and a maximum dose difference of 1.4% less than planned. Furthermore, applying our results to the Van Herk margin formula to ensure that 90% of patients receive 95% of the prescribed dose, the calculated CTV margins were comparable to the current departmental procedure used. Based on the in-field boost images acquired and the feasible application of these results to the margin formula the current CTV-planning target volume margins used are appropriate for the accurate treatment of the SIB boost volume without additional imaging.

An imaging evaluation of the simultaneously integrated boost breast radiotherapy technique

International Nuclear Information System (INIS)

Turley, Jessica; Claridge Mackonis, Elizabeth

2015-01-01

To evaluate in-field megavoltage (MV) imaging of simultaneously integrated boost (SIB) breast fields to determine its feasibility in treatment verification for the SIB breast radiotherapy technique, and to assess whether the current-imaging protocol and treatment margins are sufficient. For nine patients undergoing SIB breast radiotherapy, in-field MV images of the SIB fields were acquired on days that regular treatment verification imaging was performed. The in-field images were matched offline according to the scar wire on digitally reconstructed radiographs. The offline image correction results were then applied to a margin recipe formula to calculate safe margins that account for random and systematic uncertainties in the position of the boost volume when an offline correction protocol has been applied. After offline assessment of the acquired images, 96% were within the tolerance set in the current department-imaging protocol. Retrospectively performing the maximum position deviations on the Eclipse™ treatment planning system demonstrated that the clinical target volume (CTV) boost received a minimum dose difference of 0.4% and a maximum dose difference of 1.4% less than planned. Furthermore, applying our results to the Van Herk margin formula to ensure that 90% of patients receive 95% of the prescribed dose, the calculated CTV margins were comparable to the current departmental procedure used. Based on the in-field boost images acquired and the feasible application of these results to the margin formula the current CTV-planning target volume margins used are appropriate for the accurate treatment of the SIB boost volume without additional imaging

Radiotherapy Boost Following Conservative Surgery for Locally Advanced Breast Cancer

International Nuclear Information System (INIS)

Cendales, Ricardo; Ospino, Rosalba; Torres, Felipe; Cotes, Martha

2009-01-01

Nearly half of breast cancer patients in developing countries present with a locally advanced cancer. Treatment is centered on a multimodal approach based on chemotherapy, surgery and radiotherapy. The growing use of neoadjuvant chemotherapy has led to a more conservative surgical approach; nonetheless, it is not yet considered as a standard. There are no clear recommendations on the use of a radiotherapy boost in such situation. A Medline search was developed. Most articles are retrospective series. Survival free of locoregional relapse in patients treated with neoadjuvant chemotherapy, breast conserving surgery and radiotherapy is good. All articles described a boost administered to nearly all patients without regard to their prognostic factors, given that a locally advanced tumor is already considered as a poor prognostic factor. Even tough the poor level of evidence, a recommendation can be made: radiotherapy boost should be administered to all patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and breast conserving surgery.

Wide Temperature Range DC-DC Boost Converters for Command/Control/Drive Electronics, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — We shall develop wide temperature range DC-DC boost converters that can be fabricated using commercial CMOS foundries. The boost converters will increase the low...

Niacin to Boost Your HDL "Good" Cholesterol

Science.gov (United States)

Niacin can boost 'good' cholesterol Niacin is a B vitamin that may raise your HDL ("good") cholesterol. But side effects might outweigh benefits for most ... been used to increase high-density lipoprotein (HDL) cholesterol — the "good" cholesterol that helps remove low-density ...

Four weeks of paritaprevir/ritonavir/ombitasvir plus dasabuvir encountering dengue fever resulted in sustained virological response in an HCV patient: A case report.

Science.gov (United States)

Huang, Chung-Feng; Jang, Tyng-Yuan; Lu, Po-Liang; Yu, Ming-Lung

2016-11-01

Direct antiviral agent (DAA) has been the standard of care for patients with hepatitis C virus (HCV) infection. Twelve weeks of paritaprevir/ritonavir/ombitasvir plus dasabuvir (PROD) with or without ribavirin has shown to have a sustained virological response at post-treatment 12 weeks (SVR12) rate of >90% in HCV genotype 1 (HCV-1) patients. We report a HCV-1b patient who received only 25 days of PROD treatment. The patient early terminated treatment due to dengue fever but eventually achieved SVR12. It may attribute to low baseline viral loads and extraordinarily rapid suppression of HCV after treatment day1. The finding may shed light for possible response-guided-therapy for so-called ultra-super-responders in the DAA era. Whether the dengue virus, the Flaviviridae family as with HCV, enhanced the HCV clearance remains unclear and needs further exploration.

Closed-loop waveform control of boost inverter

DEFF Research Database (Denmark)

Zhu, Guo Rong; Xiao, Cheng Yuan; Wang, Haoran

2016-01-01

The input current of single-phase inverter typically has an AC ripple component at twice the output frequency, which causes a reduction in both the operating lifetime of its DC source and the efficiency of the system. In this paper, the closed-loop performance of a proposed waveform control method...... to eliminate such a ripple current in boost inverter is investigated. The small-signal stability and the dynamic characteristic of the inverter system for input voltage or wide range load variations under the closed-loop waveform control method are studied. It is validated that with the closedloop waveform...... control, not only was stability achieved, the reference voltage of the boost inverter capacitors can be instantaneously adjusted to match the new load, thereby achieving improved ripple mitigation for a wide load range. Furthermore, with the control and feedback mechanism, there is minimal level of ripple...

Protecting livelihoods, boosting food security in Kenya | IDRC ...

International Development Research Centre (IDRC) Digital Library (Canada)

2015-05-21

May 21, 2015 ... Protecting livelihoods, boosting food security in Kenya ... livestock fodder, with important outcomes for household food security. ... and all counties have since committed funding toward scaling up successful technologies.

No impact of HIV-1 protease minority resistant variants on the virological response to a first-line PI-based regimen containing darunavir or atazanavir.

Science.gov (United States)

Perrier, Marine; Visseaux, Benoit; Landman, Roland; Joly, Véronique; Todesco, Eve; Yazdanpanah, Yazdan; Calvez, Vincent; Marcelin, Anne-Geneviève; Descamps, Diane; Charpentier, Charlotte

2018-01-01

To evaluate, in a clinical cohort of HIV-1-infected patients, the prevalence of PI minority resistant variants (MRV) at ART baseline and their impact on the virological response to a first-line PI-based regimen. In an observational single-centre cohort, we assessed all ART-naive patients initiating a first-line regimen including two NRTI and one boosted PI, darunavir/ritonavir or atazanavir/ritonavir, between January 2012 and March 2015. Ultra-deep sequencing of the pol gene was performed using Illumina® technology. Protease mutations were identified using the WHO transmitted drug resistance list and major PI resistance mutations (IAS-USA drug resistance mutations list). Ninety-four and 16 patients initiating a darunavir/ritonavir-based regimen and an atazanavir/ritonavir-based regimen, respectively, were assessed. Twenty-eight percent of the patients were HIV-1 subtype B, 39% CRF02_AG and 33% other non-B subtypes. Thirteen patients (13.8%) in the darunavir group and three patients (18.8%) in the atazanavir group experienced a virological failure (VF). Overall, 13 (11.8%) subjects had PI MRV at baseline in the median proportion of 1.3% (IQR = 1.1-1.7). The most prevalent PI MRV were G73C (n = 5) and M46I (n = 3). The proportion of patients harbouring baseline PI MRV was similar between those with virological success (10.6%) and those experiencing VF (18.8%) (P = 0.40). No difference was observed in the rate of PI MRV by viral subtype (P = 0.51) or by PI drug (P = 0.40). This study showed a prevalence of 11.8% of PI MRV among 110 ART-naive subjects, without significant impact on the virological response to a first-line PI-based regimen containing darunavir or atazanavir. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Boosted PWM open loop control of hydraulic proportional valves

International Nuclear Information System (INIS)

Amirante, R.; Innone, A.; Catalano, L.A.

2008-01-01

This paper presents an innovative open loop control technique for direct single stage hydraulic proportional valves whose response rate is significantly higher than that obtained by standard open loop control techniques, even comparable to more costly commercial closed loop systems. Different from standard open loop techniques, which provide the coil with a constant current proportional to the target position, the control strategy proposed in this paper employs the peak and hold (P and H) technique, widely used in Diesel engine modern supply systems, to boost the duty cycle value of the pulse width modulation (PWM) signal for a short time, namely during the spool displacement, while maintaining a lower duty cycle for holding the spool in the required opening position. The developed 'boosted PWM' technique only requires a low cost microcontroller, such as a peripheral interface controller (PIC) equipped with a metal oxide semiconductor (MOS) power driver. The PWM parameters are calibrated as a function of the spool displacement so as to maximize the response rate without introducing overshoots: the collected data are stored in the PIC. Different valve opening procedures with step response have been compared to demonstrate the merits of the proposed boosted PWM technique. No overshoots have been registered. Moreover, the proposed method is characterized by a significantly higher response rate with respect to a standard open loop control, which approximately has the same cost. Similar experimental tests show that the proposed boosted PWM technique has a response rate even higher than that provided by the more costly commercial closed loop system mounted on the valve, and it produces no overshoots

Boosted PWM open loop control of hydraulic proportional valves

Energy Technology Data Exchange (ETDEWEB)

Amirante, R.; Catalano, L.A. [Dipartimento di Ingegneria Meccanica e Gestionale, Politecnico di Bari, Via Re David 200, 70125 Bari (Italy); Innone, A. [Universita degli Studi di Foggia, via Napoli, 25 Foggia (Italy)

2008-08-15

This paper presents an innovative open loop control technique for direct single stage hydraulic proportional valves whose response rate is significantly higher than that obtained by standard open loop control techniques, even comparable to more costly commercial closed loop systems. Different from standard open loop techniques, which provide the coil with a constant current proportional to the target position, the control strategy proposed in this paper employs the peak and hold (P and H) technique, widely used in Diesel engine modern supply systems, to boost the duty cycle value of the pulse width modulation (PWM) signal for a short time, namely during the spool displacement, while maintaining a lower duty cycle for holding the spool in the required opening position. The developed 'boosted PWM' technique only requires a low cost microcontroller, such as a peripheral interface controller (PIC) equipped with a metal oxide semiconductor (MOS) power driver. The PWM parameters are calibrated as a function of the spool displacement so as to maximize the response rate without introducing overshoots: the collected data are stored in the PIC. Different valve opening procedures with step response have been compared to demonstrate the merits of the proposed boosted PWM technique. No overshoots have been registered. Moreover, the proposed method is characterized by a significantly higher response rate with respect to a standard open loop control, which approximately has the same cost. Similar experimental tests show that the proposed boosted PWM technique has a response rate even higher than that provided by the more costly commercial closed loop system mounted on the valve, and it produces no overshoots. (author)

Experimental Research in Boost Driver with EDLCs

Science.gov (United States)

Matsumoto, Hirokazu

The supply used in servo systems tends to have a high voltage in order to reduce loss and improve the response of motor drives. We propose a new boost motor driver that comprises EDLCs. The proposed driver has a simple structure, wherein the EDLCs are connected in series to the supply, and comprises a charge circuit to charge the EDLCs. The proposed driver has three advantages over conventional boost drivers. The first advantage is that the driver can easily attain the stable boost voltage. The second advantage is that the driver can reduce input power peaks. In a servo system, the input power peaks become greater than the rated power in order to accelerate the motor rapidly. This implies that the equipments that supply power to servo systems must have sufficient power capacity to satisfy the power peaks. The proposed driver can suppress the increase of the power capacity of supply facilities. The third advantage is that the driver can store almost all of the regenerative energy. Conventional drivers have a braking resistor to suppress the increase in the DC link voltage. This causes a considerable reduction in the efficiency. The proposed driver is more efficient than conventional drivers. In this study, the experimental results confirmed the effectiveness of the proposed driver and showed that the drive performance of the proposed driver is the same as that of a conventional driver. Furthermore, it was confirmed that the results of the simulation of a model of the EDLC module, whose capacitance is dependent on the frequency, correspond well with the experimental results.

Closed Loop Fuzzy Logic Controlled PV Based Cascaded Boost Five-Level Inverter System

Science.gov (United States)

Revana, Guruswamy; Kota, Venkata Reddy

2018-04-01

Recent developments in intelligent control methods and power electronics have produced PV based DC to AC converters related to AC drives. Cascaded boost converter and inverter find their way in interconnecting PV and Induction Motor. This paper deals with digital simulation and implementation of closed loop controlled five-level inverter based Photo-Voltaic (PV) system. The objective of this work is to reduce the harmonics using Multi Level Inverter based system. The DC output from the PV panel is boosted using cascaded-boost-converters. The DC output of these cascaded boost converters is applied to the bridges of the cascaded inverter. The AC output voltage is obtained by the series cascading of the output voltage of the two inverters. The investigations are done with Induction motor load. Cascaded boost-converter is proposed in the present work to produce the required DC Voltage at the input of the bridge inverter. A simple FLC is applied to CBFLIIM system. The FLC is proposed to reduce the steady state error. The simulation results are compared with the hardware results. The results of the comparison are made to show the improvement in dynamic response in terms of settling time and steady state error. Design procedure and control strategy are presented in detail.

Design and Testing of Boost Type DC/DC Converter for DC Motor Control Applications

OpenAIRE

Samman, Faizal Arya; Akil, Yusri Syam; Noor, Nirwan A.

2017-01-01

in The Proceeding of The 2nd International Symposium on Smart Material and Mechatronics 2015 This paper presents the design and testing of a boost type DC/DC converter circuit, which can be used for DC motor control applications. The Boost converter is designed using DC chopper and DC chopper cascade configurations. The experimental setup was made by connecting the boost converter circuit with four types of DC motor, i.e. self-excited DC motor shunt, series, compound and separately exci...

Concomitant boost radiotherapy for squamous carcinoma of the tonsillar fossa

International Nuclear Information System (INIS)

Gwozdz, John T.; Morrison, William H.; Garden, Adam S.; Weber, Randal S.; Peters, Lester J.; Ang, K. Kian

1997-01-01

Purpose: To assess the efficacy of a concomitant boost fractionation schedule of radiotherapy for treating patients with squamous carcinoma of the tonsillar fossa. Patients and Methods: Between December 1983 and November 1992, 83 patients with squamous carcinoma of the tonsil were treated with concomitant boost fractionation. The distribution of American Joint Committee on Cancer T stages was TX-4, T1-5, T2-29, T3-41, T4-4; N stages were NX-1, N0-26, N1-13, N2-31, N3-12. Patients were treated with standard large fields to 54 Gy in 6 weeks. The boost treatment consisted of a second daily 1.5 Gy fraction for 10-12 fractions, usually delivered during the final phase of treatment. The tumor dose was 69-72 Gy, given over 6 weeks. Twenty-one patients, who all had N2 or N3 regional disease, underwent neck dissections, either before (13 patients) or 6 weeks after radiotherapy (8 patients); the other patients were treated with radiotherapy alone. Results: The 5-year actuarial disease-specific survival and overall survival rates were 71 and 60%, respectively. Patients with T2 and T3 primary tumors had 5-year actuarial local control rates of 96 and 78%, respectively. Patients with T3 disease who received the final-phase boost had a 5-year actuarial local control rate of 82%. Actuarial 5-year regional disease control rates were N0, 92%; N1, 76%; N2, 89%; and N3, 89%. The 21 patients who had neck dissections all had their disease regionally controlled. Patients presenting with nodal disease or after a node excision who were treated with radiation alone had a 5-year actuarial regional disease control rate of 79%. All but five patients had confluent Grade 4 mucositis during treatment. Severe late complications attributable to radiation included mandibular necrosis, in-field osteosarcoma, and chronic dysphagia for solid foods. Conclusions: High rates of local and regional disease control were achieved with the concomitant boost fractionation schedule, with few cases of severe late

GeoBoost: accelerating research involving the geospatial metadata of virus GenBank records.

Science.gov (United States)

Tahsin, Tasnia; Weissenbacher, Davy; O'Connor, Karen; Magge, Arjun; Scotch, Matthew; Gonzalez-Hernandez, Graciela

2018-05-01

GeoBoost is a command-line software package developed to address sparse or incomplete metadata in GenBank sequence records that relate to the location of the infected host (LOIH) of viruses. Given a set of GenBank accession numbers corresponding to virus GenBank records, GeoBoost extracts, integrates and normalizes geographic information reflecting the LOIH of the viruses using integrated information from GenBank metadata and related full-text publications. In addition, to facilitate probabilistic geospatial modeling, GeoBoost assigns probability scores for each possible LOIH. Binaries and resources required for running GeoBoost are packed into a single zipped file and freely available for download at https://tinyurl.com/geoboost. A video tutorial is included to help users quickly and easily install and run the software. The software is implemented in Java 1.8, and supported on MS Windows and Linux platforms. gragon@upenn.edu. Supplementary data are available at Bioinformatics online.

Adaptive Replanning to Account for Lumpectomy Cavity Change in Sequential Boost After Whole-Breast Irradiation

Energy Technology Data Exchange (ETDEWEB)

Chen, Xiaojian [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Qiao, Qiao [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Department of Radiotherapy, First Hospital of China Medical University, Shenyang (China); DeVries, Anthony [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Li, Wenhui [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Department of Radiotherapy, Yunnan Tumor Hospital, Kunming (China); Currey, Adam; Kelly, Tracy; Bergom, Carmen; Wilson, J. Frank [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Li, X. Allen, E-mail: ali@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

2014-12-01

Purpose: To evaluate the efficiency of standard image-guided radiation therapy (IGRT) to account for lumpectomy cavity (LC) variation during whole-breast irradiation (WBI) and propose an adaptive strategy to improve dosimetry if IGRT fails to address the interfraction LC variations. Methods and Materials: Daily diagnostic-quality CT data acquired during IGRT in the boost stage using an in-room CT for 19 breast cancer patients treated with sequential boost after WBI in the prone position were retrospectively analyzed. Contours of the LC, treated breast, ipsilateral lung, and heart were generated by populating contours from planning CTs to boost fraction CTs using an auto-segmentation tool with manual editing. Three plans were generated on each fraction CT: (1) a repositioning plan by applying the original boost plan with the shift determined by IGRT; (2) an adaptive plan by modifying the original plan according to a fraction CT; and (3) a reoptimization plan by a full-scale optimization. Results: Significant variations were observed in LC. The change in LC volume at the first boost fraction ranged from a 70% decrease to a 50% increase of that on the planning CT. The adaptive and reoptimization plans were comparable. Compared with the repositioning plans, the adaptive plans led to an improvement in target coverage for an increased LC case (1 of 19, 7.5% increase in planning target volume evaluation volume V{sub 95%}), and breast tissue sparing for an LC decrease larger than 35% (3 of 19, 7.5% decrease in breast evaluation volume V{sub 50%}; P=.008). Conclusion: Significant changes in LC shape and volume at the time of boost that deviate from the original plan for WBI with sequential boost can be addressed by adaptive replanning at the first boost fraction.

Boosted objects and jet substructure at the LHC. Report of BOOST2012, held at IFIC Valencia, 23rd-27th of July 2012

International Nuclear Information System (INIS)

Altheimer, A.; Thompson, E.N.; Arce, A.; Bjergaard, D.; Asquith, L.; Backus Mayes, J.; Hook, A.; Izaguirre, E.; Jankowiak, M.; Larkoski, A.; Nef, P.; Schwartzman, A.; Swiatlowski, M.; Wacker, J.; Kuutmann, E.B.; Berger, J.; Bryngemark, L.; Buckley, A.; Debenedetti, C.; Butterworth, J.; Campanelli, M.; Davison, A.; Cacciari, M.; Carli, T.; Roeck, A. de; Chala, M.; Chapleau, B.; Chen, C.; Chou, J.P.; Cornelissen, T.; Fleischmann, S.; Curtin, D.; Dasgupta, M.; Almeida Dias, F. de; De Cosa, A.; Doglioni, C.; Guescini, F.; Ellis, S.D.; Hornig, A.; Scholtz, J.; Fassi, F.; Hoz, S.G. de la; Kaci, M.; Oliver Garcia, E.; Rodrigo, G.; Salt, J.; Sanchez Martinez, V.; Villaplana, M.; Vos, M.; Ferrando, J.; Kar, D.; Nordstrom, K.; Freytsis, M.; Gonzalez Silva, M.L.; Han, Z.; Lopez Mateos, D.; Schwartz, M.D.; Juknevich, J.; Kasieczka, G.; Plehn, T.; Schaetzel, S.; Takeuchi, M.; Kogler, R.; Loch, P.; Marzani, S.; Spannowsky, M.; Masetti, L.; Mateu, V.; Stewart, I.; Thaler, J.; Miller, D.W.; Mishra, K.; Tran, N.V.; Penwell, J.; Pilot, J.; Rappoccio, S.; Rizzi, A.; Safonov, A.; Salam, G.P.; Schioppa, M.; Schmidt, A.; Segala, M.; Son, M.; Soyez, G.; Strom, D.; Vermilion, C.; Walsh, J.

2014-01-01

This report of the BOOST2012 workshop presents the results of four working groups that studied key aspects of jet substructure. We discuss the potential of first-principle QCD calculations to yield a precise description of the substructure of jets and study the accuracy of state-of-the-art Monte Carlo tools. Limitations of the experiments' ability to resolve substructure are evaluated, with a focus on the impact of additional (pile-up) proton proton collisions on jet substructure performance in future LHC operating scenarios. A final section summarizes the lessons learnt from jet substructure analyses in searches for new physics in the production of boosted top quarks. (orig.)

Boosted objects and jet substructure at the LHC. Report of BOOST2012, held at IFIC Valencia, 23rd-27th of July 2012

Energy Technology Data Exchange (ETDEWEB)

Altheimer, A.; Thompson, E.N. [Columbia University, Nevis Laboratory, Irvington, NY (United States); Arce, A.; Bjergaard, D. [Duke University, Durham, NC (United States); Asquith, L. [Argonne National Laboratory, Lemont, IL (United States); Backus Mayes, J.; Hook, A.; Izaguirre, E.; Jankowiak, M.; Larkoski, A.; Nef, P.; Schwartzman, A.; Swiatlowski, M.; Wacker, J. [SLAC National Accelerator Laboratory, Menlo Park, CA (United States); Kuutmann, E.B. [Deutsches Elektronen-Synchrotron, DESY, Zeuthen (Germany); Humboldt University, Berlin (Germany); Berger, J. [Cornell University, Ithaca, NY (United States); Bryngemark, L. [Lund University, Lund (Sweden); Buckley, A.; Debenedetti, C. [University of Edinburgh, Edinburgh (United Kingdom); Butterworth, J.; Campanelli, M.; Davison, A. [University College London, London (United Kingdom); Cacciari, M. [CERN, Geneva 23 (Switzerland); Carli, T.; Roeck, A. de [LPTHE, UPMC Univ. Paris 6 et CNRS UMR, Paris (France); Chala, M. [CAFPE and Univ. of Granada, Granada (Spain); Chapleau, B. [McGill University, Montreal, QC (Canada); Chen, C. [Iowa State University, Ames, IA (United States); Chou, J.P. [Rutgers University, Piscataway, NJ (United States); Cornelissen, T.; Fleischmann, S. [Bergische Universitaet Wuppertal, Wuppertal (Germany); Curtin, D. [YITP, Stony Brook University, Stony Brook, NY (United States); Dasgupta, M. [University of Manchester, Manchester (United Kingdom); Almeida Dias, F. de [UNESP-Universidade Estadual Paulista, Sao Paulo (Brazil); De Cosa, A. [INFN, Naples (Italy); University of Naples, Naples (Italy); Doglioni, C.; Guescini, F. [University of Geneva, Geneva 4 (Switzerland); Ellis, S.D.; Hornig, A.; Scholtz, J. [University of Washington, Seattle, WA (United States); Fassi, F.; Hoz, S.G. de la; Kaci, M.; Oliver Garcia, E.; Rodrigo, G.; Salt, J.; Sanchez Martinez, V.; Villaplana, M.; Vos, M. [Instituto de Fisica Corpuscular, IFIC/CSIC-UVEG, Valencia (Spain); Ferrando, J.; Kar, D.; Nordstrom, K. [University of Glasgow, Glasgow (United Kingdom); Freytsis, M. [University of California, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); University of California, Berkeley, CA (United States); Gonzalez Silva, M.L. [Universidad de Buenos Aires, Buenos Aires (Argentina); Han, Z.; Lopez Mateos, D.; Schwartz, M.D. [Harvard University, Cambridge, MA (United States); Juknevich, J. [Weizmann Institute, Rehovot (Israel); Kasieczka, G.; Plehn, T.; Schaetzel, S.; Takeuchi, M. [Universitaet Heidelberg, Heidelberg (Germany); Kogler, R. [Universitaet Hamburg, Hamburg (Germany); Loch, P. [University of Arizona, Tucson, AZ (United States); Marzani, S.; Spannowsky, M. [IPPP, University of Durham, Durham (United Kingdom); Masetti, L. [Universitaet Mainz, Mainz (Germany); Mateu, V.; Stewart, I.; Thaler, J. [MIT, Cambridge, MA (United States); Miller, D.W. [University of Chicago, Chicago, IL (United States); Mishra, K.; Tran, N.V. [Fermi National Accelerator Laboratory, Batavia, IL (United States); Penwell, J. [Indiana University, Bloomington, IN (United States); Pilot, J. [University of California, Davis, CA (United States); Rappoccio, S. [Johns Hopkins University, Baltimore, MD (United States); University at Buffalo, State University of New York, Buffalo, NY (United States); Rizzi, A. [INFN, Pisa (Italy); University of Pisa, Pisa (Italy); Safonov, A. [Texas A and M University, College Station, TX (United States); Salam, G.P. [CERN, Geneva 23 (Switzerland); LPTHE, UPMC Univ. Paris 6 et CNRS UMR, Paris (France); Schioppa, M. [INFN, Rende (IT); University of Calabria, Rende (IT); Schmidt, A. [Universitaet Hamburg, Hamburg (DE); Universitaet Heidelberg, Heidelberg (DE); Segala, M. [Brown University, Richmond, RI (US); Son, M. [Yale University, New Haven, CT (US); Soyez, G. [CEA Saclay, Gif-sur-Yvette (FR); Strom, D. [University of Illinois, Chicago, IL (US); Vermilion, C. [University of California, Lawrence Berkeley National Laboratory, Berkeley, CA (US); Walsh, J. [University of California, Berkeley, CA (US)

2014-03-15

This report of the BOOST2012 workshop presents the results of four working groups that studied key aspects of jet substructure. We discuss the potential of first-principle QCD calculations to yield a precise description of the substructure of jets and study the accuracy of state-of-the-art Monte Carlo tools. Limitations of the experiments' ability to resolve substructure are evaluated, with a focus on the impact of additional (pile-up) proton proton collisions on jet substructure performance in future LHC operating scenarios. A final section summarizes the lessons learnt from jet substructure analyses in searches for new physics in the production of boosted top quarks. (orig.)

Protecting livelihoods, boosting food security in Kenya | IDRC ...

International Development Research Centre (IDRC) Digital Library (Canada)

2015-05-21

May 21, 2015 ... Protecting livelihoods, boosting food security in Kenya ... America, and the Caribbean with funds from the Government of Canada's fast-start financing. ... Water management and food security in vulnerable regions of China.

Differences in response to antiretroviral therapy in HIV-positive patients being treated for tuberculosis in Eastern Europe, Western Europe and Latin America

DEFF Research Database (Denmark)

Caro-Vega, Yanink; Schultze, Anna; W Efsen, Anne Marie

2018-01-01

-positive patients aged ≥16 years with a diagnosis of tuberculosis recruited to the TB:HIV study between Jan 1, 2011, and Dec 31, 2013 in 19 countries in Eastern Europe (EE), Western Europe (WE), and Latin America (LA) who received ART concomitantly with TB treatment were included. Patients either received efavirenz......-containing ART, and 318 a non-efavirenz regimen) 50% were from EE, 28% from WE, and 22% from LA. Among those not receiving efavirenz-containing ART, regimens mainly contained a ritonavir-boosted protease inhibitor (57%), or raltegravir (22%). At 12 months 1.4% of patients in WE had died, compared to 20% in EE...

Hybrid-mode interleaved boost converter design for fuel cell electric vehicles

International Nuclear Information System (INIS)

Wen, Huiqing; Su, Bin

2016-01-01

Highlights: • A high power interleaved boost converter is designed for a 150 kW high-power fuel cell electric vehicle application. • A hybrid-mode scheme is used: Mode I and mode II are used with each boost converter operating in continuous conduction mode and discontinuous conduction mode. • Boundary conditions for different modes are determined with respect to switching duty ratio and load conditions. • With the proposed scheme, the power density is improved by 44.2% and 34.3% in terms of the converter volume and weight. - Abstract: For Fuel Cell Electric Vehicles, DC-DC power converters are essential to provide energy storage buffers between fuel cell stacks and the traction system because fuel cells show characteristics of low-voltage high-current output and wide output voltage variation. This paper presents a hybrid-mode two-phase interleaved boost converter for fuel cell electric vehicle application in order to improve the power density, minimize the input current ripple, and enhance the system efficiency. Two operation modes are adopted in the practical design: mode I and mode II are used with each boost converter operating in continuous conduction mode and discontinuous conduction mode. The operation, design and control of the interleaved boost converter for different operating modes are discussed with their equivalent circuits. The boundary conditions are distinguished with respect to switching duty ratio and load conditions. Transitions between continuous conduction mode and discontinuous conduction mode are illustrated for the whole duty ratio range. The expressions for inductor current ripple, input current ripple and output voltage ripple are derived and verified by simulation and experimental tests. The efficiency and power density improvements are illustrated to verify the effectiveness of the proposed design scheme.

B-tagging in boosted h → b anti b decays

Energy Technology Data Exchange (ETDEWEB)

Jacobs, Ruth; Gaycken, Goetz; Hageboeck, Stephan; Kostyukhin, Vadim; Lenz, Tatjana; Schopf, Elisabeth; Toerne, Eckhard von; Wermes, Norbert [Physikalisches Institut, University of Bonn (Germany)

2015-07-01

The most likely decay channel of the standard model Higgs boson is the decay into a b- and an anti-b-quark. The properties of b-jets formed by the hadronization of b-quarks are essential input variables to all ATLAS h → b anti b analyses. In boosted topologies the performance of standard b-tagging algorithms is diminished due to the merging of close - by jets. The aim of the study presented is the optimization of a b-tagging algorithm for boosted h → b anti b decays using track jets with a smaller than standard cone radius. The study is based on simulated events containing boosted Higgs bosons from the decay of a new heavy gauge boson W{sup '} → Wh. A motivation for the use of track jets for b-tagging is the fact that the reconstructed jet axis for track jets more closely describes the b-hadron flight direction than for calorimeter jets. Using jets with a smaller cone radius allows to resolve topologies where larger radius jets are already merged.

SU-G-BRC-12: Isotoxic Dose Escalation for Advanced Lung Cancer: Comparison of Different Boosting Strategiesfor Patients with Recurrent Disease

Energy Technology Data Exchange (ETDEWEB)

Shusharina, N; Khan, F; Sharp, G; Choi, N [Massachusetts General Hospital, Boston, MA (United States)

2016-06-15

Purpose: To determine the dose level and timing of the boost in locally advanced lung cancer patients with confirmed tumor recurrence by comparing different boosting strategies by an impact of dose escalation in improvement of the therapeutic ratio. Methods: We selected eighteen patients with advanced NSCLC and confirmed recurrence. For each patient, a base IMRT plan to 60 Gy prescribed to PTV was created. Then we compared three dose escalation strategies: a uniform escalation to the original PTV, an escalation to a PET-defined target planned sequentially and concurrently. The PET-defined targets were delineated by biologically-weighed regions on a pre-treatment 18F-FDG PET. The maximal achievable dose, without violating the OAR constraints, was identified for each boosting method. The EUD for the target, spinal cord, combined lung, and esophagus was compared for each plan. Results: The average prescribed dose was 70.4±13.9 Gy for the uniform boost, 88.5±15.9 Gy for the sequential boost and 89.1±16.5 Gy for concurrent boost. The size of the boost planning volume was 12.8% (range: 1.4 – 27.9%) of the PTV. The most prescription-limiting dose constraints was the V70 of the esophagus. The EUD within the target increased by 10.6 Gy for the uniform boost, by 31.4 Gy for the sequential boost and by 38.2 for the concurrent boost. The EUD for OARs increased by the following amounts: spinal cord, 3.1 Gy for uniform boost, 2.8 Gy for sequential boost, 5.8 Gy for concurrent boost; combined lung, 1.6 Gy for uniform, 1.1 Gy for sequential, 2.8 Gy for concurrent; esophagus, 4.2 Gy for uniform, 1.3 Gy for sequential, 5.6 Gy for concurrent. Conclusion: Dose escalation to a biologically-weighed gross tumor volume defined on a pre-treatment 18F-FDG PET may provide improved therapeutic ratio without breaching predefined OAR constraints. Sequential boost provides better sparing of OARs as compared with concurrent boost.

SU-G-BRC-12: Isotoxic Dose Escalation for Advanced Lung Cancer: Comparison of Different Boosting Strategiesfor Patients with Recurrent Disease

International Nuclear Information System (INIS)

Shusharina, N; Khan, F; Sharp, G; Choi, N

2016-01-01

Purpose: To determine the dose level and timing of the boost in locally advanced lung cancer patients with confirmed tumor recurrence by comparing different boosting strategies by an impact of dose escalation in improvement of the therapeutic ratio. Methods: We selected eighteen patients with advanced NSCLC and confirmed recurrence. For each patient, a base IMRT plan to 60 Gy prescribed to PTV was created. Then we compared three dose escalation strategies: a uniform escalation to the original PTV, an escalation to a PET-defined target planned sequentially and concurrently. The PET-defined targets were delineated by biologically-weighed regions on a pre-treatment 18F-FDG PET. The maximal achievable dose, without violating the OAR constraints, was identified for each boosting method. The EUD for the target, spinal cord, combined lung, and esophagus was compared for each plan. Results: The average prescribed dose was 70.4±13.9 Gy for the uniform boost, 88.5±15.9 Gy for the sequential boost and 89.1±16.5 Gy for concurrent boost. The size of the boost planning volume was 12.8% (range: 1.4 – 27.9%) of the PTV. The most prescription-limiting dose constraints was the V70 of the esophagus. The EUD within the target increased by 10.6 Gy for the uniform boost, by 31.4 Gy for the sequential boost and by 38.2 for the concurrent boost. The EUD for OARs increased by the following amounts: spinal cord, 3.1 Gy for uniform boost, 2.8 Gy for sequential boost, 5.8 Gy for concurrent boost; combined lung, 1.6 Gy for uniform, 1.1 Gy for sequential, 2.8 Gy for concurrent; esophagus, 4.2 Gy for uniform, 1.3 Gy for sequential, 5.6 Gy for concurrent. Conclusion: Dose escalation to a biologically-weighed gross tumor volume defined on a pre-treatment 18F-FDG PET may provide improved therapeutic ratio without breaching predefined OAR constraints. Sequential boost provides better sparing of OARs as compared with concurrent boost.

Cooperatives boost opportunities for Moroccan women | IDRC ...

International Development Research Centre (IDRC) Digital Library (Canada)

2010-10-22

Oct 22, 2010 ... Cooperatives boost opportunities for Moroccan women. October 22 ... Substantial support for argan oil development continues with a €12 million grant. Half comes from the ... Research aims to identify and remove barriers faced by Africa's women entrepreneurs ... Solutions. Careers · Contact Us · Site map.

Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials

Directory of Open Access Journals (Sweden)

Julia L. Hurwitz

2010-02-01

Full Text Available Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans.

The Palatability of Lopinavir and Ritonavir Delivered by an Innovative Freeze-Dried Fast-Dissolving Tablet Formulation

Directory of Open Access Journals (Sweden)

David W. Pittman

2018-01-01

Full Text Available Negative hedonic sensory qualities of HIV antiretroviral drugs often reduce patient adherence particularly in pediatric populations requiring oral consumption. This study examines the palatability of an innovative delivery mechanism utilizing a freeze-drying-in-blister approach to create fast-dissolving tablets (FDTs containing a fixed-dose combination of lopinavir and ritonavir (LPV/r. Consumption patterns of solutions during brief-access and long-term testing and baby foodstuff consumption were analyzed to evaluate the orosensory detection and avoidance of placebo FDTs containing no LPV/r (FDT− and FDTs containing LPV/r (FDT+. Rats showed no change in consumption patterns for the placebo FDT− compared with control solutions. Rats can detect but do not avoid FDT+ at body-weight-adjusted dosages in both brief-access (30-s and long-term (23 h consumption tests. There is an aversive response to concentrated doses of FDT+ during brief-access tests that cannot be masked by 25% sucrose. However, the strongest FDT+ concentration was not rejected when mixed with 50 g of applesauce, banana sauce, or rice cereal baby foodstuffs. The averseness of the FDT+ was associated with the presence of LPV/r and not the FDT− formulation itself. The novel FDT formulation appears to be a palatable delivery mechanism for oral antiretroviral pharmaceuticals especially when mixed with baby foodstuffs.

A new interleaved double-input three-level boost converter

DEFF Research Database (Denmark)

Chen, Jianfei; Hou, Shiying; Sun, Tao

2016-01-01

This paper proposes a new interleaved double-input three-level Boost (DITLB) converter, which is composed of two boost converters indirectly in series. Thus, a high voltage gain, together with a low component stress and a small input current ripple due to the interleaved control scheme, is achieved....... The operating principle of the DITLB converter under the individual supplying power (ISP) and simultaneous supplying power (SSP) mode is analyzed. In addition, closed-loop control strategies composed of a voltage-current loop and a voltage-balance loop, have been researched to make the converter operate...... steadily and to alleviate the neutral-point imbalance issue. Experimental results verify correctness and feasibility of the proposed topology and control strategies....

The use of stereotactic radiosurgical boost in the treatment of medulloblastomas

International Nuclear Information System (INIS)

Woo, Charles; Stea, Baldassarre; Lulu, Bruce; Hamilton, Allan; Cassady, J. Robert

1997-01-01

Purpose: Starting in 1992, we began using a stereotactic radiosurgical (SRS) boost for the treatment of medulloblastomas. Four patients ranging in age from 7 to 42 years old have since been treated and are the subject of this retrospective study. Methods and Materials: All patients were initially treated with a maximally debulking surgery and external beam radiotherapy, which were then followed by a stereotactic radiosurgical boost using a modified 6 MeV linear accelerator. Radiosurgical boost doses ranged from 4.50 to 10.0 Gy. Target volumes ranged from 1.1 to 8.1 cc. The procedure was well tolerated with minimal acute toxicities. Results: All four patients are alive without evidence of recurrence (at 8 to 35 months). Acute nausea and vomiting was elicited during the radiosurgical procedure in the first patient treated. We have since begun premedicating patients with antiemetics or treating under general anesthesia. Late complications consisted of panhypopituitarism in one patient, which was thought to be attributable to the previous course of whole-brain radiotherapy. We have not observed any incidence of radionecrosis in this small cohort of patients. Conclusions: Our preliminary results with the use of radiosurgery for medulloblastomas are optimistic, and we would like to suggest the inclusion of a radiosurgery boost in future clinical trials for treatment of this disease

Concurrent Boost with Adjuvant Breast Hypofractionated Radiotherapy and Toxicity Assessment

Directory of Open Access Journals (Sweden)

Mona M. Sayed

2015-01-01

Full Text Available Background: The use of shorter radiotherapy schedules has an economic and logistic advantage for radiotherapy departments, as well as a high degree of patient convenience. The aim of this study is to assess the acute and short-term late toxicities of a hypofractionated radiotherapy schedule with a concomitant boost. Methods: We enrolled 57 eligible patients as group A. These patients received 42.5 Gy in 16 fractions of 2.66 Gy each to the whole breast over 3.2 weeks. A concomitant electron boost of 12 Gy in 16 fractions was also administered which gave an additional 0.75 Gy daily to the lumpectomy area for a total radiation dose of 54.5 Gy. Toxicity was recorded at three weeks and at three months for this group as well as for a control group (group B. The control group comprised 76 eligible patients treated conventionally with 50 Gy to the whole breast over five weeks followed by a sequential electron boost of 12 Gy in 2 Gy per fraction. Results: There were no statistically significant differences observed in the incidence of acute skin toxicity, breast pain, and edema recorded at three weeks or pigmentation and fibrosis recorded at three months between the two groups (P0.05. Conclusion: The results of this study suggest there are no increased acute and shortterm late toxicities affiliated with the hypofractionated schedule plus a concomitant boost as prescribed compared to the conventional fractionation of adjuvant breast radiotherapy. Large randomized trials and long-term follow-up are needed to confirm these favorable findings.

Boosting youth employment in agri-business | IDRC - International ...

International Development Research Centre (IDRC) Digital Library (Canada)

Boosting youth employment in agri-business ... economic importance and could provide jobs for women and youth while increasing food security. ... “The main challenge youth face is poor access to credit and extension services,” she says.

Long-Term Results of Targeted Intraoperative Radiotherapy (Targit) Boost During Breast-Conserving Surgery

Energy Technology Data Exchange (ETDEWEB)

Vaidya, Jayant S., E-mail: jayant.vaidya@ucl.ac.uk [Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London (United Kingdom); Baum, Michael [Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London (United Kingdom); Tobias, Jeffrey S. [Department of Radiation Oncology, University College London Hospitals, London (United Kingdom); Wenz, Frederik [Radiation Oncology and Gynaecology, University Medical Centre of Mannheim (Germany); Massarut, Samuele [Surgery and Radiation Oncology, Centro di Riferimento Oncologico (CRO), Aviano (Italy); Keshtgar, Mohammed [Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London (United Kingdom); Hilaris, Basil [Radiation Oncology, Our Lady of Mercy, New York Medical College, New York (United States); Saunders, Christobel [Institute of Health and Rehabilitation Research, University of Notre Dame, Fremantle, Western Australia (Australia); Williams, Norman R.; Brew-Graves, Chris [Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London (United Kingdom); Corica, Tammy [Institute of Health and Rehabilitation Research, University of Notre Dame, Fremantle, Western Australia (Australia); Roncadin, Mario [Surgery and Radiation Oncology, Centro di Riferimento Oncologico (CRO), Aviano (Italy); Kraus-Tiefenbacher, Uta; Suetterlin, Marc [Radiation Oncology and Gynaecology, University Medical Centre of Mannheim (Germany); Bulsara, Max [Institute of Health and Rehabilitation Research, University of Notre Dame, Fremantle, Western Australia (Australia); Joseph, David [Radiation Oncology, Sir Charles Gairdner Hospital and School of Surgery, University of Western Australia, Perth (Australia)

2011-11-15

Purpose: We have previously shown that delivering targeted radiotherapy to the tumour bed intraoperatively is feasible and desirable. In this study, we report on the feasibility, safety, and long-term efficacy of TARGeted Intraoperative radioTherapy (Targit), using the Intrabeam system. Methods and Materials: A total of 300 cancers in 299 unselected patients underwent breast-conserving surgery and Targit as a boost to the tumor bed. After lumpectomy, a single dose of 20 Gy was delivered intraoperatively. Postoperative external beam whole-breast radiotherapy excluded the usual boost. We also performed a novel individualized case control (ICC) analysis that computed the expected recurrences for the cohort by estimating the risk of recurrence for each patient using their characteristics and follow-up period. Results: The treatment was well tolerated. The median follow up was 60.5 months (range, 10-122 months). Eight patients have had ipsilateral recurrence: 5-year Kaplan Meier estimate for ipsilateral recurrence is 1.73% (SE 0.77), which compares well with that seen in the boosted patients in the European Organization for Research and Treatment of Cancer study (4.3%) and the UK STAndardisation of breast RadioTherapy study (2.8%). In a novel ICC analysis of 242 of the patients, we estimated that there should be 11.4 recurrences; in this group, only 6 recurrences were observed. Conclusions: Lumpectomy and Targit boost combined with external beam radiotherapy results in a low local recurrence rate in a standard risk patient population. Accurate localization and the immediacy of the treatment that has a favorable effect on tumour microenvironment may contribute to this effect. These long-term data establish the long-term safety and efficacy of the Targit technique and generate the hypothesis that Targit boost might be superior to an external beam boost in its efficacy and justifies a randomized trial.

Targeted intraoperative radiotherapy (TARGIT) yields very low recurrence rates when given as a boost

International Nuclear Information System (INIS)

Vaidya, Jayant S.; Baum, Michael; Tobias, Jeffrey S.; Massarut, Samuele; Wenz, Frederik; Murphy, Olive; Hilaris, Basil; Houghton, Joan B.Sc.; Saunders, Christobel; Corica, Tammy; Roncadin, Mario; Kraus-Tiefenbacher, Uta; Melchaert, Frank; Keshtgar, Mohammed; Sainsbury, Richard; Douek, Michael; Harrison, Elly; Thompson, Alastair; Joseph, David

2006-01-01

Purpose: Patients undergoing breast-conserving surgery were offered boost radiotherapy with targeted intraoperative radiotherapy (TARGIT) using the Intrabeam system to test the feasibility, safety, and efficacy of the new approach. Methods and Materials: We treated 302 cancers in 301 unselected patients. This was not a low-risk group. One-third of patients (98/301) were younger than 51 years of age. More than half of the tumors (172, 57%) were between 1 cm and 2 cm, and one-fifth (62, 21%) were >2 cm; 29% (86) had a Grade 3 tumor and, in 29% (87), axillary lymph nodes contained metastasis. After primary surgery, 20 Gy was delivered intraoperatively to the surface of the tumor bed, followed by external-beam radiotherapy (EBRT), but excluding the usual boost. Results: The treatment was well tolerated. The follow-up ranged from 3 to 80 months (164 and 90 patients completed 2 and 3 years follow-up, respectively). Four patients (1.3%) had local recurrence. The Kaplan-Meier estimate of local recurrence is 2.6% (SE = 1.7) at 5 years. This compares favorably with the 4.3% recurrence rate in boosted patients from the EORTC boost study, in which only 8.1% patients were node-positive, as opposed to 29% in our series. Conclusion: Targeted intraoperative radiotherapy combined with EBRT results in a low local recurrence rate. This could be attributed to both accurate targeting and timeliness of the treatment. These data support the need for a randomized trial to test whether the TARGIT boost is superior to conventional external boost, especially in high-risk women

Boosted performance of a compression-ignition engine with a displaced piston

Science.gov (United States)

Moore, Charles S; Foster, Hampton H

1936-01-01

Performance tests were made using a rectangular displacer arranged so that the combustion air was forced through equal passages at either end of the displacer into the vertical-disk combustion chamber of a single-cylinder, four-stroke-cycle compression-ignition test engine. After making tests to determine optimum displacer height, shape, and fuel-spray arrangement, engine-performance tests were made at 1,500 and 2,000 r.p.m. for a range of boost pressures from 0 to 20 inches of mercury and for maximum cylinder pressures up to 1,150 pounds per square inch. The engine operation for boosted conditions was very smooth, there being no combustion shock even at the highest maximum cylinder pressures. Indicated mean effective pressures of 240 pounds per square inch for fuel consumptions of 0.39 pound per horsepower-hour have been readily reproduced during routine testing at 2,000 r.p.m. at a boost pressure of 20 inches of mercury.

A New Method of Cloud Detection Based on Cascaded AdaBoost

International Nuclear Information System (INIS)

Ma, C; Chen, F; Liu, J; Duan, J

2014-01-01

Cloud detection of remote sensing image is a critical step in the processing of the remote sensing images. How to quickly, accurately and effectively detect cloud on remote sensing images, is still a challenging issue in this area. In order to avoid disadvantages of the current algorithms, the cascaded AdaBoost classifier algorithm is successfully applied to the cloud detection. A new algorithm combined cascaded AdaBoost classifier and multi-features, is proposed in this paper. First, multi-features based on the color, texture and spectral features are extracted from the remote sensing image. Second, the automatic cloud detection model is obtained based on the cascaded AdaBoost algorithm. In this paper, the results show that the new algorithm can determine cloud detection model and threshold values adaptively for different resolution remote sensing training data. The accuracy of cloud detection is improved. So it is a new effective algorithm for the cloud detection of remote sensing images

Impact of Boost Radiation in the Treatment of Ductal Carcinoma In Situ: A Population-Based Analysis

Energy Technology Data Exchange (ETDEWEB)

Rakovitch, Eileen, E-mail: Eileen.rakovitch@sunnybrook.ca [Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario (Canada); Institute for Clinical Evaluative Sciences, Toronto, Ontario (Canada); University of Toronto, Toronto, Ontario (Canada); Narod, Steven A. [University of Toronto, Toronto, Ontario (Canada); Women’s College Research Institute, Toronto, Ontario (Canada); Nofech-Moses, Sharon; Hanna, Wedad [Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario (Canada); University of Toronto, Toronto, Ontario (Canada); Thiruchelvam, Deva; Saskin, Refik; Taylor, Carole [Institute for Clinical Evaluative Sciences, Toronto, Ontario (Canada); Tuck, Alan [London Health Sciences Center, London, Ontario (Canada); Youngson, Bruce; Miller, Naomi; Done, Susan J. [University Health Network, Toronto, Ontario (Canada); Sengupta, Sandip [Kingston General Hospital, Kingston, Ontario (Canada); Elavathil, Leela [University of Toronto, Toronto, Ontario (Canada); Henderson General Hospital, 711 Concession Street, Hamilton, Ontario (Canada); Jani, Prashant A. [University of Toronto, Toronto, Ontario (Canada); Regional Health Sciences Centre, Thunder Bay, Ontario (Canada); Bonin, Michel [Sudbury Regional Hospital, Sudbury, Ontario (Canada); Metcalfe, Stephanie [Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario (Canada); Paszat, Lawrence [Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario (Canada); Institute for Clinical Evaluative Sciences, Toronto, Ontario (Canada); University of Toronto, Toronto, Ontario (Canada)

2013-07-01

Purpose: To report the outcomes of a population of women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and radiation and to evaluate the independent effect of boost radiation on the development of local recurrence. Methods and Materials: All women diagnosed with DCIS and treated with breast-conserving surgery and radiation therapy in Ontario from 1994 to 2003 were identified. Treatments and outcomes were identified through administrative databases and validated by chart review. The impact of boost radiation on the development of local recurrence was determined using survival analyses. Results: We identified 1895 cases of DCIS that were treated by breast-conserving surgery and radiation therapy; 561 patients received boost radiation. The cumulative 10-year rate of local recurrence was 13% for women who received boost radiation and 12% for those who did not (P=.3). The 10-year local recurrence-free survival (LRFS) rate among women who did and who did not receive boost radiation was 88% and 87%, respectively (P=.27), 94% and 93% for invasive LRFS (P=.58), and was 95% and 93% for DCIS LRFS (P=.31). On multivariable analyses, boost radiation was not associated with a lower risk of local recurrence (hazard ratio = 0.82, 95% confidence interval 0.59-1.15) (P=.25). Conclusions: Among a population of women treated with breast-conserving surgery and radiation for DCIS, additional (boost) radiation was not associated with a lower risk of local or invasive recurrence.

Can we predict Acute Medical readmissions using the BOOST tool? A retrospective case note review.

Science.gov (United States)

Lee, Geraldine A; Freedman, Daniel; Beddoes, Penelope; Lyness, Emily; Nixon, Imogen; Srivastava, Vivek

2016-01-01

Readmissions within 30-days of hospital discharge are a problem. The aim was to determine if the Better Outcomes for Older Adults through Safe Transitions (BOOST) risk assessment tool was applicable within the UK. Patients over 65 readmitted were identified retrospectively via a casenote review. BOOST assessment was applied with 1 point for each risk factor. 324 patients were readmitted (mean age 77 years) with a median of 7 days between discharge and readmission. The median BOOST score was 3 (IQR 2-4) with polypharmacy evident in 88% and prior hospitalisation in 70%. The tool correctly predicted 90% of readmissions using two or more risk factors and 99.1% if one risk factor was included. The BOOST assessment tool appears appropriate in predicting readmissions however further analysis is required to determine its precision.

Searches with boosted objects at ATLAS and CMS

CERN Document Server

Moran, Dermot Anthony

2018-01-01

An overview of searches for beyond the standard model physics using boosted objects is presented. The searches are based on proton-proton collision data collected with the ATLAS and CMS detectors at the LHC during the 2015 and 2016 running periods.

Evaluating complications of local anesthesia administration and reversal with phentolamine mesylate in a portable pediatric dental clinic.

Science.gov (United States)

Boynes, Sean G; Riley, Amah E; Milbee, Sarah; Bastin, Meghan R; Price, Maylyn E; Ladson, Andrea

2013-08-01

This study sought to identify and quantify complications with local anesthetic administration and reversal on consecutive patients seen for comprehensive dental care in a school-based, portable dental clinic, and includes data on the patients seen by the participating portable dental providers. In 923 dental visits where local anesthetic was administered, a standardized form was used to gain further information and identify any complications; this was accompanied by a questionnaire for the student's teacher, in order to quantify the student's distraction and disruption ratings following the dental visit. After statistical analysis of the 923 consecutive cases, the overall complication rate was 5.3%. All of the complications were considered to be mild or moderate, and there were no severe event reports. The complications encountered most frequently (n = 49) were associated with self-inflicted soft tissue injury. The results of this study indicate that comprehensive care with local anesthesia delivered by a school-based portable dental clinic has a low risk of complications. Whereas safe administration of dental care is achievable with or without phentolamine mesylate as a local anesthetic reversal agent, its use was determined to improve safety outcomes. Three factors appeared to directly increase the incidence of complications: the administration of an inferior alveolar nerve block, attention deficit disorder, and obesity. Teacher evaluations demonstrated that children receiving care by a portable dental team were able to reorient back to classwork and were not disruptive to classmates.

Enhancing treatment of osteoarthritis knee pain by boosting expectancy: A functional neuroimaging study

Directory of Open Access Journals (Sweden)

Jian Kong

Full Text Available Objectives: Expectation can significantly modulate pain and treatment effects. This study aims to investigate if boosting patients' expectancy can enhance the treatment of knee osteoarthritis (KOA, and its underlying brain mechanism. Methods: Seventy-four KOA patients were recruited and randomized to three groups: boosted acupuncture (with a manipulation to enhance expectation, standard acupuncture, or treatment as usual (TAU. Each patient underwent six treatments before being debriefed, and four additional treatments after being debriefed. The fMRI scans were applied during the first and sixth treatment sessions. Results: We found significantly decreased knee pain in the boosted acupuncture group compared to the standard acupuncture or TAU groups after both six and ten treatments. Resting state functional connectivity (rsFC analyses using the nucleus accumbens (NAc as the seed showed rsFC increases between the NAc and the medial prefrontal cortex (MPFC/rostral anterior cingulate cortex (rACC and dorsolateral prefrontal cortex in the boosted group as compared to the standard acupuncture group after multiple treatments. Expectancy scores after the first treatment were significantly associated with increased NAc-rACC/MPFC rsFC and decreased knee pain following treatment. Conclusions: Our study provides a novel method and mechanism for boosting the treatment of pain in patients with KOA. Our findings may shed light on enhancing outcomes of pharmacological and integrative medicines in clinical settings. Keywords: Knee osteoarthritis, Expectancy, Acupuncture, Reward, Resting state functional connectivity

Detecting Boosted Dark Matter from the Sun with Large Volume Neutrino Detectors

Energy Technology Data Exchange (ETDEWEB)

Berger, Joshua; /SLAC; Cui, Yanou; /Perimeter Inst. Theor. Phys.; Zhao, Yue; /Stanford U., ITP /Stanford U., Phys. Dept.

2015-04-02

We study novel scenarios where thermal dark matter (DM) can be efficiently captured in the Sun and annihilate into boosted dark matter. In models with semi-annihilating DM, where DM has a non-minimal stabilization symmetry, or in models with a multi-component DM sector, annihilations of DM can give rise to stable dark sector particles with moderate Lorentz boosts. We investigate both of these possibilities, presenting concrete models as proofs of concept. Both scenarios can yield viable thermal relic DM with masses O(1)-O(100) GeV. Taking advantage of the energetic proton recoils that arise when the boosted DM scatters off matter, we propose a detection strategy which uses large volume terrestrial detectors, such as those designed to detect neutrinos or proton decays. In particular, we propose a search for proton tracks pointing towards the Sun. We focus on signals at Cherenkov-radiation-based detectors such as Super-Kamiokande (SK) and its upgrade Hyper-Kamiokande (HK). We find that with spin-dependent scattering as the dominant DM-nucleus interaction at low energies, boosted DM can leave detectable signals at SK or HK, with sensitivity comparable to DM direct detection experiments while being consistent with current constraints. Our study provides a new search path for DM sectors with non-minimal structure.

Black brane entropy and hydrodynamics: The boost-invariant case

International Nuclear Information System (INIS)

Booth, Ivan; Heller, Michal P.; Spalinski, Michal

2009-01-01

The framework of slowly evolving horizons is generalized to the case of black branes in asymptotically anti-de Sitter spaces in arbitrary dimensions. The results are used to analyze the behavior of both event and apparent horizons in the gravity dual to boost-invariant flow. These considerations are motivated by the fact that at second order in the gradient expansion the hydrodynamic entropy current in the dual Yang-Mills theory appears to contain an ambiguity. This ambiguity, in the case of boost-invariant flow, is linked with a similar freedom on the gravity side. This leads to a phenomenological definition of the entropy of black branes. Some insights on fluid/gravity duality and the definition of entropy in a time-dependent setting are elucidated.

Enhanced Buck-Boost Three-Level Neutral-Point-Clamped Inverters

DEFF Research Database (Denmark)

Tan, K. K.; Gao, F.; Chiang Loh, Poh

2009-01-01

In traditional three-level neutral-point-clamped (NPC) inverters, a major issue is capacitor voltage imbalance, which results in low order harmonics. The compensation of the capacitor voltages often require additional control complexity, which cannot be conveniently implemented. The "alternative...... phase opposition disposition" (APOD) modulation method used in traditional NPC topologies also has lower harmonics performance as compared to the "phase disposition" (PD) modulation method.In this paper, we introduce a new three-level NPC topology that utilises the harmonically superior PD modulation...... method, with the ability to easily adjust for capacitor voltage imbalances. To further improve the boost capability of the three-level NPC inverters, another new topology introduces 2 additional diodes,achieving higher boost performance while totally eliminating thepossibility of capacitor voltage...

The performance of the DC motor by the PID controlling PWM DC-DC boost converter

OpenAIRE

Can, Erol; Sayan, Hasan Hüseyin

2017-01-01

This paper presents the PID controlling direct current (DC) to the direct current boost converter feds DC motor which has a 3.68 kW and 240 V of DC voltage input on its characteristics. What is first formed is the boost converter mathematical model at the design stage. Secondly, a mathematical model of the DC motor is created so that the boost converter with the machine can be established and modeled at the Matlab Simulink. The PID controller is considered for arranging a pulse width modulati...

Boosted Higgs boson tagging using jet substructures

CERN Document Server

Shvydkin, Pavel

2016-01-01

Searching BSM particles via the Higgs boson final state has now become common. The mass of desired BSM particle is more than 1 TeV, thereby its decay products are highly Lorentz-boosted. Hence the jets from b quark-antiquark pair - which the Higgs boson mostly decays into - are very closed to each other, and merged into one jet, that is typically reconstructed using large jet sizes (∆R = 0.8). In this work regression technique is applied to AK8 jets (which defined by anti-kT algorithm, using ΔR = 0.8). The regression makes use of boosted jets with substructure information, coupled with the pecularities of a b quark decay, like the presence of a soft lepton (SL) inside the jet. It has allowed to improve the resolution of the mass reconstruction and transverse momentum of the Higgs boson. This application results in improvement of the mass reconstruction by 3-4 percent. These result may be improved firstly by making more careful pileup rejection. Then it is possible to combine base regression train for dif...

Boosted Objects: A Probe of Beyond the Standard Model Physics

Energy Technology Data Exchange (ETDEWEB)

Abdesselam, A.; /Oxford U.; Kuutmann, E.Bergeaas; /DESY; Bitenc, U.; /Freiburg U.; Brooijmans, G.; /Columbia U.; Butterworth, J.; /University Coll. London; Bruckman de Renstrom, P.; /Cracow, INP; Buarque Franzosi, D.; /Turin U.; Buckingham, R.; /Oxford U.; Chapleau, B.; /McGill U.; Dasgupta, M.; /Manchester U.; Davison, A.; /University Coll. London; Dolen, J.; /UC, Davis; Ellis, S.; /Washington U., Seattle; Fassi, F.; /Lyon, IPN; Ferrando, J.; /Oxford U.; Frandsen, M.T.; /Oxford U.; Frost, J.; /Cambridge U.; Gadfort, T.; /Brookhaven; Glover, N.; /Durham U.; Haas, A.; /SLAC; Halkiadakis, E.; /Rutgers U., Piscataway /INFN, Milan Bicocca /Oxford U. /Ohio State U. /Rutherford /Oxford U. /Oxford U. /Maryland U. /Bristol U. /Princeton U. /Oxford U. /Oxford U. /Arizona U. /Johns Hopkins U. /Oxford U. /Fermilab /Rutherford /Bristol U. /Karlsruhe U., EKP /Weizmann Inst. /Washington U., Seattle /Johns Hopkins U. /Oslo U. /Durham U. /Princeton U. /Paris, LPTHE /CERN /Southern Denmark U., CP3-Origins /Granada U. /SLAC /Rutherford /Toronto U. /Stockholm U., OKC /Stockholm U. /Yale U.; /more authors..

2012-06-12

We present the report of the hadronic working group of the BOOST2010 workshop held at the University of Oxford in June 2010. The first part contains a review of the potential of hadronic decays of highly boosted particles as an aid for discovery at the LHC and a discussion of the status of tools developed to meet the challenge of reconstructing and isolating these topologies. In the second part, we present new results comparing the performance of jet grooming techniques and top tagging algorithms on a common set of benchmark channels. We also study the sensitivity of jet substructure observables to the uncertainties in Monte Carlo predictions.

Boosted objects: a probe of beyond the Standard Model physics

CERN Document Server

Abdesselam, A; Bitenc, U; Brooijmans, G; Butterworth, J; Bruckman de Renstrom, P; Buarque Franzosi, D; Buckingham, R; Chapleau, B; Dasgupta, M; Davison, A; Dolen, J; Ellis, S; Fassi, F; Ferrando, J; Frandsen, M T; Frost, J; Gadfort, T; Glover, N; Haas, A; Halkiadakis, E; Hamilton, K; Hays, C; Hill, C; Jackson, J; Issever, C; Karagoz, M; Katz, A; Kreczko, L; Krohn, D; Lewis, A; Livermore, S; Loch, P; Maksimovic, P; March-Russell, J; Martin, A; McCubbin, N; Newbold, D; Ott, J; Perez, G; Policchio, A; Rappoccio, S; Raklev, A R; Richardson, P; Salam, G P; Sannino, F; Santiago, J; Schwartzman, A; Shepherd-Themistocleous, C; Sinervo, P; Sjoelin, J; Son, M; Spannowsky, M; Strauss, E; Takeuchi, M; Tseng, J; Tweedie, B; Vermillion, C; Voigt, J; Vos, M; Wacker, J; Wagner-Kuhr, J; Wilson, M G

2011-01-01

We present the report of the hadronic working group of the BOOST2010 workshop held at the University of Oxford in June 2010. The first part contains a review of the potential of hadronic decays of highly boosted particles as an aid for discovery at the LHC and a discussion of the status of tools developed to meet the challenge of reconstructing and isolating these topologies. In the second part, we present new results comparing the performance of jet grooming techniques and top tagging algorithms on a common set of benchmark channels. We also study the sensitivity of jet substructure observables to the uncertainties in Monte Carlo predictions.

Dosimetric evaluation of simultaneous integrated boost during stereotactic body radiation therapy for pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Yang, Wensha, E-mail: wensha.yang@cshs.org [Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States); Reznik, Robert; Fraass, Benedick A. [Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States); Nissen, Nicholas [Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA (United States); Hendifar, Andrew [Department of Gastrointestinal Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States); Wachsman, Ashley [Department of Cross-Sectional Imaging Interventional Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States); Sandler, Howard; Tuli, Richard [Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States)

2015-04-01

Stereotactic body radiation therapy (SBRT) provides a promising way to treat locally advanced pancreatic cancer and borderline resectable pancreatic cancer. A simultaneous integrated boost (SIB) to the region of vessel abutment or encasement during SBRT has the potential to downstage otherwise likely positive surgical margins. Despite the potential benefit of using SIB-SBRT, the ability to boost is limited by the local geometry of the organs at risk (OARs), such as stomach, duodenum, and bowel (SDB), relative to tumor. In this study, we have retrospectively replanned 20 patients with 25 Gy prescribed to the planning target volume (PTV) and 33~80 Gy to the boost target volume (BTV) using an SIB technique for all patients. The number of plans and patients able to satisfy a set of clinically established constraints is analyzed. The ability to boost vessels (within the gross target volume [GTV]) is shown to correlate with the overlap volume (OLV), defined to be the overlap between the GTV + a 1(OLV1)- or 2(OLV2)-cm margin with the union of SDB. Integral dose, boost dose contrast (BDC), biologically effective BDC, tumor control probability for BTV, and normal tissue complication probabilities are used to analyze the dosimetric results. More than 65% of the cases can deliver a boost to 40 Gy while satisfying all OAR constraints. An OLV2 of 100 cm{sup 3} is identified as the cutoff volume: for cases with OLV2 larger than 100 cm{sup 3}, it is very unlikely the case could achieve 25 Gy to the PTV while successfully meeting all the OAR constraints.

Performance of Jet Substructure Techniques and Boosted Object Identification in ATLAS

CERN Document Server

Lacey, J; The ATLAS collaboration

2014-01-01

ATLAS has implemented and commissioned many new jet substructure techniques to aid in the identification and interpretation of hadronic final states originating from Lorentz-boosted heavy particles produced at the LHC. These techniques include quantum jets, jet charge, jet shapes, quark/gluon, boosted boson and top quark tagging, along with grooming methods such as pruning, trimming, and filtering. These techniques have been validated using the large 2012 ATLAS dataset. Presented here is a summary of the state of the art jet substructure and tagging techniques developed in ATLAS, their performance and recent results.

Shrinkage Degree in $L_{2}$ -Rescale Boosting for Regression.

Science.gov (United States)

Xu, Lin; Lin, Shaobo; Wang, Yao; Xu, Zongben

2017-08-01

L 2 -rescale boosting ( L 2 -RBoosting) is a variant of L 2 -Boosting, which can essentially improve the generalization performance of L 2 -Boosting. The key feature of L 2 -RBoosting lies in introducing a shrinkage degree to rescale the ensemble estimate in each iteration. Thus, the shrinkage degree determines the performance of L 2 -RBoosting. The aim of this paper is to develop a concrete analysis concerning how to determine the shrinkage degree in L 2 -RBoosting. We propose two feasible ways to select the shrinkage degree. The first one is to parameterize the shrinkage degree and the other one is to develop a data-driven approach. After rigorously analyzing the importance of the shrinkage degree in L 2 -RBoosting, we compare the pros and cons of the proposed methods. We find that although these approaches can reach the same learning rates, the structure of the final estimator of the parameterized approach is better, which sometimes yields a better generalization capability when the number of sample is finite. With this, we recommend to parameterize the shrinkage degree of L 2 -RBoosting. We also present an adaptive parameter-selection strategy for shrinkage degree and verify its feasibility through both theoretical analysis and numerical verification. The obtained results enhance the understanding of L 2 -RBoosting and give guidance on how to use it for regression tasks.

The Attentional Boost Effect and Context Memory

Science.gov (United States)

Mulligan, Neil W.; Smith, S. Adam; Spataro, Pietro

2016-01-01

Stimuli co-occurring with targets in a detection task are better remembered than stimuli co-occurring with distractors--the attentional boost effect (ABE). The ABE is of interest because it is an exception to the usual finding that divided attention during encoding impairs memory. The effect has been demonstrated in tests of item memory but it is…

Simple grain mill boosts production and eases women's workload ...

International Development Research Centre (IDRC) Digital Library (Canada)

... grain mill boosts production and eases women's workload. 11 janvier 2013. Image ... It aims to increase the production, improve the processing, develop new ... farmer societies, women's self-help groups, and the food-processing industry.

7th International Workshop on Boosted Object Phenomenology, Reconstruction and Searches in HEP

CERN Document Server

2015-01-01

BOOST2015 is the seventh of a series of successful joint theory/experiment workshops which bring together the world leading experts from theory and the Tevatron and LHC experiments to discuss the latest progress and develop new approaches on the reconstruction and use of boosted decay topologies as search tools for new physics. This year, the workshop is hosted by the University of Chicago.

Cross-Regulation Assessment of DIDO Buck-Boost Converter for Renewable Energy Application

Directory of Open Access Journals (Sweden)

Deepak Elamalayil Soman

2017-06-01

Full Text Available When medium- or high-voltage power conversion is preferred for renewable energy sources, multilevel power converters have received much of the interest in this area as methods for enhancing the conversion efficiency and cost effectiveness. In such cases, multilevel, multi-input multi-output (MIMO configurations of DC-DC converters come to the scenario for integrating several sources together, especially considering the stringent regulatory needs and the requirement of multistage power conversion systems. Considering the above facts, a three-level dual input dual output (DIDO buck-boost converter, as the simplest form of MIMO converter, is proposed in this paper for DC-link voltage regulation. The capability of this converter for cross regulating the DC-link voltage is analyzed in detail to support a three-level neutral point clamped inverter-based grid connection in the future. The cross-regulation capability is examined under a new type of pulse delay control (PDC strategy and later compared with a three-level boost converter (TLBC. Compared to conventional boost converters, the high-voltage three-level buck boost converter (TLBBC with PDC exhibits a wide controllability range and cross regulation capability. These enhanced features are extremely important for better regulating variable output renewable energy sources such as solar, wind, wave, marine current, etc. The simulation and experimental results are provided to validate the claim.

A Battery Power Bank with Series-Connected Buck–Boost-Type Battery Power Modules

Directory of Open Access Journals (Sweden)

Tsung-Hsi Wu

2017-05-01

Full Text Available The operation of a battery power bank with series-connected buck–boost-type battery power modules (BPMs was investigated in this study. Each BPM consisted of a battery pack with an associated buck–boost converter for individually controlling battery currents. With a proposed discharging scenario, load voltage regulation with charge equalization among batteries was performed by controlling the battery currents in accordance with their state-of-charges (SOCs estimated by real-time battery-loaded voltages detected under the same operating condition. In addition, the fault tolerance was executed to isolate exhausted or faulty batteries from the battery power bank without interrupting the system operation. Experiments were conducted to verify the effectiveness of the discharging scenario for a laboratory battery power bank with four series buck–boost BPMs.

SU-E-T-210: Comparison of Proton with Electron Boost in Breast Cancer Treatment

Energy Technology Data Exchange (ETDEWEB)

Zheng, Y; Chang, A [Procure Proton Therapy Center, Oklahoma City, OK (United States); Liu, Y [INTEGRIS Cancer Institute of Oklahoma, Oklahoma City, OK (United States)

2015-06-15

Purpose: Electron beams are commonly used for boost radiation following whole breast irradiation (WBI) to improve the in-breast local control. Proton beams have a finite range and a sharper distal dose falloff compared to electron beams, thus potentially sparing more heart and lung in breast treatment. The purpose of the study is to compare protons with electrons for boost breast treatment in terms of target coverage and normal tissue sparing. Methods: Six breast cancer patients were included in this study. All women received WBI to 45–50 Gy, followed by a 10–16.2 Gy boost with standard fractionation. If proton beams were used for the boost treatment, an electron plan was retrospectively generated for comparison using the same CT set and structures, and vice versa if electron beams were used for treatment. Proton plans were generated using the treatment planning system (TPS) with two to three uniform scanning proton beams. Electron plans were generated using the Pinnacle TPS with one single en face beam. Dose-volume histograms (DVH) were calculated and compared between proton and electron boost plans. Results: Proton plans show a similar boost target coverage, similar skin dose, and much better heart and lung sparing. For an example patient, V95% for PTV was 99.98% and skin (5 mm shell) received a max dose close to the prescription dose for both protons and electrons; however, V2 and V5 for the ipsilateral lung and heart were 37.5%, 17.9% and 19.9%, 4.9% respectively for electrons, but were essentially 0 for protons. Conclusions: This dosimetric comparison demonstrates that while both proton therapy and electron therapy provided similar coverage and skin dose, proton therapy could largely reduce the dose to lung and heart, thus leading to potential less side effects.

Reduction in Radiation-Induced Morbidity by Use of an Intercurrent Boost in the Management of Early-Stage Breast Cancer

International Nuclear Information System (INIS)

Trombetta, Mark; Julian, Thomas B.; Valakh, Vladimir; Greenberg, Larisa; Labban, George; Khalid, Mian K.; Werts, E. Day; Parda, David

2010-01-01

Purpose: Electron or photon boost immediately following whole-breast irradiation performed after conservation surgery for early-stage breast cancer is the accepted standard of care. This regimen frequently results in Grade III dermatitis, causing discomfort or treatment interruption. Herein, we compare patients treated with whole-breast irradiation followed by boost compared with a cohort with a planned intercurrent radiation boost. Methods and Materials: The records of 650 consecutive breast cancer patients treated at Allegheny General Hospital (AGH) between 2000 and 2008 were reviewed. Selected for this study were 327 patients with T1 or T2 tumors treated with external beam radiotherapy postlumpectomy. One hundred and sixty-nine patients were treated by whole-breast radiotherapy (WBRT) followed by boost at completion. One hundred fifty-eight were treated with a planned intercurrent boost (delivered following 3,600 cGy WBRT). The mean whole breast radiation dose in the conventionally treated group was 5,032 cGy (range, 4500-5400 cGy), and the mean whole breast dose was 5,097 cGy (range, 4860-5040 cGy) in the group treated with a planned intercurrent boost. Results: The occurrence of Grade III dermatitis was significantly reduced in the WBRT/intercurrent boost group compared with the WBRT/boost group (0.6% vs. 8.9%), as was the incidence of treatment interruption (1.9% vs. 14.2%). With a median follow-up of 32 months and 27 months, respectively, no significant difference in local control was identified. Conclusions: Patients treated with intercurrent boost developed less Grade III dermatitis and unplanned treatment interruptions with similar local control.

Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.

Science.gov (United States)

Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Amara, Rama Rao; Plikaytis, Bonnie B; Posey, James E; Sable, Suraj B

2016-05-13

Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans.

BioBoost. Biomass based energy intermediates boosting bio-fuel production

Energy Technology Data Exchange (ETDEWEB)

Niebel, Andreas [Karlsruher Institut fuer Technologie (KIT), Karlsruhe (Germany). Institut fuer Katalyseforschung und -technologie (IKFT)

2013-10-01

To increase the share of biomass for renewable energy in Europe conversion pathways which are economic, flexible in feedstock and energy efficient are needed. The BioBoost project concentrates on dry and wet residual biomass and wastes as feedstock for de-central conversion by fast pyrolysis, catalytic pyrolysis and hydrothermal carbonization to the intermediate energy carriers oil, coal or slurry. Based on straw the energy density increases from 2 to 20-30 GJ/m{sup 3}, enabling central GW scale gasification plants for bio-fuel production. A logistic model for feedstock supply and connection of de-central with central conversion is set up and validated allowing the determination of costs, the number and location of de-central and central sites. Techno/economic and environmental assessment of the value chain supports the optimization of products and processes. The utilization of energy carriers is investigated in existing and coming applications of heat and power production and synthetic fuels and chemicals. (orig.)

CMOS single-stage input-powered bridge rectifier with boost switch and duty cycle control

Science.gov (United States)

Radzuan, Roskhatijah; Mohd Salleh, Mohd Khairul; Hamzah, Mustafar Kamal; Ab Wahab, Norfishah

2017-06-01

This paper presents a single-stage input-powered bridge rectifier with boost switch for wireless-powered devices such as biomedical implants and wireless sensor nodes. Realised using CMOS process technology, it employs a duty cycle switch control to achieve high output voltage using boost technique, leading to a high output power conversion. It has only six external connections with the boost inductance. The input frequency of the bridge rectifier is set at 50 Hz, while the switching frequency is 100 kHz. The proposed circuit is fabricated on a single 0.18-micron CMOS die with a space area of 0.024 mm2. The simulated and measured results show good agreement.

Soft switching PWM isolated boost converter for fuel cell application

Energy Technology Data Exchange (ETDEWEB)

Rezaei, M.; Adib, E. [Isfahan Univ. of Technology, Isfahan (Iran, Islamic Republic of)

2009-07-01

This presentation introduced a newly developed soft switching, isolated boost type converter for fuel cell applications. With a simple PWM control circuit, the converter achieves zero voltage switching the main switch. Since the auxiliary circuit is soft switched, the converter can operate at high powers which make it suitable for fuel cell applications. In particular, the converter is suitable for the interface of fuel cell and inverters because of its high voltage gain and isolation between input and output sources. In addition, the input current of the converter (current drained from the fuel cell) is almost constant since it is a boost type converter. The converter was analyzed and the simulation results validate the theoretical analysis.

Dihydroergotamine mesylate-loaded dissolving microneedle patch made of polyvinylpyrrolidone for management of acute migraine therapy.

Science.gov (United States)

Tas, Cetin; Joyce, Jessica C; Nguyen, Hiep X; Eangoor, Padmanabhan; Knaack, Jennifer S; Banga, Ajay K; Prausnitz, Mark R

2017-12-28

Migraine is a widespread neurological disease with negative effects on quality of life and productivity. Moderate to severe acute migraine attacks can be treated with dihydroergotamine mesylate (DHE), an ergot derivative that is especially effective in non-responders to triptan derivatives. To overcome limitations of current DHE formulations in subcutaneous injection and nasal spray such as pain, adverse side effects and poor bioavailability, a new approach is needed for DHE delivery enabling painless self-administration, quick onset of action, and high bioavailability. In this study, we developed a dissolving microneedle patch (MNP) made of polyvinylpyrrolidone, due to its high aqueous solubility and solubility enhancement properties, using a MNP design previously shown to be painless and simple to administer. DHE-loaded MNPs were shown to have a content uniformity of 108±9% with sufficient mechanical strength for insertion to pig skin ex vivo and dissolution within 2min. In vivo pharmacokinetic studies were carried out on hairless rats, and DHE plasma levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under curve (AUC) value after DHE delivery by MNP (1259±917ng/mL min) was not significantly different (p>0.05) as compared to subcutaneous injection, with a relative bioavailability of 97%. Also, appreciable plasma levels of DHE were seen within 5min for both delivery methods and t max value of MNPs (38±23min) showed no significant difference (p>0.05) compared to subcutaneous injection (24±13min). These results suggest that DHE-loaded MNPs have promise as an alternative DHE delivery method that can be painlessly self-administered with rapid onset and high bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of high voltage step-up nonisolated DC-DC boost converters

Science.gov (United States)

Alisson Alencar Freitas, Antônio; Lessa Tofoli, Fernando; Junior, Edilson Mineiro Sá; Daher, Sergio; Antunes, Fernando Luiz Marcelo

2016-05-01

A high voltage step-up nonisolated DC-DC converter based on coupled inductors suitable to photovoltaic (PV) systems applications is proposed in this paper. Considering that numerous approaches exist to extend the voltage conversion ratio of DC-DC converters that do not use transformers, a detailed comparison is also presented among the proposed converter and other popular topologies such as the conventional boost converter and the quadratic boost converter. The qualitative analysis of the coupled-inductor-based topology is developed so that a design procedure can be obtained, from which an experimental prototype is implemented to validate the theoretical assumptions.

No Evidence for Decay of the Latent Reservoir in HIV-1–Infected Patients Receiving Intensive Enfuvirtide-Containing Antiretroviral Therapy

Science.gov (United States)

Gandhi, Rajesh T.; Bosch, Ronald J.; Aga, Evgenia; Albrecht, Mary; Demeter, Lisa M.; Dykes, Carrie; Bastow, Barbara; Para, Michael; Lai, Jun; Siliciano, Robert F.; Siliciano, Janet D.; Eron, Joseph J.

2010-01-01

Human immunodeficiency virus type 1 (HIV-1) persists in a latent reservoir of infected resting memory CD4 cells in patients receiving antiretroviral therapy. We assessed whether multitarget therapy with enfuvirtide, 2 reverse-transcriptase inhibitors, and a ritonavir-boosted protease inhibitor leads to decay of this reservoir. Nineteen treatment-naive patients initiated this regimen; 9 experienced virologic suppression and continued enfuvirtide-containing therapy for at least 48 weeks. In enfuvirtide-treated patients with virological suppression, there was no decay of the latent reservoir (95% confidence interval for half-life, 11 months to infinity). The stability of the latent reservoir despite intensive therapy suggests that new strategies are needed to eradicate HIV-1 from this reservoir. PMID:20001856

Image objects detection based on boosting neural network

NARCIS (Netherlands)

Liang, N.; Hegt, J.A.; Mladenov, V.M.

2010-01-01

This paper discusses the problem of object area detection of video frames. The goal is to design a pixel accurate detector for grass, which could be used for object adaptive video enhancement. A boosting neural network is used for creating such a detector. The resulted detector uses both textural

Circuit Simulation for Solar Power Maximum Power Point Tracking with Different Buck-Boost Converter Topologies

Directory of Open Access Journals (Sweden)

Jaw-Kuen Shiau

2014-08-01

Full Text Available The power converter is one of the essential elements for effective use of renewable power sources. This paper focuses on the development of a circuit simulation model for maximum power point tracking (MPPT evaluation of solar power that involves using different buck-boost power converter topologies; including SEPIC, Zeta, and four-switch type buck-boost DC/DC converters. The circuit simulation model mainly includes three subsystems: a PV model; a buck-boost converter-based MPPT system; and a fuzzy logic MPPT controller. Dynamic analyses of the current-fed buck-boost converter systems are conducted and results are presented in the paper. The maximum power point tracking function is achieved through appropriate control of the power switches of the power converter. A fuzzy logic controller is developed to perform the MPPT function for obtaining maximum power from the PV panel. The MATLAB-based Simulink piecewise linear electric circuit simulation tool is used to verify the complete circuit simulation model.

Boosted Higgs shapes

International Nuclear Information System (INIS)

Schlaffer, Matthias; Spannowsky, Michael; Wymant, Chris

2014-05-01

The inclusive Higgs production rate through gluon fusion has been measured to be in agreement with the Standard Model (SM). We show that even if the inclusive Higgs production rate is very SM-like, a precise determination of the boosted Higgs transverse momentum shape offers the opportunity to see effects of natural new physics. These measurements are generically motivated by effective field theory arguments and specifically in extensions of the SM with a natural weak scale, like composite Higgs models and natural supersymmetry. We show in detail how a measurement at high transverse momentum of H→2l+p T via H→ττ and H→WW * could be performed and demonstrate that it offers a compelling alternative to the t anti tH channel. We discuss the sensitivity to new physics in the most challenging scenario of an exactly SM-like inclusive Higgs cross-section.

Impact of intensity-modulated radiation therapy as a boost treatment on the lung-dose distributions for non-small-cell lung cancer

International Nuclear Information System (INIS)

Choi, Youngmin; Kim, Jeung Kee; Lee, Hyung Sik; Hur, Won Joo; Chai, Gyu Young; Kang, Ki Mun

2005-01-01

Purpose: To investigate the feasibility of intensity-modulated radiotherapy (IMRT) as a method of boost radiotherapy after the initial irradiation by the conventional anterior/posterior opposed beams for centrally located non-small-cell lung cancer through the evaluation of dose distributions according to the various boost methods. Methods and Materials: Seven patients with T3 or T4 lung cancer and mediastinal node enlargement who previously received radiotherapy were studied. All patients underwent virtual simulation retrospectively with the previous treatment planning computed tomograms. Initial radiotherapy plans were designed to deliver 40 Gy to the primary tumor and involved nodal regions with the conventional anterior/posterior opposed beams. Two radiation dose levels, 24 and 30 Gy, were used for the boost radiotherapy plans, and four different boost methods (a three-dimensional conformal radiotherapy [3DCRT], five-, seven-, and nine-beam IMRT) were applied to each dose level. The goals of the boost plans were to deliver the prescribed radiation dose to 95% of the planning target volume (PTV) and minimize the volumes of the normal lungs and spinal cord irradiated above their tolerance doses. Dose distributions in the PTVs and lungs, according to the four types of boost plans, were compared in the boost and sum plans, respectively. Results: The percentage of lung volumes irradiated >20 Gy (V20) was reduced significantly in the IMRT boost plans compared with the 3DCRT boost plans at the 24- and 30-Gy dose levels (p 0.007 and 0.0315 respectively). Mean lung doses according to the boost methods were not different in the 24- and 30-Gy boost plans. The conformity indexes (CI) of the IMRT boost plans were lower than those of the 3DCRT plans in the 24- and 30-Gy plans (p = 0.001 in both). For the sum plans, there was no difference of the dose distributions in the PTVs and lungs according to the boost methods. Conclusions: In the boost plans the V20s and CIs were

The tyrosine kinase inhibitor imatinib mesylate suppresses uric acid crystal-induced acute gouty arthritis in mice.

Directory of Open Access Journals (Sweden)

Laurent L Reber

Full Text Available Gouty arthritis is caused by the deposition of monosodium urate (MSU crystals in joints. Despite many treatment options for gout, there is a substantial need for alternative treatments for patients unresponsive to current therapies. Tyrosine kinase inhibitors have demonstrated therapeutic benefit in experimental models of antibody-dependent arthritis and in rheumatoid arthritis in humans, but to date, the potential effects of such inhibitors on gouty arthritis has not been evaluated. Here we demonstrate that treatment with the tyrosine kinase inhibitor imatinib mesylate (imatinib can suppress inflammation induced by injection of MSU crystals into subcutaneous air pouches or into the ankle joint of wild type mice. Moreover, imatinib treatment also largely abolished the lower levels of inflammation which developed in IL-1R1-/- or KitW-sh/W-sh mice, indicating that this drug can inhibit IL-1-independent pathways, as well as mast cell-independent pathways, contributing to pathology in this model. Imatinib treatment not only prevented ankle swelling and synovial inflammation when administered before MSU crystals but also diminished these features when administrated after the injection of MSU crystals, a therapeutic protocol more closely mimicking the clinical situation in which treatment occurs after the development of an acute gout flare. Finally, we also assessed the efficiency of local intra-articular injections of imatinib-loaded poly(lactic-co-glycolic acid (PLGA nanoparticles in this model of acute gout. Treatment with low doses of this long-acting imatinib:PLGA formulation was able to reduce ankle swelling in a therapeutic protocol. Altogether, these results raise the possibility that tyrosine kinase inhibitors might have utility in the treatment of acute gout in humans.

Biochar boosts tropical but not temperate crop yields

NARCIS (Netherlands)

Jeffery, Simon; Abalos Rodriguez, Diego; Prodana, Marija; Bastos, Ana Catarina; Groenigen, van Jan Willem; Hungate, Bruce A.; Verheijen, Frank

2017-01-01

Applying biochar to soil is thought to have multiple benefits, from helping mitigate climate change [1, 2], to managing waste [3] to conserving soil [4]. Biochar is also widely assumed to boost crop yield [5, 6], but there is controversy regarding the extent and cause of any yield benefit [7].

Endoscope-guided interstitial intensity-modulated brachytherapy and intracavitary brachytherapy as boost radiation for primary early T stage nasopharyngeal carcinoma.

Directory of Open Access Journals (Sweden)

Xiang-Bo Wan

Full Text Available BACKGROUND: Intracavitary brachytherapy (ICBT is usually applied as boost radiotherapy for superficial residual of nasopharyngeal carcinoma (NPC after primary extern-beam radiptherapy (ERT. Here, we evaluated the outcome of endoscope-guided interstitial intensity-modulated brachytherapy (IMBT boost radiation for deep-seated residual NPC. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred and thirteen patients with residual NPC who were salvaged with brachytherapy boost radiation during 2005-2009 were analyzed retrospectively. Among these patients, 171 patients had superficial residual NPC (≤1 cm below the nasopharyngeal epithelium were treated with ICBT boost radiation, and interstitial IMBT boost radiation was delivered to 42 patients with deep-seated residual NPC (>1 cm below the nasopharyngeal epithelium. We found that IMBT boost subgroup had a higher ratio of T2b (81.0% VS 34.5%, P<0.001 and stage II (90.5% VS 61.4%, P = 0.001 than that of ICBT boost subgroup. The dosage of external-beam radiotherapy in the nasopharyngeal (63.0±3.8 VS 62.6±4.3 Gray (Gy, P = 0.67 and regional lymph nodes (55.8±5.0 VS 57.5±5.7 Gy, P = 0.11 was comparable in both groups. For brachytherapy, IMBT subgroup had a lower boost radiation dosage than ICBT subgroup (11.0±2.9 VS 14.8±3.2 Gy, P<0.01. Though the IMBT group had deeper residual tumors and received lower boost radiation dosages, both subgroups had the similar 5-year actuarial overall survival rate (IMBT VS ICBT group: 96.8% VS 93.6%, P = 0.87, progression-free survival rate (92.4% VS 86.5%, P = 0.41 and distant metastasis-free survival rate (94.9% VS 92.7%, P = 0.64. Moreover, IMBT boost radiation subgroup had a similar local (97.4% VS 94.4%, P = 0.57 and regional (95.0% VS 97.2%, P = 0.34 control to ICBT subgroup. The acute and late toxicities rates were comparable between the both subgroups. CONCLUSIONS/SIGNIFICANCE: IMBT boost radiation may be a promising therapeutic

Non Isolated and Non-Inverting Cockcroft Walton Multiplier Based Hybrid 2Nx Interleaved Boost Converter For Renewable Energy Applications

DEFF Research Database (Denmark)

Bhaskar, Mahajan Sagar; Padamanaban, Sanjeevi Kumar; Blaabjerg, Frede

2016-01-01

In this paper hybrid non isolated and non-invertingCockcroft-Walton multiplier based 2Nx InterleavedBoost converter (2Nx IBC) for renewable energy applications is presented. The presented hybrid boost converter topology is derived from non-inverting Nx Multilevel Boost Converter (Nx MBC......) and inverting Nx Multilevel Boost Converter (Nx MBC). In renewable energy applications, generated voltage needs to be stepped up with high conversion ratio using a DC-DC converter at voltage levels as per the application requirement. The advantages of the presentedtopology of interleaved converter are high...

Effective local control of vertebral metastases by simultaneous integrated boost radiotherapy. Preliminary results

Energy Technology Data Exchange (ETDEWEB)

Lubgan, Dorota; Ziegaus, Anke; Semrau, Sabine; Lambrecht, Ulrike; Lettmaier, Sebastian; Fietkau, Rainer [Erlangen University Hospital, Department of Radiation Oncology, Erlangen (Germany)

2014-11-14

The primary endpoint was to improve local tumour control of patients with metastatic spinal tumours by stereotactic body radiotherapy (SBRT) and dose escalation by simultaneous, integrated boost (PTV-boost). We used a whole vertebral body (PTV-elective) contouring approach. Secondary endpoints were severity of acute and chronic adverse effects and overall survival. In all, 33 patients with metastases of the vertebral column were treated at Erlangen University Hospital. SBRT was given in 12 or 10 fractions. The metastatic lesion (PTV-boost) received 3.6 Gy (range 3.0-4.51 Gy) per fraction for a total of 42.0 Gy (24.36-48.0 Gy) and the whole vertebra (PTV-elective) received 2.85 Gy (range 1.8-3.6 Gy) per fraction for a total of 32.39 Gy (range 21.60-38.0 Gy). Patients were followed up every 3 months. Local control rate of all patients was 93 % at 12 and 24 months. The overall survival rate was 54 % at 12 months, 38 % at 24 months and 18 % at 36 months. No radiation myelopathy occurred. The most frequently observed adverse events in 3 cases was oesophagitis grade 2. SBRT with simultaneous, integrated boost was associated with excellent local control of 93 % after 24 months. This result shows the possibility of delivering escalated doses to the target while still keeping the incidence of side effects low. This study forms the basis for a future randomised controlled trial comparing conventional radiotherapy (10 fractions of 3 Gy) with hypofractionated dose intensified SBRT (12 fractions of 3 Gy + integrated boost 12 fractions of 4 Gy) for improvement of local tumour control and pain. (orig.) [German] Das primaere Ziel der Studie war die Verbesserung der lokalen Tumorkontrolle von Patienten mit Wirbelkoerpermetastasen mittels stereotaktischer Radiotherapie (SBRT) mit Dosiseskalation durch einen simultan integrierten Boost (PTV-Boost). Dabei wurde der ganze Wirbelkoerper konturiert (PTV-Elektive). Zu den sekundaeren Endpunkten der Studie gehoerten der Schweregrad von

Modeling and Simulation of PMSG Wind Turbine with Boost Converter Working under Discontinuous Conduction Mode

DEFF Research Database (Denmark)

Qin, Nan; Xu, Zhao

2008-01-01

in the discontinuous conducting mode (DCM). The new wind turbine model with the variable speed control of the PMSG based on duty cycle control of the boost converter has been developed in Matlab Simulink. Simulation studies show that DCM working mode of the boost converter provides more flexibility in controlling...

Adaptive Kernel in Meshsize Boosting Algorithm in KDE ...

African Journals Online (AJOL)

This paper proposes the use of adaptive kernel in a meshsize boosting algorithm in kernel density estimation. The algorithm is a bias reduction scheme like other existing schemes but uses adaptive kernel instead of the regular fixed kernels. An empirical study for this scheme is conducted and the findings are comparatively ...

Fixed switching frequency applied in single-phase boost AC to DC converter

International Nuclear Information System (INIS)

Chen, T.-C.; Ren, T.-J.; Ou, J.-C.

2009-01-01

The fixed switching frequency control for a single-phase boost AC to DC converter to achieve a sinusoidal line current and unity power factor is proposed in this paper. The relation between the line current error and the fixed switching frequency was developed. For a limit line current error, the minimum switching frequency for a boost AC to DC converter can be achieved. The proposed scheme was implemented using a 32-bit digital signal processor TMS320C32. Simulations and experimental results demonstrate the feasibility and fast dynamic response of the proposed control strategy.

Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report

International Nuclear Information System (INIS)

Hughes, Brett; Yip, Desmond; Goldstein, David; Waring, Paul; Beshay, Victoria; Chong, Guan

2004-01-01

The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs) has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial. The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply) but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression occurred. This case illustrates that the brain can be a

Role of Brachytherapy in the Boost Management of Anal Carcinoma With Node Involvement (CORS-03 Study)

Energy Technology Data Exchange (ETDEWEB)

Moureau-Zabotto, Laurence, E-mail: moureaul@ipc.unicancer.fr [Department of Radiation Therapy, Institut Paoli Calmettes, Marseille (France); Ortholan, Cecile [Department of Radiation Therapy, Monaco (France); Hannoun-Levi, Jean-Michel [Department of Radiation Therapy, Antoine Lacassagne Cancer Center, Nice (France); Teissier, Eric [Azurean Cancer Center, Mougins (France); Cowen, Didier [Department of Radiation Therapy, Timone Academic Hospital and North Academic Hospital, Marseille (France); Department of Radiation Therapy, Val d' Aurelle Cancer Center, Montpellier (France); Salem, Nagi [Department of Radiation Therapy, Institut Paoli Calmettes, Marseille (France); Lemanski, Claire [Catalan Oncology Center, Perpignan (France); Ellis, Steve [French Red Cross Center, Toulon (France); Resbeut, Michel [Department of Radiation Therapy, Institut Paoli Calmettes, Marseille (France); French Red Cross Center, Toulon (France)

2013-03-01

Purpose: To assess retrospectively the clinical outcome in anal cancer patients, with lymph node involvement, treated with split-course radiation therapy and receiving a boost through external beam radiation therapy (EBRT) or brachytherapy (BCT). Methods and Materials: From 2000 to 2005, among 229 patients with invasive nonmetastatic anal squamous cell carcinoma, a selected group of 99 patients, with lymph node involvement, was studied. Tumor staging reported was T1 in 4 patients, T2 in 16 patients, T3 in 49 patients, T4 in 16 patients, and T unknown in 14 patients and as N1 in 67 patients and N2/N3 in 32 patients. Patients underwent a first course of EBRT (mean dose, 45.1 Gy) followed by a boost (mean dose, 18 Gy) using EBRT (50 patients) or BCT (49 patients). All characteristics of patients and tumors were well balanced between the BCT and EBRT groups. Prognostic factors of cumulative rate of local recurrence (CRLR), cumulative rate of distant (including nodal) recurrence (CRDR), colostomy-free survival (CFS) rate, and overall survival (OS) rate were analyzed for the overall population and according to the nodal status classification. Results: The median follow-up was 71.5 months. The 5-year CRLR, CRDR, CFS rate, and OS rate were 21%, 19%, 63%, and 74.4%, respectively. In the overall population, the type of node involvement (N1 vs N2/N3) was the unique independent prognostic factor for CRLR. In N1 patients, by use of multivariate analysis, BCT boost was the unique prognostic factor for CRLR (4% for BCT vs 31% for EBRT; hazard ratio, 0.08; P=.042). No studied factors were significantly associated with CRDR, CFS, and OS. No difference with regard to boost technique and any other factor studied was observed in N2/N3 patients for any kind of recurrence. Conclusion: In anal cancer, even in the case of initial perirectal node invasion, BCT boost is superior to EBRT boost for CRLR, without an influence on OS, suggesting that N1 status should not be a contraindication to

Prostate stereotactic body radiotherapy with simultaneous integrated boost: which is the best planning method?

International Nuclear Information System (INIS)

Tree, Alison; Jones, Caroline; Sohaib, Aslam; Khoo, Vincent; As, Nicholas van

2013-01-01

The delivery of a simultaneous integrated boost to the intra-prostatic tumour nodule may improve local control. The ability to deliver such treatments with hypofractionated SBRT was attempted using RapidArc (Varian Medical systems, Palo Alto, CA) and Multiplan (Accuray inc, Sunnyvale, CA). 15 patients with dominant prostate nodules had RapidArc and Multiplan plans created using a 5 mm isotropic margin, except 3 mm posteriorly, aiming to deliver 47.5 Gy in 5 fractions to the boost whilst treating the whole prostate to 36.25 Gy in 5 fractions. An additional RapidArc plan was created using an 8 mm isotropic margin, except 5 mm posteriorly, to account for lack of intrafraction tracking. Both RapidArc and Multiplan can produce clinically acceptable boost plans to a dose of 47.5 Gy in 5 fractions. The mean rectal doses were lower for RapidArc plans (D50 13.2 Gy vs 15.5 Gy) but the number of missed constraints was the same for both planning methods (11/75). When the margin was increased to 8 mm/5 mm for the RapidArc plans to account for intrafraction motion, 37/75 constraints were missed. RapidArc and Multiplan can produce clinically acceptable simultaneous integrated boost plans, but the mean rectal D50 and D20 with RapidArc are lower. If the margins are increased to account for intrafraction motion, the RapidArc plans exceed at least one dose constraint in 13/15 cases. Delivering a simultaneous boost with hypofractionation appears feasible, but requires small margins needing intrafraction motion tracking

Superconducting Electric Boost Pump for Nuclear Thermal Propulsion, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — A submersible, superconducting electric boost pump sized to meet the needs of future Nuclear Thermal Propulsion systems in the 25,000 lbf thrust range is proposed....

Multistage switched inductor boost converter for renewable energy application

DEFF Research Database (Denmark)

Maroti, Pandav Kiran; Padmanaban, Sanjeevikumar; Bhaskar, Mahajan Sagar

2017-01-01

In this paper Multistage Switched Inductor Boost Converter (Multistage SIBC) is uttered for renewable energy applications. The projected converter is derived from an amalgamation of the conventional step-up converter and inductor stack. The number of inductor and duty ratio decides the overall...

Digitally-controlled PC-interfaced Boost Converter for Educational Purposes

DEFF Research Database (Denmark)

Ljusev, Petar; Andersen, Michael A. E.

2004-01-01

This paper describes implementation of a simple digital PID control algorithm for a boost converter using a cheap fixed-point 8-bit microcontroller. Serial communication to a PC server program is established for easier downloading of compensator parameters and current and voltage waveform...

Primary Parallel Isolated Boost Converter with Bidirectional Operation

DEFF Research Database (Denmark)

Hernandez Botella, Juan Carlos; Mira Albert, Maria del Carmen; Sen, Gökhan

2012-01-01

This paper presents a bidirectional dc/dc converter operated with batteries both in the input and output. Primary parallel isolated boost converter (PPIBC) with transformer series connection on the high voltage side is preferred due to its ability to handle high currents in the low voltage side. ...... and output battery banks with a defined ramp....

Boosting structured additive quantile regression for longitudinal childhood obesity data.

Science.gov (United States)

Fenske, Nora; Fahrmeir, Ludwig; Hothorn, Torsten; Rzehak, Peter; Höhle, Michael

2013-07-25

Childhood obesity and the investigation of its risk factors has become an important public health issue. Our work is based on and motivated by a German longitudinal study including 2,226 children with up to ten measurements on their body mass index (BMI) and risk factors from birth to the age of 10 years. We introduce boosting of structured additive quantile regression as a novel distribution-free approach for longitudinal quantile regression. The quantile-specific predictors of our model include conventional linear population effects, smooth nonlinear functional effects, varying-coefficient terms, and individual-specific effects, such as intercepts and slopes. Estimation is based on boosting, a computer intensive inference method for highly complex models. We propose a component-wise functional gradient descent boosting algorithm that allows for penalized estimation of the large variety of different effects, particularly leading to individual-specific effects shrunken toward zero. This concept allows us to flexibly estimate the nonlinear age curves of upper quantiles of the BMI distribution, both on population and on individual-specific level, adjusted for further risk factors and to detect age-varying effects of categorical risk factors. Our model approach can be regarded as the quantile regression analog of Gaussian additive mixed models (or structured additive mean regression models), and we compare both model classes with respect to our obesity data.

The effect of boost pressure on the performance characteristics of a diesel engine: A neuro-fuzzy approach

Energy Technology Data Exchange (ETDEWEB)

Al-Hinti, I.; Sakhrieh, A. [Department of Mechanical Engineering, The Hashemite University, Zarqa 13115 (Jordan); Samhouri, M.; Al-Ghandoor, A. [Department of Industrial Engineering, The Hashemite University, Zarqa 13115 (Jordan)

2009-01-15

This paper uses a neuro-fuzzy interface system (ANFIS) to study the effect of boost pressure on the efficiency, brake mean effective pressure (BMEP), and the brake specific fuel consumption (BSFC) of a single cylinder diesel engine. Experimental data were used as inputs to ANFIS to simulate the engine performance characteristics. The experimental as well as the model results emphasize the role of boost pressure in improving the different engine characteristics. The results show that the ANFIS technique can be used adequately to identify the effect of boost pressure on the different engine characteristics. In addition, different data points that were not used for ANFIS training were used to validate the developed models. The results suggest that ANFIS can be used accurately to predict the effect of boost pressure on the different engine characteristics. (author)

3-D conformal treatment of prostate cancer to 74 Gy vs. high-dose-rate brachytherapy boost: A cross-sectional quality-of-life survey

International Nuclear Information System (INIS)

Vordermark, Dirk

2006-01-01

The effects of two modalities of dose-escalated radiotherapy on health-related quality of life (HRQOL) were compared. Forty-one consecutive patients were treated with a 3-D conformal (3-DC) boost to 74 Gy, and 43 with high-dose rate (HDR) brachytherapy boost (2x9 Gy), following 3-D conformal treatment to 46 Gy. Median age was 70 years in both groups, median initial PSA was 7.9 μg/l in 3-DC boost patients and 8.1 μg/l in HDR boost patients. Stage was 7 in 52% and 47%, respectively. HRQOL was assessed cross-sectionally using EORTC QLQ-C30 and organ-specific PR25 modules 3-32 (median 19) and 4-25 (median 14) months after treatment, respectively. Questionnaires were completed by 93% and 97% of patients, respectively. Diarrhea and insomnia scores were significantly increased in both groups. In the PR25 module, scores of 3-DC boost and HDR boost patients for urinary, bowel and treatment-related symptoms were similar. Among responders, 34% of 3-DC boost patients and 86% of HDR boost patients had severe erectile problems. Dose escalation in prostate cancer by either 3-DC boost to 74 Gy or HDR brachytherapy boost appears to result in similar HRQOL profiles

A cosmetic evaluation of breast cancer treatment: A randomized study of radiotherapy boost technique

International Nuclear Information System (INIS)

Vass, Sylvie; Bairati, Isabelle

2005-01-01

Purpose: To compare cosmetic results of two different radiotherapy (RT) boost techniques used in the treatment of breast cancer after whole breast radiotherapy and to identify factors affecting cosmetic outcomes. Methods and Materials: Between 1996 and 1998, 142 patients with Stage I and II breast cancer were treated with breast conservative surgery and adjuvant RT. Patients were then randomly assigned to receive a boost dose of 15 Gy delivered to the tumor bed either by iridium 192, or a combination of photons and electrons. Cosmetic evaluations were done on a 6-month basis, with a final evaluation at 36 months after RT. The evaluations were done using a panel of global and specific subjective scores, a digitized scoring system using the breast retraction assessment (BRA) measurement, and a patient's self-assessment evaluation. As cosmetic results were graded according to severity, the comparison of boost techniques was done using the ordinal logistic regression model. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) are presented. Results: At 36 months of follow-up, there was no significant difference between the two groups with respect to the global subjective cosmetic outcome (OR = 1.40; 95%CI = 0.69-2.85, p = 0.35). Good to excellent scores were observed in 65% of implant patients and 62% of photon/electron patients. At 24 months and beyond, telangiectasia was more severe in the implant group with an OR of 9.64 (95%CI = 4.05-22.92, p < 0.0001) at 36 months. The only variable associated with a worse global cosmetic outcome was the presence of concomitant chemotherapy (OR = 3.87; 95%CI = 1.74-8.62). The BRA value once adjusted for age, concomitant chemotherapy, and boost volume showed a positive association with the boost technique. The BRA value was significantly greater in the implant group (p 0.03). There was no difference in the patient's final self-assessment score between the two groups. Three variables were statistically associated with

Cash boost to Great British science unveiled

CERN Multimedia

2002-01-01

"Trade and Industry Secretary, Patricia Hewitt today unveiled new plans for the DTI's record science budget over the next three years, to keep Britain at the forefront of world science. The plans include funding to develop life saving new health techniques, to seek alternative energy sources, to help our rural economy, to develop the computers of tomorrow and boost business with the next generation of leading edge technologies" (1 page).

Search for New Physics in Boosted Topologies

CERN Document Server

Cochran, James; The ATLAS collaboration

2014-01-01

The presentation is expected to focus on the opportunities of discovery of new physics profiting of the latest reconstruction tools for boosted top-quark or boson (W,Z,H) reconstruction and their large effect on increasing the analysis efficiency. A summary of Run 1 results showing latest techniques for background suppression and data-driven background estimate should be included pointing out the possibilities and improvements for Run 2.

PH-Induced Nanosegregation of Ritonavir to Lyotropic Liquid Crystal of Higher Solubility Than Crystalline Polymorphs

International Nuclear Information System (INIS)

Rodriguez-Spong, B.; Acciacca, A.; Fleisher, D.; Rodriguez-Hornedo, N.

2009-01-01

Birefringent spherical vesicles of ritonavir (RTV) are formed by increasing the pH of aqueous solutions from 1 to 3 or to 7 and by addition of water to ethanol solutions at room temperature. Increasing the pH creates supersaturation levels of 30--400. Upon this change in pH, the solutions become translucent, implying that some kind of RTV assembly was formed. Small spherical vesicles of narrow size distribution are detectable only after a few hours by optical microscopy. The vesicles show similar X-ray diffraction patterns and differential scanning calorimetry (DSC) behavior to amorphous RTV prepared by melt-quenching crystalline RTV. Examination by polarized optical microscopy suggests that these are lyotropic liquid crystalline (LLC) assemblies. Small-angle X-ray scattering and synchrotron X-ray diffraction further support the presence of orientational order that is associated with a nematic structure. RTV self-organizes into various phases as a result of the supersaturation created in aqueous solutions. The LLC vesicles do not fuse but slowly transform to the polymorphs of RTV (in days), Form I and finally Form II. Amorphous RTV in aqueous suspension also undergoes a transformation to a mesophase of similar morphology. Transformation pathways are consistent with measured dissolution rates and solubilities: amorphous > LLC >> Form I > Form II. The dissolution and solubility of LLC is slightly lower than that of the amorphous phase and about 20 times higher than that of Form II. RTV also self-assembles at the air/water interface as indicated by the decrease in surface tension of aqueous solutions. This behavior is similar to that of amphiphilic molecules that induce LLC formation.

Can role models boost entrepreneurial attitudes?

Science.gov (United States)

Fellnhofer, Katharina; Puumalainen, Kaisu

2017-01-01

This multi-country study used role models to boost perceptions of entrepreneurial feasibility and desirability. The results of a structural equation model based on a sample comprising 426 individuals who were primarily from Austria, Finland and Greece revealed a significant positive influence on perceived entrepreneurial desirability and feasibility. These findings support the argument for embedding entrepreneurial role models in entrepreneurship education courses to promote entrepreneurial activities. This direction is not only relevant for the academic community but also essential for nascent entrepreneurs, policymakers and society at large.

Mixed Lorentz boosted $Z^{0}'s$

CERN Document Server

Kjaer, N J

2001-01-01

A novel technique is proposed to study systematic errors on jet reconstruction in W physics measurements at LEP2 with high statistical precision. The method is based on the emulation of W pair events using Mixed Lorentz Boosted Z0 events. The scope and merits of the method and its statistical accuracy are discussed in the context of the DELPHI W mass measurement in the fully hadronic channel. The numbers presented are preliminary in the sense that they do not constitute the final DELPHI systematic errors.

Reconstruction of boosted $W^{\\pm}$ and $Z^{0}$ bosons from fat jets

CERN Document Server

Heinrich, Jochen Jens; Petersen, Troels Christian

We present the reconstruction of heavily boosted $W^{\\pm}$ and $Z^{0}$ bosons from large R-parameter jets (fat jets) in all-hadronic proton-proton collisions at $\\sqrt{s} = 8$ TeV at the LHC. The electroweak gauge bosons are boosted to a degree at which their hadronic decay products are collimated enough to be reconstructed as a single fat jet. A mass-drop filtering procedure which is validated in studies on Monte Carlo (MC) samples is then applied to the fat jets with $p_{T} > 420$ GeV to suppress pileup and soft radiation. $W^{\\pm}$ and $Z^{0}$ bosons are identified based on their filtered jet mass. The efficiency of common substructure observables and event shape variables, in distinguishing between signal and QCD background is evaluated on MC and the optimized observable selection used for the training of two boosted decision trees (BDT), in order to reduce the dijet background not originating from the decay of an electroweak gauge boson. For the first BDT, signal MC has been trained against background MC...

Modeling and Control of Primary Parallel Isolated Boost Converter

DEFF Research Database (Denmark)

Mira Albert, Maria del Carmen; Hernandez Botella, Juan Carlos; Sen, Gökhan

2012-01-01

In this paper state space modeling and closed loop controlled operation have been presented for primary parallel isolated boost converter (PPIBC) topology as a battery charging unit. Parasitic resistances have been included to have an accurate dynamic model. The accuracy of the model has been...

Novel process windows, part 1: Boosted micro process technology

NARCIS (Netherlands)

Hessel, V.; Wang, Q.

2011-01-01

Novel Process Windows (NPW) is the use of highly intensified, unusual and typically harsh process conditions to boost micro process technology and flow chemistry for the production of high-added value fine chemicals, pharmaceuticals, etc.. It is far from conventional processing and also from

Multi criteria decision making to select the best method for the preparation of solid lipid nanoparticles of rasagiline mesylate using analytic hierarchy process

Directory of Open Access Journals (Sweden)

Viveksarathi Kunasekaran

2014-01-01

Full Text Available The objective of this study was to select best method for the development of rasagiline mesylate (RM loaded nanoscale solid lipid particles using analytic hierarchy process (AHP. Improper method selection may lead to waste of time, loss of material and financial resources. One of the possibilities to overcome these difficulties, AHP was employed to find the suitable method. In the AHP, a decision of hierarchy was constructed with a goal, criteria, sub-criteria, and alternatives. After constructing the AHP, the expert choice software was used to compute the overall priority of criteria, sub-criteria and alternatives. The best alternative selected was based on the highest priority. Nanoscale solid lipid particles of RM was formulated by the selected microemulsion method (M4 and it shows the particle size, polydispersity index and zeta potential were within acceptable limits. Drug content and entrapment efficiency of the RM-solid lipid nanoparticles were 97.26% and 86.57%, respectively. This study concludes that the AHP was viable and effective tool for selecting a most suitable method for the fabrication of RM loaded nanoscale solid lipid particles.

Single stage buck-boost DC-AC neutral point clamped inverter

DEFF Research Database (Denmark)

Mo, Wei; Loh, Poh Chiang; Andrew, A.

2012-01-01

This paper proposes a new single stage buck-boost DC-AC neutral point clamped inverter topology which integrates the cascaded configurations of recently introduced inductor-capacitor-capacitor-transformer impedance source network (by Adamowicz) and classic NPC configuration. As a consequence......, it has enhanced buck-boost functionality and low output voltage distortions compared to the traditional Z-source inverter; it has continuous input current which reduces the source stress and inverter noise; it also contains two built-in capacitors which can block the DC current in the transformer...... windings thus preventing the core from saturation; lowers the voltage stresses and power losses of inverter switches and reduces the sizes of filtering devices and as well as obtains better output performance compared to the original two-level Z-source inverters. A phase disposition pulse width modulation...

Boosted $H\\rightarrow b \\bar{b}$ Tagger in Run II

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00394595; The ATLAS collaboration

2016-01-01

Many searches for Higgs bosons decaying to b quark pairs benefit from the increased Run II centre of mass energy by exploiting the large transverse momentum (boosted) Higgs boson regime, where the two b-jets are merged into one large radius jet. ATLAS uses a boosted $H \\rightarrow b\\bar{b}$ tagger algorithm to separate Higgs signal from background processes (QCD, W and Z bosons, top quarks). The tagger takes as input a large R=1.0 jet with calibrated pseudorapidity, energy and mass scale. It employs b-tagging, Higgs candidate mass, and substructure information. The performance of several operating points in Higgs boson signal, QCD and $t\\bar{t}$ all-hadronic backgrounds are presented. Systematic uncertainties are evaluated so that this tagger can be used in analyses.

Dosimetric comparison of the related parameters between simultaneous integrated boost intensity-modulated radiotherapy and sequential boost conformal radiotherapy for postoperative malignant glioma of the brain

International Nuclear Information System (INIS)

Shao Qian; Lu Jie; Li Jianbin; Sun Tao; Bai Tong; Liu Tonghai; Yin Yong

2011-01-01

Objective: To compare the dosimetric of different parameter of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) with sequential boost conformal radiotherapy (SB-CRT) for postoperative malignant glioma of the brain. Methods: Ten patients with malignant glioma of brain were selected to study. Each patient was simulated all by CT and MRI, and the imagings of CT and MRI were all sent to Pinnacle 3 planning system. The fusion technology with MR-CT imaging was used on Pinnacle 3 planning system. The target volume was delineated and defined based on MRI. The postoperative residual lesion and resection cavity were defined as gross tumor volume (GTV) and expanded GTV some scope was defined as clinical target volume (CTV). The margins of GTV expanded 10 mm and 25 mm were defined as CTV1 and CTV2 respectively. CTV1 and CTV2 all enlarged 5 mm were defined as PTV1 and PTV2 respectively. The plans of simultaneous integrated boost intensity-modulated radiotherapy and sequential boost conformal radiotherapy were respectively designed for each patient using Pinnacle 3 planning system and the dosimetric of different parameter was compared. The prescribe dose of SIB-IMRT was PTV1: 62.5 Gy/25 f, PTV2: 50.0 Gy/25 f; and SB-CRT was PTV1: 66.0 Gy/33 f, PTV2: 50.0 Gy/25 f. The dosimetries of different parameters of SIB-IMRT and SB-CRT were compared by using Paired-Samples T Test. Results: The maximum and mean dose of PTV1, PTV2, and brainstem were of significant difference (P 0.05). Conclusion: The SIB-IMRT plan is better than the SB-CRT plan. The CI and HI of SIB-IMRT are superior to SB-CRT. At the same time, it can preserve the important organs such as brainstem and reduce the mean dose of whole brain. On the other hand it can shorten the total period of therapy time. (authors)

Using Boosted Decision Trees to look for displaced Jets in the ATLAS Calorimeter

CERN Multimedia

CERN. Geneva

2017-01-01

A boosted decision tree is used to identify unique jets in a recently released conference note describing a search for long lived particles decaying to hadrons in the ATLAS Calorimeter. Neutral Long lived particles decaying to hadrons are “typical” signatures in a lot of models including Hidden Valley models, Higgs Portal Models, Baryogenesis, Stealth SUSY, etc. Long lived neutral particles that decay in the calorimeter leave behind an object that looks like a regular Standard Model jet, with subtle differences. For example, the later in the calorimeter it decays, the less energy will be deposited in the early layers of the calorimeter. Because the jet does not originate at the interaction point, it will likely be more narrow as reconstructed by the standard Anti-kT jet reconstruction algorithm used by ATLAS. To separate the jets due to neutral long lived decays from the standard model jets we used a boosted decision tree with thirteen variables as inputs. We used the information from the boosted decision...

Heterologous prime-boost vaccinations for poverty-related diseases: advantages and future prospects.

Science.gov (United States)

Radosević, Katarina; Rodriguez, Ariane; Lemckert, Angelique; Goudsmit, Jaap

2009-05-01

Classical vaccination approaches, based on a single vaccine administered in a homologous prime-boost schedule and optimized to induce primarily neutralizing antibodies, are unlikely to be sufficiently efficacious to prevent TB, malaria or HIV infections. Novel vaccines, capable of inducing a more powerful immune response, in particular T-cell immunity, are desperately needed. Combining different vaccine modalities that are able to complement each other and induce broad and sustainable immunity is a promising approach. This review provides an overview of heterologous prime-boost vaccination modalities currently in development for the 'big three' poverty-related diseases and emphasizes the need for innovative vaccination approaches.

Desarrollo tecnológico de una formulación de dihidroergotoxina mesilato 0,3 mg/mL inyectable Technological development of an injectable formulation of dihydroergotoxine mesylate 0.3 mg/mL

Directory of Open Access Journals (Sweden)

Anna Karelia Collado Coello

2008-08-01

Full Text Available Los vasodilatadores cerebrales y periféricos son un conjunto de medicamentos muy heterogéneo, que tienen en común la capacidad de producir vasodilatación cerebral o periférica por mecanismos muy diferentes.Dentro de ese grupo se encuentra el fármaco que le da razón a este artículo, la dihidroergotoxina mesilato el cual estimula el ritmo del electroencefalograma e incrementa la utilización de glucosa en el cerebro. Se desarrolló una formulación inyectable estéril compuesta por dihidroergotoxina mesilato polvo, y cantidad suficiente del vehículo acuoso envasada en ampolletas de 1 mL de capacidad. Se desarrolló y validó una técnica analítica por cromatografía líquida de alta resolución para estudiar la estabilidad de la formulación y determinar la fecha de vencimiento de esta. Se comprobó la calidad microbiológica de la preparación, y se logró un producto que cumple satisfactoriamente con todas las especificaciones establecidas para preparaciones estériles. La tecnología obtenida fue fácilmente escalable.Cerebral and peripheral vasodilators are a group of very heterogeneous drugs that have in common the capacity to produce cerebral or peripheral vasodilatation by different mechanisms. The drug that gave rise to this paper, dihydroergotoxine mesylate, is within this group. It stimulates the rhythm of the electroencephalogram and increases the utilization of glucose in the brain. A sterile injectable formulation composed of dihydroergotoxine mesylate powder and enough amount of aqueous vehicle was developed and bottled in ampoules of 1 mL. An analytical technique was developed and validated by high resolution liquid chromatography to study the stability of the formulation and to determine its expiration date. The quality of the microbiological preparation was proved, and a product that satisfactorily meets all the specifications established for sterile preparations was obtained. The technology obtained was easily scalable

3-D conformal treatment of prostate cancer to 74 Gy vs. high-dose-rate brachytherapy boost: A cross-sectional quality-of-life survey

Energy Technology Data Exchange (ETDEWEB)

Vordermark, Dirk [Univ. of Wuerzburg (DE). Dept. of Radiation Oncology] (and others)

2006-09-15

The effects of two modalities of dose-escalated radiotherapy on health-related quality of life (HRQOL) were compared. Forty-one consecutive patients were treated with a 3-D conformal (3-DC) boost to 74 Gy, and 43 with high-dose rate (HDR) brachytherapy boost (2x9 Gy), following 3-D conformal treatment to 46 Gy. Median age was 70 years in both groups, median initial PSA was 7.9 {mu}g/l in 3-DC boost patients and 8.1 {mu}g/l in HDR boost patients. Stage was 7 in 52% and 47%, respectively. HRQOL was assessed cross-sectionally using EORTC QLQ-C30 and organ-specific PR25 modules 3-32 (median 19) and 4-25 (median 14) months after treatment, respectively. Questionnaires were completed by 93% and 97% of patients, respectively. Diarrhea and insomnia scores were significantly increased in both groups. In the PR25 module, scores of 3-DC boost and HDR boost patients for urinary, bowel and treatment-related symptoms were similar. Among responders, 34% of 3-DC boost patients and 86% of HDR boost patients had severe erectile problems. Dose escalation in prostate cancer by either 3-DC boost to 74 Gy or HDR brachytherapy boost appears to result in similar HRQOL profiles.

Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.

Science.gov (United States)

Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

2006-08-01

Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

Simple grain mill boosts production and eases women's workload ...

International Development Research Centre (IDRC) Digital Library (Canada)

2013-01-11

Jan 11, 2013 ... Simple grain mill boosts production and eases women's workload ... Farmers also like the design because, unlike other machines, it can be easily adjusted for different millet varieties and sizes. ... Local manufacturing. Discussions have begun with local entrepreneurs to manufacture the grain mill, which ...

Award-winning machine boosts sorghum farming in Sudan | IDRC ...

International Development Research Centre (IDRC) Digital Library (Canada)

2016-04-28

Apr 28, 2016 ... Award-winning machine boosts sorghum farming in Sudan ... The new planter, developed by researchers at Sudan's Agricultural ... Senegal: Staying home at all costs ... This ICT4D article series features results from innovative research on participatory geographic information systems (P-GIS) in Africa.

Tricky treats: how and when temptations boost self-control

NARCIS (Netherlands)

Kroese, F.M.|info:eu-repo/dai/nl/313869871

2012-01-01

The overall aim of this dissertation was to explore how and when temptations boost self-control. More specifically, we aimed to a) replicate and extend previous findings showing that temptations yield enhanced self-control on cognitive as well as behavioral measures; b) examine the role of

A prediction model of short-term ionospheric foF2 based on AdaBoost

Science.gov (United States)

Zhao, Xiukuan; Ning, Baiqi; Liu, Libo; Song, Gangbing

2014-02-01

In this paper, the AdaBoost-BP algorithm is used to construct a new model to predict the critical frequency of the ionospheric F2-layer (foF2) one hour ahead. Different indices were used to characterize ionospheric diurnal and seasonal variations and their dependence on solar and geomagnetic activity. These indices, together with the current observed foF2 value, were input into the prediction model and the foF2 value at one hour ahead was output. We analyzed twenty-two years' foF2 data from nine ionosonde stations in the East-Asian sector in this work. The first eleven years' data were used as a training dataset and the second eleven years' data were used as a testing dataset. The results show that the performance of AdaBoost-BP is better than those of BP Neural Network (BPNN), Support Vector Regression (SVR) and the IRI model. For example, the AdaBoost-BP prediction absolute error of foF2 at Irkutsk station (a middle latitude station) is 0.32 MHz, which is better than 0.34 MHz from BPNN, 0.35 MHz from SVR and also significantly outperforms the IRI model whose absolute error is 0.64 MHz. Meanwhile, AdaBoost-BP prediction absolute error at Taipei station from the low latitude is 0.78 MHz, which is better than 0.81 MHz from BPNN, 0.81 MHz from SVR and 1.37 MHz from the IRI model. Finally, the variety characteristics of the AdaBoost-BP prediction error along with seasonal variation, solar activity and latitude variation were also discussed in the paper.

Hybrid Non-Isolated and Non Inverting Nx Interleaved DC-DC Multilevel Boost Converter for Renewable Energy Applications

DEFF Research Database (Denmark)

Bhaskar, Mahajan Sagar; Kulkarni, Rishi M.; Padmanaban, Sanjeevi Kumar

2016-01-01

In this paper hybrid non isolated/ non inverting Nx interleaved DC-DC multilevel Boost Converter for renewable energy applications is presented. The presented hybrid topology is derived from the conventional interleaved converter and the Nx Multilevel boost converter. In renewable energy...... applications, generated energy cannot be directly used at application end. In most of the cases it needs to be stepped up with DC-DC converter at operating voltage levels as per the requirement of the application. Though conventional boost converter can theoretically be used for this purpose, but obtaining...

Subcellular distribution of [3H]-dexamethasone mesylate binding sites in Leydig cells using electron microscope radioautography

International Nuclear Information System (INIS)

Stalker, A.; Hermo, L.; Antakly, T.

1991-01-01

The present view is that glucocorticoid hormones bind to their cytoplasmic receptors before reaching their nuclear target sites, which include specific DNA sequences. Although it is believed that cytoplasmic sequestration of steroid receptors and other transcription factors (such as NFKB) may regulate the overall activity of these factors, there is little information on the exact subcellular sites of steroid receptors or even of any other transcription factors. Tritiated (3H)-dexamethasone 21-mesylate (DM) is an affinity label that binds covalently to the glucocorticoid receptor (GR), thereby allowing morphological localization of the receptor at the light and electron microscope levels as well as for quantitative radioautographic (RAG) analysis. After injection of 3H-DM into the testis, a specific radioautographic signal was observed in Leydig cells, which correlated with a high level of immunocytochemically demonstrable GR in these cells at the light-microscope level. To localize the 3H-DM binding sites at the electron microscope (EM) level, the testes of 5 experimental and 3 control adrenalectomized rats were injected directly with 20 microCi 3H-DM; control rats received simultaneously a 25-fold excess of unlabeled dexamethasone; 15 min later, rats were fixed with glutaraldehyde and the tissue was processed for EM RAG analysis combined with quantitative morphometry. The radioautographs showed that the cytosol, nucleus, smooth endoplasmic reticulum (sER), and mitochondria were labeled. Since the cytosol was always adjacent to tubules of the sER, the term sER-rich cytosol was used to represent label over sER networks, which may also represent cytosol labeling due to the limited resolution of the radioautographic technique. Labeling was highest in sER-rich cytosol and mitochondria, at 53% and 31% of the total, respectively

In vitro inhibitory effects of imatinib mesylate on stromal cells and hematopoietic progenitors from bone marrow

Directory of Open Access Journals (Sweden)

P.B. Soares

2013-01-01

Full Text Available Imatinib mesylate (IM is used to treat chronic myeloid leukemia (CML because it selectively inhibits tyrosine kinase, which is a hallmark of CML oncogenesis. Recent studies have shown that IM inhibits the growth of several non-malignant hematopoietic and fibroblast cells from bone marrow (BM. The aim of the present study was to evaluate the effects of IM on stromal and hematopoietic progenitor cells, specifically in the colony-forming units of granulocyte/macrophage (CFU-GM, using BM cultures from 108 1.5- to 2-month-old healthy Swiss mice. The results showed that low concentrations of IM (1.25 µM reduced the growth of CFU-GM in clonogenic assays. In culture assays with stromal cells, fibroblast proliferation and α-SMA expression by immunocytochemistry analysis were also reduced in a concentration-dependent manner, with a survival rate of approximately 50% with a dose of 2.5 µM. Cell viability and morphology were analyzed using MTT and staining with acrydine orange/ethidium bromide. Most cells were found to be viable after treatment with 5 µM IM, although there was gradual growth inhibition of fibroblastic cells while the number of round cells (macrophage-like cells increased. At higher concentrations (15 µM, the majority of cells were apoptotic and cell growth ceased completely. Oil red staining revealed the presence of adipocytes only in untreated cells (control. Cell cycle analysis of stromal cells by flow cytometry showed a blockade at the G0/G1 phases in groups treated with 5-15 µM. These results suggest that IM differentially inhibits the survival of different types of BM cells since toxic effects were achieved.

The Role of Concomitant Radiation Boost in Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

Science.gov (United States)

Badakhshi, Harun; Ismail, Mahmoud; Boskos, Christos; Zhao, Kuaile; Kaul, David

2017-06-01

This study analyzed the impact of concomitant boost on long-term clinical outcomes in locally advanced rectal cancer. A total of 141 patients (median age=61 years) were treated with neoadjuvant chemoradiotherapy. Median total dose was 50.4 Gy. Forty-three patients received a concomitant boost. Concurrent chemotherapy consisted of 5-fluorouracil (5-FU), given as a 24-h continuous infusion. Mean follow-up was 83.7 months. The 3, 5-, and 10-year overall survival (OS) rates were 91.9%, 84.6%, and 52.9%, respectively. Recurrence-free survival (RFS) rates at 3, 5, and 10 years were 91.4%, 88.9%, and 79.3%, respectively. Metastasis-free survival (MFS) rates at 3, 5, and 10 years were 84.6%, 75.4%, and 49.9%, respectively. Overall, 9.9% of all patients achieved pathological complete response. Down-staging of T- or N-stage was achieved in 55.1% and 41.5% of patients. Multivariate analysis revealed that female sex (p=0.011), concomitant boost-radiotherapy (p=0.014), and the presence of fewer than five positive lymph nodes (prectal cancer in terms of local outcomes. Intensified radiotherapy using a concomitant boost has a positive effect on OS. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Urban Link Travel Time Prediction Based on a Gradient Boosting Method Considering Spatiotemporal Correlations

Directory of Open Access Journals (Sweden)

Faming Zhang

2016-11-01

Full Text Available The prediction of travel times is challenging because of the sparseness of real-time traffic data and the intrinsic uncertainty of travel on congested urban road networks. We propose a new gradient–boosted regression tree method to accurately predict travel times. This model accounts for spatiotemporal correlations extracted from historical and real-time traffic data for adjacent and target links. This method can deliver high prediction accuracy by combining simple regression trees with poor performance. It corrects the error found in existing models for improved prediction accuracy. Our spatiotemporal gradient–boosted regression tree model was verified in experiments. The training data were obtained from big data reflecting historic traffic conditions collected by probe vehicles in Wuhan from January to May 2014. Real-time data were extracted from 11 weeks of GPS records collected in Wuhan from 5 May 2014 to 20 July 2014. Based on these data, we predicted link travel time for the period from 21 July 2014 to 25 July 2014. Experiments showed that our proposed spatiotemporal gradient–boosted regression tree model obtained better results than gradient boosting, random forest, or autoregressive integrated moving average approaches. Furthermore, these results indicate the advantages of our model for urban link travel time prediction.

Malampaya to boost flow of foreign investment

International Nuclear Information System (INIS)

Skrebowski, C.

1995-01-01

The petroleum industry in the Philippines has recently enjoyed a boost with the commissioning of a new modern refinery, and the development of sophisticated off-shore technology in the Malampaya/Camago oil and gas field. The foreign investment, which has made these initiatives possible, came about because of the countries new found political stability. It also reflects the rapid economic growth which has occurred and the accompanying increase in energy demand. (UK)

Study of an innovative ejector heat pump-boosted district heating system

International Nuclear Information System (INIS)

Zhang, Bo; Wang, Yuanchao; Kang, Lisha; Lv, Jinsheng

2013-01-01

An Ejector heat pump-boosted District Heating (EDH) system is proposed to improve the heating capacity of existing district heating systems with Combined Heat and Power (CHP). In the EDH, two ejector heat pumps are installed: a primary heat pump (HP 1 ) at the heating station and a secondary heat pump (HP 2 ) at the heating substation. With the EDH, the low-grade waste heat from circulating cooling water in the CHP is recycled and the temperature difference between the water supply and the return of the primary heating network is increased. A thermodynamic model was provided. An experimental study was carried out for both HP 1 and HP 2 to verify the predicting performance. The results show that the COP of HP 1 can reach 1.5–1.9, and the return water temperature of the primary heating network could be decreased to 35 °C with HP 2 . A typical case study for the EDH was analyzed. -- Highlights: • An ejector heat pump-boosted district heating (EDH) is proposed. • The 1st ejector heat pump in EDH recycles heat from cooling water of the CHP. • The 2nd ejector heat pump in EDH boosts the thermal energy utilization of the primary heating network. • Modeling and experimental studies are presented

Dose analysis of boost irradiation of parapharyngeal space in nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Wu, V.W.C.

2000-01-01

Parapharyngeal space (PPS) is one of the common spreads of nasopharyngeal carcinoma (NPC). Since early eighties boost treatment has been routinely given to patients with PPS involvement. The use of oblique facio-cervical field in this treatment posed difficulty in assessing the dose distribution before the 3-D computer systems are available. This study evaluated the variations of dose distribution by different boost techniques on fifteen patients with PPS involvement using 3-D computer planning system. Comparisons were made between different radiation types, photon energies and modes of collimation respectively. Results showed that the dose distributions in the boost treatment were acceptable, as they did not bring the total doses of the normal structures exceeding their tolerance. There was little difference between 6 and 10 MV photons, but significant differences were found between photon and electron beams. Photon beams were better than the electron beams in giving lower doses to the spinal cord and the TM joint with more homogeneous dose to the target volume, whereas electron beams gave better sparing of the lens and temporal lobe. For the photon beams, half-blocked beam was superior to symmetrical beam in reducing the brain stem dose, but there was no advantage to the rest of normal structures. Copyright (1999) Australian Institute of Radiography

A 1 MEGAWATT POLYPHASE BOOST CONVERTER-MODULATOR FOR KLYSTRON PULSE APPLICATION

International Nuclear Information System (INIS)

Reass, W.A.; Doss, J.D.; Gribble, R.F.

2001-01-01

This paper describes electrical design criteria and first operational results a 140 kV, 1 MW average, 11 MW peak, zero-voltage-switching 20 kHz polyphase bridge, boost converter/modulator for klystron pulse application. The DC-DC converter derives the buss voltages from a standard 13.8 kV to 2300 Y substation cast-core transformer. Energy storage and filtering is provided by self-clearing metallized hazy polypropylene traction capacitors. Three ''H-Bridge'' Insulated Gate Bipolar Transistor (IGBT) switching networks are used to generate the polyphase 20 kHz transformer primary drive waveforms. The 20 kHz drive waveforms are chirped the appropriate duration to generate the desired klystron pulse width. PWM (pulse width modulation) of the individual 20 kHz pulses is utilized to provide regulated output waveforms with adaptive feedforward and feedback techniques. The boost transformer design utilizes amorphous nanocrystalline material that provides the required low core loss at design flux levels and switching frequencies. Resonant shunt-peaking is used on the transformer secondary to boost output voltage and resonate transformer leakage inductance. With the appropriate transformer leakage inductance and peaking capacitance, zero-voltage-switching of the IGBT's is attained, minimizing switching losses. A review of these design parameters and the first results of the performance characteristics will be presented

Thermal Performance and Efficiency Investigation of Conventional Boost, Z-source and Y-source Converters

DEFF Research Database (Denmark)

Gadalla, Brwene Salah Abdelkarim; Schaltz, Erik; Siwakoti, Yam Prasad

2016-01-01

Boost converters are needed in many applications that require the output voltage to be higher than the input voltage. Recently, boost type converters have been attracted by the industrial applications, and hence it has become an extremely hot topic of research. Recently, many researchers proposed...... the impedance source converters with their unique advantages as having a high voltage gain in a small range of duty cycle ratio. However, the thermal behaviour of the semiconductor devices and passive elements in the impedance source converter is an important issue from a reliability point of view and has...... not been investigated yet. Therefore this paper presents a comparison between the conventional boost, the Z-source, and the Y-source converters based on the thermal evaluation of semiconductors. In addition, the three topologies are also compared with respect to their efficiency. The operational principle...

Characterisation of moisture uptake effects on the glass transitional behaviour of an amorphous drug using modulated temperature DSC.

Science.gov (United States)

Royall, P G; Craig, D Q; Doherty, C

1999-12-01

The purpose of this study was to investigate the depression of the glass transition temperature, T(g), of the protease inhibitor saquinavir in the first heating scan as a function of the quantity of sorbed water by the application of modulated temperature differential scanning calorimetry (MTDSC). Samples of amorphous saquinavir were pretreated under various humidity conditions and the quantity of sorbed water measured by thermogravimetric analysis. MTDSC runs were performed using hermetically and non-hermetically sealed pans in order to determine the glass transition temperature. MTDSC allowed the separation of the glass transition from the enthalpic relaxation, thereby allowing clear visualisation of T(g) for amorphous saquinavir in the first heating scan. The plasticizing effects of water were assessed, with the depression in T(g) related to the mole fraction of water sorbed via the Gordon-Taylor relationship. An expression has been derived which allows estimation of the water content which lowers the T(g) to the storage temperature, thereby considerably increasing the risk of recrystallisation. It is argued that this model may aid prediction of the optimal storage conditions for amorphous drugs.

Five-Level Current-Source Inverters With Buck–Boost and Inductive-Current Balancing Capabilities

DEFF Research Database (Denmark)

Gao, Feng; Loh, Poh Chiang; Blaabjerg, Frede

2010-01-01

This paper presents new five-level current-source inverters (CSIs) with voltage/current buck–boost capability, unlike existing five-level CSIs where only voltage–boost operation is supported. The proposed inverters attain self-inductive-currentbalancing per switching cycle at their dc front ends...... without having to include additional balancing hardware or complex control manipulation. The inverters can conveniently be controlled by using the well-established phase-shifted carrier modulation scheme with only two additional linear references and a mapping logic table needed. Existing modulators can...

A new DC/AC boost transformerless converter in application of photovoltaic power generation

DEFF Research Database (Denmark)

Wei, Mo; Loh, Poh Chiang; Blaabjerg, Frede

2011-01-01

This paper presents a new DC/AC boost transformerless converter in the applications of photovoltaic (PV) power generation. A new circuit topology of single phase full bridge power inverter with additional DC/DC boost stage is proposed. The proposed topology overcomes two commonly existing......, and then converts the DC into AC to supply the load. A special modulation technique is proposed to eliminate the leakage current which is commonly presents in PV transformerless power generation, helps to increase the system efficiency and output performance....

Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness two years after treatment with Ombitasvir/Paritaprevir/Ritonavir ±Dasabuvir ±Ribavirin in the AMBER, real-world experience study.

Science.gov (United States)

Flisiak, Robert; Janczewska, Ewa; Łucejko, Mariusz; Karpińska, Ewa; Zarębska-Michaluk, Dorota; Nazzal, Khalil; Bolewska, Beata; Białkowska, Jolanta; Berak, Hanna; Fleischer-Stępniewska, Katarzyna; Tomasiewicz, Krzysztof; Karwowska, Kornelia; Simon, Krzysztof; Piekarska, Anna; Tronina, Olga; Tuchendler, Ewelina; Garlicki, Aleksander

2018-06-11

We followed for 2 years patients treated with Direct Acting Agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction of liver stiffness (LS), and risk of hepatocellular carcinoma (HCC).The study included patients from 16 hepatologic centers involved in the AMBER, investigators initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of Ombitasvir/Paritaprevir/ritonavir±Dasabuvir±Ribavirin. A total of 204 patients among 209 from the primary study were enrolled; 200 with available testing at 2 years follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 non-responders retreated). During 2yFU 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses was lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, two-years follow-up confirmed durability of virologic response after treatment of HCV infection with Ombitasvir/Paritaprevir/ritonavir±Dasabuvir±Ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics, that support the need for longer than 2-year monitoring for possible disease progression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Automated Detection of Driver Fatigue Based on AdaBoost Classifier with EEG Signals

Directory of Open Access Journals (Sweden)

Jianfeng Hu

2017-08-01

Full Text Available Purpose: Driving fatigue has become one of the important causes of road accidents, there are many researches to analyze driver fatigue. EEG is becoming increasingly useful in the measuring fatigue state. Manual interpretation of EEG signals is impossible, so an effective method for automatic detection of EEG signals is crucial needed.Method: In order to evaluate the complex, unstable, and non-linear characteristics of EEG signals, four feature sets were computed from EEG signals, in which fuzzy entropy (FE, sample entropy (SE, approximate Entropy (AE, spectral entropy (PE, and combined entropies (FE + SE + AE + PE were included. All these feature sets were used as the input vectors of AdaBoost classifier, a boosting method which is fast and highly accurate. To assess our method, several experiments including parameter setting and classifier comparison were conducted on 28 subjects. For comparison, Decision Trees (DT, Support Vector Machine (SVM and Naive Bayes (NB classifiers are used.Results: The proposed method (combination of FE and AdaBoost yields superior performance than other schemes. Using FE feature extractor, AdaBoost achieves improved area (AUC under the receiver operating curve of 0.994, error rate (ERR of 0.024, Precision of 0.969, Recall of 0.984, F1 score of 0.976, and Matthews correlation coefficient (MCC of 0.952, compared to SVM (ERR at 0.035, Precision of 0.957, Recall of 0.974, F1 score of 0.966, and MCC of 0.930 with AUC of 0.990, DT (ERR at 0.142, Precision of 0.857, Recall of 0.859, F1 score of 0.966, and MCC of 0.716 with AUC of 0.916 and NB (ERR at 0.405, Precision of 0.646, Recall of 0.434, F1 score of 0.519, and MCC of 0.203 with AUC of 0.606. It shows that the FE feature set and combined feature set outperform other feature sets. AdaBoost seems to have better robustness against changes of ratio of test samples for all samples and number of subjects, which might therefore aid in the real-time detection of driver

Congress OKs $2 Billion Boost for the NIH.

Science.gov (United States)

2017-07-01

President Donald Trump last week signed a $1.1 trillion spending bill for fiscal year 2017, including a welcome $2 billion boost for the NIH that will support former Vice President Joe Biden's Cancer Moonshot initiative, among other priorities. However, researchers who rely heavily on NIH grant funding remain concerned about proposed cuts for 2018. ©2017 American Association for Cancer Research.

Effects of hyperbolic rotation in Minkowski space on the modeling of plasma accelerators in a Lorentz boosted frame

International Nuclear Information System (INIS)

Vay, J.-L.; Geddes, C. G. R.; Cormier-Michel, E.; Grote, D. P.

2011-01-01

The effects of hyperbolic rotation in Minkowski space resulting from the use of Lorentz boosted frames of calculation on laser propagation in plasmas are analyzed. Selection of a boost frame at the laser group velocity is shown to alter the laser spectrum, allowing the use of higher boost velocities. The technique is applied to simulations of laser driven plasma wakefield accelerators, which promise much smaller machines and whose development requires detailed simulations that challenge or exceed current capabilities. Speedups approaching the theoretical optima are demonstrated, producing the first direct simulations of stages up to 1 TeV. This is made possible by a million times speedup thanks to a frame boost with a relativistic factor γ b as high as 1300, taking advantage of the rotation to mitigate an instability that limited previous work.

Study Of Boosted W-Jets And Higgs-Jets With the SiFCC Detector

Energy Technology Data Exchange (ETDEWEB)

Yu, Shin-Shan [Taiwan, Natl. Central U.; Chekanov, Sergei [Argonne; Gray, Lindsey [Fermilab; Kotwal, Ashutosh [Duke U.; Sen, Sourav [Duke U.; Tran, Nhan Viet [Fermilab

2016-11-04

We study the detector performance in the reconstruction of hadronically-decaying W bosons and Higgs bosons at very high energy proton colliders using a full GEANT4 simulation of the SiFCC detector. The W and Higgs bosons carry transverse momentum in the multi-TeV range, which results in collimated decay products that are reconstructed as a single jet. We present a measurement of the energy response and resolution of boosted W-jets and Higgs-jets and show the separation of two sub-jets within the boosted boson jet.

Advanced Airfoils Boost Helicopter Performance

Science.gov (United States)

2007-01-01

Carson Helicopters Inc. licensed the Langley RC4 series of airfoils in 1993 to develop a replacement main rotor blade for their Sikorsky S-61 helicopters. The company's fleet of S-61 helicopters has been rebuilt to include Langley's patented airfoil design, and the helicopters are now able to carry heavier loads and fly faster and farther, and the main rotor blades have twice the previous service life. In aerial firefighting, the performance-boosting airfoils have helped the U.S. Department of Agriculture's Forest Service control the spread of wildfires. In 2003, Carson Helicopters signed a contract with Ducommun AeroStructures Inc., to manufacture the composite blades for Carson Helicopters to sell

ATLAS boosted object tagging 2

CERN Document Server

Caudron, Julien; The ATLAS collaboration

2015-01-01

A detailed study into the optimal techniques for identifying boosted hadronically decaying W or Z bosons is presented. Various algorithms for reconstructing, grooming and tagging bosonic jets are compared for W bosons with a wide range of transverse momenta using 8 TeV data and 8 TeV and 13 TeV MC simulations. In addition, given that a hadronic jet has been identified as resulting from the hadronic decay of a W or Z, a technique is developed to discriminate between W and Z bosons. The modeling of the tagging variables used in this technique is studied using 8 TeV pp collision data and systematic uncertainties for the tagger efficiency and fake rates are evaluated.

Photovoltaic optimizer boost converters: Temperature influence and electro-thermal design

International Nuclear Information System (INIS)

Graditi, G.; Adinolfi, G.; Tina, G.M.

2014-01-01

Highlights: • The influence of temperature on DC–DC converter devices properties is considered. • An electro-thermal design method for PV power optimizer converters is proposed. • The electro-thermal design method proposed is applied to DR boost and SR boost. • Efficiency results of the designed SR converter and DR converters are presented. - Abstract: Objective: Photovoltaic (PV) systems can operate in presence of not uniform working conditions caused by continuously changing temperature and irradiance values and mismatching and shadowing phenomena. The more the PV system works in these conditions, the more its energy performances are negatively affected. Distributed Maximum Power Point Tracking (DMPPT) converters are now increasingly used to overcome this problem and to improve PV applications efficiency. A DMPPT system consists in a DC–DC converters equipped with a suitable controller dedicated to the Maximum Power Point Tracking (MPPT) of a single PV module. It is arranged either inside the junction-box or in a separate box close to the PV generator. Many power optimizers are now commercially available. In spite of different adopted DC–DC converter topologies, the shared interests of DMPPT systems designers are the high efficiency and reliability values. It is worth noting that to obtain so high performances converters, electronic components have to be carefully selected between the whole commercial availability and appropriately matched together. In this scenario, an electro-thermal design methodology is proposed and a reliability study by means of the Military Handbook 217F is carried out. Method: The developed DMPPT converters design method is constituted by many steps. In fact, beginning from installation site, PV generators and load data, this process selects power optimizers commercially available devices and it verifies their electro-thermal behavior to the aim to identify a set of suitable components for DMPPT applications. Repeating this

Designing signal-enriched triggers for boosted jets.

CERN Document Server

Toumazou, Marina

2017-01-01

Triggers designed to favour the selection of hadronically decaying massive particles have been studied. Both triggers using solely ET and mass cuts (similar to new 2017 triggers) and triggers exploiting polarization information have been studied. The mass cut triggers show substantial gains in rate reduction, while the benefits of polarization triggers are less obvious. The final conclusion is that it is more useful to identify and trigger on generic boosted decays, irrespective of the polarization of the decaying particle

ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer

International Nuclear Information System (INIS)

Rodda, Sree; Tyldesley, Scott; Morris, W. James; Keyes, Mira; Halperin, Ross; Pai, Howard; McKenzie, Michael; Duncan, Graeme; Morton, Gerard; Hamm, Jeremy; Murray, Nevin

2017-01-01

Purpose: To report the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer. Methods and Materials: ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) enrolled 398 men, median age 68 years, who were then randomized to either a standard arm that included 12 months of androgen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic visits, investigators recorded GU and GI morbidity and information on urinary continence, catheter use, and erectile function. Exclusion of 15 who received nonprotocol treatment and correction of 14 crossover events left 195 men who actually received a DE-EBRT boost and 188, an LDR-PB boost. Median follow-up was 6.5 years. Results: The LDR-PB boost increased the risk of needing temporary catheterization and/or requiring incontinence pads. At 5 years the cumulative incidence of grade 3 GU events was 18.4% for LDR-PB, versus 5.2% for DE-EBRT (P<.001). Compared with the cumulative incidence, the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms (8.6% vs 2.2%, P=.058). The 5-year cumulative incidence of grade 3 GI events was 8.1% for LDR-PB, versus 3.2% for DE-EBRT (P=.124). The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms (1.0% vs 2.2%, respectively). Among men reporting adequate baseline erections, 45% of LDR-PB patients reported similar erectile function at 5 years, versus 37% after DE-EBRT (P=.30). Conclusions: The incidence of acute and late GU morbidity was higher after LDR-PB boost, and there was a nonsignificant trend for worse GI morbidity. No differences in the frequency of

ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Rodda, Sree [British Columbia (BC) Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); Tyldesley, Scott [British Columbia (BC) Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Morris, W. James, E-mail: jmorris@bccancer.bc.ca [British Columbia (BC) Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Keyes, Mira [British Columbia (BC) Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Halperin, Ross [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency, Centre for the Southern Interior, Kelowna, British Columbia (Canada); Pai, Howard [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency, Vancouver Island Centre, Victoria, British Columbia (Canada); McKenzie, Michael; Duncan, Graeme [British Columbia (BC) Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Morton, Gerard [Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Hamm, Jeremy [Department of Population Oncology, BC Cancer Agency, Vancouver, British Columbia (Canada); Murray, Nevin [British Columbia (BC) Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); Department of Medicine, University of British Columbia, Vancouver, British Columbia (Canada)

2017-06-01

Purpose: To report the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer. Methods and Materials: ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) enrolled 398 men, median age 68 years, who were then randomized to either a standard arm that included 12 months of androgen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic visits, investigators recorded GU and GI morbidity and information on urinary continence, catheter use, and erectile function. Exclusion of 15 who received nonprotocol treatment and correction of 14 crossover events left 195 men who actually received a DE-EBRT boost and 188, an LDR-PB boost. Median follow-up was 6.5 years. Results: The LDR-PB boost increased the risk of needing temporary catheterization and/or requiring incontinence pads. At 5 years the cumulative incidence of grade 3 GU events was 18.4% for LDR-PB, versus 5.2% for DE-EBRT (P<.001). Compared with the cumulative incidence, the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms (8.6% vs 2.2%, P=.058). The 5-year cumulative incidence of grade 3 GI events was 8.1% for LDR-PB, versus 3.2% for DE-EBRT (P=.124). The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms (1.0% vs 2.2%, respectively). Among men reporting adequate baseline erections, 45% of LDR-PB patients reported similar erectile function at 5 years, versus 37% after DE-EBRT (P=.30). Conclusions: The incidence of acute and late GU morbidity was higher after LDR-PB boost, and there was a nonsignificant trend for worse GI morbidity. No differences in the frequency of

Glucose starvation boosts Entamoeba histolytica virulence.

Directory of Open Access Journals (Sweden)

Ayala Tovy

2011-08-01

Full Text Available The unicellular parasite, Entamoeba histolytica, is exposed to numerous adverse conditions, such as nutrient deprivation, during its life cycle stages in the human host. In the present study, we examined whether the parasite virulence could be influenced by glucose starvation (GS. The migratory behaviour of the parasite and its capability to kill mammalian cells and to lyse erythrocytes is strongly enhanced following GS. In order to gain insights into the mechanism underlying the GS boosting effects on virulence, we analyzed differences in protein expression levels in control and glucose-starved trophozoites, by quantitative proteomic analysis. We observed that upstream regulatory element 3-binding protein (URE3-BP, a transcription factor that modulates E.histolytica virulence, and the lysine-rich protein 1 (KRiP1 which is induced during liver abscess development, are upregulated by GS. We also analyzed E. histolytica membrane fractions and noticed that the Gal/GalNAc lectin light subunit LgL1 is up-regulated by GS. Surprisingly, amoebapore A (Ap-A and cysteine proteinase A5 (CP-A5, two important E. histolytica virulence factors, were strongly down-regulated by GS. While the boosting effect of GS on E. histolytica virulence was conserved in strains silenced for Ap-A and CP-A5, it was lost in LgL1 and in KRiP1 down-regulated strains. These data emphasize the unexpected role of GS in the modulation of E.histolytica virulence and the involvement of KRiP1 and Lgl1 in this phenomenon.

Higher-Order Hybrid Gaussian Kernel in Meshsize Boosting Algorithm

African Journals Online (AJOL)

In this paper, we shall use higher-order hybrid Gaussian kernel in a meshsize boosting algorithm in kernel density estimation. Bias reduction is guaranteed in this scheme like other existing schemes but uses the higher-order hybrid Gaussian kernel instead of the regular fixed kernels. A numerical verification of this scheme ...

Adaptive Kernel In The Bootstrap Boosting Algorithm In KDE ...

African Journals Online (AJOL)

This paper proposes the use of adaptive kernel in a bootstrap boosting algorithm in kernel density estimation. The algorithm is a bias reduction scheme like other existing schemes but uses adaptive kernel instead of the regular fixed kernels. An empirical study for this scheme is conducted and the findings are comparatively ...

FULL ELECTROMAGNETIC SIMULATION OF COHERENT SYNCHROTRON RADIATION VIA THE LORENTZ-BOOSTED FRAME APPROACH

International Nuclear Information System (INIS)

Fawley, William M.; Vay, Jean-Luc

2010-01-01

Numerical simulation of some systems containing charged particles with highly relativistic directed motion can by speeded up by orders of magnitude by choice of the proper Lorentz-boosted frame. Orders of magnitude speedup has been demonstrated for simulations from first principles of laser-plasma accelerator, free electron laser, and particle beams interacting with electron clouds. Here we address the application of the Lorentz-boosted frame approach to coherent synchrotron radiation (CSR), which can be strongly present in bunch compressor chicanes. CSR is particularly relevant to the next generation of x-ray light sources and is simultaneously difficult to simulate in the lab frame because of the large ratio of scale lengths. It can increase both the incoherent and coherent longitudinal energy spread, effects that often lead to an increase in transverse emittance. We have adapted the WARP code to simulate CSR emission along a simple dipole bend. We present some scaling arguments for the possible computational speed up factor in the boosted frame and initial 3D simulation results.

Cura Annonae-Chemically Boosting Crop Yields Through Metabolic Feeding of a Plant Signaling Precursor.

Science.gov (United States)

Vocadlo, David J

2017-05-22

The cream of the crop: With the world facing a projected shortfall of crops by 2050, new approaches are needed to boost crop yields. Metabolic feeding of plants with photocaged trehalose-6-phosphate (Tre6P) can increase levels of the signaling metabolite Tre6P in the plant. Reprogramming of cellular metabolism by Tre6P stimulates a program of plant growth and enhanced crop yields, while boosting starch content. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Integrated Current Balancing Transformer for Primary Parallel Isolated Boost Converter

DEFF Research Database (Denmark)

Sen, Gökhan; Ouyang, Ziwei; Thomsen, Ole Cornelius

2011-01-01

A simple, PCB compatible integrated solution is proposed for the current balancing requirement of the primary parallel isolated boost converter (PPIBC). Input inductor and the current balancing transformer are merged into the same core, which reduces the number of components allowing a cheaper...

Boosting capacitive blue-energy and desalination devices with waste heat

NARCIS (Netherlands)

Janssen, Mathijs; Härtel, Andreas; Van Roij, René

2014-01-01

We show that sustainably harvesting "blue" energy from the spontaneous mixing process of fresh and salty water can be boosted by varying the water temperature during a capacitive mixing process. Our modified Poisson-Boltzmann calculations predict a strong temperature dependence of the electrostatic

Intraoperative HDR implant boost for breast cancer (preliminary results)

International Nuclear Information System (INIS)

Rodriguez, I.; Torre, M. de la; Gonzalez, E.; Bourel, V.

1996-01-01

Introduction: In spite of the fact that it is been discussed whether or not a boost is necessary for all conservative treated breast cancer patients, it is a generalized radiotherapy practice. Since september 1993 we developed a breast conservative protocol for early stage breast cancer (T1-T2) with intraoperative HDR implant boost. Side effects, cosmetic results and recurrence rates are reviewed. Method and Material: From September 1993 we treated 55 patients with intraoperative HDR implant boost to the lumpectomy site for clinical T1 or T2 invasive breast cancer, followed by external megavoltage radiotherapy to the entire breast. We used the Nucletron microselectron HDR remote afterloading system with flexible implant tubes. The geometric distribution of the tubes was performed according to the 'Paris' configuration. Each implant was evaluated by calculating the dose-volume natural histograms. The HDR fractionation schedule consists of three fractions of 4.5Gy each given at least 48 hs apart, and starting between 48-72hs from surgical procedure. The external radiotherapy to the entire breast started one week after the completion of brachytherapy, using conventional fractionation of 5 fractions per week, 1,8Gy per fraction up to 45-50Gy. Results: So far there is not any local recurrence, but medium follow up is only 18 months. We did not observe any acute damage and the cosmetic outcome was 60% excellent, 30% good and 10% acceptable. Two patients developed localized fibrosis, in both the implant involved the submamary fold. Conclusion: The intraoperative implant is the most accurate way to localize the lumpectomy site, to define the target volume, decrease the total treatment time and avoid a second anesthetic procedure without delaying the inpatient time or the initial wound healing process

Early Boost and Slow Consolidation in Motor Skill Learning

Science.gov (United States)

Hotermans, Christophe; Peigneux, Philippe; de Noordhout, Alain Maertens; Moonen, Gustave; Maquet, Pierre

2006-01-01

Motor skill learning is a dynamic process that continues covertly after training has ended and eventually leads to delayed increments in performance. Current theories suggest that this off-line improvement takes time and appears only after several hours. Here we show an early transient and short-lived boost in performance, emerging as early as…

Boosting food security in sub-Saharan Africa through cassava ...

African Journals Online (AJOL)

Boosting food security in sub-Saharan Africa through cassava production: a case study of Nigeria. ... Nigerian Journal of Economic History ... The paper argues that cassava which is widely grown in Sub-Saharan Africa with a lot of variety of food derivatives from it can reduce to the barest minimum the present state of food ...

Boosting long-term memory via wakeful rest: intentional rehearsal is not necessary, consolidation is sufficient.

Science.gov (United States)

Dewar, Michaela; Alber, Jessica; Cowan, Nelson; Della Sala, Sergio

2014-01-01

People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as 'foreign names in a bridge club abroad' and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is not dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is sufficient for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.

Comparison of three boosting methods in parent-offspring trios for genotype imputation using simulation study

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Abbas Mikhchi

2016-01-01

Full Text Available Abstract Background Genotype imputation is an important process of predicting unknown genotypes, which uses reference population with dense genotypes to predict missing genotypes for both human and animal genetic variations at a low cost. Machine learning methods specially boosting methods have been used in genetic studies to explore the underlying genetic profile of disease and build models capable of predicting missing values of a marker. Methods In this study strategies and factors affecting the imputation accuracy of parent-offspring trios compared from lower-density SNP panels (5 K to high density (10 K SNP panel using three different Boosting methods namely TotalBoost (TB, LogitBoost (LB and AdaBoost (AB. The methods employed using simulated data to impute the un-typed SNPs in parent-offspring trios. Four different datasets of G1 (100 trios with 5 k SNPs, G2 (100 trios with 10 k SNPs, G3 (500 trios with 5 k SNPs, and G4 (500 trio with 10 k SNPs were simulated. In four datasets all parents were genotyped completely, and offspring genotyped with a lower density panel. Results Comparison of the three methods for imputation showed that the LB outperformed AB and TB for imputation accuracy. The time of computation were different between methods. The AB was the fastest algorithm. The higher SNP densities resulted the increase of the accuracy of imputation. Larger trios (i.e. 500 was better for performance of LB and TB. Conclusions The conclusion is that the three methods do well in terms of imputation accuracy also the dense chip is recommended for imputation of parent-offspring trios.

EORTC 22972-26991/MRC BR10 trial: Fractionated stereotactic boost following conventional radiotherapy of high grade gliomas

International Nuclear Information System (INIS)

Baumert, Brigitta G.; Brada, Michael; Bernier, Jacques; Kortmann, Rolf D.; Dehing-Oberije, Cary; Collette, Laurence; Davis, J. Bernard

2008-01-01

Background and purpose: The EORTC trial No. 22972 investigated the role of an additional fractionated stereotactic boost (fSRT) to conventional radiotherapy for patients with high grade gliomas. A quality-assurance (QA) programme was run in conjunction with the study and was the first within the EORTC addressing the quality of a supposedly highly accurate treatment technique such as stereotactic radiotherapy. A second aim was to investigate a possible relation between the clinical results of the stereotactic boost arm and the results of the QA. Materials and methods: The trial was closed in 2001 due to low accrual. In total, 25 patients were randomized: 14 into the experimental arm and 11 into the control arm. Six centres randomized patients, 8 centres had completed the dummy run (DR) for the stereotactic boost part. All participating centres (9) were asked to complete a quality-assurance questionnaire. The DR consisted of treatment planning according to the guidelines of the protocol on 3 different tumour volumes drawn on CT images of a humanized phantom. The SRT technique to be used was evaluated by the questionnaire. Clinical data from patients recruited to the boost arm from 6 participating centres were analysed. Results: There was a full compliance to the protocol requirements for 5 centres. Major and minor deviations in conformality were observed for 2 and 3 centres, respectively. Of the 8 centres which completed the DR, one centre did not comply with the requirements of stereotactic radiotherapy concerning accuracy, dosimetry and planning. Median follow-up and median overall survival were 39.2 and 21.4 months, respectively. Acute and late toxicities of the stereotactic boost were low. One radiation necrosis was seen for a patient who has not received the SRT boost. Three reported serious adverse events were all seizures and probably therapy-related. Conclusions: Overall compliance was good but not ideal from the point of view of this highly precise radiation

Hospitality industry veteran to lead workshop on boosting sales and business

OpenAIRE

Crumbley, Liz

2009-01-01

Hospitality industry expert Howard Feiertag will teach participants how to energize sales and boost business during the "Hospitality Sales" workshop, April 27 and 28 at the Hotel Roanoke and Conference Center in Roanoke, Va.

Grid Connected Solar PV System with SEPIC Converter Compared with Parallel Boost Converter Based MPPT

Directory of Open Access Journals (Sweden)

T. Ajith Bosco Raj

2014-01-01

Full Text Available The main objective of this work is to study the behaviour of the solar PV systems and model the efficient Grid-connected solar power system. The DC-DC MPPT circuit using chaotic pulse width modulation has been designed to track maximum power from solar PV module. The conversion efficiency of the proposed MPPT system is increased when CPWM is used as a control scheme. This paper also proposes a simplified multilevel (seven level inverter for a grid-connected photovoltaic system. The primary goal of these systems is to increase the energy injected to the grid by keeping track of the maximum power point of the panel, by reducing the switching frequency, and by providing high reliability. The maximum power has been tracked experimentally. It is compared with parallel boost converter. Also this model is based on mathematical equations and is described through an equivalent circuit including a PV source with MPPT, a diode, a series resistor, a shunt resistor, and dual boost converter with active snubber circuit. This model can extract PV power and boost by using dual boost converter with active snubber. By using this method the overall system efficiency is improved thereby reducing the switching losses and cost.

Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report

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Waring Paul

2004-10-01

Full Text Available Abstract Background The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. Case presentation A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial. The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression

Analysis, control and design of a non-inverting buck-boost converter

DEFF Research Database (Denmark)

Almasi, Omid Naghash; Fereshtehpoor, Vahid; Khooban, Mohammad Hassan

2017-01-01

In this paper, a new modified fuzzy Two-Level Control Scheme (TLCS) is proposed to control a non-inverting buck-boost converter. Each level of fuzzy TLCS consists of a tuned fuzzy PI controller. In addition, a Takagi–Sugeno–Kang (TSK) fuzzy switch proposed to transfer the fuzzy PI controllers...... to eliminate these oscillations and improve the system performance. Some simulations and digital signal processor based experiments are conducted on a non-inverting buck-boost converter to support the effectiveness of the proposed TLCS in controlling the converter output voltage....... to each other in the control system. The major difficulty in designing fuzzy TLCS which degrades its performance is emerging unwanted drastic oscillations in the converter output voltage during replacing the controllers. Thereby, the fuzzy PI controllers in each level of TLCS structure are modified...

Control analysis and experimental verification of a practical dc–dc boost converter

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Saswati Swapna Dash

2015-12-01

Full Text Available This paper presents detailed open loop and closed loop analysis on boost dc–dc converter for both voltage mode control and current mode control. Here the boost dc–dc converter is a practical converter considering all possible parasitic elements like ESR and on state voltage drops. The open loop control, closed loop current mode control and voltage mode control are verified. The comparative study of all control techniques is presented. The PI compensator for closed loop current mode control is designed using these classical techniques like root locus technique and bode diagram. The simulation results are validated with the experimental results of voltage mode control for both open loop and closed loop control.

Imputing data that are missing at high rates using a boosting algorithm

Energy Technology Data Exchange (ETDEWEB)

Cauthen, Katherine Regina [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lambert, Gregory [Apple Inc., Cupertino, CA (United States); Ray, Jaideep [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Lefantzi, Sophia [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

2016-09-01

Traditional multiple imputation approaches may perform poorly for datasets with high rates of missingness unless many m imputations are used. This paper implements an alternative machine learning-based approach to imputing data that are missing at high rates. Here, we use boosting to create a strong learner from a weak learner fitted to a dataset missing many observations. This approach may be applied to a variety of types of learners (models). The approach is demonstrated by application to a spatiotemporal dataset for predicting dengue outbreaks in India from meteorological covariates. A Bayesian spatiotemporal CAR model is boosted to produce imputations, and the overall RMSE from a k-fold cross-validation is used to assess imputation accuracy.

Population pharmacokinetics of imatinib mesylate and its metabolite in children and young adults.

Science.gov (United States)

Menon-Andersen, Divya; Mondick, John T; Jayaraman, Bhuvana; Thompson, Patrick A; Blaney, Susan M; Bernstein, Mark; Bond, Mason; Champagne, Martin; Fossler, Michael J; Barrett, Jeffrey S

2009-01-01

Imatinib mesylate (Gleevec) is a small molecule tyrosine kinase inhibitor approved for use in the management of chronic myeloid leukemia in adults and children and in gastrointestinal stromal tumors in adults. Population pharmacokinetic (PPK) studies evaluating the effect of population covariates on the pharmacokinetics of imatinib and its active metabolite have been developed in adults with chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). However, this still remains to be described in children. The objectives of the analysis were to develop a PPK model of imatinib and its active metabolite, CGP74588, to describe exposure in children and young adults and to identify covariates that are predictors of variability in disposition. Plasma concentrations from 26 subjects with Philadelphia (Ph+) leukemia (Phase I study) and 15 subjects with refractory solid tumors (Phase II study), who received oral imatinib at doses ranging from 260 to 570 mg/m(2), were available for the PPK analysis in NONMEM. Blood samples were drawn prior to dosing and over 24-48 h on days 1 and 8 of the studies. Covariates studied included weight, age, albumin, alanine aminotransferase and the study population. The pharmacokinetics of imatinib and CGP 74588 were well described by one and two compartment models, respectively. Total body weight was the only covariate found to significantly affect Cl/F and V/F. The final imatinib-CGP 74588 model is summarized as follows: CL/F (imatinib) (L/h) = 10.8 x (WT/70)(0.75), V/F (imatinib) (L) = 284 x (WT/70) and D1(duration of zero order absorption,imatinib) (h) = 1.67 and CL/F (CGP 74588) (L/h) = 9.65 x (WT/70)(0.75), V1/F (CGP 74588) (L) = 11.6 x (WT/70), Q (CGP 74588) (L/h) = 2.9 x (WT/70)(0.75) and V2/F (CGP 74588) (L) = 256*(WT/70). Model evaluation indicated that the final model was robust and satisfactory. Current imatinib dosing guidelines in pediatrics is based on the achievement of exposures consistent with doses known to be

Maximizing the Therapeutic Efficacy of Imatinib Mesylate-Loaded Niosomes on Human Colon Adenocarcinoma Using Box-Behnken Design.

Science.gov (United States)

Kassem, Mohammed A; El-Sawy, Hossam S; Abd-Allah, Fathy I; Abdelghany, Tamer M; El-Say, Khalid M

2017-01-01

This research purposed to formulate an optimized imatinib mesylate (IM)-loaded niosomes to improve its chemotherapeutic efficacy. The influence of 3 formulation factors on niosomal vesicular size (Y 1 ), zeta potential (Y 2 ), entrapment capacity percentage (Y 3 ), the percentage of initial drug release after 2 h (Y 4 ), and the percentage of cumulative drug release after 24 h (Y 5 ) were studied and optimized using Box-Behnken design. Optimum desirability was specified and the optimized formula was prepared, stability tested, morphologically examined, checked for vesicular bilayer formation and evaluated for its in vitro cytotoxicity on 3 different cancer cell lines namely MCF-7, HCT-116, and HepG-2 in addition to 1 normal cell line to ensure its selectivity against cancer cells. The actual responses of the optimized IM formulation were 425.36 nm, -62.4 mV, 82.96%, 18.93%, and 89.45% for Y 1 , Y 2 , Y 3 , Y 4 , and Y 5 , respectively. The optimized IM-loaded niosomes confirmed the spherical vesicular shape imaged by both light and electron microscopes and further proven by differential scanning calorimetry. Moreover, the optimized formula exhibited improved stability on storage at 4 ± 2°C and superior efficacy on MCF7, HCT-116, and HepG2 as IC 50 values were 6.7, 16.4, and 7.3 folds less than those of free drug, respectively. Interestingly, IC 50 of the optimized formula against normal cell line was ranged from 3 to 11 folds higher than in different cancer cells indicating a higher selectivity of the optimized formula to cancer cells. In conclusion, the incorporation of IM in niosomes enhanced its efficacy and selectivity toward cancer cells, presenting a promising tool to fight cancer using this approach. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Search for new resonances with boosted signatures at CMS

CERN Multimedia

CERN. Geneva

2015-01-01

The LHC and its experiments are ideally suited to search for these new resonances in order to validate or constrain the corresponding theories. At resonance masses well above 1 TeV, these searches face specific challenges. The decay products have large Lorentz boosts, resulting in very collimated final state topologies. Jet substructure methods and the use of non-isolate...

Boosting iterative stochastic ensemble method for nonlinear calibration of subsurface flow models

KAUST Repository

Elsheikh, Ahmed H.

2013-06-01

A novel parameter estimation algorithm is proposed. The inverse problem is formulated as a sequential data integration problem in which Gaussian process regression (GPR) is used to integrate the prior knowledge (static data). The search space is further parameterized using Karhunen-Loève expansion to build a set of basis functions that spans the search space. Optimal weights of the reduced basis functions are estimated by an iterative stochastic ensemble method (ISEM). ISEM employs directional derivatives within a Gauss-Newton iteration for efficient gradient estimation. The resulting update equation relies on the inverse of the output covariance matrix which is rank deficient.In the proposed algorithm we use an iterative regularization based on the ℓ2 Boosting algorithm. ℓ2 Boosting iteratively fits the residual and the amount of regularization is controlled by the number of iterations. A termination criteria based on Akaike information criterion (AIC) is utilized. This regularization method is very attractive in terms of performance and simplicity of implementation. The proposed algorithm combining ISEM and ℓ2 Boosting is evaluated on several nonlinear subsurface flow parameter estimation problems. The efficiency of the proposed algorithm is demonstrated by the small size of utilized ensembles and in terms of error convergence rates. © 2013 Elsevier B.V.

Comparison of IPV to tOPV week 39 boost of primary OPV vaccination in Indian infants: an open labelled randomized controlled trial

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Suman Kanungo

2017-01-01

Conclusions: This study indicates that an IPV boost at week 39 is equivalent to tOPV in intestinal immunity, and provides higher seroconversion compared to tOPV. The major limitation of the study was the additional OPV doses receive by infants during pulse polio immunization resulted in additional mucosal boosting, diminishing the impact of IPV or tOPV boost at week 39. However, IPV for OPV boost should prove to be a step forward in the global polio eradication initiative to reduce the problem of circulating vaccine-derived poliovirus (cVDPV.

Individualized planning target volumes for intrafraction motion during hypofractionated intensity-modulated radiotherapy boost for prostate cancer

International Nuclear Information System (INIS)

Cheung, Patrick; Sixel, Katharina; Morton, Gerard; Loblaw, D. Andrew; Tirona, Romeo; Pang, Geordi; Choo, Richard; Szumacher, Ewa; DeBoer, Gerrit; Pignol, Jean-Philippe

2005-01-01

Purpose: The objective of the study was to access toxicities of delivering a hypofractionated intensity-modulated radiotherapy (IMRT) boost with individualized intrafraction planning target volume (PTV) margins and daily online correction for prostate position. Methods and materials: Phase I involved delivering 42 Gy in 21 fractions using three-dimensional conformal radiotherapy, followed by a Phase II IMRT boost of 30 Gy in 10 fractions. Digital fluoroscopy was used to measure respiratory-induced motion of implanted fiducial markers within the prostate. Electronic portal images were taken of fiducial marker positions before and after each fraction of radiotherapy during the first 9 days of treatment to calculate intrafraction motion. A uniform 10-mm PTV margin was used for the first phase of treatment. PTV margins for Phase II were patient-specific and were calculated from the respiratory and intrafraction motion data obtained from Phase I. The IMRT boost was delivered with daily online correction of fiducial marker position. Acute toxicity was measured using National Cancer Institute Common Toxicity Criteria, version 2.0. Results: In 33 patients who had completed treatment, the average PTV margin used during the hypofractionated IMRT boost was 3 mm in the lateral direction, 3 mm in the superior-inferior direction, and 4 mm in the anteroposterior direction. No patients developed acute Grade 3 rectal toxicity. Three patients developed acute Grade 3 urinary frequency and urgency. Conclusions: PTV margins can be reduced significantly with daily online correction of prostate position. Delivering a hypofractionated boost with this high-precision IMRT technique resulted in acceptable acute toxicity

ATLAS Jet Reconstruction, Calibration, and Tagging of Lorentz-boosted Objects

CERN Document Server

Schramm, Steven; The ATLAS collaboration

2017-01-01

Jet reconstruction in the ATLAS detector takes multiple forms, as motivated by the intended usage of the jet. Different jet definitions are used in particular for the study of QCD jets and jets containing the hadronic decay of boosted massive particles. These different types of jets are calibrated through a series of mostly sequential steps, providing excellent uncertainties, including a first in situ calibration of the jet mass scale. Jet tagging is investigated, including both not-top-quark vs gluon discrimination as well as W/Z boson, H$\\to$bb, and top-quark identification. This includes a first look at the use of Boosted Decision Trees and Deep Neural Networks built from jet substructure variables, as well as Convolutional Neural Networks built from jet images. In all cases, these advanced techniques are seen to provide gains over the standard approaches, with the magnitude of the gain depending on the use case. Future methods for improving jet tagging are briefly discussed, including jet substructure-ori...

Boosting the Direct CP Measurement of the Higgs-Top Coupling.

Science.gov (United States)

Buckley, Matthew R; Gonçalves, Dorival

2016-03-04

Characterizing the 125 GeV Higgs boson is a critical component of the physics program at the LHC Run II. In this Letter, we consider tt[over ¯]H associated production in the dileptonic mode. We demonstrate that the difference in azimuthal angle between the leptons from top decays can directly reveal the CP structure of the top-Higgs coupling with the sensitivity of the measurement substantially enhanced in the boosted Higgs regime. We first show how to access this channel via H→bb[over ¯] jet-substructure tagging, then demonstrate the ability of the new variable to measure CP. Our analysis includes all signal and background samples simulated via the MC@NLO algorithm including hadronization and underlying-event effects. Using a boosted Higgs substructure with dileptonic tops, we find that the top-Higgs coupling strength and the CP structure can be directly probed with achievable luminosity at the 13 TeV LHC.

Comparison of posterior fossa and tumor bed boost in medulloblastoma.

Science.gov (United States)

Paulino, A C; Saw, C B; Wen, B C

2000-10-01

To quantify the difference between the area of brain irradiated using the posterior fossa boost (PFB) and tumor bed boost (TBB) in medulloblastoma, we studied 15 simulation radiographs of patients treated in our institution from 1990 and 1999. The PFB was compared with the TBB, which was defined as the tumor bed plus 2-cm margin as demonstrated by postoperative magnetic resonance imaging. The PFB field treated a mean area of 9.43 cm2 more brain than the TBB. In 3 patients (20%), the area of the brain in the TBB was larger than the PFB. In 11 patients (73.3%), the PFB field had more than 10% more brain than the TBB. The cochlea was in the PFB and TBB field in all patients. In more than two thirds of patients, the area of brain irradiated with the PFB was at least 10% greater than the TBB. Future studies are needed to determine whether the TBB can replace the PFB in patients with medulloblastoma.

Results of brachytherapy boost in high risk breast cancer patients

International Nuclear Information System (INIS)

Battermann, J.J.

1996-01-01

Introduction: in breast conserving therapy the role of brachytherapy as a boost after whole breast irradiation is not clear. The series from the Netherlands Cancer Institute show a very high local control rate, but the question could be raised whether all these patients need a brachy boost. Therefore, it was decided at our institute, to deliver a brachy boost only to high risk patients, viz. patients with incomplete resection margins and/or extensive in situ cancer (ECI). Materials and methods: in the period 1988 through 1993 a total of 148 patients with 151 breast tumours received a boost on the tumour bed using brachytherapy. Age varied from 25 till 74 years, with a mean age of 52.3 years. Incomplete resection margins were found in 60 patients, ECI in 31 and both in 49 patients. In the majority of patients, the ECI component was not completely removed. T-stage was unknown in 9 patients. T1 in 83, T2 in 49 and T3 in 10. Nodal status was N0 in 119 and N1 in 33 patients. Infiltrating duct carcinoma was the most common histology. No infiltrating growth was found in 6 patients, but one patient presented a positive node. The interval period between day of operation and day of brachytherapy implantation was between 3 and 4 months in 62%. The mean interval between completion of beam irradiation and day of implantation was 18 days, while 12 patients received their brachytherapy previous to the beam irradiation. External irradiation was with two tangential fields and a total dose of 50 Gy in 25 fractions over 6 weeks (9 fractions in two weeks). The number of needles in two planes. Most patients were implanted under local anaesthesia. Dose rate in 97 patients was 51 - 60 cGy/h. Results: follow-up for patients alive varied from 2 years till 7 years with a mean follow-up period of 4 years. One hundred and twenty five patients are alive, including 6 patients with manifest metastases. Local recurrence was encountered in 8 patients (interval 14 - 60 months, mean 30 months), with

Análise morfológica e fisiológica dos fígados e rins de ratas prenhes e seus fetos tratados pela associação zidovudina, lamivudina e ritonavir durante toda a prenhez Morphological and physiological analysis of livers and kidneys of pregnant rats and their fetuses treated by the association of zidovudine, lamivudine and ritonavir for the whole period of pregnancy

Directory of Open Access Journals (Sweden)

Adriana Wagner

2010-11-01

Full Text Available OBJETIVO: avaliar os efeitos da administração da associação zidovudina-lamivudina-ritonavir nos fígados e rins de ratas prenhes e seus conceptos do ponto de vista morfológico e fisiológico. MÉTODOS: 40 ratas albinas prenhes foram aleatoriamente divididas em 4 grupos: 1 controle (Ctrl: controle de veículo e 3 experimentais (Exp1x, Exp3x e Exp9x. Estes últimos foram tratados por solução oral de zidovudina/lamivudina/ritonavir (Exp1x: 10/5/20 mg/kg; Exp3x: 30/15/60 mg/kg; Exp9x: 90/45/180 mg/kg. As drogas e o veículo foram administrados por gavagem, desde o 1º até o 20º dia de prenhez. No último dia do experimento, todos os animais foram anestesiados e sangue foi retirado da cavidade cardíaca para avaliação sérica das enzimas aspartato aminotransferase (AST e alanina aminotransferase (ALT, por método calorimétrico, bem como da ureia, determinada por método cinético-enzimático, e creatinina, por método cinético-colorimétrico. Em seguida, fragmentos dos fígados e rins maternos e fetais foram coletados, fixados em formol a 10% e processados segundo os métodos histológicos para inclusão em parafina. Cortes com 5 µm de espessura foram corados pela hematoxilina-eosina (HE e analisados por microscopia de luz. Na leitura das lâminas, considerou-se o padrão de normalidade para fígado e rins, tais como: hepatócitos, espaço porta íntegros e veias hepáticas bem definidas. Nos rins, a presença de corpúsculos renais, túbulos contorcidos e alças de Henle típicos. Nos fígados fetais considerou-se, ainda, a morfologia das células da linhagem eritrocitária nas diferentes fases do desenvolvimento, bem como os megacariócitos. Quando houve alteração da coloração padrão estabelecida para as estruturas hepáticas e renais, alteração na morfologia de núcleos, rompimento de limites de alguma organela citoplasmática, presença de congestão vascular, tudo isso foi entendido como provavelmente provocado pelas drogas

Boosting long-term memory via wakeful rest: intentional rehearsal is not necessary, consolidation is sufficient.

Directory of Open Access Journals (Sweden)

Michaela Dewar

Full Text Available People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as 'foreign names in a bridge club abroad' and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is not dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is sufficient for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.

Boost Converter with Active Snubber Network

Directory of Open Access Journals (Sweden)

HIMMELSTOSS, F. A.

2017-02-01

Full Text Available A new concept for reducing the losses in a boost converter is described. With the help of an auxiliary switch and a resonant circuit, zero-voltage switching at turn-off and zero-current switching during turn-on are achieved. The modes of the circuit are shown in detail. The energy recovery of the turn-off is analyzed and the recovered energy is calculated; an optimized switching concept therefore is described. The influence of the parasitic capacity of the switch is discussed. Dimensioning hints for the converter and the design of the recuperation circuit are given. A bread-boarded design shows the functional efficiency of the concept.

Multimodal nanoparticles as alignment and correlation markers in fluorescence/soft X-ray cryo-microscopy/tomography of nucleoplasmic reticulum and apoptosis in mammalian cells

International Nuclear Information System (INIS)

Hagen, Christoph; Werner, Stephan; Carregal-Romero, Susana; Malhas, Ashraf N.; Klupp, Barbara G.; Guttmann, Peter; Rehbein, Stefan; Henzler, Katja; Mettenleiter, Thomas C.

2014-01-01

Correlative fluorescence and soft X-ray cryo-microscopy/tomography on flat sample holders is perfectly suited to study the uncompromised physiological status of adherent cells at its best possible preservation by imaging after fast cryo-immobilization. To understand the mechanism by which herpesviruses induce nucleoplasmic reticulum, i.e. invaginations of the nuclear envelope, during their egress from the host cell nucleus, morphologically similar structures found in laminopathies and after chemical induction were investigated as a potentially more easily accessible model system. For example, anti-retroviral protease inhibitors like Saquinavir also induce invaginations of the nuclear membranes. With the help of newly designed multimodal nanoparticles as alignment and correlation markers, and by optimizing fluorescence cryo-microscopy data acquisition, an elaborate three-dimensional network of nucleoplasmic reticulum was demonstrated in nuclei of Saquinavir-treated rabbit kidney cells expressing a fluorescently labeled inner nuclear membrane protein. In part of the protease inhibitor-treated samples, nuclei exhibited dramatic ultrastructural changes indicative of programmed cell death/apoptosis. This unexpected observation highlights another unique feature of soft X-ray microscopy, i.e. high absorption contrast information not relying on labeled cellular components, at a 3D resolution of approximately 40 nm (half-pitch) and through a sample thickness of several micrometers. These properties make it a valuable part of the cell biology imaging toolbox to visualize the cellular ultrastructure in its completeness. - Highlights: • Nucleoplasmic reticulum was demonstrated in nuclei of Saquinavir-treated cells. • New polyelectrolyte-Qdot ® 605 coated gold beads were employed as fiducials. • Saquinavir can induce a strong apoptotic phenotype in the nucleus. • CryoXT is an auspicious imaging technique in apoptosis research

Interstitial high-dose rate brachytherapy as boost for anal canal cancer

International Nuclear Information System (INIS)

Falk, Alexander Tuan; Claren, Audrey; Benezery, Karen; François, Eric; Gautier, Mathieu; Gerard, Jean-Pierre; Hannoun-Levi, Jean-Michel

2014-01-01

To assess clinical outcomes of patients treated with a high-dose rate brachytherapy boost for anal canal cancer (ACC). From August 2005 to February 2013, 28 patients presenting an ACC treated by split-course external beam radiotherapy (EBRT) and HDR brachytherapy with or without chemotherapy in a French regional cancer center in Nice were retrospectively analyzed. Median age was 60.6 years [34 – 83], 25 patients presented a squamous cell carcinoma and 3 an adenocarcinoma; 21 received chemotherapy. Median dose of EBRT was 45 Gy [43.2 – 52]. Median dose of HDR brachytherapy was 12 Gy [10 - 15] with a median duration of 2 days. Median overall treatment time was 63 days and median delay between EBRT and brachytherapy was 20 days. Two-year local relapse free, metastatic free, disease free and overall survivals were 83%, 81.9%, 71.8% and 87.7% respectively. Acute toxicities were frequent but not severe with mostly grade 1 toxicities: 37% of genito-urinary, 40.7% of gastro-intestinal and 3.7% of cutaneous toxicities. Late toxicities were mainly G1 (43.1%) and G2 (22%). Two-year colostomy-free survival was 75.1%, one patient had a definitive sphincter amputation. High-dose rate brachytherapy for anal canal carcinoma as boost represents a feasible technique compared to low or pulsed-dose rate brachytherapy. This technique remains an excellent approach to precisely boost the tumor in reducing the overall treatment time

Combining Boosted Global

Directory of Open Access Journals (Sweden)

Szidónia Lefkovits

2011-06-01

Full Text Available The domain of object detection presents a wide range of interest due to its numerous application possibilities especially real time applications. All of them require high detection rate correlated with short processing time. One of the most efficient systems, working with visual information, were presented in the publication of Viola et al. [1], [2].This detection system uses classifiers based on Haar-like separating features combined with the AdaBoost learning algorithm. The most important bottleneck of the system is the big number of false detections at high hit rate. In this paper we propose to overcome this disadvantage by using specialized parts classifiers. This aim comes from the observation that the target object does not resemble the false detections at all.The reason of this fact is the coding manner of Haar-like features which attend to handle image patches and neglect the edges and contours. In order to obtain a more robust classifier, a global aspect method is combined with a part-based method, having the goal to improve the performance of the detector without significant increase of the detection time.

A prediction model of short-term ionospheric foF2 Based on AdaBoost

Science.gov (United States)

Zhao, Xiukuan; Liu, Libo; Ning, Baiqi

Accurate specifications of spatial and temporal variations of the ionosphere during geomagnetic quiet and disturbed conditions are critical for applications, such as HF communications, satellite positioning and navigation, power grids, pipelines, etc. Therefore, developing empirical models to forecast the ionospheric perturbations is of high priority in real applications. The critical frequency of the F2 layer, foF2, is an important ionospheric parameter, especially for radio wave propagation applications. In this paper, the AdaBoost-BP algorithm is used to construct a new model to predict the critical frequency of the ionospheric F2-layer one hour ahead. Different indices were used to characterize ionospheric diurnal and seasonal variations and their dependence on solar and geomagnetic activity. These indices, together with the current observed foF2 value, were input into the prediction model and the foF2 value at one hour ahead was output. We analyzed twenty-two years’ foF2 data from nine ionosonde stations in the East-Asian sector in this work. The first eleven years’ data were used as a training dataset and the second eleven years’ data were used as a testing dataset. The results show that the performance of AdaBoost-BP is better than those of BP Neural Network (BPNN), Support Vector Regression (SVR) and the IRI model. For example, the AdaBoost-BP prediction absolute error of foF2 at Irkutsk station (a middle latitude station) is 0.32 MHz, which is better than 0.34 MHz from BPNN, 0.35 MHz from SVR and also significantly outperforms the IRI model whose absolute error is 0.64 MHz. Meanwhile, AdaBoost-BP prediction absolute error at Taipei station from the low latitude is 0.78 MHz, which is better than 0.81 MHz from BPNN, 0.81 MHz from SVR and 1.37 MHz from the IRI model. Finally, the variety characteristics of the AdaBoost-BP prediction error along with seasonal variation, solar activity and latitude variation were also discussed in the paper.

Designing of new structure PID controller of boost converter for solar photovoltaic stability

Science.gov (United States)

Shabrina, Hanifati Nur; Setiawan, Eko Adhi; Sabirin, Chip Rinaldi

2017-03-01

Nowadays, the utilization of renewable energy as the source on distributed generation system is increasing. It aims to reduce reliance and power losses from utility grid and improve power stability in near loads. One example of renewable energy technology that have been highly proven on the market is solar photovoltaic (PV). This technology converts photon from sunlight into electricity. However, the fluctuation of solar radiation that often occurs become the main problem for this system. Due to this condition, the power conversion is needed to convert the change frequently in photovoltaic panel into a stable voltage to the system. Developing control of boost converter has important role to keep ability of system stabilization. A conventional PID (Proportional, Integral, Derivative) control is mostly used to achieve this goal. In this research, a design of new structure PID controller of boost converter is offered to better optimize system stability comparing to the conventional PID. Parameters obtained from this PID structure have been successfully yield a stable boost converter output at 200 V with 10% overshoot, 1.5 seconds of settling time, and 1.5% of steady-state error.

Intraoperative Boost Radiotherapy during Targeted Oncoplastic Breast Surgery: Overview and Single Center Experiences

Directory of Open Access Journals (Sweden)

Wolfram Malter

2014-01-01

Full Text Available Breast-conserving surgery followed by whole-breast irradiation is the standard local therapy for early breast cancer. The international discussion of reduced importance of wider tumor-free resection margins than “tumor not touching ink” leads to the development of five principles in targeted oncoplastic breast surgery. IORT improves local recurrence risk and diminishes toxicity since there is less irradiation of healthy tissue. Intraoperative radiotherapy (IORT can be delivered in two settings: an IORT boost followed by a conventional regimen of external beam radiotherapy or a single IORT dose. The data from TARGIT-A and ELIOT reinforce the conviction that intraoperative radiotherapy during breast-conserving surgery is a reliable alternative to conventional postoperative fractionated irradiation, but only in a carefully selected population at low risk of local recurrence. We describe our experiences with IORT boost (50 kV energy X-rays; 20 Gy in combination with targeted oncoplastic breast surgery in a routine clinical setting. Our experiences demonstrate the applicability and reliability of combining IORT boost with targeted oncoplastic breast surgery in breast-conserving therapy of early breast cancer.

High Current Planar Transformer for Very High Efficiency Isolated Boost DC-DC Converters

DEFF Research Database (Denmark)

Pittini, Riccardo; Zhang, Zhe; Andersen, Michael A. E.

2014-01-01

This paper presents a design and optimization of a high current planar transformer for very high efficiency dc-dc isolated boost converters. The analysis considers different winding arrangements, including very high copper thickness windings. The analysis is focused on the winding ac-resistance a......This paper presents a design and optimization of a high current planar transformer for very high efficiency dc-dc isolated boost converters. The analysis considers different winding arrangements, including very high copper thickness windings. The analysis is focused on the winding ac......-resistance and transformer leakage inductance. Design and optimization procedures are validated based on an experimental prototype of a 6 kW dcdc isolated full bridge boost converter developed on fully planar magnetics. The prototype is rated at 30-80 V 0-80 A on the low voltage side and 700-800 V on the high voltage side...... with a peak efficiency of 97.8% at 80 V 3.5 kW. Results highlights that thick copper windings can provide good performance at low switching frequencies due to the high transformer filling factor. PCB windings can also provide very high efficiency if stacked in parallel utilizing the transformer winding window...

Novel vehicle detection system based on stacked DoG kernel and AdaBoost

Science.gov (United States)

Kang, Hyun Ho; Lee, Seo Won; You, Sung Hyun

2018-01-01

This paper proposes a novel vehicle detection system that can overcome some limitations of typical vehicle detection systems using AdaBoost-based methods. The performance of the AdaBoost-based vehicle detection system is dependent on its training data. Thus, its performance decreases when the shape of a target differs from its training data, or the pattern of a preceding vehicle is not visible in the image due to the light conditions. A stacked Difference of Gaussian (DoG)–based feature extraction algorithm is proposed to address this issue by recognizing common characteristics, such as the shadow and rear wheels beneath vehicles—of vehicles under various conditions. The common characteristics of vehicles are extracted by applying the stacked DoG shaped kernel obtained from the 3D plot of an image through a convolution method and investigating only certain regions that have a similar patterns. A new vehicle detection system is constructed by combining the novel stacked DoG feature extraction algorithm with the AdaBoost method. Experiments are provided to demonstrate the effectiveness of the proposed vehicle detection system under different conditions. PMID:29513727

Optimal infrastructure selection to boost regional sustainable economy

OpenAIRE

Martín Utrillas, Manuel Guzmán; Juan-Garcia, F.; Cantó Perelló, Julián; Curiel Esparza, Jorge

2015-01-01

The role of infrastructures in boosting the economic growth of the regions is widely recognized. In many cases, an infrastructure is selected by subjective reasons. Selection of the optimal infrastructure for sustainable economic development of a region should be based on objective and founded reasons, not only economical, but also environmental and social. In this paper is developed such selection through a hybrid method based on Delphi, analytical hierarchy process (AHP), and VIKOR (from Se...